Ribosome profiling data report on the distribution of translating ribosomes, at steady-state, with codon-level resolution. We present a robust method to extract codon translation rates and protein synthesis rates from these data, and identify causal features associated with elongation and translation efficiency in physiological conditions in yeast. We show that neither elongation rate nor translational efficiency is improved by experimental manipulation of the abundance or body sequence of the rare AGG tRNA. Deletion of three of the four copies of the heavily used ACA tRNA shows a modest efficiency decrease that could be explained by other rate-reducing signals at gene start. This suggests that correlation between codon bias and efficiency arises as selection for codons to utilize translation machinery efficiently in highly translated genes. We also show a correlation between efficiency and RNA structure calculated both computationally and from recent structure probing data, as well as the Kozak initiation motif, which may comprise a mechanism to regulate initiation.
To determine the breadth and underpinning of changes in immunocyte gene expression due to genetic variation in mice we performed, as part of the Immunological Genome Project, gene expression profiling for CD4+ T cells and neutrophils purified from 39 inbred strains of the Mouse Phenome Database. Considering both cell types, a large number of transcripts showed significant variation across the inbred strains, 22% of the transcriptome varying by two-fold or more. These included 119 loci with apparently complete loss-of-function, where the corresponding transcript was not expressed in some of the strains, representing a useful resource of “natural knockouts”. We identified 1,222 cis- expression quantitative trait loci (cis-eQTL) that control some of this variation. Most (60%) cis-eQTLs were shared between T cells and neutrophils, but a significant portion uniquely impacted one of the cell types, suggesting cell-type specific regulatory mechanisms. Using a conditional regression algorithm we predicted regulatory interactions between transcription factors and potential targets, and demonstrated that these predictions overlap with regulatory interactions inferred from transcriptional changes during immunocyte differentiation. Finally, comparison of these and parallel data from CD4+ T cells of healthy humans demonstrated intriguing similarities in variability of a gene's expression: the most variable genes tended to be the same in both species, and there was an overlap in genes subject to strong cis-acting genetic variants. We speculate that this “conservation of variation” reflects a differential constraint on intra-species variation in expression levels of different genes, either through lower pressure for some genes, or by favoring variability for others.
The world is facing major societal challenges because of an aging population that is putting increasing pressure on the sustainability of care. While demand for care and social services is steadily increasing, the supply is constrained by the decreasing workforce. The development of smart, physical, social and age-friendly environments is identified by World Health Organization (WHO) as a key intervention point for enabling older adults, enabling them to remain as much possible in their residences, delay institutionalization, and ultimately, improve quality of life. In this study, we survey smart environments, machine learning and robot assistive technologies that can offer support for the independent living of older adults and provide age-friendly care services. We describe two examples of integrated care services that are using assistive technologies in innovative ways to assess and deliver of timely interventions for polypharmacy management and for social and cognitive activity support in older adults. We describe the architectural views of these services, focusing on details about technology usage, end-user interaction flows and data models that are developed or enhanced to achieve the envisioned objective of healthier, safer, more independent and socially connected older people.
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