Impact of the Uremic Milieu on the Osteogenic Potential of Mesenchymal Stem Cells

Human mesenchymal stem cells (hMSCs), the precursors of osteoblasts during osteogenesis, play a role in the balance of bone formation and resorption, but their functioning in uremia has not been well defined. To study the effects of the uremic milieu on osteogenic properties, we applied an in vitro assay culturing hMSCs in osteogenic medium supplemented with serum from healthy donors and from uremic patients on hemodialysis. Compared to control, serum from uremic patients induces, in hMSC cultures, a modification of several key regulators of bone remodeling, in particular a reduction of the ratio Receptor Activator of Nuclear factor Kappa B Receptor (RANKL) over osteoprotegerin, indicating an adaptive response of the system to favor osteogenesis over osteoclastosis. However, the levels of osteopontin, osteocalcin, and collagen type I, are increased in cell medium, while BMP-2, and alizarin red staining were decreased, pointing to a reduction of bone formation favoring resorption. Selected uremic toxins, such as p-cresylsulfate, p-cresylglucuronide, parathyroid hormone, indoxyl sulfate, asymmetric dimethylarginine, homocysteine, were able to mimic some of the effects of whole serum from uremic patients. Serum from cinacalcet-treated patients antagonizes these effects. Hydrogen sulfide (H2S) donors as well as hemodialysis treatment are able to induce beneficial effects. In conclusion, bone modifications in uremia are influenced by the capability of the uremic milieu to alter hMSC osteogenic differentiation. Cinacalcet, H2S donors and a hemodialysis session can ameliorate the hampered calcium deposition.     

Using Satellite Tracking and Isotopic Information to Characterize the Impact of South American Sea Lions on Salmonid Aquaculture in Southern Chile

Apex marine predators alter their foraging behavior in response to spatial and/or seasonal changes in natural prey distribution and abundance. However, few studies have identified the impacts of aquaculture that represents a spatially and temporally predictable and abundant resource on their foraging behavior. Using satellite telemetry and stable isotope analysis we examined the degree of spatial overlap between the South American sea lion (SASL) and salmon farms, and quantify the amount of native prey versus farmed salmonids in SASL diets. We instrumented eight SASL individuals with SRDL-GPS tags. Vibrissae, hair and skin samples were collected for δ¹³C and δ¹⁵N analyses from five of the tagged individuals and from four males captured in a haul-out located adjacent to salmon farms. Tracking results showed that almost all the foraging areas of SASL are within close proximity to salmon farms. The most important prey for the individuals analyzed was farmed salmonids, with an estimated median (±SD) contribution of 19.7 ± 13.5‰ and 15.3 ± 9.6‰ for hair and skin, respectively. Using vibrissae as a temporal record of diet for each individual, we observed a remarkable switch in diet composition in two SASL, from farmed salmonids to pelagic fishes, which coincided with the decrease of salmon production due to the infectious salmon anemia virus that affected salmon farms in Chile at the end of 2008. Our study demonstrates the usefulness of integrating stable isotope derived dietary data with movement patterns to characterize the impacts of a non-native prey on the foraging ecology of an apex marine predator, providing important applied implications in situations where interactions between aquaculture and wildlife are common.     

How different from random are docking predictions when ranked by scoring functions?

Docking algorithms predict the structure of protein–protein interactions. They sample the orientation of two unbound proteins to produce various predictions about their interactions, followed by a scoring step to rank the predictions. We present a statistical assessment of scoring functions used to rank near‐native orientations, applying our statistical analysis to a benchmark dataset of decoys of protein–protein complexes and assessing the statistical significance of the outcome in the Critical Assessment of PRedicted Interactions (CAPRI) scoring experiment. A P value was assigned that depended on the number of near‐native structures in the sampling. We studied the effect of filtering out redundant structures and tested the use of pair‐potentials derived using ZDock and ZRank. Our results show that for many targets, it is not possible to determine when a successful reranking performed by scoring functions results merely from random choice. This analysis reveals that changes should be made in the design of the CAPRI scoring experiment. We propose including the statistical assessment in this experiment either at the preprocessing or the evaluation step. Proteins 2010. © 2010 Wiley‐Liss, Inc.     

