The adult myocardium responds to a variety of pathologic stimuli by hypertrophic growth that frequently progresses to heart failure. The calcium/calmodulin-dependent protein phosphatase calcineurin ...is a potent transducer of hypertrophic stimuli. Calcineurin dephosphorylates members of the nuclear factor of activated T cell (NFAT) family of transcription factors, which results in their translocation to the nucleus and activation of calcium-dependent genes. Glycogen synthase kinase-3 (GSK-3) phosphorylates NFAT proteins and antagonizes the actions of calcineurin by stimulating NFAT nuclear export. To determine whether activated GSK-3 can act as an antagonist of hypertrophic signaling in the adult heart in vivo, we generated transgenic mice that express a constitutively active form of GSK-3β under control of a cardiac-specific promoter. These mice were physiologically normal under nonstressed conditions, but their ability to mount a hypertrophic response to calcineurin activation was severely impaired. Similarly, cardiac-specific expression of activated GSK-3β diminished hypertrophy in response to chronic β-adrenergic stimulation and pressure overload. These findings reveal a role for GSK-3β as an inhibitor of hypertrophic signaling in the intact myocardium and suggest that elevation of cardiac GSK-3β activity may provide clinical benefit in the treatment of pathologic hypertrophy and heart failure.
beta-Adrenergic receptor (betaAR) signaling, which elevates intracellular cAMP and enhances cardiac contractility, is severely impaired in the failing heart. Protein kinase A (PKA) is activated by ...cAMP, but the long-term physiological effect of PKA activation on cardiac function is unclear. To investigate the consequences of chronic cardiac PKA activation in the absence of upstream events associated with betaAR signaling, we generated transgenic mice that expressed the catalytic subunit of PKA in the heart. These mice developed dilated cardiomyopathy with reduced cardiac contractility, arrhythmias, and susceptibility to sudden death. As seen in human heart failure, these abnormalities correlated with PKA-mediated hyperphosphorylation of the cardiac ryanodine receptor/Ca(2+)-release channel, which enhances Ca(2+) release from the sarcoplasmic reticulum, and phospholamban, which regulates the sarcoplasmic reticulum Ca(2+)-ATPase. These findings demonstrate a specific role for PKA in the pathogenesis of heart failure, independent of more proximal events in betaAR signaling, and support the notion that PKA activity is involved in the adverse effects of chronic betaAR signaling.
The heart responds to stress signals by hypertrophic growth, which is accompanied by activation of the MEF2 transcription factor and reprogramming of cardiac gene expression. We show here that class ...II histone deacetylases (HDACs), which repress MEF2 activity, are substrates for a stress-responsive kinase specific for conserved serines that regulate MEF2-HDAC interactions. Signal-resistant HDAC mutants lacking these phosphorylation sites are refractory to hypertrophic signaling and inhibit cardiomyocyte hypertrophy. Conversely, mutant mice lacking the class II HDAC, HDAC9, are sensitized to hypertrophic signals and exhibit stress-dependent cardiomegaly. Thus, class II HDACs act as signal-responsive suppressors of the transcriptional program governing cardiac hypertrophy and heart failure.
The transcription factor NFAT5/TonEBP, a member of the NFAT/Rel family of transcription factors, has been implicated in diverse cellular responses, including the response to osmotic stress, ...integrin-dependent cell migration, T cell activation, and the Ras pathway in Drosophila. To clarify the in vivo role of NFAT5, we generated NFAT5-null mice. Homozygous mutants were genetically underrepresented after embryonic day 14.5. Surviving mice manifested a progressive and profound atrophy of the kidney medulla with impaired activation of several osmoprotective genes, including those encoding aldose reductase, Na+/ Cl--coupled betaine/γ-aminobutyric acid transporter, and the Na+/myo-inositol cotransporter. The aldose reductase gene is controlled by a tonicity-responsive enhancer, which was refractory to hypertonic stress in fibroblasts lacking NFAT5, establishing this enhancer as a direct transcriptional target of NFAT5. Our findings demonstrate a central role for NFAT5 as a tonicity-responsive transcription factor required for kidney homeostasis and function.
