Clinical research:Developing an appropriate career structure

The veterinary profession needs to become more successful in producing the next generation of clinician scientists, say Richard Mellanby and others, who set out a roadmap for future academic postgraduate clinical training

Evidence of an active volcanic heat source beneath the Pine Island Glacier

Tectonic landforms reveal that the West Antarctic Ice Sheet (WAIS) lies atop a major volcanic rift system. However, identifying subglacial volcanism is challenging. Here we show geochemical evidence of a volcanic heat source upstream of the fast-melting Pine Island Ice Shelf, documented by seawater helium isotope ratios at the front of the Ice Shelf cavity. The localization of mantle helium to glacial meltwater reveals that volcanic heat induces melt beneath the grounded glacier and feeds the subglacial hydrological network crossing the grounding line. The observed transport of mantle helium out of the Ice Shelf cavity indicates that volcanic heat is supplied to the grounded glacier at a rate of ~ 2500 ± 1700 MW, which is ca. half as large as the active Grimsvötn volcano on Iceland. Our finding of a substantial volcanic heat source beneath a major WAIS glacier highlights the need to understand subglacial volcanism, its hydrologic interaction with the marine margins, and its potential role in the future stability of the WAIS

A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE

Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (Pmeta=0.00010 and Pmeta=0.00040, respectively). STAT1 was also associated with SLE in this cohort (Pmeta=3.3 × 10−5), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis

A shared MHC supertype motif emerges by convergent evolution in macaques and mice, but is totally absent in human MHC molecules

The SIV-infected rhesus macaque (Macaca mulatta) is the most established model of AIDS disease systems, providing insight into pathogenesis and a model system for testing novel vaccines. The understanding of cellular immune responses based on the identification and study of Major Histocompatibility Complex (MHC) molecules, including their MHC:peptide-binding motif, provides valuable information to decipher outcomes of infection and vaccine efficacy. Detailed characterization of Mamu-B*039:01, a common allele expressed in Chinese rhesus macaques, revealed a unique MHC:peptide-binding preference consisting of glycine at the second position. Peptides containing a glycine at the second position were shown to be antigenic from animals positive for Mamu-B*039:01. A similar motif was previously described for the Dd mouse MHC allele, but for none of the human HLA molecules for which a motif is known. Further investigation showed that one additional macaque allele, present in Indian rhesus macaques, Mamu-B*052:01, shares this same motif. These “G2” alleles were associated with the presence of specific residues in their B pocket. This pocket structure was found in 6% of macaque sequences but none of 950 human HLA class I alleles. Evolutionary studies using the “G2” alleles points to common ancestry for the macaque sequences, while convergent evolution is suggested when murine and macaque sequences are considered. This is the first detailed characterization of the pocket residues yielding this specific motif in nonhuman primates and mice, revealing a new supertype motif not present in humans

Microbial control and quorum sensing inhibition by phenolic compounds of acerola (Malpighia emarginata).

Recently, phenolic compounds have been tested for their ability to inhibit bacterial communication known as quorum sensing. The objective of this study was to characterize acerola pulp (Malpighia emarginata) regarding its centesimal composition and mineral content as determined by Total Reflection X-Ray Fluorescence as well as to determine the total phenolic content and the antioxidant, antimicrobial and anti-quorum sensing activities of the phenolic extract obtained from the pulp. The centesimal and mineral content presented values in good agreement with those shown for fruits of the Malpighia generum. The total phenolic content for the fruit was 5848.74 ? 4.18 mg GAE/L. The antioxidant activity determined by the ABTS method was 127.18 ? 6.6 ?M Trolox/g of fruit and 112.02 ? 0.03 ?M Trolox/g of fruit in the DPPH assay, expressive values as compared to other fruits. The phenolic extract inhibited all the evaluated bacteria with minimal inhibitory concentrations ranging from 487.39 mg GAE /L to 1462.18 mg GAE /L of extract. Interestingly, in sub-MIC concentrations the phenolic extract of acerola did not interfere with bacterial growth, but inhibited quorum sensing controlled phenotypes such as violacein production in Chromobacterium violaceum, swarming motility in Aeromonas hydrophila and more importantly, biofilm formation in these bacteria and also in Serratia marcencens. The phenolic extract from acerola presents important bioactive properties including the newly described ability to inhibit quorum sensing in bacteria which can be further explored as a means to control bacterial activities in foods

Antioxidant, antimicrobial and anti - quorum sensing activities of Rubus rosaefolius phenolic extract.

Phenolic compounds are plant secondary metabolites that present many biological effects includingantioxidant and antimicrobial activities. Studies have shown that these compounds can also inhibitquorum sensing bacterial communication. The aim of this study was to characterize the centesimalcomposition, mineral and phenolic content, to determine the antioxidant and antimicrobial effect aswell as the inhibition of quorum sensing by the phenolic extract obtained from wild strawberry (Rubusrosaefolius). Centesimal composition and minerals were in the range expected for fruits of the Rubusgenerum, even though Fe and Zn presented higher levels. The phenolic content was 5902.89 mg GAE/L,also approaching the levels found for fruits of Rubus sp. The antioxidant activity determined throughthe ABTS method was 162.4 ? 5.6 and 120.8 ? 1.5 _M Trolox/g of fruit in the DPPH assay, indicating anelevated potential for ABTS and medium potential for DPPH method. The phenolic extract was able toinhibit all the evaluated bacteria presenting MICs in the range of 491.90?1475.74 mg GAE/L. In sub-MIC concentrations, the phenolic extract inhibited all the phenotypes typically regulated by quorum sens-ing in bacteria, including violacein production, swarming motility and biofilm formation. The phenolicextract of R. rosaefolius presented antioxidant, antimicrobial and anti-quorum sensing activities whichare in agreement with previous studies linking phenolic compounds to these properties

Rapid submarine ice melting in the grounding zones of ice shelves in West Antarctica

Enhanced submarine ice-shelf melting strongly controls ice loss in the Amundsen Sea embayment (ASE) of West Antarctica, but its magnitude is not well known in the critical grounding zones of the ASE's major glaciers. Here we directly quantify bottom ice losses along tens of kilometres with airborne radar sounding of the Dotson and Crosson ice shelves, which buttress the rapidly changing Smith, Pope and Kohler glaciers. Melting in the grounding zones is found to be much higher than steady-state levels, removing 300–490 m of solid ice between 2002 and 2009 beneath the retreating Smith Glacier. The vigorous, unbalanced melting supports the hypothesis that a significant increase in ocean heat influx into ASE sub-ice-shelf cavities took place in the mid-2000s. The synchronous but diverse evolutions of these glaciers illustrate how combinations of oceanography and topography modulate rapid submarine melting to hasten mass loss and glacier retreat from West Antarctica