Translational regulation shapes the molecular landscape of complex disease phenotypes.

The extent of translational control of gene expression in mammalian tissues remains largely unknown. Here we perform genome-wide RNA sequencing and ribosome profiling in heart and liver tissues to investigate strain-specific translational regulation in the spontaneously hypertensive rat (SHR/Ola). For the most part, transcriptional variation is equally apparent at the translational level and there is limited evidence of translational buffering. Remarkably, we observe hundreds of strain-specific differences in translation, almost doubling the number of differentially expressed genes. The integration of genetic, transcriptional and translational data sets reveals distinct signatures in 3'UTR variation, RNA-binding protein motifs and miRNA expression associated with translational regulation of gene expression. We show that a large number of genes associated with heart and liver traits in human genome-wide association studies are primarily translationally regulated. Capturing interindividual differences in the translated genome will lead to new insights into the genes and regulatory pathways underlying disease phenotypes

Probing photo-ionization: simulations of positive streamers in varying N2:O2 mixtures

Photo-ionization is the accepted mechanism for the propagation of positive streamers in air though the parameters are not very well known; the efficiency of this mechanism largely depends on the presence of both nitrogen and oxygen. But experiments show that streamer propagation is amazingly robust against changes of the gas composition; even for pure nitrogen with impurity levels below 1 ppm streamers propagate essentially with the same velocity as in air, but their minimal diameter is smaller, and they branch more frequently. Additionally, they move more in a zigzag fashion and sometimes exhibit a feathery structure. In our simulations, we test the relative importance of photo-ionization and of the background ionization from pulsed repetitive discharges, in air as well as in nitrogen with 1 ppm O2 . We also test reasonable parameter changes of the photo-ionization model. We find that photo- ionization dominates streamer propagation in air for repetition frequencies of at least 1 kHz, while in nitrogen with 1 ppm O2 the effect of the repetition frequency has to be included above 1 Hz. Finally, we explain the feather-like structures around streamer channels that are observed in experiments in nitrogen with high purity, but not in air.Comment: 12 figure

Probing photo-ionization: Experiments on positive streamers in pure gasses and mixtures

Positive streamers are thought to propagate by photo-ionization whose parameters depend on the nitrogen:oxygen ratio. Therefore we study streamers in nitrogen with 20%, 0.2% and 0.01% oxygen and in pure nitrogen, as well as in pure oxygen and argon. Our new experimental set-up guarantees contamination of the pure gases to be well below 1 ppm. Streamers in oxygen are difficult to measure as they emit considerably less light in the sensitivity range of our fast ICCD camera than the other gasses. Streamers in pure nitrogen and in all nitrogen/oxygen mixtures look generally similar, but become somewhat thinner and branch more with decreasing oxygen content. In pure nitrogen the streamers can branch so much that they resemble feathers. This feature is even more pronounced in pure argon, with approximately 10^2 hair tips/cm^3 in the feathers at 200 mbar; this density could be interpreted as the free electron density creating avalanches towards the streamer stem. It is remarkable that the streamer velocity is essentially the same for similar voltage and pressure in all nitrogen/oxygen mixtures as well as in pure nitrogen, while the oxygen concentration and therefore the photo-ionization lengths vary by more than five orders of magnitude. Streamers in argon have essentially the same velocity as well. The physical similarity of streamers at different pressures is confirmed in all gases; the minimal diameters are smaller than in earlier measurements.Comment: 28 pages, 14 figures. Major differences with v1: - appendix and spectra removed - subsection regarding effects of repetition frequency added - many more smaller change

Multiple-gap spark gap switch

A triggered multiple-gap spark gap switch has been developed and tested under atmosphere. By means of an LCR trigger circuit, the multiple-gap switch can be used very reliably. For the same switching voltage (35.5 kV), with increasing the number of gaps from 2 to 6, the switching current rise time is reduced from 13.5 to 6 ns, and the energy efficiency is increased from 87% to 92%. An eight-gap switch was also tested, and the switching current rise time is much smaller than the usable rise time of the current probe (3.5 ns). One interesting application of the multiple-gap switch is to improve the switching performance in the multiple-switch and transmission lines based pulsed power circuit. To verify this application, a six-gap switch was tested. In contrast to a single-gap switch, the output current rise time was improved from 21 to 11 ns by the six-gap switch

A qualitative study of older adults' responses to sitting-time questions: do we get the information we want?

In the last decade, there has been increasing interest in the health effects of sedentary behavior, which is often assessed using self-report sitting-time questions. The aim of this qualitative study was to document older adults' understanding of sitting-time questions from the International Physical Activity (PA) Questionnaire (IPAQ) and the PA Scale for the Elderly (PASE)

A human ESC-based screen identifies a role for the translated lncRNA LINC00261 in pancreatic endocrine differentiation

Long noncoding RNAs (lncRNAs) are a heterogenous group of RNAs, which can encode small proteins. The extent to which developmentally regulated lncRNAs are translated and whether the produced microproteins are relevant for human development is unknown. Using a human embryonic stem cell (hESC)-based pancreatic differentiation system, we show that many lncRNAs in direct vicinity of lineage-determining transcription factors (TFs) are dynamically regulated, predominantly cytosolic, and highly translated. We genetically ablated ten such lncRNAs, most of them translated, and found that nine are dispensable for pancreatic endocrine cell development. However, deletion of LINC00261 diminishes insulin(+) cells, in a manner independent of the nearby TF FOXA2. One-by-one deletion of each of LINC00261's open reading frames suggests that the RNA, rather than the produced microproteins, is required for endocrine development. Our work highlights extensive translation of lncRNAs during hESC pancreatic differentiation and provides a blueprint for dissection of their coding and noncoding roles