Greenland subglacial lakes detected by radar

This is the final version of the article. Available from AGU via the DOI in this record.Subglacial lakes are an established and important component of the basal hydrological system of the Antarctic ice sheets, but none have been reported from Greenland. Here we present airborne radio echo sounder (RES) measurements that provide the first clear evidence for the existence of subglacial lakes in Greenland. Two lakes, with areas ~8 and ~10 km2, are found in the northwest sector of the ice sheet, ~40 km from the ice margin, and below 757 and 809 m of ice, respectively. The setting of the Greenland lakes differs from those of Antarctic subglacial lakes, being beneath relatively thin and cold ice, pointing to a fundamental difference in their nature and genesis. Possibilities that the lakes consist of either ancient saline water in a closed system or are part of a fresh, modern open hydrological system are discussed, with the latter interpretation considered more likely.Funding was provided by NERC grant NE/ H020667. Additional support was provided by NASA grant NNX11AD33G and the G. Unger Vetlesen foundation

Intrinsic processes drive variability in basal melting of the Totten Glacier Ice Shelf

Over the period 2003–2008, the Totten Ice Shelf (TIS) was shown to be rapidly thinning, likely due to basal melting. However, a recent study using a longer time series found high interannual variability present in TIS surface elevation without any apparent trend. Here we show that low-frequency intrinsic ocean variability potentially accounts for a large fraction of the variability in the basal melting of TIS. Specifically, numerical ocean model simulations show that up to 44% of the modelled variability in basal melting in the 1–5 year timescale (and up to 21% in the 5–10 year timescale) is intrinsic, with a similar response to the full climate forcing. We identify the important role of intrinsic ocean variability in setting the observed interannual variation in TIS surface thickness and velocity. Our results further demonstrate the need to account for intrinsic ocean processes in the detection and attribution of change

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Association of Age with Mortality and Virological and Immunological Response to Antiretroviral Therapy in Rural South African Adults

OBJECTIVE: To assess whether treatment outcomes vary with age for adults receiving antiretroviral therapy (ART) in a large rural HIV treatment cohort. DESIGN: Retrospective cohort analysis using data from a public HIV Treatment & Care Programme. METHODS: Adults initiating ART 1(st) August 2004-31(st) October 2009 were stratified by age at initiation: young adults (16-24 years) mid-age adults (25-49 years) and older (≥50 years) adults. Kaplan-Meier survival analysis was used to estimate mortality rates and age and person-time stratified Cox regression to determine factors associated with mortality. Changes in CD4 cell counts were quantified using a piecewise linear model based on follow-up CD4 cell counts measured at six-monthly time points. RESULTS: 8846 adults were included, 808 (9.1%) young adults; 7119 (80.5%) mid-age adults and 919 (10.4%) older adults, with 997 deaths over 14,778 person-years of follow-up. Adjusting for baseline characteristics, older adults had 32% excess mortality (p = 0.004) compared to those aged 25-49 years. Overall mortality rates (MR) per 100 person-years were 6.18 (95% CI 4.90-7.78); 6.55 (95% CI 6.11-7.02) and 8.69 (95% CI 7.34-10.28) for young, mid-age and older adults respectively. In the first year on ART, for older compared to both young and mid-aged adults, MR per 100 person-years were significantly higher; 0-3 months (MR: 27.1 vs 17.17 and 21.36) and 3-12 months (MR: 9.5 vs 4.02 and 6.02) respectively. CD4 count reconstitution was lower, despite better virological response in the older adults. There were no significant differences in MR after 1 year of ART. Baseline markers of advanced disease were independently associated with very early mortality (0-3 months) whilst immunological and virological responses were associated with mortality after 12 months. CONCLUSIONS: Early ART initiation and improving clinical care of older adults are required to reduce high early mortality and enhance immunologic recovery, particularly in the initial phases of ART

Uncovering packaging features of co-regulated modules based on human protein interaction and transcriptional regulatory networks

<p>Abstract</p> <p>Background</p> <p>Network co-regulated modules are believed to have the functionality of packaging multiple biological entities, and can thus be assumed to coordinate many biological functions in their network neighbouring regions.</p> <p>Results</p> <p>Here, we weighted edges of a human protein interaction network and a transcriptional regulatory network to construct an integrated network, and introduce a probabilistic model and a bipartite graph framework to exploit human co-regulated modules and uncover their specific features in packaging different biological entities (genes, protein complexes or metabolic pathways). Finally, we identified 96 human co-regulated modules based on this method, and evaluate its effectiveness by comparing it with four other methods.</p> <p>Conclusions</p> <p>Dysfunctions in co-regulated interactions often occur in the development of cancer. Therefore, we focussed on an example co-regulated module and found that it could integrate a number of cancer-related genes. This was extended to causal dysfunctions of some complexes maintained by several physically interacting proteins, thus coordinating several metabolic pathways that directly underlie cancer.</p