Recent progress in understanding and projecting regional and global mean sea-level change

Considerable progress has been made in understanding the present and future regional and global sea level in the 2 years since the publication of the Fifth Assessment Report (AR5) of the Intergovernmental Panel on Climate Change. Here, we evaluate how the new results affect the AR5’s assessment of (i) historical sea level rise, including attribution of that rise and implications for the sea level budget, (ii) projections of the components and of total global mean sea level (GMSL), and (iii) projections of regional variability and emergence of the anthropogenic signal. In each of these cases, new work largely provides additional evidence in support of the AR5 assessment, providing greater confidence in those findings. Recent analyses confirm the twentieth century sea level rise, with some analyses showing a slightly smaller rate before 1990 and some a slightly larger value than reported in the AR5. There is now more evidence of an acceleration in the rate of rise. Ongoing ocean heat uptake and associated thermal expansion have continued since 2000, and are consistent with ocean thermal expansion reported in the AR5. A significant amount of heat is being stored deeper in the water column, with a larger rate of heat uptake since 2000 compared to the previous decades and with the largest storage in the Southern Ocean. The first formal detection studies for ocean thermal expansion and glacier mass loss since the AR5 have confirmed the AR5 finding of a significant anthropogenic contribution to sea level rise over the last 50 years. New projections of glacier loss from two regions suggest smaller contributions to GMSL rise from these regions than in studies assessed by the AR5; additional regional studies are required to further assess whether there are broader implications of these results. Mass loss from the Greenland Ice Sheet, primarily as a result of increased surface melting, and from the Antarctic Ice Sheet, primarily as a result of increased ice discharge, has accelerated. The largest estimates of acceleration in mass loss from the two ice sheets for 2003–2013 equal or exceed the acceleration of GMSL rise calculated from the satellite altimeter sea level record over the longer period of 1993–2014. However, when increased mass gain in land water storage and parts of East Antarctica, and decreased mass loss from glaciers in Alaska and some other regions are taken into account, the net acceleration in the ocean mass gain is consistent with the satellite altimeter record. New studies suggest that a marine ice sheet instability (MISI) may have been initiated in parts of the West Antarctic Ice Sheet (WAIS), but that it will affect only a limited number of ice streams in the twenty-first century. New projections of mass loss from the Greenland and Antarctic Ice Sheets by 2100, including a contribution from parts of WAIS undergoing unstable retreat, suggest a contribution that falls largely within the likely range (i.e., two thirds probability) of the AR5. These new results increase confidence in the AR5 likely range, indicating that there is a greater probability that sea level rise by 2100 will lie in this range with a corresponding decrease in the likelihood of an additional contribution of several tens of centimeters above the likely range. In view of the comparatively limited state of knowledge and understanding of rapid ice sheet dynamics, we continue to think that it is not yet possible to make reliable quantitative estimates of future GMSL rise outside the likely range. Projections of twenty-first century GMSL rise published since the AR5 depend on results from expert elicitation, but we have low confidence in conclusions based on these approaches. New work on regional projections and emergence of the anthropogenic signal suggests that the two commonly predicted features of future regional sea level change (the increasing tilt across the Antarctic Circumpolar Current and the dipole in the North Atlantic) are related to regional changes in wind stress and surface heat flux. Moreover, it is expected that sea level change in response to anthropogenic forcing, particularly in regions of relatively low unforced variability such as the low-latitude Atlantic, will be detectable over most of the ocean by 2040. The east-west contrast of sea level trends in the Pacific observed since the early 1990s cannot be satisfactorily accounted for by climate models, nor yet definitively attributed either to unforced variability or forced climate change

Regulation of microRNA biogenesis and turnover by animals and their viruses

Item does not contain fulltextMicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes

Gas emissions and crustal deformation from the Krýsuvík high temperature geothermal system, Iceland

