A Screenable In Vivo Assay for Mitochondrial Modulators Using Transgenic Bioluminescent Caenorhabditis elegans

Acknowledgements The authors would like to thank David Gray from the Dundee Drug discovery unit for kindly donating firefly luciferase inhibitory compounds DDD00001434, DDD0001477, DDD00000635 and DDD00023047; Tibor Harkani (Medical University of Vienna) for the suggestion of oxaloacetate as a test compound; and Charlie Dear (University of Aberdeen) for illustrations. This work was funded by a BBSRC Pathfinder award (BB/FOF/PF/4/11) and the University of Aberdeen.Peer reviewedPublisher PD

Bridging the phenotypic gap: Real-time assessment of mitochondrial function and metabolism of the nematode Caenorhabditis elegans

Peer reviewedPublisher PD

Impact of sublethal levels of environmental pollutants found in sewage sludge on a novel Caenorhabditis elegans model biosensor

Peer reviewedPublisher PD

Control of gag-pol gene expression in the Candida albicans retrotransposon Tca2

Non peer reviewedPublisher PD

Differential response of archaeal and bacterial communities to nitrogen inputs and pH changes in upland pasture rhizosphere soil

Grassland management regimens influence the structure of archaeal communities in upland pasture soils, which appear to be dominated by as yet uncultivated non-thermophilic Crenarchaeota. In an attempt to determine which grassland management factors select for particular crenarchaeal community structures, soil microcosm experiments were performed examining the effect of increased pH, application of inorganic fertilizer (ammonium nitrate) and sheep urine deposition on both archaeal and bacterial communities in unmanaged grassland soil. As grassland management typically increases pH, a further experiment examined the effect of a reduction in pH, to that typical of unimproved grassland soils, on archaeal and bacterial communities. The RT-PCR amplification of 16S rRNA followed by denaturing gradient gel electrophoresis analysis demonstrated a distinct and reproducible effect on bacterial communities after incubation for 28 or 30 days. In contrast, none of the treatments had a significant effect on the structure of the crenarchaeal community, indicating that these factors are not major drivers of crenarchaeal community structures in grassland soil

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy