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  1. Free, publicly-accessible full text available February 7, 2025
  2. Abstract

    Recombinant adeno‐associated virus (rAAV) is among the most commonly used in vivo gene delivery vehicles and has seen a number of successes in clinical application. Current manufacturing processes of rAAV employ multiple plasmid transfection or rely on virus infection and face challenges in scale‐up. A synthetic biology approach was taken to generate stable cell lines with integrated genetic modules, which produced rAAV upon induction albeit at a low productivity. To identify potential factors that restrained the productivity, we systematically characterized virus production kinetics through targeted quantitative proteomics and various physical assays of viral components. We demonstrated that reducing the excessive expression of gene of interest by its conditional expression greatly increased the productivity of these synthetic cell lines. Further enhancement was gained by optimizing induction profiles and alleviating proteasomal degradation of viral capsid protein by the addition of proteasome inhibitors. Altogether, these enhancements brought the productivity close to traditional multiple plasmid transfection. The rAAV produced had comparable full particle contents as those produced by conventional transient plasmid transfection. The present work exemplified the versatility of our synthetic biology‐based viral vector production platform and its potential for plasmid‐ and virus‐free rAAV manufacturing.

     
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    Free, publicly-accessible full text available January 1, 2025
  3. Free, publicly-accessible full text available January 17, 2025
  4. Abstract

    The functionality of atomic quantum emitters is intrinsically linked to their host lattice coordination. Structural distortions that spontaneously break the lattice symmetry strongly impact their optical emission properties and spin-photon interface. Here we report on the direct imaging of charge state-dependent symmetry breaking of two prototypical atomic quantum emitters in mono- and bilayer MoS2by scanning tunneling microscopy (STM) and non-contact atomic force microscopy (nc-AFM). By changing the built-in substrate chemical potential, different charge states of sulfur vacancies (VacS) and substitutional rhenium dopants (ReMo) can be stabilized. Vac$${}_{{{{{{{{\rm{S}}}}}}}}}^{-1}$$S1as well as Re$${}_{{{{{{{{\rm{Mo}}}}}}}}}^{0}$$Mo0and Re$${}_{{{{{{{{\rm{Mo}}}}}}}}}^{-1}$$Mo1exhibit local lattice distortions and symmetry-broken defect orbitals attributed to a Jahn-Teller effect (JTE) and pseudo-JTE, respectively. By mapping the electronic and geometric structure of single point defects, we disentangle the effects of spatial averaging, charge multistability, configurational dynamics, and external perturbations that often mask the presence of local symmetry breaking.

     
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  5. Free, publicly-accessible full text available November 13, 2024
  6. Abstract

    RZ Piscium (RZ Psc) is well known in the variable star field because of its numerous irregular optical dips in the past 5 decades, but the nature of the system is heavily debated in the literature. We present multiyear infrared monitoring data from Spitzer and WISE to track the activities of the inner debris production, revealing stochastic infrared variability as short as weekly timescales that is consistent with destroying a 90 km sized asteroid every year. ALMA 1.3 mm data combined with spectral energy distribution modeling show that the disk is compact (∼0.1–13 au radially) and lacks cold gas. The disk is found to be highly inclined and has a significant vertical scale height. These observations confirm that RZ Psc hosts a close to edge-on, highly perturbed debris disk possibly due to migration of recently formed giant planets that might be triggered by the low-mass companion RZ Psc B if the planets formed well beyond the snowlines.

     
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    Free, publicly-accessible full text available December 1, 2024
  7. Free, publicly-accessible full text available January 18, 2025
  8. ABSTRACT

    We present a new analysis of the rest-frame ultraviolet (UV) and optical spectra of a sample of three z > 8 galaxies discovered behind the gravitational lensing cluster RX J2129.4+0009. We combine these observations with z > 7.5 galaxies from the literature, for which similar measurements are available. As already pointed out in other studies, the high [O iii]λ5007/[O ii]λ3727 ratios (O32) and steep UV continuum slopes (β) are consistent with the values observed for low-redshift Lyman continuum emitters, suggesting that such galaxies contribute to the ionizing budget of the intergalactic medium. We construct a logistic regression model to estimate the probability of a galaxy being a Lyman continuum emitter based on the measured MUV, β, and O32. Using this probability and the UV luminosity function, we construct an empirical model that estimates the contribution of high-redshift galaxies to reionization. The preferred scenario in our analysis shows that at z ∼ 8, the average escape fraction of the galaxy population [i.e. including both LyC emitters (LCEs) and non-emitters] varies with MUV, with intermediate UV luminosity (−19 < MUV < −16) galaxies having larger escape fraction. Galaxies with faint UV luminosity (−16 < MUV < −13.5) contribute most of the ionizing photons. The relative contribution of faint versus bright galaxies depends on redshift, with the intermediate UV galaxies becoming more important over time. UV bright galaxies, although more likely to be LCEs at a given log(O32) and β, contribute the least of the total ionizing photon budget.

     
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  9. Genes that regulate hormone release are essential for maintaining metabolism and energy balance. Egr1 encodes a transcription factor that regulates hormone production and release, and a decreased in growth hormones has been reported in Egr1 knockout mice. A reduction in growth hormones has also been observed in Nestin-Cre mice, a model frequently used to study the nervous system. Currently, it is unknown how Egr1 loss or the Nestin-Cre driver disrupt pituitary gene expression. Here, we compared the growth curves and pituitary gene expression profiles of Nestin-Cre-mediated Egr1 conditional knockout (Egr1cKO) mice with those of their controls. Reduced body weight was observed in both the Nestin-Cre and Egr1cKO mice, and the loss of Egr1 had a slightly more severe impact on female mice than on male mice. RNA-seq data analyses revealed that the sex-related differences were amplified in the Nestin-Cre-mediated Egr1 conditional knockout mice. Additionally, in the male mice, the influence of Egr1cKO on pituitary gene expression may be overridden by the Nestin-Cre driver. Differentially expressed genes associated with the Nestin-Cre driver were significantly enriched for genes related to growth factor activity and binding. Altogether, our results demonstrate that Nestin-Cre and the loss of Egr1 in the neuronal cell lineage have distinct impacts on pituitary gene expression in a sex-specific manner.

     
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    Free, publicly-accessible full text available July 1, 2024