The Krýsuvík volcanic system is located on the oblique spreading Reykjanes Peninsula, SW Iceland. Since early 2009 the region has been undergoing episodes of localized ground uplift and subsidence. From April–November 2013, we operated near-real time monitoring of gas emissions in Krýsuvík, using a Multi-component Gas Analyzer System (Multi-GAS), collecting data on gas composition from a fumarole (H₂O, CO₂, SO₂, H₂S). The dataset in this study, comprises a near-continuous gas composition time series, the quantification of diffuse CO₂ gas flux, analytical results for direct samples of dry gas, seismic records, and GPS data. Gas emissions from the Krýsuvík geothermal system were examined and compared with crustal deformation and seismicity. The gas emissions from the Krýsuvík system are H₂O-dominated, with CO₂ as the most abundant dry gas species, followed by smaller concentrations of H₂S. The average subsurface equilibrium temperature was calculated as 278 °C. This is consistent with previous observations made through sporadic spot sampling campaigns. In addition, the semi-continuous Multi-GAS dataset reveals higher variations in gas composition than previously reported by spot sampling. The diffuse soil CO₂ flux is found to be variable between the three studied degassing areas in Krýsuvík, ranging from 10.9–70.9 T/day, with the highest flux in Hveradalir where the Multi-GAS station is located. The total flux is estimated as 101 T/day. Comparison between Multi-GAS and geophysical data shows that peaks of H₂O-rich emissions appears to follow crustal movements. Coinciding with the H₂O-rich peaks, SO₂ is detected in minor amounts (~0.6 ppmv), allowing for calculations of H₂O/SO₂, CO₂/SO₂ and H₂S/SO₂ ratios. This is the first time SO₂ has been detected in the Krýsuvík area. The large variations in H₂O/CO₂ and H₂O/H₂S ratios are considered to reflect variable degassing activity in the fumarole. The activity of the fumarole appears less intense during intervals of low or no recorded seismic events. The H2₂O/CO₂ and H₂O/H₂S ratios are lower, presumably due to H₂O condensation affecting the steam jet before reaching the Multi-GAS inlet tube

Tamarindus indica Extract Alters Release of Alpha Enolase, Apolipoprotein A-I, Transthyretin and Rab GDP Dissociation Inhibitor Beta from HepG2 Cells

Background: The plasma cholesterol and triacylglycerol lowering effects of Tamarindus indica extract have been previously described. We have also shown that the methanol extract of T. indica fruit pulp altered the expression of lipid-associated genes including ABCG5 and APOAI in HepG2 cells. In the present study, effects of the same extract on the release of proteins from the cells were investigated using the proteomics approach. Methodology/Principal Findings: When culture media of HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp were subjected to 2-dimensional gel electrophoresis, the expression of seven proteins was found to be significantly different (p<0.03125). Five of the spots were subsequently identified as alpha enolase (ENO1), transthyretin (TTR), apolipoprotein A-I (ApoA-I; two isoforms), and rab GDP dissociation inhibitor beta (GDI-2). A functional network of lipid metabolism, molecular transport and small molecule biochemistry that interconnects the three latter proteins with the interactomes was identified using the Ingenuity Pathways Analysis software. Conclusion/Significance: The methanol extract of T. indica fruit pulp altered the release of ENO1, ApoA-I, TTR and GDI-2 from HepG2 cells. Our results provide support on the effect of T. indica extract on cellular lipid metabolism, particularly that of cholesterol

Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders

Ras-associated binding (Rab) proteins and Rab-associated proteins are key regulators of vesicle transport, which is essential for the delivery of proteins to specific intracellular locations. More than 60 human Rab proteins have been identified, and their function has been shown to depend on their interaction with different Rab-associated proteins regulating Rab activation, post-translational modification and intracellular localization. The number of known inherited disorders of vesicle trafficking due to Rab cycle defects has increased substantially during the past decade. This review describes the important role played by Rab proteins in a number of rare monogenic diseases as well as common multifactorial human ones. Although the clinical phenotype in these monogenic inherited diseases is highly variable and dependent on the type of tissue in which the defective Rab or its associated protein is expressed, frequent features are hypopigmentation (Griscelli syndrome), eye defects (Choroideremia, Warburg Micro syndrome and Martsolf syndrome), disturbed immune function (Griscelli syndrome and Charcot–Marie–Tooth disease) and neurological dysfunction (X-linked non-specific mental retardation, Charcot–Marie–Tooth disease, Warburg Micro syndrome and Martsolf syndrome). There is also evidence that alterations in Rab function play an important role in the progression of multifactorial human diseases, such as infectious diseases and type 2 diabetes. Rab proteins must not only be bound to GTP, but they need also to be ‘prenylated’—i.e. bound to the cell membranes by isoprenes, which are intermediaries in the synthesis of cholesterol (e.g. geranyl geranyl or farnesyl compounds). This means that isoprenylation can be influenced by drugs such as statins, which inhibit isoprenylation, or biphosphonates, which inhibit that farnesyl pyrophosphate synthase necessary for Rab GTPase activity. Conclusion: Although protein-trafficking disorders are clinically heterogeneous and represented in almost every subspeciality of pediatrics, the identification of common pathogenic mechanisms may provide a better diagnosis and management of patients with still unknown Rab cycle defects and stimulate the development of therapeutic agents

