17 research outputs found
Polymorphic Cis- and Trans-Regulation of Human Gene Expression
Using genetic and molecular analyses, we identified over 1,000 polymorphic regulators that regulate expression levels of human genes
The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts
Biodiversity continues to decline in the face of increasing anthropogenic pressures
such as habitat destruction, exploitation, pollution and introduction of
alien species. Existing global databases of species’ threat status or population
time series are dominated by charismatic species. The collation of datasets with
broad taxonomic and biogeographic extents, and that support computation of
a range of biodiversity indicators, is necessary to enable better understanding of
historical declines and to project – and avert – future declines. We describe and
assess a new database of more than 1.6 million samples from 78 countries representing
over 28,000 species, collated from existing spatial comparisons of
local-scale biodiversity exposed to different intensities and types of anthropogenic
pressures, from terrestrial sites around the world. The database contains
measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35)
biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains
more than 1% of the total number of all species described, and more than
1% of the described species within many taxonomic groups – including flowering
plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans
and hymenopterans. The dataset, which is still being added to, is
therefore already considerably larger and more representative than those used
by previous quantitative models of biodiversity trends and responses. The database
is being assembled as part of the PREDICTS project (Projecting Responses
of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk).
We make site-level summary data available alongside this article. The full database
will be publicly available in 2015
Retrotranslocation of Prion Proteins from the Endoplasmic Reticulum by Preventing GPI Signal Transamidation
Neurodegeneration in diseases caused by altered metabolism of mammalian prion protein (PrP) can be averted by reducing PrP expression. To identify novel pathways for PrP down-regulation, we analyzed cells that had adapted to the negative selection pressure of stable overexpression of a disease-causing PrP mutant. A mutant cell line was isolated that selectively and quantitatively routes wild-type and various mutant PrPs for ER retrotranslocation and proteasomal degradation. Biochemical analyses of the mutant cells revealed that a defect in glycosylphosphatidylinositol (GPI) anchor synthesis leads to an unprocessed GPI-anchoring signal sequence that directs both ER retention and efficient retrotranslocation of PrP. An unprocessed GPI signal was sufficient to impart ER retention, but not retrotranslocation, to a heterologous protein, revealing an unexpected role for the mature domain in the metabolism of misprocessed GPI-anchored proteins. Our results provide new insights into the quality control pathways for unprocessed GPI-anchored proteins and identify transamidation of the GPI signal sequence as a step in PrP biosynthesis that is absolutely required for its surface expression. As each GPI signal sequence is unique, these results also identify signal recognition by the GPI-transamidase as a potential step for selective small molecule perturbation of PrP expression