7 research outputs found
On Scores, Losing Scores and Total Scores in Hypertournaments
A -hypertournament is a complete -hypergraph with each -edge endowed with an orientation, that is, a linear arrangement of the vertices contained in the edge. In a -hypertournament, the score (losing score ) of a vertex is the number of arcs containing in which is not the last element (in which is the last element). The total score of is defined as . In this paper we obtain stronger inequalities for the quantities , and , where . Furthermore, we discuss the case of equality for these inequalities. We also characterize total score sequences of strong -hypertournaments
Loss of MicroRNA-17∼92 in Smooth Muscle Cells Attenuates Experimental Pulmonary Hypertension via Induction of PDZ and LIM Domain 5
Rationale: Recent studies suggest that microRNAs (miRNAs) play important roles in regulation of pulmonary artery smooth muscle cell (PASMC) phenotype and are implicated in pulmonary arterial hypertension (PAH). However, the underlying molecular mechanisms remain elusive. Objectives: This study aims to understand the mechanisms regulating PASMC proliferation and differentiation by microRNA-17∼92 (miR-17∼92) and to elucidate its implication in PAH. Methods: We generated smooth muscle cell (SMC)-specific miR-17∼92 and PDZ and LIM domain 5 (PDLIM5) knockout mice and overexpressed miR-17∼92 and PDLIM5 by injection of miR-17∼92 mimics or PDLIM5-V5-His plasmids and measured their responses to hypoxia. We used miR-17∼92 mimics, inhibitors, overexpression vectors, small interfering RNAs against PDLIM5, Smad, and transforming growth factor (TGF)-β to determine the role of miR-17∼92 and its downstream targets in PASMC proliferation and differentiation. Measurements and Main Results: We found that human PASMC (HPASMC) from patients with PAH expressed decreased levels of the miR-17∼92 cluster, TGF-β, and SMC markers. Overexpression of miR-17∼92 increased and restored the expression of TGF-β(3), Smad3, and SMC markers in HPASMC of normal subjects and patients with idiopathic PAH, respectively. Knockdown of Smad3 but not Smad2 prevented miR-17∼92-induced expression of SMC markers. SMC-specific knockout of miR-17∼92 attenuated hypoxia-induced pulmonary hypertension (PH) in mice, whereas reconstitution of miR-17∼92 restored hypoxia-induced PH in these mice. We also found that PDLIM5 is a direct target of miR-17/20a, and hypertensive HPASMC and mouse PASMC expressed elevated PDLIM5 levels. Suppression of PDLIM5 increased expression of SMC markers and enhanced TGF-β/Smad2/3 activity in vitro and enhanced hypoxia-induced PH in vivo, whereas overexpression of PDLIM5 attenuated hypoxia-induced PH. Conclusions: We provided the first evidence that miR-17∼92 inhibits PDLIM5 to induce the TGF-β(3)/SMAD3 pathway, contributing to the pathogenesis of PAH
Intratracheal Instillation of High Dose Adenoviral Vectors Is Sufficient to Induce Lung Injury and Fibrosis in Mice
Synthesis and properties of processable poly(benzimidazole-imide)s based on 2-(3-aminophenyl)-5-aminobenzimidazole
The tail domain of PRRSV NSP2 plays a key role in aggrephagy by interacting with 14-3-3ε
Fuzzy Nonlinear Proximal Support Vector Machine for Land Extraction Based on Remote Sensing Image
IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial cells
IL-11 has been detected in inflamed joints; however, its role in the pathogenesis of arthritis is not yet clear. Studies were conducted to characterize the expression and functional significance of IL-11 and IL-11R alpha in rheumatoid arthritis (RA). IL-11 levels were elevated in RA synovial fluid (SF) compared to osteoarthritis (OA) SF and plasma from RA, OA and normal individuals (NLs). Morphologic studies established that IL-11 was detected in lining fibroblasts and macrophages in addition to sublining endothelial cells and macrophages at higher levels in RA compared to NL synovial tissues. Since IL-11R alpha was exclusively expressed in RA fibroblasts and endothelial cells, macrophages were not involved in IL-11 effector function. Ligation of IL-11 to IL-11R alpha strongly provoked fibroblast infiltration into RA joint, while cell proliferation was unaffected by this process. Secretion of IL-8 and VEGF from IL-11 activated RA fibroblasts was responsible for the indirect effect of IL-11 on endothelial cell transmigration and tube formation. Moreover, IL-11 blockade impaired RA SF capacity to elicit endothelial cell transmigration and tube formation. We conclude that IL-11 binding to endothelial IL-11R alpha can directly induce RA angiogenesis. In addition, secretion of proangiogenic factors from migrating fibroblasts potentiated by IL-11 can indirectly contribute to RA neovascularization