Semiquantitative RT-PCR analysis to assess the expression levels of multiple transcripts from the same sample

We describe a semiquantitative RT-PCR protocol optimized in our laboratory to extract RNA from as little as 10,000 cells and to measure the expression levels of several target mRNAs from each sample. This procedure was optimized on the human erythroleukemia cell line TF-1 but was successfully used on primary cells and on different cell lines. We describe the detailed procedure for the analysis of Bcl-2 levels. Aldolase A was used as an internal control to normalize for sample to sample variations in total RNA amounts and for reaction efficiency. As for all quantitative techniques, great care must be taken in all optimization steps: the necessary controls to ensure a rough quantitative (semi-quantitative) analysis are described here, together with an example from a study on the effects of TGF-β1 in TF-1 cells

Decreased wheel-running activity in hamsters post myocardial infarction

Reduced exercise capacity is a key symptom and an independent determinant of mortality in patients with heart failure. We analyzed the running activity of hamsters with cardiac dysfunction after myocardial infarction. In 39 male Syrian hamsters aged 10 to 12 weeks, a myocardial infarction (MI) was produced by permanent ligation of the left coronary artery. Spontaneous running activity in a wheel was monitored daily. After four weeks, left ventricular (LV) hemodynamics (catheter tip manometry) were measured at baseline and during inotropic stimulation (isoprenaline 0.03, 0.1 and 0.3 μg/kg/min i.v.). LV infarct size was quantified using planimetry. Four weeks post MI, daily running distance was reduced stepwise in animals with small (4–15 % of LV: 9.8 ± 3.4 km/d) and large (> 15 % of LV: 7.5 ± 3.5 km/d) MI, compared to sham-operated hamsters (11.5 ± 1.5 km/d). Similar reductions were observed in maximum speed and distance of longest running period. MI size influenced daily running distance, maximum speed, and longest running period (linear correlations, all p < 0.05). MI size also impaired LV systolic and diastolic function under isoprenaline stimulation. The results suggest that myocardial infarction reduces running capacity and isoprenaline stimulated LV function in hamsters, mimicking impaired exercise performance in patients with heart failure. Analysis of running activity in hamsters with myocardial infarction offers a unique opportunity for non-invasive and serial functional assessment of heart failure in the experimental setting

The use of evidence in public governmental reports on health policy: an analysis of 17 Norwegian official reports (NOU)

<p>Abstract</p> <p>Background</p> <p>Governments increasingly require policy documents to be evidence-based. This paper analyses the use of scientific evidence in such documents by reviewing reports from government-appointed committees in Norway to assess the committees' handling of questions of effect.</p> <p>Methods</p> <p>This study uses the 'Index of Scientific Quality' (ISQ) to analyse all Norwegian official reports (NOUs) that were: (1) published by the Norwegian Ministry of Health and Care Services during 1994-1998 (N = 20); and (2) concerned with questions of effect either because these were included in the mandate or as a result of the committee's interpretation of the mandate. The ISQ is based on scientific criteria common in all research concerning questions of effect. The primary outcome measure is an ISQ score on a five-point scale.</p> <p>Results</p> <p>Three reports were excluded because their mandates, or the committees' interpretations of them, did not address questions of effect. For the remaining 17 NOUs in our study, overall ISQ scores were low for systematic literature search and for explicit validation of research. Two reports had an average score of three or higher, while scores for five other reports were not far behind. How committees assessed the relevant factors was often unclear.</p> <p>Conclusion</p> <p>The reports' evaluations of health evidence in relation to questions of effect lacked transparency and, overall, showed little use of systematic processes. A systematic, explicit and transparent approach, following the standards laid down in the ISQ, may help generate the evidence-based decision-making that Norway, the UK, the EU and the WHO desire and seek. However, policy-makers may find the ISQ criteria for assessing the scientific quality of a report too narrow to adequately inform policy-making.</p