Insights into the regulation of intrinsically disordered proteins in the human proteome by analyzing sequence and gene expression data

Background: Disordered proteins need to be expressed to carry out specified functions; however, their accumulation in the cell can potentially cause major problems through protein misfolding and aggregation. Gene expression levels, mRNA decay rates, microRNA (miRNA) targeting and ubiquitination have critical roles in the degradation and disposal of human proteins and transcripts. Here, we describe a study examining these features to gain insights into the regulation of disordered proteins. Results: In comparison with ordered proteins, disordered proteins have a greater proportion of predicted ubiquitination sites. The transcripts encoding disordered proteins also have higher proportions of predicted miRNA target sites and higher mRNA decay rates, both of which are indicative of the observed lower gene expression levels. The results suggest that the disordered proteins and their transcripts are present in the cell at low levels and/or for a short time before being targeted for disposal. Surprisingly, we find that for a significant proportion of highly disordered proteins, all four of these trends are reversed. Predicted estimates for miRNA targets, ubiquitination and mRNA decay rate are low in the highly disordered proteins that are constitutively and/or highly expressed. Conclusions: Mechanisms are in place to protect the cell from these potentially dangerous proteins. The evidence suggests that the enrichment of signals for miRNA targeting and ubiquitination may help prevent the accumulation of disordered proteins in the cell. Our data also provide evidence for a mechanism by which a significant proportion of highly disordered proteins (with high expression levels) can escape rapid degradation to allow them to successfully carry out their function

Kinematic variations due to changes in pace during men's and women's 5 km road running

The purpose of this study was to investigate variations in kinematic parameters in men's and women's 5 km road racing. Athletes often vary their pace and changes particularly tend to occur towards the end of a race due to fatigue and sprint finishes. Twenty competitive distance runners (10 male, 10 female) were videoed as they completed the English National 5 km championships. Three-dimensional kinematic data were analysed using motion analysis software (SIMI, Munich). Data were recorded at 950 m, 2,400 m and 3,850 m. Repeated measures ANOVA showed significant decreases in speed due to reduced step length and cadence in both men and women. These decreases predominantly occurred between the first two measurement points. The hip, knee, ankle and shoulder angles at both initial contact and toe-off did not change significantly, but there were significant reductions in the elbow angle for both men (at initial contact) and women (at toe-off)

Physical Activity, Sedentary Behavior, and Retirement: The Multi-Ethnic Study of Atherosclerosis

Introduction: Physical activity and sedentary behavior are major risk factors for chronic disease. These behaviors may change at retirement, with implications for health in later life. The study objective was to describe longitudinal patterns of moderate to vigorous and domain-specific physical activity and TV watching by retirement status. Methods: Participants in the Multi-Ethnic Study of Atherosclerosis (n=6,814) were recruited from six U.S. communities and were aged 45–84 years at baseline. Retirement status and frequency and duration of domain-specific physical activity (recreational walking, transport walking, non-walking leisure activity, caregiving, household, occupational/volunteer) and TV watching were self-reported at four study exams (2000 to 2012). Fixed effect linear regression models were used to describe longitudinal patterns in physical activity and TV watching by retirement status overall and stratified by socioeconomic position. Analyses were conducted in 2017. Results: Of 4,091 Multi-Ethnic Study of Atherosclerosis participants not retired at baseline, 1,012 (25%) retired during a median of 9 years follow-up. Retirement was associated with a 10% decrease (95% CI= –15%, –5%) in moderate to vigorous physical activity and increases of 13% to 29% in recreational walking, household activity, and TV watching. Among people of low socioeconomic position, the magnitude of association was larger for moderate to vigorous physical activity. Among people of high socioeconomic position, the magnitude of association was larger for non-walking leisure and household activity. Conclusions: The retirement transition was associated with changes in physical activity and TV watching. To inform intervention development, future research is needed on the determinants of behavior change after retirement, particularly among individuals of low socioeconomic position. © 2018 American Journal of Preventive Medicin

Benchmark low-mass objects in Moving Groups

This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.In order to compile a sample of ultracool dwarfs that will serve as benchmarks for testing theoretical formation and evolutionary models, we selected low-mass cool (>M7) objects that are potentially members of five known young Moving Groups in the solar neighbourhood. We have studied the kinematics of the sample, finding that 49 targets belong to the young disk area, from which 36 are kinematic member of one of the five moving groups under study. Some of the identified low-mass members have been spectroscopically characterised (T-eff, log g) and confirmed as young members through a detailed study of age indicators

Characterisation of vertical BrO distribution during events of enhanced tropospheric BrO in Antarctica, from combined remote and in-situ measurements

Tropospheric BrO was measured by a ground-based remote-sensing spectrometer at Halley in Antarctica in spring 2007, and BrO was measured by satellite-borne remote-sensing spectrometers using similar spectral regions and similar Differential Optical Absorption Spectroscopy (DOAS) analyses. Near-surface BrO was simultaneously measured in situ at Halley by Chemical Ionisation Mass Spectrometer (CIMS), and in an earlier year near-surface BrO was measured at Halley over a long path by a ground-based DOAS spectrometer. During enhancement episodes, total amounts of tropospheric BrO from the ground-based remote-sensor were similar to those from space, but if we assume that the BrO was confined to the mixed layer they were very much larger than values measured by either near-surface technique. This large apparent discrepancy can be resolved if substantial amounts of BrO were in the free troposphere during most enhancement episodes. Amounts observed by the ground-based remote sensor at different elevation angles, and their formal inversions to vertical profiles, demonstrate that much of the BrO was indeed often in the free troposphere. This is consistent with the ~5 day lifetime of Bry and with the enhanced BrO observed during some Antarctic blizzards

