Two Types of Planning in Neighborhoods

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68338/2/10.1177_0739456X8400300209.pd

Discoidin domain receptor-1 : a novel molecular switch regulating fibrocalcific response in vascular smooth muscle cells

Background: Extracellular vesicle (EV)-derived microcalcifications formed in collagen-poor fibrous caps contribute to plaque rupture. Collagen accumulation and calcification are major determinants of plaque stability, although the mechanisms linking fibrotic and calcific responses are unknown. The collagen receptor discoidin domain receptor-1 (DDR-1) regulates plaque calcification in vivo; however, its role in the release of calcifying EVs remains unclear. We hypothesize that DDR-1 regulates the processes of fibrosis and EV-induced calcification in atherosclerotic plaques. Methods and results: Smooth muscle cells (SMC) from the carotid arteries of wild type and DDR-1 knockout (DDR-1-/-) mice (n=5 per group) were cultured in control or calcifying media. At days 14 and 21, cells were harvested and EVs isolated for analysis. Compared to wild type cells, DDR-1-/- SMCs exhibited a 3.5-fold increase in EV release (p<0.001) as well as elevated EV calcifying potential determined by EV-bound alkaline phosphatase (ALP) activity (470.4+/-30.0 vs. 19.1+/-2.3 ng/well/mg protein). DDR-1-/- SMCs showed an increase in ALP activity (220.3+/-31.2 vs. 6.9+/-1.2 ng/well/mg protein), calcification measured by alizarin red S absorbance (3.56+/-0.11 vs. 0.10+/-0.0008), and collagen type I accumulation (p=0.04). Transforming growth factor-[beta] (TGF[beta]) signaling has been implicated in both fibrotic and calcific responses. DDR-1-/- cells released significantly more TGF[beta] in calcifying medium (253.4+/-12.4 vs. 167.2+/-8.8 pg/ml, p<0.001), suggesting a connection between DDR-1 and TGF[beta] signaling. A selective TGF[beta] receptor I inhibitor mitigated the osteogenic potential of the DDR-1-/- phenotype with a significant decrease in EV release, ALP activity in SMCs and EVs, extracellular matrix calcification and collagen production. Analysis of TGF[beta]-associated pathways in DDR-1-/- SMCs revealed significantly increased p38 phosphorylation while phosphorylated Smad3 and JNK were inhibited

Discoidin domain receptor-1 regulates calcific extracellular vesicle release in vascular smooth muscle cell fibrocalcific response via transforming growth factor-β signaling

Objective - Collagen accumulation and calcification are major determinants of atherosclerotic plaque stability. Extracellular vesicle (EV)-derived microcalcifications in the collagen-poor fibrous cap may promote plaque rupture. In this study, we hypothesize that the collagen receptor discoidin domain receptor-1 (DDR-1) regulates collagen deposition and release of calcifying EVs by vascular smooth muscle cells (SMCs) through the transforming growth factor-β (TGF-β) pathway. Approach and Results - SMCs from the carotid arteries of DDR-1-/- mice and wild-type littermates (n=5-10 per group) were cultured in normal or calcifying media. At days 14 and 21, SMCs were harvested and EVs isolated for analysis. Compared with wild-type, DDR-1-/- SMCs exhibited a 4-fold increase in EV release (P-/- phenotype was characterized by increased mineralization (Alizarin Red S and Osteosense, P-/- SMCs in calcifying media (P-/- phenotype, corroborating a causal relationship between DDR-1 and TGF-β in EV-mediated vascular calcification. Conclusions - DDR-1 interacts with the TGF-β pathway to restrict calcifying EV-mediated mineralization and fibrosis by SMCs. We therefore establish a novel mechanism of cell-matrix homeostasis in atherosclerotic plaque formation

Preferência por estratos florestais e por substâncias odoríferas em abelhas Euglossinae (Hymenoptera, Apidae) Stratification and scents baits preferences in Euglossinae bees (Hymenoptera, Apidae)

<abstract language="eng">Euglossinae bees of two areas of Terra Firme forest, near Manaus, Amazonas, Brazil were studied. During one year the collections were done fortnightly, using traps with eight kinds of scent baits. The traps were placed in the understory and in tree crowns. Some species showed a very clear vertical stratification in the forest. The comparison between the strata studied showed that the fauna of one understory is more similar to other than fauna of crowns and the similarity between fauna of understory and fauna of crown of the the two areaswas low. Some species were specialists while most were generalists in their choice of scent baits. Some species varied its preferences during the year