Improved skeletal muscle oxidative enzyme activity and restoration of PGC-1α and PPARß/δ gene expression upon rosiglitazone treatment in obese patients with type 2 diabetes mellitus

Objective: To examine whether rosiglitazone alters gene expression of some key genes involved in mitochondrial biogenesis and oxidative capacity in skeletal muscle of type 2 diabetic patients, and whether this is associated with alterations in skeletal muscle oxidative capacity and lipid content.

Design: Skeletal muscle gene expression, mitochondrial protein content, oxidative capacity and lipid accumulation were measured in muscle biopsies obtained from diabetic patients, before and after 8 weeks of rosiglitazone treatment, and matched controls. Furthermore, whole-body insulin sensitivity and substrate utilization were assessed.

Subjects: Ten obese type 2 diabetic patients and 10 obese normoglycemic controls matched for age and BMI.

Methods: Gene expression and mitochondrial protein content of complexes I–V of the respiratory chain were measured by quantitative polymerase chain reaction and Western blotting, respectively. Histochemical staining was used to quantify lipid accumulation and complex II succinate dehydrogenase (SDH) activity. Insulin sensitivity and substrate utilization were measured during a hyperinsulinemic–euglycemic clamp with indirect calorimetry.

Results: Skeletal-muscle mRNA of PGC-1a and PPARb/d – but not of other genes involved in glucose, fat and oxidative metabolism – was significantly lower in diabetic patients (Po0.01). Rosiglitazone significantly increased PGC-1a (B2.2-fold, Po0.01) and PPARb/d (B2.6-fold, Po0.01), in parallel with an increase in insulin sensitivity, SDH activity and metabolic flexibility (Po0.01). Surprisingly, none of the measured mitochondrial proteins was reduced in type 2 diabetic patients, nor affected by rosiglitazone treatment. No alterations were seen in muscular fat accumulation upon treatment.

Conclusion: These results suggest that the insulin-sensitizing effect of rosiglitazone may involve an effect on muscular oxidative capacity, via PGC-1a and PPARb/d, independent of mitochondrial protein content and/or changes in intramyocellular lipid.

Reduced Skeletal Muscle Uncoupling Protein-3 Content in Prediabetic Subjects and Type 2 Diabetic Patients: Restoration by Rosiglitazone Treatment

Context: The mitochondrial uncoupling protein-3 (UCP3) has been implicated in the protection of the mitochondrial matrix against lipid-induced mitochondrial damage. Recent evidence points toward mitochondrial aberrations as a major contributor to the development of insulin resistance and diabetes, and UCP3 is reduced in diabetes.
Objective: We compared skeletal muscle UCP3 protein levels in prediabetic subjects [i.e. impaired glucose tolerance (IGT)], diabetic patients, and healthy controls and examined whether rosiglitazone treatment was able to restore UCP3.
Patients, Design, Intervention: Ten middle-aged obese men with type 2 diabetes mellitus [age, 61.4 ± 3.1 yr; body mass index (BMI), 29.8 ± 2.9 kg/m2], nine IGT subjects (age, 59.0 ± 6.6 yr; BMI, 29.7 ± 3.0 kg/m2), and 10 age- and BMI-matched healthy controls (age, 57.3 ± 7.4 yr; BMI, 30.1 ± 3.9 kg/m2) participated in this study. After baseline comparisons, diabetic patients received rosiglitazone (2 x 4 mg/d) for 8 wk.
Main Outcome Measures: Muscle biopsies were sampled to determine UCP3 and mitochondrial protein (complex I–V) content.
Results: UCP3 protein content was significantly lower in prediabetic IGT subjects and in diabetic patients compared with healthy controls (39.0 ± 28.5, 47.2 ± 24.7, and 72.0 ± 23.7 arbitrary units, respectively; P < 0.05), whereas the levels of the mitochondrial protein complex I–V were similar between groups. Rosiglitazone treatment for 8 wk significantly increased insulin sensitivity and muscle UCP3 content (from 53.2 ± 29.9 to 66.3 ± 30.9 arbitrary units; P < 0.05).
Conclusion: We show that UCP3 protein content is reduced in prediabetic subjects and type 2 diabetic patients. Eight weeks of rosiglitazone treatment restores skeletal muscle UCP3 protein in diabetic patients.

Restoration of the habitat-forming fucoid alga Hormosira banksii at effluent-affected sites : competitive exclusion by coralline turfs

Fucoid algae often dominate intertidal rocky shores, providing habitat and modifying ecosystem resources for other species, but are susceptible to discharge of sewage effluent. In this study we assessed the potential for competition from coralline turfs to inhibit restoration of the intertidal fucoid macroalga Hormosira banksii at sites associated with an ocean outfall a scenario of improving following water quality in the nearshore coastal environment. The percentage cover and number of individuals of H. banksii were negatively correlated with both the percentage cover and turf height of Corallina officinalis. In contrast, H. banksii was positively associated with rocky substrata and recruited well to rock-surface substrata. Importantly, there appears to be a threshold abundance where the percentage cover of H. banksii rarely reaches above 20% cover amongst coralline turfs with >40% cover. These data support a model of alternative community states: H. banksii dominated canopy on rocky substrata versus C. officinalis turf. In field and laboratory experiments, extensive coralline turfs (up to 4 cm thick) were shown to inhibit recruitment of H. banksii. This study shows competitive exclusion by coralline turfs may limit the successful restoration of habitat provided by H. banksii to shores that have been affected by sustained discharge of secondarily treated sewage effluent. We suggest potential strategies for management authorities to consider when seeking ways of restoring fucoid communities affected by anthropogenic disturbances such as wastewater disposal.

