Engrailed 1 coordinates cytoskeletal reorganization to induce myofibroblast differentiation

Transforming growth factor-β (TGFβ) is a key mediator of fibroblast activation in fibrotic diseases, including systemic sclerosis. Here we show that Engrailed 1 (EN1) is reexpressed in multiple fibroblast subpopulations in the skin of SSc patients. We characterize EN1 as a molecular amplifier of TGFβ signaling in myofibroblast differentiation: TGFβ induces EN1 expression in a SMAD3-dependent manner, and in turn, EN1 mediates the profibrotic effects of TGFβ. RNA sequencing demonstrates that EN1 induces a profibrotic gene expression profile functionally related to cytoskeleton organization and ROCK activation. EN1 regulates gene expression by modulating the activity of SP1 and other SP transcription factors, as confirmed by ChIP-seq experiments for EN1 and SP1. Functional experiments confirm the coordinating role of EN1 on ROCK activity and the reorganization of cytoskeleton during myofibroblast differentiation, in both standard fibroblast culture systems and in vitro skin models. Consistently, mice with fibroblast-specific knockout of En1 demonstrate impaired fibroblast-to-myofibroblast transition and are partially protected from experimental skin fibrosis

Homotopy minimal period self-maps on flat manifolds

This paper studies the homotopical minimal period set for self-maps on flat manifolds. We introduce a new invariant: the density of the homotopical minimal period set in the natural numbers. Some conditions on self-maps and flat manifolds are obtained so that the corresponding density is positive. © 2013 Elsevier Inc

Compaction Rate of an Early Permian Volcanic Tuff from Wuda Coalfield, Inner Mongolia

Compaction rates of sediments or volcaniclastic material are needed to reconstruct original thickness of a bed, which in turn is required to reconstruct subsidence rates, sea-level rise, or in the case of volcaniclastic, the location or direction of the eruption site. The knowledge of compaction rates can also aid in the reconstruction of deformed fossils. The known shape of deformed fossils can allow the determination of the compaction they experienced. Here we report the compaction rate in an early Permian volcanic tuff from Wuda, Inner Mongolia, determined from the deformation of standing tree fern stems of known anatomy. The compaction rate has been found to be 0.56 in this case, indicating that 44% of original thickness remains

An Enhanced Lattice Algorithm for Range Estimation Using Noisy Measurement With Phase Ambiguity

An Enhanced Lattice Algorithm for Range Estimation Using Noisy Measurement With Phase Ambiguit

Distinct Roles of Phosphoinositide-3 Kinase and Phospholipase Cγ2 in B-Cell Receptor-Mediated Signal Transduction

During B-cell receptor (BCR) signaling, phosphoinositide-3 kinase (PI3K) is thought to function upstream of phospholipase Cγ2 (PLCγ2). PLCγ2 deficiency specifically impedes transitional type 2 (T2) to follicular (FO) mature B-cell transition. Here, we demonstrate that PI3K deficiency specifically impaired T2-to-FO mature B-cell transition and marginal zone B-cell development. Furthermore, we investigated the functional relationship between PI3K and PLCγ2 using PI3K(−/−), PLCγ2(−/−), and PI3K(−/−) PLCγ2(−/−) B cells. Interestingly, PLCγ2 deficiency had no effect on BCR-mediated PI3K activation, whereas PI3K deficiency only partially blocked activation of PLCγ2. Moreover, whereas PI3K(−/−) PLCγ2(−/−) double deficiency did not affect hematopoiesis, it resulted in embryonic lethality. PI3K(−/−) PLCγ2(−/−) fetal liver cells transplanted into B-cell null JAK3(−/−) mice failed to restore development of peripheral B cells and failed to progress through early B-cell development at the pro-B- to pre-B-cell transition, a more severe phenotype than was observed with either PI3K or PLCγ2 single-deficiency B cells. Consistent with this finding, BCR signaling was more severely impaired in the absence of both PI3K and PLCγ2 genes than in the absence of either one alone. Taken together, these results demonstrate that whereas PI3K functions upstream of PLCγ2, activation of PLCγ2 can occur independently of PI3K and that PI3K and PLCγ2 also have distinct functions in BCR signal transduction

Methyl Methacrylate Synthesis: Thermodynamic Analysis for Oxidative Esterification of Methacrolein and Aldol Condensation of Methyl Acetate

Methyl methacrylate (MMA) as a specialty monomer of polymers has motivated industry to develop clean and sustainable technologies for its production. Herein, a comprehensive thermodynamic analysis of MMA production from petroleum-based and coal/biomass-based resources is conducted through the Gibbs free energy minimization method. For the petroleum-based route via oxidative esterification of methacrolein (MAL), the production of MMA is sensitive to the composition of methanol (MeOH) and O2 in the feed, but insensitive to the reaction temperature and pressure. For the coal/biomass-based route via aldol condensation of methyl acetate (MeOAc), a moderate temperature (350–400 °C) and large MeOH/MeOAc ratio (>2) give rise to the efficient production of MMA. Hence, significant improvements in the MMA yield could be achieved by optimizing the reaction conditions, which could almost reach the maximal value theoretically of 1.0 mol from per mole of MAL or MeOAc. This study would shed new light on the thermodynamics of MMA production, which is foundational for the development of new processes at the industrial scale