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We recently described an unconventional mode of gene regulation in budding yeast by which transcriptional and translational interference collaborate to down-regulate protein expression. Developmentally timed transcriptional interference inhibited production of a well translated mRNA isoform and resulted in the production of an mRNA isoform containing inhibitory upstream open reading frames (uORFs) that prevented translation of the main ORF. Transcriptional interference and uORF-based translational repression are established mechanisms outside of yeast, but whether this type of integrated regulation was conserved was unknown. Here we find that, indeed, a similar type of regulation occurs at the locus for the human oncogene MDM2 We observe evidence of transcriptional interference between the two MDM2 promoters, which produce a poorly translated distal promoter-derived uORF-containing mRNA isoform and a well-translated proximal promoter-derived transcript. Down-regulation of distal promoter activity markedly up-regulates proximal promoter-driven expression and results in local reduction of histone H3K36 trimethylation. Moreover, we observe that this transcript toggling between the two MDM2 isoforms naturally occurs during human embryonic stem cell differentiation programs.

Levels of the ribosome, the conserved molecular machine that mediates translation, are tightly linked to cellular growth rate. In humans, ribosomopathies are diseases associated with cell-type-specific pathologies and reduced ribosomal protein (RP) levels. Because gene expression defects resulting from ribosome deficiency have not yet been experimentally defined, we systematically probed mRNA, translation, and protein signatures that were either unlinked from or linked to cellular growth rate in RP-deficient yeast cells. Ribosome deficiency was associated with altered translation of gene subclasses, and profound general secondary effects of RP loss on the spectrum of cellular mRNAs were seen. Among these effects, growth-defective 60S mutants increased synthesis of proteins involved in proteasome-mediated degradation, whereas 40S mutants accumulated mature 60S subunits and increased translation of ribosome biogenesis genes. These distinct signatures of protein synthesis suggest intriguing and currently mysterious differences in the cellular consequences of deficiency for small and large ribosomal subunits.

Natural biological systems are selected by evolution to continue to exist and evolve. Evolution likely gives rise to complicated systems that are difficult to understand and manipulate. Here, we redesign the genome of a natural biological system, bacteriophage T7, in order to specify an engineered surrogate that, if viable, would be easier to study and extend. Our initial design goals were to physically separate and enable unique manipulation of primary genetic elements. Implicit in our design are the hypotheses that overlapping genetic elements are, in aggregate, nonessential for T7 viability and that our models for the functions encoded by elements are sufficient. To test our initial design, we replaced the left 11,515 base pairs (bp) of the 39,937 bp wild-type genome with 12,179 bp of engineered DNA. The resulting chimeric genome encodes a viable bacteriophage that appears to maintain key features of the original while being simpler to model and easier to manipulate. The viability of our initial design suggests that the genomes encoding natural biological systems can be systematically redesigned and built anew in service of scientific understanding or human intention.

In Mal 2021, Singapore reopened the discussion to introduce no-fault divorce into its divorce laws and sought the public's opinion on its consultation paper. This article posits that no-fault divorce is not against the best interests of society but is in the best interests of the family. This is because no-fault divorce can benefit parties (especially the children) and does not erode the sanctity Of mar-Wage. An empirical study of divorce in Hong Kong shows that there is no con relation between no-fault divorce and the increase in divorces. In a similar vein and in line with therapeutic justice, the authors also propose interdisciplinary measures to better support marriages and children to complement the introducdori of no-fault divorce in Singapore. [ABSTRACT FROM AUTHOR]

Different jurisdictions have adopted different approaches to the division of matrimonial property. While some have greater certainty and predictability from a rules-based approach that adopts equal division as a starting point, others have adopted a discretionary approach with little to no guidance from the legislation. Using statistical methods, this empirical quantitative study seeks to show how trends (and in turn certainty and predictability) can be obtained from a discretionary system, using Singapore's contributions-based approach as a case study. Analysing 265 Singaporean judgements, the authors observed, amongst other trends, that division for both single-income and dual-income marriage tend to incline towards equality as the marriage length increases; there are divergences in collective outcomes from the Singapore Court of Appeal and Singapore High Court, and judgements from the Singapore Family Justice Courts; direct contributions have a significant impact on division for dual-income marriages; and the presence of child(ren) significantly influences division. [ABSTRACT FROM AUTHOR]