Islamic gardens between restoration and replacement

Architecture is considered the visible reflection of the local character of contexts. Therefore, conserving the architectural heritage is becoming one of the critical concepts in life, especially with the rapid change and transformation characterizing the globalization era. As a vital part of the broader context of the architecture; landscape architecture is also considered an effective tool of societies’ self representation. Gardens reflect a very special relationship between the man and nature and represent the history of the state of societies in which they were developed. Islamic gardens are one of the historic gardens having a special charm of their own. Gardens associated with Islamic period over several hundred years, are designed according to certain ideological principles employing certain physical elements shown in the west as well as the east. They represent an ideological continuity which is unique in its spread and development over a wide range of geographical and cultural regions. The Islamic architectural heritage is usually well protected. In the restoration process, the historic buildings are returned back to their original conditions. However, with the changing nature of gardens; it is sometimes hard to track back their original state. In that case, in order to conserve those gardens; it is important to study the design principles upon which the physical elements were chosen. In this paper, the principles of design of the original Islamic gardens will be reviewed through a quantitative analysis of a questionnaire. These principles will be compared to the current situation of the garden of Humayun’s Tomb built in the Mughal era in India, after its conservation in 2003.

Reinstating indigenous landscape planning curatorship : the Lake Condah restoration project

While contemporary Western planning traditions in Australia talk of the last 200 years of innovation and transposition of European and North American planning traditions upon the Australian landscape, they neglect to mention some 40-50,000 years of Indigenous landscape planning initiatives and practice. The ancestral country of the Gunditjmara people is in the Western District of Victoria focused upon the Lake Condah and Mount Eccles localities. The Gunditjmara had, and continue to have a strong social, cultural and land management and planning presence in the region, in particular linked to environmental engineering initiatives and aquaculture curatorship of eel and fish resources. Archaeological evidence confirms that some 10,000 years of pre-European contact landscape planning practice has been applied by the Gunditjmara to construct resources management infrastructure to service a regional food need as well as a community need. Within contemporary reconciliation discourses, the Gunditjmara have activity sought over the last 25 years the rehabilitation of Lake Condah, which is now coming into fruition, and the restoration of their traditional landscape planning and management responsibilities. This paper reviews the restoration of Indigenous landscape planning and management theory and practice by the Gunditjmara, pointing to significant policy and practice success as well as the need to better appreciate this culturally-attuned and ecologically-responsive approach to landscape planning borne out of generations of knowledge.

Ecosystem restoration with teeth : what role for predators?

Recent advances highlight the potential for predators to restore ecosystems and confer resilience against globally threatening processes, including climate change and biological invasions. However, releasing the ecological benefits of predators entails significant challenges. Here, we discuss the economic, environmental and social considerations affecting predator-driven ecological restoration programmes, and suggest approaches for reducing the undesirable impacts of predators. Because the roles of predators are context dependent, we argue for increased emphasis on predator functionality in ecosystems and less on the identities and origins of species and genotypes. We emphasise that insufficient attention is currently given to the importance of variation in the social structures and behaviours of predators in influencing the dynamics of trophic interactions. Lastly, we outline experiments specifically designed to clarify the ecological roles of predators and their potential utility in ecosystem restoration.

Imprinted CDKN1C is a tumor suppressor in rhabdoid tumor and activated by restoration of SMARCB1 and histone deacetylase inhibitors

SMARCB1 is deleted in rhabdoid tumor, an aggressive paediatric malignancy affecting the kidney and CNS. We hypothesized that the oncogenic pathway in rhabdoid tumors involved epigenetic silencing of key cell cycle regulators as a consequence of altered chromatin-remodelling, attributable to loss of SMARCB1, and that this hypothesis if proven could provide a biological rationale for testing epigenetic therapies in this disease. We used an inducible expression system to show that the imprinted cell cycle inhibitor CDKN1C is a downstream target for SMARCB1 and is transcriptionally activated by increased histone H3 and H4 acetylation at the promoter. We also show that CDKN1C expression induces cell cycle arrest, CDKN1C knockdown with siRNA is associated with increased proliferation, and is able to compete against the anti-proliferative effect of restored SMARCB1 expression. The histone deacetylase inhibitor (HDACi), Romidepsin, specifically restored CDKN1C expression in rhabdoid tumor cells through promoter histone H3 and H4 acetylation, recapitulating the effect of SMARCB1 on CDKNIC allelic expression, and induced cell cycle arrest in G401 and STM91-01 rhabdoid tumor cell lines. CDKN1C expression was also shown to be generally absent in clinical specimens of rhabdoid tumor, however CDKN1A and CDKN1B expression persisted. Our observations suggest that maintenance of CDKN1C expression plays a critical role in preventing rhabdoid tumor growth. Significantly, we report for the first time, parallels between the molecular pathways of SMARCB1 restoration and Romidepsin treatment, and demonstrate a biological basis for the further exploration of histone deacetylase inhibitors as relevant therapeutic reagents in the treatment of rhabdoid tumor.

