Biological heterogeneity in idiopathic pulmonary arterial hypertension identified through unsupervised transcriptomic profiling of whole blood

Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease diagnosed by right heart catheterisation and the exclusion of other forms of pulmonary arterial hypertension, producing a heterogeneous population with varied treatment response. Here we show unsupervised machine learning identification of three major patient subgroups that account for 92% of the cohort, each with unique whole blood transcriptomic and clinical feature signatures. These subgroups are associated with poor, moderate, and good prognosis. The poor prognosis subgroup is associated with upregulation of the ALAS2 and downregulation of several immunoglobulin genes, while the good prognosis subgroup is defined by upregulation of the bone morphogenetic protein signalling regulator NOG, and the C/C variant of HLA-DPA1/DPB1 (independently associated with survival). These findings independently validated provide evidence for the existence of 3 major subgroups (endophenotypes) within the IPAH classification, could improve risk stratification and provide molecular insights into the pathogenesis of IPAH

DASAR ANALISIS TEGANGAN/SM-06/SM-14

vii+190hlm;14x23c

Dasar analisis tegangan

165 p.; 21 cm

The early effects of afforestation on biodiversity of grasslands in Ireland

Abstract The target rate of afforestation in Ireland over the next 30 years is 20,000 ha per year, which would result in an increase of the forest cover from the current 10% to 17%. In order to promote sustainable forest management practices, it is essential to know the composition and conservation value of habitats where afforestation is planned and the effects of subsequent planting upon biodiversity. The objectives of this study were to investigate changes in vegetation composition and diversity of grasslands 5 years after afforestation with Sitka spruce (Picea sitchensis) and determine the primary ecological and management factors responsible for these changes. Species cover, environmental and management data were collected from 16 afforested and unplanted improved and wet grassland site pairs in Ireland. Our results indicate that 5 years after tree planting, there were significant changes in richness, composition, and abundance of species. Competitive and vigorous grasses were more abundant in planted than in unplanted sites, as were generalist species found in both open and wooded habitats, while small-stature shade-sensitive species were less abundant. Vascular plant species richness and Shannon’s diversity index were higher in unplanted wet grassland, than in the planted sites. Bryophyte species richness was higher in planted improved grassland than in unplanted sites. The differences were primarily the result of the exclusion of grazing, ground preparation, changes in nutrient management and drainage for afforestation. Drainage ditches provided a temporary habitat for less competitive species, but the overall effect of drainage was to reduce the diversity of species dependent on wet conditions. Variance partitioning showed differences in the relative influences of environmental and management variables on biodiversity in the two habitats, probably due to the greater pre-afforestation grazing pressure and fertilisation levels in improved grasslands. The differences in biodiversity between planted and unplanted grasslands indicate that afforestation represents a threat to semi-natural habitats where distinctive and highly localised plant communities could potentially occur