1 Seedling banks, made up of small individuals of tree species in the understorey, are an important component of many forests. 2 We collected and aged 4992 individuals up to 1.3 m in height of Abies ...amabilis, Chamaecyparis nootkatensis, Tsuga mertensiana and T. heterophylla from the seedling bank of an ancient forest in coastal British Columbia, Canada. 3 Growth was extremely slow. Some individuals < 1.3 m tall were more than 150 years old. Very few plants attained an above-ground stem length of 1 m in less than 100 years. Regressions of above-ground stem length vs. age indicated that net terminal growth averaged only c. 2 mm per year up to age 50. 4 Although species differed in age structure, all had slow-growing, persistent individuals. 5 These trees can be considered to be adapted to survive for long periods under the high levels of biotically induced stress of the forest understorey. Such a high potential for stress tolerance in forest trees presents a challenge for the classification of life histories. 6 The seedling bank contributes to the canopy composition in ancient forests. Forest ecology must consider not only tree regeneration in relation to disturbance, but also the dynamics of tree populations under intact canopies.
The urban landscape encompasses a broad spectrum of variable environments ranging from remnant patches to highly modified streetscapes. Despite the expansion of urban environments, few studies have ...examined the influence of urbanization on faunal diversity, particularly in the Southern Hemisphere. In this study, four broad habitat types were recognized in the urban environment, representing a continuum of modification ranging from parks with remnant vegetation to streetscapes dominated by native vegetation and those dominated by exotic vegetation to recently developed streetscapes. Bird censuses were conducted at 36 sites throughout urban Melbourne, with nine sites surveyed in each habitat type. The four habitat types supported significantly different bird communities based on species richness, abundance and composition suggesting that bird assemblages of urban environments are non-uniform. Parks and native streetscapes generally supported fewer introduced species than exotic and recently developed streetscapes. Overall abundance and richness of species were lower in the exotic and recently developed streetscapes than in parks and native streetscapes. Significant differences were also observed in foraging guilds within the four habitat types, with parks having the most foraging guilds and recently developed streetscapes having the fewest. The transition from native to exotic streetscapes saw the progressive loss of insectivorous and nectarivorous species reflecting a reliance by these species on structurally diverse and/or native vegetation for both shelter and food resources. The implementation of effective strategies and incentives which encourage the planting of structurally diverse native vegetation in streetscapes and gardens should be paramount if avian biodiversity is to be retained and enhanced in urban environments. It is also critical to encourage the maintenance of the existing remnant vegetation in the urban environment.
Forest encroachment threatens the biological diversity of grasslands globally. Positive feedbacks can reinforce the process, affecting soils and ground vegetation, ultimately leading to replacement ...of grassland by forest species. We tested whether restoration treatments (tree removal, with or without fire) reversed effects of nearly two centuries of encroachment by
Abies grandis
and
Pinus contorta
into dry, montane meadows in the Cascade Range, Oregon, USA. In nine, 1-ha plots containing a patchy mosaic of meadow openings and forests of varying age (20 to >140 yr), we compared three treatments affecting the ground vegetation: control (no trees removed), unburned (trees removed, slash burned in piles leaving 90% of the area unburned), and burned (trees removed, slash broadcast burned). We quantified changes over 3-4 years in soils, abundance and richness of species with differing habitat associations (meadow, forest, and ruderal), and recruitment of conifers. Except for a transient increase in available N (especially in burn scars), effects of burning on soils were minimal due, in part, to mixing by gophers. Tree removal greatly benefited meadow species at the expense of forest herbs. Cover and richness of meadow species increased by 47% and 38% of initial values in unburned plots, but changed minimally in burned plots. In contrast, cover and richness of forest herbs declined by 44% and 26% in unburned plots and by 79% and 58% in burned plots. Ruderal species and conifer seedlings were uncommon in both treatments. Although vegetation was consumed beneath burn piles, meadow species recovered significantly after three years. Long-term tree presence did not preclude recovery of meadow species; in fact, colonization was greater in older than in younger forests. In sum, temporal trends were positive for most indicators, suggesting strong potential for restoration. Contrary to conventional wisdom, tree removal without fire may be sufficient to shift the balance from forest to meadow species. In meadows characterized by historically infrequent fire, small-scale disturbances and competitive interactions may be more critical to ecosystem maintenance and restoration. Managers facing the worldwide phenomenon of tree invasion should critically evaluate the ecological vs. operational need for fire in ecosystem restoration.
