Identification and Validation of Proteinase 3 and Latent Matrix-Metalloproteinase 9 as Potential Biomarkers for Chronic Lung Transplant Rejection

Introduction

This study examined potential biomarkers for the diagnosis and early detection of chronic allograft rejection after lung transplantation.

Methods

Protein ratios in pooled samples of bronchoalveolar lavage fluid (BALF) from lung transplant recipients at different stages of pre- and postchronic rejection were determined by iTRAQ labeling and mass spectrometry. The potential biomarkers were validated using enzyme-linked immunosorbent assay (ELISA) assay.

Results

Two hundred sixty-five proteins were identified, about two thirds of which showed more than a twofold difference between a pooled control sample (individuals who did not develop chronic rejection in 100 months) and a pooled sample from those with chronic rejection. Proteinase 3 (PR-3) and matrix metalloproteinase 9 (MMP-9) were validated by ELISA assay of 124 individual samples. PR-3 and the latent form of MMP-9 (proMMP9) both demonstrated a specificity of 92% with sensitivities of 76% and 82%, respectively, for disease diagnosis; both were also predictors of developing chronic rejection up to 15 months before diagnosis. While immunoglobulin M (IgM) was upregulated in the pooled samples, individual sample analysis revealed that this arose from outlier values.

Conclusions

iTRAQ can be used to detect a large number of proteins in pooled samples for the discovery of potential biomarkers, but the findings must be validated with technology capable of distinguishing broadly based changes from outcomes as a result of a few extreme cases. The proteins identified in this study expanded the panel of potential biomarkers for the diagnosis and prediction of chronic rejection and provided additional insight into the mechanism of the disease.     

A century of conservation: The ongoing recovery of Svalbard reindeer

Several caribou and reindeer (Rangifer tarandus) populations have experienced recent population declines, often attributed to anthropogenic stressors such as harvesting, landscape fragmentation, and climate change. Svalbard reindeer (R. t. platyrhynchus), the wild reindeer subspecies endemic to the high-Arctic Svalbard archipelago, was protected in 1925, after most subpopulations had been eradicated by harvest. Although direct pressure from harvest has ceased, indirect anthropogenic stressors from environmental changes have increased in this climate change hot spot. An assessment of the current distribution and abundance is therefore urgently needed. We combined distance sampling (300 km transects, n = 489 reindeer groups) and total counts (1,350 km², n = 1,349 groups) to estimate the Svalbard reindeer distribution and abundance across its entire range, which we compared with historical data from the literature and radiocarbon-dated bones. Reindeer have now recolonized nearly all non-glaciated land (i.e., areas occupied prior to human presence), and their spatial variation in abundance reflects vegetation productivity. Independent of vegetation productivity, however, recently recolonized areas have lower reindeer densities than areas not subject to past extirpation. This suggests that recovery from past overharvesting is still in progress. These incompletely recovered areas are potential targets for increased monitoring frequency and maintaining strict conservation to follow the Svalbard management goal (i.e., virtually untouched wilderness areas). Because of such ongoing recolonization, possibly combined with vegetation greening effects of recent warming, our status estimate of Svalbard reindeer abundance (22,435 [95% CI = 21,452–23,425]) is more than twice a previous estimate based on opportunistic counts. Thus, although our study demonstrates the successful outcome of strict harvesting control implemented a century ago, current and future population trajectories are likely shaped by climate change. © 2019 The Authors. Journal of Wildlife Management Published by Wiley Periodicals, Inc. on behalf of The Wildlife Society.     

Extracellular hemoglobin combined with an O2-generating material overcomes O2 limitation in the bioartificial pancreas

The bioartificial pancreas encapsulating pancreatic islets in immunoprotective hydrogel is a promising therapy for Type 1 diabetes. As pancreatic islets are highly metabolically active and exquisitely sensitive to hypoxia, maintaining O₂ supply after transplantation remains a major challenge. In this study, we address the O₂ limitation by combining silicone-encapsulated CaO₂ (silicone-CaO₂) to generate O₂ with an extracellular hemoglobin O₂-carrier coencapsulated with islets. We showed that the hemoglobin improved by 37% the O₂-diffusivity through an alginate hydrogel and displayed antioxidant properties neutralizing deleterious reactive O₂ species produced by silicone-CaO₂. While the hemoglobin alone failed to maintain alginate macroencapsulated neonate pig islets under hypoxia, silicone-CaO₂ alone or combined to the hemoglobin restored islet viability and insulin secretion and prevented proinflammatory metabolism (PTGS2 expression). Interestingly, the combination took the advantages of the two individual strategies, improved neonate pig islet viability and insulin secretion in normoxia, and VEGF secretion and PDK1 normalization in hypoxia. Moreover, we confirmed the specific benefits of the combination compared to silicone-CaO₂ alone on murine pseudo-islet viability in normoxia and hypoxia. For the first time, our results show the interest of combining an O₂ provider with hemoglobin as an effective strategy to overcome O₂ limitations in tissue engineering.     

Food sharing and affiliation: An experimental and longitudinal study in cockatiels (Nymphicus hollandicus)

Food sharing has attracted much attention because of its apparently altruistic nature and its link to prosociality. However, food sharing has been mostly studied in a reproductive context, during courtship and parental care, where the fitness benefits are obvious. We still lack a clear understanding of the functions of food sharing outside any reproductive context and within social groups of same‐aged peers. Previous studies suggest that cofeeding, the action to let another animal feed from the same monopolizable food source, may be used to build and strengthen bonds between individuals. This may be particularly crucial in social birds forming long‐term associations between mates or siblings such as psittacids and corvids. Here, we investigated food sharing and affiliative behaviors such as allopreening in a psittacine species, namely in a group of captive juvenile cockatiels (Nymphicus hollandicus) consisting of five siblings and five unrelated birds. Our main objective was to study the developmental pattern of food sharing over time and its implication in social bonding depending on kinship, affiliation, and sex. Studying cockatiels in this context is providing many new information since most of the studies on food sharing in birds focused on corvids. We found that, contrary to jackdaws, cockatiels continued to share food with multiple individuals, although the frequency of cofeeding as well as the number of cofeeding partners decreased over time. Cockatiels shared more food with their siblings than with other conspecifics but they were not more likely to do cofeeding with birds of the opposite sex. We also found evidence that young cockatiels exchanged more food with those from whom they received food (reciprocity) and, to a lesser extent, allopreening (interchange), than from other cockatiels. Our findings suggest that in cockatiels, food sharing within social groups serves the formation (and maintenance) of affiliative bonds, especially between siblings, rather than pair bonds, but might additionally be explained by reciprocity, interchange, and harassment avoidance.     

Weeds as a predominant food source: a review of the diet of common hamsters Cricetus cricetus in farmlands and urban habitats

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