Impact of the new definition for pulmonary hypertension in patients with lung disease: an analysis of the United Network for Organ Sharing database

The implications of the recent change in the definition of pulmonary hypertension on epidemiology and outcomes are not known. We sought to determine the percentage of patients with the two most common lung diseases that would be reclassified regarding the presence/absence of pulmonary hypertension with the revised definition. A query of the United Network for Organ Sharing database was performed. The percentage of patients meeting the current and previous definition of pulmonary hypertension was described. Outcomes of patients stratified by the current and previous definitions were compared. There were 15,563 patients with right heart catheterization data analyzed. Pulmonary hypertension was more prevalent in both chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis under the new definition at 52.4% versus 82.4%, and 47.6% versus 73.6%, respectively. 'Pre-capillary' pulmonary hypertension by the new definition was lower at 28.1% for chronic obstructive pulmonary disease and 36.8% for idiopathic pulmonary fibrosis. Of the patients with pulmonary hypertension by the old definition, 23.9% of chronic obstructive pulmonary disease patients and 18.7% of idiopathic pulmonary fibrosis patients were not classified as pulmonary hypertension by the new definition. Conversely, 15.9% of chronic obstructive pulmonary disease patients and 15.1% of idiopathic pulmonary fibrosis patients who did not meet diagnostic criteria for pulmonary hypertension by the old definition did have pulmonary hypertension by the new definition. Patients in both disease categories had shorter transplant-free waitlist survival in the presence of pulmonary hypertension by both the new and old definitions. There was a trend toward the new definition of pre-capillary pulmonary hypertension better discerning outcomes compared to the old definition of pulmonary hypertension in idiopathic pulmonary fibrosis patients. Most patients with advanced lung disease who are listed for lung transplantation have pulmonary hypertension, but fewer have pre-capillary pulmonary hypertension than pulmonary hypertension by the old definition. Both the old and new definition of precapillary pulmonary hypertension appear to discern outcomes among the two groups of lung disease analyzed, with some evidence to suggest that the new definition performs slightly better in the idiopathic pulmonary fibrosis population

YB-1 promotes microtubule assembly in vitro through interaction with tubulin and microtubules

<p>Abstract</p> <p>Background</p> <p>YB-1 is a major regulator of gene expression in eukaryotic cells. In addition to its role in transcription, YB-1 plays a key role in translation and stabilization of mRNAs.</p> <p>Results</p> <p>We show here that YB-1 interacts with tubulin and microtubules and stimulates microtubule assembly <it>in vitro</it>. High resolution imaging via electron and atomic force microscopy revealed that microtubules assembled in the presence of YB-1 exhibited a normal single wall ultrastructure and indicated that YB-1 most probably coats the outer microtubule wall. Furthermore, we found that YB-1 also promotes the assembly of MAPs-tubulin and subtilisin-treated tubulin. Finally, we demonstrated that tubulin interferes with RNA:YB-1 complexes.</p> <p>Conclusion</p> <p>These results suggest that YB-1 may regulate microtubule assembly <it>in vivo </it>and that its interaction with tubulin may contribute to the control of mRNA translation.</p

Polyamine Sharing between Tubulin Dimers Favours Microtubule Nucleation and Elongation via Facilitated Diffusion

We suggest for the first time that the action of multivalent cations on microtubule dynamics can result from facilitated diffusion of GTP-tubulin to the microtubule ends. Facilitated diffusion can promote microtubule assembly, because, upon encountering a growing nucleus or the microtubule wall, random GTP-tubulin sliding on their surfaces will increase the probability of association to the target sites (nucleation sites or MT ends). This is an original explanation for understanding the apparent discrepancy between the high rate of microtubule elongation and the low rate of tubulin association at the microtubule ends in the viscous cytoplasm. The mechanism of facilitated diffusion requires an attraction force between two tubulins, which can result from the sharing of multivalent counterions. Natural polyamines (putrescine, spermidine, and spermine) are present in all living cells and are potent agents to trigger tubulin self-attraction. By using an analytical model, we analyze the implication of facilitated diffusion mediated by polyamines on nucleation and elongation of microtubules. In vitro experiments using pure tubulin indicate that the promotion of microtubule assembly by polyamines is typical of facilitated diffusion. The results presented here show that polyamines can be of particular importance for the regulation of the microtubule network in vivo and provide the basis for further investigations into the effects of facilitated diffusion on cytoskeleton dynamics

Ion exchange and DNA molecular dip sticks: studying the nanoscale surface wetting of muscovite mica

Mica is an abundant crystal mineral that has important and interesting bulk and surface properties for a variety of applications. These properties arise from its anisotropic structure, in which layers of aluminum silicate, 1 nm thick, are ionically bonded together, typically with K+ ions. The surface properties of mica can be varied through ion exchange with the exposed lattice sites. In this study, the effect of kinetics on ion exchange with nickel ions (Ni2+) and its influence on surface water accumulation as a function of time has been investigated. Mica was ion-exchanged for 30 s or 5 min for a range of Ni2+ concentrations (i.e., 1.0-20.0 mM), and its surface properties were measured for up to 96 h after incubation in a controlled environment. The nanoscale physicochemical properties of nickel-functionalized muscovite mica (Ni-mica) were investigated by reconstructing the conservative force profile between an atomic force microscopy (AFM) tip and the surface. This information provides a hint of the surface water accumulation and enables details of the spatial and temporal variations in surface properties due to the ion-mediated adsorption of water to be elucidated. Variations in the water-layer accumulation were confirmed using noncontact AFM imaging under ambient conditions and DNA molecules as "molecular dip sticks". It was found that the surface properties were largely independent of the incubating concentration but did depend on the incubation time during ion exchange and the aging time. For the longer incubation time of 5 min, the water-layer accumulation remained constant at around ∼1.5 nm deep, whereas for the short incubation time of 30 s, the accumulation was initially subnanometer but grew with aging time and converged to a similar final value after 96 h. The extracted force of adhesion (FAD) also showed the same trends, where reduced values of FAD indicated increased screening of the van der Waals interaction through thicker water layers