Derivation and validation of a multivariate model to predict mortality from pulmonary embolism with cancer: The POMPE-C tool

BackgroundClinical guidelines recommend risk stratification of patients with acute pulmonary embolism (PE). Active cancer increases risk of PE and worsens prognosis, but also causes incidental PE that may be discovered during cancer staging. No quantitative decision instrument has been derived specifically for patients with active cancer and PE. Methods Classification and regression technique was used to reduce 25 variables prospectively collected from 408 patients with AC and PE. Selected variables were transformed into a logistic regression model, termed POMPE-C, and compared with the pulmonary embolism severity index (PESI) score to predict the outcome variable of death within 30 days. Validation was performed in an independent sample of 182 patients with active cancer and PE. Results POMPE-C included eight predictors: body mass, heart rate > 100, respiratory rate, SaO2%, respiratory distress, altered mental status, do not resuscitate status, and unilateral limb swelling. In the derivation set, the area under the ROC curve for POMPE-C was 0.84 (95% CI: 0.82-0.87), significantly greater than PESI (0.68, 0.60-0.76). In the validation sample, POMPE-C had an AUC of 0.86 (0.78-0.93). No patient with POMPE-C estimate ≤ 5% died within 30 days (0/50, 0-7%), whereas 10/13 (77%, 46-95%) with POMPE-C estimate > 50% died within 30 days. Conclusion In patients with active cancer and PE, POMPE-C demonstrated good prognostic accuracy for 30 day mortality and better performance than PESI. If validated in a large sample, POMPE-C may provide a quantitative basis to decide treatment options for PE discovered during cancer staging and with advanced cancer

Nonlinear waves in a cylindrical Bose-Einstein condensate

We present a complete calculation of solitary waves propagating in a steady state with constant velocity v along a cigar-shaped Bose-Einstein trap approximated as infinitely-long cylindrical. For sufficiently weak couplings (densities) the main features of the calculated solitons could be captured by effective one-dimensional (1D) models. However, for stronger couplings of practical interest, the relevant solitary waves are found to be hybrids of quasi-1D solitons and 3D vortex rings. An interesting hierarchy of vortex rings occurs as the effective coupling constant is increased through a sequence of critical values. The energy-momentum dispersion of the above structures is shown to exhibit characteristics similar to a mode proposed sometime ago by Lieb within a strictly 1D model, as well as some rotonlike features.Comment: 10 pages, 12 figure

Disruption of marine habitats by artificial light at night from global coastal megacities

Half of globally significant megacities are situated near the coast, exposing urban marine ecosystems to multiple stressors such as waste-water discharge containing a host of organic and inorganic pollutants, air and noise pollution. In addition to these well recognized sources, artificial light at night (ALAN) pollution is inseparable from cities but poorly quantified in marine ecosystems to date. We have developed a time- and wavelength-resolving hydrological optical model that includes solar (daylight and twilight components), lunar and ALAN source terms and propagates these spectrally through a tidally varying water column using Beer’s Law. Our model shows that for 8 globally distributed cities surface ALAN dosages are up to a factor of 6 greater than moonlight, as ALAN intensities vary little throughout the night, over monthly or seasonal cycles. Moonlight only exceeds ALAN irradiances over the ±3-day period around full moon, and particularly during the brightest moons (mid-latitude winter, at zenith). Unlike the relatively stable surface ALAN, underwater ALAN varies spectrally and in magnitude throughout the night due to tidal cycles. The extent of ALAN in-water attenuation is location-specific, driven by the season, tidal range and cycle, and water clarity. This work highlights that marine ALAN ecosystem pollution is a particularly acute global change issue near some of the largest cities in the world

Hydrocarbons as ore fluids

Conventional wisdom holds that aqueous solutions are the only non-magmatic fluids capable of concentrating metals in the Earth’s crust. The role of hydrocarbons in metal concentration is relegated to providing geochemical barriers at which the metals are reduced and immobilised. Liquid hydrocarbons, however, are also known to be able to carry appreciable concentrations of metals, and travel considerable distances. Here we report the results of an experimental determination of bulk solubilities of Au, Zn, and U in a variety of crude oils at temperatures up to 300 °C and of the benchtop-scale transport experiments that simulate hydrocarbon-mediated re-deposition of Zn at 25–200 °C. It has been demonstrated that the metal concentrations obtained in solubility experiments are within the range of concentrations that are typically considered sufficient for aqueous fluids to form ore bodies. It has also been shown that Zn can be efficiently transported and re-deposited by hydrocarbons. These results provide direct evidence of the ability of natural crude oils to mobilise metals available in hydrocarbon-associated host rocks, and transport them in concentrations sufficient to contribute to ore-forming processes