EGFR Signaling Promotes β-Cell Proliferation and Survivin Expression during Pregnancy

Placental lactogen (PL) induced serotonergic signaling is essential for gestational β-cell mass expansion. We have previously shown that intact Epidermal growth factor –receptor (EGFR) function is a crucial component of this pathway. We now explored more specifically the link between EGFR and pregnancy-induced β-cell mass compensation. Islets were isolated from wild-type and β-cell-specific EGFR-dominant negative mice (E1-DN), stimulated with PL and analyzed for β-cell proliferation and expression of genes involved in gestational β-cell growth. β-cell mass dynamics were analyzed both with traditional morphometrical methods and three-dimensional optical projection tomography (OPT) of whole-mount insulin-stained pancreata. Insulin-positive volume analyzed with OPT increased 1.4-fold at gestational day 18.5 (GD18.5) when compared to non-pregnant mice. Number of islets peaked by GD13.5 (680 vs 1134 islets per pancreas, non-pregnant vs. GD13.5). PL stimulated beta cell proliferation in the wild-type islets, whereas the proliferative response was absent in the E1-DN mouse islets. Serotonin synthesizing enzymes were upregulated similarly in both the wild-type and E1-DN mice. However, while survivin (Birc5) mRNA was upregulated 5.5-fold during pregnancy in the wild-type islets, no change was seen in the E1-DN pregnant islets. PL induced survivin expression also in isolated islets and this was blocked by EGFR inhibitor gefitinib, mTOR inhibitor rapamycin and MEK inhibitor PD0325901. Our 3D-volumetric analysis of β-cell mass expansion during murine pregnancy revealed that islet number increases during pregnancy. In addition, our results suggest that EGFR signaling is required for lactogen-induced survivin expression via MAPK and mTOR pathways.     

Amniotic Fluid Derived Stem Cells with a Renal Progenitor Phenotype Inhibit Interstitial Fibrosis in Renal Ischemia and Reperfusion Injury in Rats

Objectives

Mesenchymal stem cells derived from human amniotic fluid (hAFSCs) are a promising source for cellular therapy, especially for renal disorders, as a subpopulation is derived from the fetal urinary tract. The purpose of this study was to evaluate if hAFSCs with a renal progenitor phenotype demonstrate a nephroprotective effect in acute ischemia reperfusion (I/R) model and prevent late stage fibrosis.

Methods

A total of 45 male 12-wk-old Wistar rats were divided into three equal groups;: rats subjected to I/R injury and treated with Chang Medium, rats subjected to I/R injury and treated with hAFSCs and sham-operated animals. In the first part of this study, hAFSCs that highly expressed CD24, CD117, SIX2 and PAX2 were isolated and characterized. In the second part, renal I/R injury was induced in male rats and cellular treatment was performed 6 hours later via arterial injection. Functional and histological analyses were performed 24 hours, 48 hours and 2 months after treatment using serum creatinine, urine protein to creatinine ratio, inflammatory and regeneration markers and histomorphometric analysis of the kidney. Statistical analysis was performed by analysis of variance followed by the Tukey’s test for multiple comparisons or by nonparametric Kruskal-Wallis followed by Dunn. Statistical significance level was defined as p <0.05.

Results

hAFSCs treatment resulted in significantly reduced serum creatinine level at 24 hours, less tubular necrosis, less hyaline cast formation, higher proliferation index, less inflammatory cell infiltration and less myofibroblasts at 48h. The treated group had less fibrosis and proteinuria at 2 months after injury.

Conclusion

hAFSCs contain a renal progenitor cell subpopulation that has a nephroprotective effect when delivered intra-arterially in rats with renal I/R injury, and reduces interstitial fibrosis on long term follow-up.     

Can long-distance dispersal shape the local and regional species pool?

