Measuring global ocean heat content to estimate the earth energy imbalance

The energy radiated by the Earth toward space does not compensate the incoming radiation from the Sun leading to a small positive energy imbalance at the top of the atmosphere (0.4–1 Wm–2). This imbalance is coined Earth’s Energy Imbalance (EEI). It is mostly caused by anthropogenic greenhouse gas emissions and is driving the current warming of the planet. Precise monitoring of EEI is critical to assess the current status of climate change and the future evolution of climate. But the monitoring of EEI is challenging as EEI is two orders of magnitude smaller than the radiation fluxes in and out of the Earth system. Over 93% of the excess energy that is gained by the Earth in response to the positive EEI accumulates into the ocean in the form of heat. This accumulation of heat can be tracked with the ocean observing system such that today, the monitoring of Ocean Heat Content (OHC) and its long-term change provide the most efficient approach to estimate EEI. In this community paper we review the current four state-of-the-art methods to estimate global OHC changes and evaluate their relevance to derive EEI estimates on different time scales. These four methods make use of: (1) direct observations of in situ temperature; (2) satellite-based measurements of the ocean surface net heat fluxes; (3) satellite-based estimates of the thermal expansion of the ocean and (4) ocean reanalyses that assimilate observations from both satellite and in situ instruments. For each method we review the potential and the uncertainty of the method to estimate global OHC changes. We also analyze gaps in the current capability of each method and identify ways of progress for the future to fulfill the requirements of EEI monitoring. Achieving the observation of EEI with sufficient accuracy will depend on merging the remote sensing techniques with in situ measurements of key variables as an integral part of the Ocean Observing System

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.

BACKGROUND & AIMS: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. METHODS: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). RESULTS: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10(-4), with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10(-6); odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028-1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09-1.26; P = 9.93 × 10(-8)), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10(-9); OR, 1.33; 95% CI, 1.21-1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). CONCLUSIONS: This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.The article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted versio