Calreticulin exploits TGF-ß for extracellular matrix induction engineering a tissue regenerative process.

Topical application of extracellular calreticulin (eCRT), an ER chaperone protein, in animal models enhances wound healing and induces tissue regeneration evidenced by epidermal appendage neogenesis and lack of scarring. In addition to chemoattraction of cells critical to the wound healing process, eCRT induces abundant neo-dermal extracellular matrix (ECM) formation by 3 days post-wounding. The purpose of this study was to determine the mechanisms involved in eCRT induction of ECM. In vitro, eCRT strongly induces collagen I, fibronectin, elastin, α-smooth muscle actin in human adult dermal (HDFs) and neonatal fibroblasts (HFFs) mainly via TGF-ß canonical signaling and Smad2/3 activation; RAP, an inhibitor of LRP1 blocked eCRT ECM induction. Conversely, eCRT induction of α5 and ß1 integrins was not mediated by TGF-ß signaling nor inhibited by RAP. Whereas eCRT strongly induces ECM and integrin α5 proteins in K41 wild-type mouse embryo fibroblasts (MEFs), CRT null MEFs were unresponsive. The data show that eCRT induces the synthesis and release of TGF-ß3 first via LRP1 or other receptor signaling and later induces ECM proteins via LRP1 signaling subsequently initiating TGF-ß receptor signaling for intracellular CRT (iCRT)-dependent induction of TGF-ß1 and ECM proteins. In addition, TGF-ß1 induces 2-3-fold higher level of ECM proteins than eCRT. Whereas eCRT and iCRT converge for ECM induction, we propose that eCRT attenuates TGF-ß-mediated fibrosis/scarring to achieve tissue regeneration.

Cold range edges of marine fishes track climate change better than warm edges.

Species around the world are shifting their ranges in response to climate change. To make robust predictions about climate-related colonizations and extinctions, it is vital to understand the dynamics of range edges. This study is among the first to examine annual dynamics of cold and warm range edges, as most global change studies average observational data over space or over time. We analyzed annual range edge dynamics of marine fishes-both at the individual species level and pooled into cold- and warm-edge assemblages-in a multi-decade time-series of trawl surveys conducted on the Northeast US Shelf during a period of rapid warming. We tested whether cold edges show stronger evidence of climate tracking than warm edges (due to non-climate processes or time lags at the warm edge; the biogeography hypothesis or extinction debt hypothesis), or whether they tracked temperature change equally (due to the influence of habitat suitability; the ecophysiology hypothesis). In addition to exploring correlations with regional temperature change, we calculated species- and assemblage-specific sea bottom and sea surface temperature isotherms and used them to predict range edge position. Cold edges shifted further and tracked sea surface and bottom temperature isotherms to a greater degree than warm edges. Mixed-effects models revealed that for a one-degree latitude shift in isotherm position, cold edges shifted 0.47 degrees of latitude, and warm edges shifted only 0.28 degrees. Our results suggest that cold range edges are tracking climate change better than warm range edges, invalidating the ecophysiology hypothesis. We also found that even among highly mobile marine ectotherms in a global warming hotspot, few species are fully keeping pace with climate.

Broadly inflicted stressors can cause ecosystem thinning.

Many anthropogenic stressors broadly inflict mortality or reduce fecundity, including habitat destruction, pollution, climate change, invasive species, and multispecies harvesting. Here, we show-in four analytical models of interspecies competition-that broadly inflicted stressors disproportionately cause competitive exclusions within groups of ecologically similar species. As a result, we predict that ecosystems become progressively thinner-that is, they have progressively less functional redundancy-as broadly inflicted stressors become progressively more intense. This may negatively affect the temporal stability of ecosystem functions, but it also buffers ecosystem productivity against stress by favoring species less sensitive to the stressors. Our main result follows from the weak limiting similarity principle: species with more similar ecological niches compete more strongly, and their coexistence can be upset by smaller perturbations. We show that stressors can cause indirect competitive exclusions at much lower stressor intensity than needed to directly cause species extinction, consistent with the finding of empirical studies that species interactions are often the proximal drivers of local extinctions. The excluded species are more sensitive to the stressor relative to their ecologically similar competitors. Moreover, broadly inflicted stressors may cause hydra effects-where higher stressor intensity results in higher abundance for a species with lower sensitivity to the stressor than its competitors. Correlations between stressor impacts and ecological niches reduce the potential for indirect competitive exclusions, but they consequently also reduce the buffering effect of ecosystem thinning on ecosystem productivity. Our findings suggest that ecosystems experiencing stress may continue to provision ecosystem services but lose functional redundancy and stability.

Biogeographic constraints to marine conservation in a changing climate.

The siting of protected areas to achieve management and conservation objectives draws heavily on biogeographic concepts of the spatial distribution and connectivity of species. However, the marine protected area (MPA) literature rarely acknowledges how biogeographic theories underpin MPA and MPA network design. We review which theories from biogeography have been incorporated into marine spatial planning and which relevant concepts have yet to be translated to inform the next generation of design principles. This biogeographic perspective will only become more relevant as climate change amplifies these spatial and temporal dynamics, and as species begin to shift in and out of existing MPAs. The scale of climate velocities predicted for the 21st century dwarfs all but the largest MPAs currently in place, raising the possibility that in coming decades many MPAs will no longer contain the species or assemblages they were established to protect. We present a number of design elements that could improve the success of MPAs and MPA networks in light of biogeographic processes and climate change. Biogeographically informed MPA networks of the future may resemble the habitat corridors currently being considered for many terrestrial regions.

Range contraction enables harvesting to extinction.

Economic incentives to harvest a species usually diminish as its abundance declines, because harvest costs increase. This prevents harvesting to extinction. A known exception can occur if consumer demand causes a declining species' harvest price to rise faster than costs. This threat may affect rare and valuable species, such as large land mammals, sturgeons, and bluefin tunas. We analyze a similar but underappreciated threat, which arises when the geographic area (range) occupied by a species contracts as its abundance declines. Range contractions maintain the local densities of declining populations, which facilitates harvesting to extinction by preventing abundance declines from causing harvest costs to rise. Factors causing such range contractions include schooling, herding, or flocking behaviors-which, ironically, can be predator-avoidance adaptations; patchy environments; habitat loss; and climate change. We use a simple model to identify combinations of range contractions and price increases capable of causing extinction from profitable overharvesting, and we compare these to an empirical review. We find that some aquatic species that school or forage in patchy environments experience sufficiently severe range contractions as they decline to allow profitable harvesting to extinction even with little or no price increase; and some high-value declining aquatic species experience severe price increases. For terrestrial species, the data needed to evaluate our theory are scarce, but available evidence suggests that extinction-enabling range contractions may be common among declining mammals and birds. Thus, factors causing range contraction as abundance declines may pose unexpectedly large extinction risks to harvested species.