Long-distance dispersal events are irregular and their role in shaping plant diversity is often discussed and modeled but rarely studied experimentally. We mimicked long-distance dispersal experimentally by sowing eleven exotic and fourteen native species into a calcareous grassland community in Estonia. Exotic species were randomly chosen from the collection of 500 herbaceous species in the Botanical Garden of the Tartu University. All exotic species were able to complete their life-cycles under the climatic and edaphic conditions in the garden. Native species originated from open dry calcareous habitats in the surroundings of the study site, but did not occur in the experimental grassland. Seven exotic species and seven native species established during the first year. In the third year, there were still three exotic species with five premature individuals, and three sown native species with sixteen individuals in the plots. These results show that long-distance dispersal both within and between regions may have an impact on species composition in target plant communities. If relatively the best established exotic speciesPhyteuma scheuchzeri would be classified as casual, one may conclude that transition among introduction and casual stages corresponds to ten’ rule. The species richness of seedlings, taking both local and sown species into account, was higher in plots with higher native established plant species richness.     

Microtopography and the Properties of Residual Peat Are Convenient Indicators for Restoration Planning of Abandoned Extracted Peatlands

The natural recovery of vegetation on abandoned peat extraction areas lasts for decades and the result of restoration succession can be unpredictable. The aim of the study was to specify environmental factors that affect the formation of the pioneer stages of mire communities and, therefore, be helpful in the prediction of the resulting ecosystem properties. We used the national inventory data from 64 milled peatlands in Estonia, distributed over the region of 300 × 200 km. This is the first national‐scale statistical evaluation of abandoned extracted peatlands. During surveys, vascular plants, bryophytes, and residual peat properties were recorded on three microtopographic forms: flats, ditch margins, and ditches. The microtopography was the main factor distinguishing the composition of plant communities on flats and ditches, while ditch margins resembled flats. The extracted indicator species suggested two successional pathways, toward fen or raised bog community. A single indicator trait—the depth of residual peat, which combines the information about peat properties (e.g. pH, ash content, and trophicity status), predicted the plant community succession in microtopographic habitats. We suggest that peatland management plans about the cost‐efficient restoration of abandoned peat mining areas should consider properties of residual peat layer as the baseline indicator: milled peatfields with thin (<2.3 m) and well‐decomposed residual peat should be restored toward fen vegetation types, whereas sites with thick (>2.3 m) and less decomposed residual peat layer should be restored toward transitional mires or raised bogs. Specific methodological suggestions are provided .     

Long‐term colonization ecology of forest‐dwelling species in a fragmented rural landscape – dispersal versus establishment

Species colonization in a new habitat patch is an efficiency indicator of biodiversity conservation. Colonization is a two‐step process of dispersal and establishment, characterized by the compatibility of plant traits with landscape structure and habitat conditions. Therefore, ecological trait profiling of specialist species is initially required to estimate the relative importance of colonization filters. Old planted parks best satisfy the criteria of a newly created and structurally matured habitat for forest‐dwelling plant species. We sampled species in 230 ancient deciduous forests (source habitat), 74 closed‐canopy manor parks (target habitats), 151 linear wooded habitats (landscape corridors), and 97 open habitats (isolating matrix) in Estonia. We defined two species groups of interest: forest (107 species) and corridor specialists (53 species). An extra group of open habitat specialists was extracted for trait scaling. Differing from expectations, forest specialists have high plasticity in reproduction mechanisms: smaller seeds, larger dispersules, complementary selfing ability, and diversity of dispersal vectors. Forest specialists are shorter, less nutrient‐demanding and mycorrhizal‐dependent, stress‐tolerant disturbance‐sensitive competitors, while corridor specialists are large‐seeded disturbance‐tolerant competitors. About 40% of species from local species pools have immigrated into parks. The historic forest area, establishment‐related traits, and stand quality enhance the colonization of forest specialists. The openness of landscape and mowing in the park facilitate corridor specialists. Species traits in parks vary between a forest and corridor specialist, except for earlier flowering and larger propagules. Forest species are not dispersal limited, but they continue to be limited by habitat properties even in the long term. Therefore, the shady parts of historic parks should be appreciated as important forest biodiversity‐enhancing landscape structures. The habitat quality of secondary stands can be improved by nurturing a heterogeneous shrub and tree layer, and modest herb layer management.