A new cryptic Sympistis from eastern North America revealed by novel larval phenotype and host plant association (Lepidoptera,Noctuidae, Oncocnemidinae)

A Triosteum-feeding species of Sympistis is described from eastern North America: Sympistis forbesi sp. n. Identity of the new species is most reliably determined from larval morphology and host plant association—both adult scaling and genitalic characters overlap with those of Sympisitis chionanthi, a Chionanthus and Fraxinus feeder.     

Inter-species variation in yolk steroid levels and a cowbird-host comparison

We examined variability in yolk hormone levels among songbird species and the role of yolk steroids as a mechanism for enhanced exploitation of hosts by the parasitic brown-headed cowbird Molothrus ater . Within-clutch variation in yolk steroids has been found in several avian species in single species studies, but few comparisons have been made among species. We found a large range of differences in yolk testosterone among the seven passerine species examined, with significant differences between those at the high end (song sparrow Melospiza melodia , red-winged blackbird Agelaius phoeniceus , and house sparrow, Passer domesticus ) and those at the low end (eastern phoebe Sayornis phoebe , and house finch Carpodacus mexicanus ). We also found that the testosterone level in cowbird eggs was intermediate in relation to host species levels and was significantly lower than that in three common cowbird hosts (song sparrow, red-winged blackbird, and house sparrow), but not significantly different from three others. Geographical comparisons of yolk testosterone levels in all cowbird subspecies and populations from several regions showed no significant differences, though a trend that deserves further exploration was the pattern of lowest level in the ancestral population of cowbirds in the central prairies and of highest level in the northwestern population where range invasion occurred approximately 40 years ago. The levels of 17 beta-estradiol were similar in the seven songbird species examined, which is consistent with current hypotheses that this hormone plays a role in embryonic sexual differentiation. Further investigation is needed to determine whether the large differences observed among species in absolute level of yolk testosterone are the relevant focal point or whether target tissue sensitivity differences mediate the effects of this yolk steroid, particularly between parasitic and non-parasitic species.     

Saikosaponin-d,a novel SERCA inhibitor,induces autophagic cell death in apoptosis-defective cells

Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase pump, leading to autophagy induction through the activation of the Ca²⁺/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells.     

Retinol-binding protein 4 is expressed in chondrocytes of developing mouse long bones: implications for a local role in formation of the secondary ossification center

Retinol-binding protein 4 (Rbp4) is the major carrier of retinol in the bloodstream, a retinoid whose metabolites influence osteogenesis, chondrogenesis and adipogenesis. Rbp4 is mainly produced in the liver where it mobilizes hepatic retinol stores to supply other tissues. However, Rbp4 is also expressed in several extrahepatic tissues, including limbs, where its role is largely unknown. This study aimed to identify the cellular localization of Rbp4 to gain insight into its involvement in limb development and bone growth. Using immunohistochemistry, we discovered that Rbp4 was present in a variety of locations in developing embryonic and postnatal mouse hindlimbs. Rbp4 was present in a restricted population of epiphyseal chondrocytes and perichondral cells correlating to the future region of secondary ossification. With the onset of secondary ossification, Rbp4 was detected in chondrocytes of the resting zone and in chondrocytes that bordered invading cartilage canals and the expanding front of ossification. Rbp4 was less abundant in proliferating chondrocytes involved in primary ossification. Our data implicate the involvement of chondrocytic Rbp4 in bone growth, particularly in the formation of the secondary ossification center of the limb.     

Differential regulation of cell functions by CSD peptide subdomains

Background

In fibrotic lung diseases, expression of caveolin-1 is decreased in fibroblasts and monocytes. The effects of this deficiency are reversed by treating cells or animals with the caveolin-1 scaffolding domain peptide (CSD, amino acids 82–101 of caveolin-1) which compensates for the lack of caveolin-1. Here we compare the function of CSD subdomains (Cav-A, Cav-B, Cav-C, Cav-AB, and Cav-BC) and mutated versions of CSD (F92A and T90A/T91A/F92A).

Methods

Migration toward the chemokine CXCL12 and the associated expression of F-actin, CXCR4, and pSmad 2/3 were studied in monocytes from healthy donors and SSc patients. Fibrocyte differentiation was studied using PBMC from healthy donors and SSc patients. Collagen I secretion and signaling were studied in fibroblasts derived from the lung tissue of healthy subjects and SSc patients.

Results

Cav-BC and CSD at concentrations as low as 0.01 μM inhibited the hypermigration of SSc monocytes and TGFβ-activated Normal monocytes and the differentiation into fibrocytes of SSc and Normal monocytes. While CSD also inhibited the migration of poorly migrating Normal monocytes, Cav-A (and other subdomains to a lesser extent) promoted the migration of Normal monocytes while inhibiting the hypermigration of TGFβ-activated Normal monocytes. The effects of versions of CSD on migration may be mediated in part via their effects on CXCR4, F-actin, and pSmad 2/3 expression. Cav-BC was as effective as CSD in inhibiting fibroblast collagen I and ASMA expression and MEK/ERK signaling. Cav-C and Cav-AB also inhibited collagen I expression, but in many cases did not affect ASMA or MEK/ERK. Cav-A increased collagen I expression in scleroderma lung fibroblasts. Full effects on fibroblasts of versions of CSD required 5 μM peptide.

Conclusions

Cav-BC retains most of the anti-fibrotic functions of CSD; Cav-A exhibits certain pro-fibrotic functions. Results obtained with subdomains and mutated versions of CSD further suggest that the critical functional residues in CSD depend on the cell type and readout being studied. Monocytes may be more sensitive to versions of CSD than fibroblasts and endothelial cells because the baseline level of caveolin-1 in monocytes is much lower than in these other cell types.