Understanding the sources of uncertainty to reduce the risks of undesirable outcomes in large-scale freshwater ecosystem restoration projects: an example from the Murray–Darling Basin, Australia

There are a growing number of large-scale freshwater ecological restoration projects worldwide. Assessments of the benefits and costs of restoration often exclude an analysis of uncertainty in the modelled outcomes. To address this shortcoming we explicitly model the uncertainties associated with measures of ecosystem health in the estuary of the Murray– Darling Basin, Australia and how those measures may change with the implementation of a Basin-wide Plan to recover water to improve ecosystem health. Specifically, we compare two metrics – one simple and one more complex – to manage end-of-system flow requirements for one ecosystem asset in the Basin, the internationally important Coorong saline wetlands. Our risk assessment confirms that the ecological conditions in the Coorong are likely to improve with implementation of the Basin Plan; however, there are risks of a Type III error (where the correct answer is found for the wrong question) associated with using the simple metric for adaptive management. 

Compositional effects on the restoration behaviour in Mg-Zn-Re alloys

Additions of rare earth elements to magnesium alloys are qualitatively reported in the literature to retard recrystallisation. However, their effect in the presence of other (non-rare earth) alloy additions has not been systematically shown nor has the effect been quantified. The microstructural restoration following the hot deformation of Mg-xZn-yRE (x = 2.5 and 5 wt.%, y = 0 and 1 wt.%, and RE = Gd and Y) alloys has been studied using double hit compression testing and microscopy. It was found that, in the absence of rare earth additions, increases in zinc level had a negligible influence on the kinetics of restoration and the microstructure developed both during extrusion and throughout double hit testing. Adding rare earth elements to Mg-Zn alloys was found to retard restoration of the microstructure and maintain finer recrystallised grains. However, in the Mg-Zn-RE alloys, increasing the zinc concentration from 2.5 wt.% to 5 wt.% accelerated the restoration process, most likely due to a depletion of rare earth elements from solid solution and modification of the particles present in the matrix.

Is there more soil carbon under nitrogen-fixing trees than under non-nitrogen-fixing trees in mixed-species restoration plantings?

Afforestation of agricultural land provides an important opportunity to mitigate climate change by storing carbon (C) in both plant biomass and the soil. Here we present results of a study in which we sought to determine whether soil under nitrogen(N)-fixing trees contained more C than soil under non-N-fixing trees in mixed-species plantings, and thus if inclusion of N-fixers is beneficial in terms of increasing soil C sequestration. Soils were sampled directly beneath N-fixing and non-N-fixing tree species in riparian and upland mixed-species plantings in southeastern Australia. Soil C and N contents were assessed at both the landscape and individual planting scales. At the landscape scale, there were higher levels of soil C and N under N-fixing trees compared with non-N-fixing trees. At the individual planting scale, the patterns were less clear with both large increases and decreases occurring across the range of sites. The results presented here indicate that the inclusion of N-fixers may help to increase soil C, and N, but that the response may be site- and species-specific. © 2014 Elsevier B.V.

N-fixing trees in restoration plantings: effects on nitrogen supply and soil microbial communities

Mixed-species restoration tree plantings are being established increasingly, contributing to mitigate climate change and restore ecosystems. Including nitrogen (N)-fixing tree species may increase carbon (C) sequestration in mixed-species plantings, as these species may substantially increase soil C beneath them. We need to better understand the role of N-fixers in mixed-species plantings to potentially maximize soil C sequestration in these systems. Here, we present a field-based study that asked two specific questions related to the inclusion of N-fixing trees in a mixed-species planting: 1) Do non-N-fixing trees have access to N derived from fixation of atmospheric N2 by neighbouring N-fixing trees? 2) Do soil microbial communities differ under N-fixing trees and non-N-fixing trees in a mixed-species restoration planting? We sampled leaves from the crowns, and litter and soils beneath the crowns of two N-fixing and two non-N-fixing tree species that dominated the planting. Using the 15N natural abundance method, we found indications that fixed atmospheric N was utilized by the non-N-fixing trees, most likely through tight root connections or organic forms of N from the litter layer, rather than through the decomposition of N-fixers litter. While the two N-fixing tree species that were studied appeared to fix atmospheric N, they were substantially different in terms of C and N addition to the soil, as well as microbial community composition beneath them. This shows that the effect of N-fixing tree species on soil carbon sequestration is species-specific, cannot be generalized and requires planting trails to determine if there will be benefits to carbon sequestration. © 2014 Elsevier Ltd.