Limitations of the MRL mouse as a model for cardiac regeneration

Objective Myocardial repair following injury in mammals is restricted such that damaged areas are replaced by scar tissue, impairing cardiac function. MRL mice exhibit exceptional regenerative healing in an ear punch wound model. Some myocardial repair with restoration of heart function has also been reported following cryoinjury. Increased cardiomyocyte proliferation and a foetal liver stem cell population were implicated. We investigated molecular mechanisms facilitating myocardial repair in MRL mice to identify potential therapeutic targets in non-regenerative species. Methods Expressions of specific cell-cycle regulators that might account for regeneration (CDKs 1, 2, 4 and 6; cyclins A, E, D1 and B1; p21, p27 and E2F5) were compared by immunoblotting in MRL and control C57BL/6 ventricles during development. Flow cytometry was used to investigate stem cell populations in livers from foetal mice, and infarct sizes were compared in coronary artery-ligated and sham-treated MRL and C57BL/6 adult mice. Key findings No differences in the expressions of cell cycle regulators were observed between the two strains. Expressions of CD34+Sca1+ckit-, CD34+Sca1+ckit+ and CD34+Sca1-ckit+ increased in livers from C57BL/6 vs MRL mice. No differences were observed in infarct sizes, levels of fibrosis, Ki67 staining or cardiac function between MRL and C57BL/6 mice. Conclusions No intrinsic differences were observed in cell cycle control molecules or stem cell populations between MRL and control C57BL mouse hearts. Pathophysiologically relevant ischaemic injury is not repaired more efficiently in MRL myocardium, questioning the use of the MRL mouse as a reliable model for cardiac regeneration in response to pathophysiologically relevant forms of injury.

Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration

Satellite cells represent the stem cell population of adult skeletal muscle. The molecular mechanisms that control the proliferation of satellite cells are not well understood. In this study, we show that in response to injury, myofibres activate Wnt ligand transcription and activate a reporter cell line that is sensitive to the canonical Wnt-signalling pathway. Activated satellite cells on isolated cultured myofibres show robust expression of activated-β-catenin (Act-β-Cat), a key downstream transcriptional coactivator of canonical Wnt signalling. We provide evidence that the Wnt family of secreted glycoproteins act on satellite cells in a ligand-specific manner. Overexpression of Wnt1, Wnt3a or Wnt5a protein causes a dramatic increase in satellite-cell proliferation. By contrast, exposure of satellite cells to Wnt4 or Wnt6 diminishes this process. Moreover, we show that the prolonged satellite-cell quiescence induced by inhibitory Wnt is reversible and exposing inhibited satellite cells to stimulatory Wnt signalling restores their proliferation rate. Stimulatory Wnt proteins induce premature satellite cell BrdU incorporation as well as nuclear translocation of Act-β-Cat. Finally, we provide evidence that the Act-β-Cat translocation observed in single fibres during in vitro culture also occurs in cases of acute and chronic skeletal muscle regeneration in rodents and humans. We propose that Wnt proteins may be key factors that regulate the rate of satellite-cell proliferation on adult muscle fibres during the wound-healing response.

Forest soil carbon cycle under elevated CO2 – a case of increased throughput?

Forest soils account for a large part of the stable carbon pool held in terrestrial ecosystems. Future levels of atmospheric CO2 are likely to increase C input into the soils through increased above- and below-ground production of forests. This increased input will result in greater sequestration of C only if the additional C enters stable pools. In this review, we compare current observations from four large-scale Free Air FACE Enrichment (FACE) experiments on forest ecosystems (EuroFACE, Aspen-FACE, Duke FACE and ORNL-FACE) and consider their predictive power for long-term C sequestration. At all sites, FACE increased fine root biomass, and in most cases higher fine root turnover resulted in higher C input into soil via root necromass. However, at all sites, soil CO2 efflux also increased in excess of the increased root necromass inputs. A mass balance calculation suggests that a large part of the stimulation of soil CO2 efflux may be due to increased root respiration. Given the duration of these experiments compared with the life cycle of a forest and the complexity of processes involved, it is not yet possible to predict whether elevated CO2 will result in increased C storage in forest soil.

Modelling of the natural chlorine cycling in a coniferous stand: implications for chlorine-36 behaviour in a contaminated forest environment

Considered as one of the most available radionuclide in soileplant system, 36Cl is of potential concern for long-term management of radioactive wastes, due to its high mobility and its long half-life. To evaluate the risk of dispersion and accumulation of 36Cl in the biosphere as a consequence of a potential contamination, there is a need for an appropriate understanding of the chlorine cycling dynamics in the ecosystems. To date, a small number of studies have investigated the chlorine transfer in the ecosystem including the transformation of chloride to organic chlorine but, to our knowledge, none have modelled this cycle. In this study, a model involving inorganic as well as organic pools in soils has been developed and parameterised to describe the biogeochemical fate of chlorine in a pine forest. The model has been evaluated for stable chlorine by performing a range of sensitivity analyses and by comparing the simulated to the observed values. Finally a range of contamination scenarios, which differ in terms of external supply, exposure time and source, has been simulated to estimate the possible accumulation of 36Cl within the different compartments of the coniferous stand. The sensitivity study supports the relevancy of the model and its compartments, and has highlighted the chlorine transfers affecting the most the residence time of chlorine in the stand. Compared to observations, the model simulates realistic values for the chlorine content within the different forest compartments. For both atmospheric and underground contamination scenarios most of the chlorine can be found in its organic form in the soil. However, in case of an underground source, about two times less chlorine accumulates in the system and proportionally more chlorine leaves the system through drainage than through volatilisation.

Spatial and temporal modeling of community non-timber forest extraction

This paper examines the interaction of spatial and dynamic aspects of resource extraction from forests by local people. Highly cyclical and varied across space and time, the patterns of resource extraction resulting from the spatial–temporal model bear little resemblance to the patterns drawn from focusing either on spatial or temporal aspects of extraction alone. Ignoring this variability inaccurately depicts villagers’ dependence on different parts of the forest and could result in inappropriate policies. Similarly, the spatial links in extraction decisions imply that policies imposed in one area can have unintended consequences in other areas. Combining the spatial–temporal model with a measure of success in community forest management—the ability to avoid open-access resource degradation—characterizes the impact of incomplete property rights on patterns of resource extraction and stocks.

The wind in the willows: flows in forest canopies in complex terrain

Forest canopies are important components of the terrestrial carbon budget, which has motivated a worldwide effort, FLUXNET, to measure CO2 exchange between forests and the atmosphere. These measurements are difficult to interpret and to scale up to estimate exchange across a landscape. Here we review the effects of complex terrain on the mean flow, turbulence, and scalar exchange in canopy flows, as exemplified by adjustment to forest edges and hills, including the effects of stable stratification. We focus on the fundamental fluid mechanics, in which developments in theory, measurements, and modeling, particularly through large-eddy simulation, are identifying important processes and providing scaling arguments. These developments set the stage for the development of predictive models that can be used in combination with measurements to estimate exchange at the landscape scale.