The defensive functions of plant inhibitors are not restricted to insect enzyme inhibition

Three plant proteinase inhibitors BbKI (kallikrein inhibitor) and BbCI (cruzipain inhibitor) from Bauhinia bauhinioides, and a BrTI (trypsin inhibitor) from B. rufa, were examined for other effects in Callosobruchus maculatus development; of these only BrTI affected bruchid emergence. BrTI and BbKI share 81% identities in their primary sequences and the major differences between them are the regions comprising the RGD and RGE motifs in BrTI. These sequences were shown to be essential for BrTI insecticidal activity, since a modified BbKI [that is a recombinant form (BbKIm) with some amino acid residues replaced by those found in BrTI sequence] also strongly inhibited insect development. By using synthetic peptides related to the BrTI sequence, YLEAPVARGDGGLA-NH₂ (RGE) and IVYYPDRGETGL-NH₂ (RGE), it was found that the peptide with an RGE sequence was able to block normal development of C. maculatus larvae (ED₅₀ 0.16% and LD₅₀ 0.09%), this being even more effective than the native protein.     

Recent developments in effector biology of filamentous plant pathogens

Filamentous pathogens, such as plant pathogenic fungi and oomycetes, secrete an arsenal of effector molecules that modulate host innate immunity and enable parasitic infection. It is now well accepted that these effectors are key pathogenicity determinants that enable parasitic infection. In this review, we report on the most interesting features of a representative set of filamentous pathogen effectors and highlight recent findings. We also list and describe all the linear motifs reported to date in filamentous pathogen effector proteins. Some of these motifs appear to define domains that mediate translocation inside host cells.     

Soil nutrient dissimilarity and litter nutrient limitation as major drivers of home field advantage in riparian tropical forests

Decomposition is a key process driving carbon and nutrient cycling in ecosystems worldwide. The home field advantage effect (HFA) has been found to accelerate decomposition rates when litter originates from “home” when compared to other (“away”) sites. It is still poorly known how HFA plays out in tropical, riparian forests, particularly in forests under restoration. We carried out three independent reciprocal litter transplant experiments to test how litter quality, soil nutrient concentrations, and successional stage (age) influenced HFA in tropical riparian forests. These experimental areas formed a wide gradient of soil and litter nutrients, which we used to evaluate the more general hypothesis that HFA varies with dissimilarity in soil nutrients and litter quality. We found that HFA increased with soil nutrient dissimilarity, suggesting that litter translocation uncouples relationships between decomposers and litter characteristics; and with litter N:P, indicating P limitation in this system. We also found negative HFA effects at a site under restoration that presented low decomposer ability, suggesting that forest restoration does not necessarily recover decomposer communities and nutrient cycling. Within each of the independent experiments, the occurrence of HFA effects was limited and their magnitude was not related to forest age, nor soil and litter quality. Our results imply that HFA effects in tropical ecosystems are influenced by litter nutrient limitation and soil nutrient dissimilarity between home and away sites, but to further disentangle major HFA drivers in tropical areas, a gradient of dissimilarity between litter and soil properties must be implemented in future experimental designs.     

Combined effects of vasoactive intestinal peptide and dopamine on adenylate cyclase in prolactin-secreting cells

VIP stimulates adenylate cyclase activity of male and female rat anterior pituitaries and human prolactinomas, while dopamine inhibits the enzyme activity of female rat pituitaries and prolactinomas. A dopamine inhibited cyclase can be detected also in male rats provided the enzyme activity is increased by VIP. The analysis of the dose-response curves for one agent (VIP or dopamine) in the absence or in the presence of the other indicates that the two agents exhibit a different pattern of interaction in the different systems. In fact, in female rat pituitaries and in human prolactinomas, the curves for dopamine±VIP and for VIP±dopamine were parallel, indicating that the two agents exherted their effects independently from one another. On the contrary, in male rat pituitaries, the curves were definitively non parallel, that is, the inhibitory effect of dopamine was greatly amplified by VIP. In no case was the apparent affinity (EC₅₀) of one agent modified by the presence of the other. It is concluded that two different modes of interaction between stimulatory and inhibitory neurohormones might exist at the level of adenylate cyclase from anterior pituitary cells.