8 research outputs found
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
A route to functionalised pores in coordination polymers via mixed phosphonate and amino-triazole linkers
Zn<sub>7</sub>O<sub>2</sub>(RCOO)<sub>10</sub> Clusters and Nitro Aromatic Linkers in a Porous Metal–Organic Framework
A new
metal–organic framework, CALF-22 comprising Zn<sub>7</sub>O<sub>2</sub>(COO)<sub>10</sub> secondary building units and 2-nitro-1,4-benzenedicarboxylate,
is reported. The porosity and gas adsorption of N<sub>2</sub>, H<sub>2</sub>, CO<sub>2</sub>, and CH<sub>4</sub> are studied, and CALF-22
has a surface area in excess of 1000 m<sup>2</sup>/g. The stability
of the larger zinc cluster and the effect of the nitro group on gas
sorption are also studied
Enhancing Water Stability of Metal–Organic Frameworks via Phosphonate Monoester Linkers
A new porous metal–organic framework (MOF), barium
tetraethyl-1,3,6,8-pyrenetetraphosphonate
(CALF-25), which contains a new phosphonate monoester ligand, was
synthesized through a hydrothermal method. The MOF is a three-dimensional
structure containing 4.6 Ă… Ă— 3.9 Ă… rectangular one-dimensional
pores lined with the ethyl ester groups from the ligand. The presence
of the ethyl ester groups makes the pores hydrophobic in nature, as
determined by the low heats of adsorption of CH<sub>4</sub>, CO<sub>2</sub>, and H<sub>2</sub>O (14.5, 23.9, and 45 kJ mol<sup>–1</sup>, respectively) despite the polar and acidic barium phosphonate ester
backbone. The ethyl ester groups within the pores also protect CALF-25
from decomposition by water vapor, with crystallinity and porosity
being retained after exposure to harsh humid conditions (90% relative
humidity at 353 K). The use of phosphonate esters as linkers for the
construction of MOFs provides a method to protect hydrolytically susceptible
coordination backbones through kinetic blocking
'Insecta exotica'
A new porous metal–organic framework (MOF), barium
tetraethyl-1,3,6,8-pyrenetetraphosphonate
(CALF-25), which contains a new phosphonate monoester ligand, was
synthesized through a hydrothermal method. The MOF is a three-dimensional
structure containing 4.6 Ă… Ă— 3.9 Ă… rectangular one-dimensional
pores lined with the ethyl ester groups from the ligand. The presence
of the ethyl ester groups makes the pores hydrophobic in nature, as
determined by the low heats of adsorption of CH<sub>4</sub>, CO<sub>2</sub>, and H<sub>2</sub>O (14.5, 23.9, and 45 kJ mol<sup>–1</sup>, respectively) despite the polar and acidic barium phosphonate ester
backbone. The ethyl ester groups within the pores also protect CALF-25
from decomposition by water vapor, with crystallinity and porosity
being retained after exposure to harsh humid conditions (90% relative
humidity at 353 K). The use of phosphonate esters as linkers for the
construction of MOFs provides a method to protect hydrolytically susceptible
coordination backbones through kinetic blocking
A nanoporous chiral metal–organic framework material that exhibits reversible guest adsorption
Epigenetic control of female puberty
The timing of puberty is controlled by many genes. The elements coordinating this process have not, however, been identified. Here we show that an epigenetic mechanism of transcriptional repression times the initiation of female puberty in rats. We identify silencers of the Polycomb group (PcG) as major contributors to this mechanism, and show that PcG proteins repress Kiss1, a puberty-activating gene. Hypothalamic expression of two key PcG genes, Eed and Cbx7, decreases and methylation of their promoters increases preceding puberty. Inhibiting DNA methylation blocks both events and results in pubertal failure. The pubertal increase in Kiss1 is accompanied by EED loss from the Kiss1 promoter and enrichment of histone H3 modifications associated with gene activation. Preventing the eviction of EED from the Kiss1 promoter disrupts pulsatile GnRH release, delays puberty, and compromises fecundity. Our results identify epigenetic silencing as a novel mechanism underlying the neuroendocrine control of female puberty