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Abstract Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) is a promising tool to study genomic rearrangements. However, the potential of SCRaMbLE to study genomic rearrangements is currently hindered, because a strain containing all 16 synthetic chromosomes is not yet available. Here, we construct SparLox83R, a yeast strain containing 83 loxPsym sites distributed across all 16 chromosomes. SCRaMbLE of SparLox83R produces versatile genome-wide genomic rearrangements, including inter-chromosomal events. Moreover, when combined with synthetic chromosomes, SCRaMbLE of hetero-diploids with SparLox83R leads to increased diversity of genomic rearrangements and relatively faster evolution of traits compared to hetero-diploids only with wild-type chromosomes. Analysis of the SCRaMbLEd strain with increased tolerance to nocodazole demonstrates that genomic rearrangements can perturb the transcriptome and 3D genome structure and consequently impact phenotypes. In summary, a genome with sparsely distributed loxPsym sites can serve as a powerful tool for studying the consequence of genomic rearrangements and accelerating strain engineering inSaccharomyces cerevisiae. 

Abstract The genome of an organism is inherited from its ancestor and continues to evolve over time, however, the extent to which the current version could be altered remains unknown. To probe the genome plasticity ofSaccharomyces cerevisiae, here we replace the native left arm of chromosome XII (chrXIIL) with a linear artificial chromosome harboring small sets of reconstructed genes. We find that as few as 12 genes are sufficient for cell viability, whereas 25 genes are required to recover the partial fitness defects observed in the 12-gene strain. Next, we demonstrate that these genes can be reconstructed individually using synthetic regulatory sequences and recoded open-reading frames with a “one-amino-acid-one-codon” strategy to remain functional. Finally, a synthetic neochromsome with the reconstructed genes is assembled which could substitutechrXIILfor viability. Together, our work not only highlights the high plasticity of yeast genome, but also illustrates the possibility of making functional eukaryotic chromosomes from entirely artificial sequences. 

Organic electronics technologies have attracted considerable interest over the last few decades and have become promising alternatives to conventional, inorganic platforms for specific applications. To fully exploit the touted potential of plastic electronics, however, other prerequisites than only electronic functions need to be fulfiled, including good mechanical stability, ease of processing and high device reliability. A possible method to overcome these issues is the employment of insulating:semiconducting polymer blends, which have been demonstrated to display favourable rheological and mechanical properties, generally provided by the insulating component, without negatively affecting the optoelectronic performance of the semiconductor. Here, we demonstrate that binary blends comprising the semicrystalline high-density polyethylene (HDPE) in combination with hole- and electron-transporting organic semiconductors allow fabrication of p-type and n-type thin-film transistors of notably improved device stability and, in some scenarios, improved device performance. We observe, for example, considerably lower subthreshold slopes and drastically reduced bias-stress effects in devices fabricated with a hole-transporting diketopyrrolopyrrole polymer derivative when blended with HDPE and significantly enhanced charge-carrier mobilities and shelf life in case of transistors made with blends between HDPE and the electron-transporting poly{[ N , N ′-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)2,6-diyl]- alt -5,5′-(2,2′-bithiophene)}, i.e. P(NDI2OD-T2), also known as N2200, compared to the neat material, highlighting the broad, versatile benefits blending semiconducting species with a semicrystalline commodity polymer can have. 

The nucleolus is the most prominent membraneless compartment within the nucleus—dedicated to the metabolism of ribosomal RNA. Nucleoli are composed of hundreds of ribosomal DNA (rDNA) repeated genes that form large chromosomal clusters, whose high recombination rates can cause nucleolar dysfunction and promote genome instability. Intriguingly, the evolving architecture of eukaryotic genomes appears to have favored two strategic rDNA locations—where a single locus per chromosome is situated either near the centromere (CEN) or the telomere. Here, we deployed an innovative genome engineering approach to cut and paste to an ectopic chromosomal location—the ~1.5 mega-base rDNA locus in a single step using CRISPR technology. This “megablock” rDNA engineering was performed in a fused-karyotype strain ofSaccharomyces cerevisiae. The strategic repositioning of this locus within the megachromosome allowed experimentally mimicking and monitoring the outcome of an rDNA migratory event, in which twin rDNA loci coexist on the same chromosomal arm. We showed that the twin-rDNA yeast readily adapts, exhibiting wild-type growth and maintaining rRNA homeostasis, and that the twin loci form a single nucleolus throughout the cell cycle. Unexpectedly, the size of each rDNA array appears to depend on its position relative to theCEN, in that the locus that isCEN-distal undergoes size reduction at a higher frequency compared to theCEN-proximal counterpart. Finally, we provided molecular evidence supporting a mechanism called paralogouscis-rDNA interference, which potentially explains why placing two identical repeated arrays on the same chromosome may negatively affect their function and structural stability. 

Abstract Next-generation wearable electronics require enhanced mechanical robustness and device complexity. Besides previously reported softness and stretchability, desired merits for practical use include elasticity, solvent resistance, facile patternability and high charge carrier mobility. Here, we show a molecular design concept that simultaneously achieves all these targeted properties in both polymeric semiconductors and dielectrics, without compromising electrical performance. This is enabled by covalently-embedded in-situ rubber matrix (iRUM) formation through good mixing of iRUM precursors with polymer electronic materials, and finely-controlled composite film morphology built on azide crosslinking chemistry which leverages different reactivities with C–H and C=C bonds. The high covalent crosslinking density results in both superior elasticity and solvent resistance. When applied in stretchable transistors, the iRUM-semiconductor film retained its mobility after stretching to 100% strain, and exhibited record-high mobility retention of 1 cm 2 V −1 s −1 after 1000 stretching-releasing cycles at 50% strain. The cycling life was stably extended to 5000 cycles, five times longer than all reported semiconductors. Furthermore, we fabricated elastic transistors via consecutively photo-patterning of the dielectric and semiconducting layers, demonstrating the potential of solution-processed multilayer device manufacturing. The iRUM represents a molecule-level design approach towards robust skin-inspired electronics.