LRP1-Dependent Endocytic Mechanism Governs the Signaling Output of the Bmp System in Endothelial Cells and in Angiogenesis

Rationale: Among the extracellular modulators of Bmp (bone morphogenetic protein) signaling, Bmper (Bmp endothelial cell precursor-derived regulator) both enhances and inhibits Bmp signaling. Recently we found that Bmper modulates Bmp4 activity via a concentration-dependent, endocytic trap-and-sink mechanism. Objective: To investigate the molecular mechanisms required for endocytosis of the Bmper/Bmp4 and signaling complex and determine the mechanism of Bmper's differential effects on Bmp4 signaling. Methods and Results: Using an array of biochemical and cell biology techniques, we report that LRP1 (LDL receptor-related protein 1), a member of the LDL receptor family, acts as an endocytic receptor for Bmper and a coreceptor of Bmp4 to mediate the endocytosis of the Bmper/Bmp4 signaling complex. Furthermore, we demonstrate that LRP1-dependent Bmper/Bmp4 endocytosis is essential for Bmp4 signaling, as evidenced by the phenotype of lrp1-deficient zebrafish, which have abnormal cardiovascular development and decreased Smad1/5/8 activity in key vasculogenic structures. Conclusions: Together, these data reveal a novel role for LRP1 in the regulation of Bmp4 signaling by regulating receptor complex endocytosis. In addition, these data introduce LRP1 as a critical regulator of vascular development. These observations demonstrate Bmper's ability to fine-tune Bmp4 signaling at the single-cell level, unlike the spatial regulatory mechanisms applied by other Bmp modulators.     

Mitochondrial genes and genomes support a cryptic species of tapeworm within Taenia taeniaeformis

Taenia taeniaeformis is a globally distributed cestode, which uses felids as definitive and rodents as intermediate hosts. The complete mitochondrial DNA (mtDNA) of T. taeniaeformis from Germany (Tt-GER) was sequenced, and compared with that of another isolate from China (GenBank NC_014768; Tt-CHN), both taken from cats. Analysis of the two mtDNAs indicated that the isolates are significantly different from one another with 12.6% and 9.9% nucleotide and amino acid divergence between them, for concatenated protein-coding genes; overall difference based on a pairwise nucleotide alignment of complete mtDNAs was 11.8%. A phylogenetic analysis based on the 12 protein-coding genes of all available taeniid mtDNAs confirmed the two T. taeniaeformis isolates as sister taxa (likely separate species) and early divergent members of the genus, as suggested previously by morphology. Phylogenetic analysis of published fragments of mt genes rrnS, cox1 and nad1, which represent multiple geographic isolates of T. taeniaeformis also resolve two distinct clades that at present do not seem to be geographically isolated. Mean pairwise (nucleotide) differences between the two clades of T. taeniaeformis were approximately 11%, 10% and 13% in partial rrnS (182bp), cox1 (371bp) and nad1 (459bp) genes, respectively. Differences between entire mtDNAs and partial mt genes of the two T. taeniaeformis isolates are of a similar magnitude between established taeniid sister species. Tt-CHN differs from all other Taenia mtDNAs in lacking a short (～69bp) non-coding region between trnY and trnL1. Partial mt fragment analysis highlighted likely misidentifications of T. taeniaeformis on GenBank.     

The structural composition of components contributes to the superiority of the geoherb Alisma orientale for “diuresis and diffusing dampness”

The purpose of this study is to explore the intrinsic reasons for the superiority of the salt-made geoherb Alisma orientale via comparing the content of various components of the salt-made geoherb Alisma orientale. The effects of “diuresis and diffusing dampness” using salt-made Alisma orientale from seven different origins were investigated through pharmacodynamic experiments in vivo and in vitro. The results indicated that salt-made Alisma orientale from different origins had diuretic efficacy; this was demonstrated by the significant increase in the volume of rat urine, the concentration of Na⁺, K⁺, and Cl⁻ in the urine, and the significant decrease in the levels of AQP-2 in rat renal medulla and HK-2 cells. It was also revealed that the diuretic effect of salt-made Alisma orientale from Fujian Province is stronger than those from other provinces. Moreover, the main components and their proportions in the salt-made Alisma orientale samples were further analyzed via principal component analysis. The results showed that alisol A 24-acetate, alisol B, and 23-acetyl alisol B are the main components of salt-made Alisma orientale, and the optimal structural ratio of alisol A 24-acetate, alisol B, and 23-acetyl alisol B was found to be 5.38 : 14.34 : 11.31 via optimizing the ratios of the three main components. It is worth noting that the optimal ratio of the three main components after optimization is the closest to the ratio of the three main components in salt-made Alisma orientale from Fujian Province. This paper reveals the “mystery” of the content ratio of the main active components and its effect on the efficacy, and showed that the proportional relationship between the content of multiple components is the key to their interactions. Therefore, this method of evaluating the quality of salt-made Alisma orientale is obviously reliable, and this study lays the foundations for quality evaluation of salt-made Alisma orientale and other herb slices.

The purpose of this study is to explore the intrinsic reasons for the superiority of the salt-made geoherb Alisma orientale via comparing the content of various components of the salt-made geoherb Alisma orientale.     

Effects of the modified excision combined with bidirectional photodynamic therapy on refractory hidradenitis suppurativa: a retrospective study

Lasers in Medical Science - To describe the clinical features of refractory hidradenitis suppurativa (HS) patients (Hurley stageII and stage III) and evaluate the efficacy of combined treatment of...     

Development of a New Index Based on Preoperative Serum Lipocalin 2 to Predict Post-LSG Weight Reduction

Obesity Surgery - Bariatric surgery is the most effective therapy for obesity, but targeted weight reduction is not always achieved. Serum lipocalin-2 (LCN2) is closely associated with obesity, but...