While urban areas are increasingly recognized as having potential value for biodiversity conservation, the relationship between biodiversity and the structure and configuration of the urban landscape ...is poorly understood. In this study we surveyed birds in 39 remnant patches of native vegetation of various sizes (range 1–107
ha) embedded in the suburban matrix in Melbourne, Australia. The total richness of species within remnants was strongly associated with the size of remnants. Remnant-reliant species displayed a much stronger response to remnant area than matrix-tolerant species indicating the importance of large remnants in maintaining representative bird assemblages. Large remnants are important for other ecological groups of species including migratory species, ground foraging birds and canopy foraging birds. Other landscape (e.g. amount of riparian vegetation) and structural components (e.g. shrub cover) of remnants have a lesser role in determining the richness of individual remnants. This research provides conservation managers and planners with a hierarchical process to reserve design and management in order to conserve the highest richness of native species within urban areas. First of all, conservation efforts should preferentially focus on the retention of larger remnants of native vegetation. Second, where possible, riparian vegetation should be included within reserves or, where it is already present, should be carefully managed to ensure its integrity. Third, efforts should be focused at maintaining appropriate habitat and vegetation structure and complexity.
A major decline in the abundance of whitebark pine (Pinus albicaulis Engelm.) has recently occurred in the United States, primarily as a result of white pine blister rust (Cronartium ribicola J.C. ...Fisch. Ex Raben.). However, no information on the status of whitebark pine in British Columbia, Canada, was available. We sampled 54 subalpine stands in British Columbia, examining all whitebark pine trees within plots for evidence of blister rust and mountain pine beetle (Dendroctonus ponderosae Hopk.) damage. About 21% of all whitebark pine stems were dead, and blister rust was the most important agent of mortality. Of all living trees sampled, 27% had obvious blister rust infection (cankers), but actual incidence was suspected of being as high as 44% (using all evidence of blister rust). Blister rust incidence and whitebark pine mortality were significantly related to differences in stand structure and the presence of Ribes spp., but relationships with local climate and site variables were absent or weak. The lack of strong relationships with climate suggests favourable conditions for the spread of the disease throughout most of British Columbia. Very little evidence of mountain pine beetle was found. Overall, the prospects for whitebark pine in British Columbia do not appear good; a large reduction in population levels seems imminent.
Old-growth forests are common in the snowy, montane environments of coastal western North America. To examine dynamics of a stand containing four canopy tree species (Abies amabilis, Chamaecyparis ...nootkatensis, Tsuga mertensiana and T. heterophylla), we used four stem-mapped, 50 m ×50 m plots. From measurements of annual rings, we obtained ages from basal discs of 1,336 live trees, developed master chronologies for each species, reconstructed early growth rates, and delineated periods of release. The stand was ancient; individuals of all four species exceeded 900 years in age, and the oldest tree exceeded 1,400 years. The four plots differed in the timing of events, and we found no evidence of major, stand-level disturbance. Instead the stand was structured by small-scale patch dynamics, resulting from events that affected one to several trees and initiated episodes of release and relatively rapid early growth. The species differed in age structure and dynamics. A. amabilis and T. heterophylla had a classical reverse-J age structure indicative of stable populations, whereas C. nootkatensis and T. mertensiana appeared to rely on local episodes of increased recruitment, which were often separated by centuries, and were probably related to multiple-tree gaps that occurred infrequently. However, such gaps could be considered normal in the long-term history of the stand, and thus these species with their long life spans can persist. Most individuals of all four species grew extremely slowly, with trees typically spending centuries in the understory before reaching the canopy, where they were able to persist for additional centuries. Thus, the key features of this forest are the very slow dynamics dominated by small-scale events, and the slow growth of stress-tolerant trees.
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