ASU Scholarship Showcase

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm³ to 62 mm³, even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

In this synthesis, we hope to accomplish two things: 1) reflect on how the analysis of the new archaeological cases presented in this special feature adds to previous case studies by revisiting a set of propositions reported in a 2006 special feature, and 2) reflect on four main ideas that are more specific to the archaeological cases: i) societal choices are influenced by robustness–vulnerability trade-offs, ii) there is interplay between robustness–vulnerability trade-offs and robustness–performance trade-offs, iii) societies often get locked in to particular strategies, and iv) multiple positive feedbacks escalate the perceived cost of societal change. We then discuss whether these lock-in traps can be prevented or whether the risks associated with them can be mitigated. We conclude by highlighting how these long-term historical studies can help us to understand current society, societal practices, and the nexus between ecology and society.

As part of an international collaboration to compare large-scale commons, we used the Social-Ecological Systems Meta-Analysis Database (SESMAD) to systematically map out attributes of and changes in the Great Barrier Reef Marine Park (GBRMP) in Australia. We focus on eight design principles from common-pool resource (CPR) theory and other key social-ecological systems governance variables, and explore to what extent they help explain the social and ecological outcomes of park management through time. Our analysis showed that commercial fisheries management and the re-zoning of the GBRMP in 2004 led to improvements in ecological condition of the reef, particularly fisheries. These boundary and rights changes were supported by effective monitoring, sanctioning and conflict resolution. Moderate biophysical connectivity was also important for improved outcomes. However, our analysis also highlighted that continued challenges to improved ecological health in terms of coral cover and biodiversity can be explained by fuzzy boundaries between land and sea, and the significance of external drivers to even large-scale social-ecological systems (SES). While ecological and institutional fit in the marine SES was high, this was not the case when considering the coastal SES. Nested governance arrangements become even more important at this larger scale. To our knowledge, our paper provides the first analysis linking the re-zoning of the GBRMP to CPR and SES theory. We discuss important challenges to coding large-scale systems for meta-analysis.

The Montreal Protocol is generally credited as a successful example of international cooperation in response to a global environmental problem. As a result, the production and consumption of ozone-depleting substances has declined rapidly, and it is expected that atmospheric ozone concentrations will return to their normal ranges toward the end of this century. This paper applies the social-ecological system framework and common-pool resource theory to explore the congruence between successful resolution of small-scale appropriation problems and ozone regulation, a large-scale pollution problem. The results of our analysis correspond closely to past studies of the Protocol that highlight the importance of attributes such as a limited number of major industrial producers, advances in scientific knowledge, and the availability of technological substitutes. However, in contrast to previous theoretical accounts that focus on one or a few variables, our analysis suggests that its success may have been the result of interactions between a wider range of SES attributes, many of which are associated with successful small-scale environmental governance. Although carefully noting the limitations of drawing conclusions from the analysis of a single case, our analysis reveals the potential for fruitful interplay between common-pool resource theory and large-scale pollution problems.

The purpose of the United Nations-guided process to establish Sustainable Development Goals is to galvanize governments and civil society to rise to the interlinked environmental, societal, and economic challenges we face in the Anthropocene. We argue that the process of setting Sustainable Development Goals should take three key aspects into consideration. First, it should embrace an integrated social-ecological system perspective and acknowledge the key dynamics that such systems entail, including the role of ecosystems in sustaining human wellbeing, multiple cross-scale interactions, and uncertain thresholds. Second, the process needs to address trade-offs between the ambition of goals and the feasibility in reaching them, recognizing biophysical, social, and political constraints. Third, the goal-setting exercise and the management of goal implementation need to be guided by existing knowledge about the principles, dynamics, and constraints of social change processes at all scales, from the individual to the global. Combining these three aspects will increase the chances of establishing and achieving effective Sustainable Development Goals.

Introduction: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet that alters metabolism by increasing the level of ketone bodies in the blood. KetoCal® (KC) is a nutritionally complete, commercially available 4∶1 (fat∶ carbohydrate+protein) ketogenic formula that is an effective non-pharmacologic treatment for the management of refractory pediatric epilepsy. Diet-induced ketosis causes changes to brain homeostasis that have potential for the treatment of other neurological diseases such as malignant gliomas.

Methods: We used an intracranial bioluminescent mouse model of malignant glioma. Following implantation animals were maintained on standard diet (SD) or KC. The mice received 2×4 Gy of whole brain radiation and tumor growth was followed by in vivo imaging.

Results: Animals fed KC had elevated levels of β-hydroxybutyrate (p = 0.0173) and an increased median survival of approximately 5 days relative to animals maintained on SD. KC plus radiation treatment were more than additive, and in 9 of 11 irradiated animals maintained on KC the bioluminescent signal from the tumor cells diminished below the level of detection (p<0.0001). Animals were switched to SD 101 days after implantation and no signs of tumor recurrence were seen for over 200 days.

Conclusions: KC significantly enhances the anti-tumor effect of radiation. This suggests that cellular metabolic alterations induced through KC may be useful as an adjuvant to the current standard of care for the treatment of human malignant gliomas.

Background: The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood.

Methods: To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma.

Results: Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4.

Conclusions: The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas.

Background: Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD) - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia.

Methods: Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet.

Results: Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS) production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4.

Conclusions: Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.

A significant challenge of our time is conserving biological diversity while maintaining economic development and cultural values. The United Nations Educational, Scientific and Cultural Organization has established biosphere reserves within its Man and the Biosphere program as a model means for accomplishing this very challenge. The East Carpathians Biosphere Reserve (ECBR), spreading across Poland, Slovakia, and Ukraine, represents a large social-ecological system (SES) that has been protected under the biosphere reserve designation since 1998. We have explored its successes and failures in improving human livelihoods while safeguarding its ecosystems. The SES framework, which includes governance system, actors, resources, and external influences, was used as a frame of analysis. The outcomes of this protected area have been mixed; its creation led to national and international collaboration, yet some actor groups remain excluded. Implementation of protocols arising from the Carpathian Convention has been slow, while deforestation, hunting, erosion, temperature extremes, and changes in species behavior remain significant threats but have also been factors in ecological adaptation. The loss of cultural links and traditional knowledge has also been significant. Nevertheless, this remains a highly biodiverse area. Political barriers and institutional blockages will have to be removed to ensure this reserve fulfills its role as a model region for international collaboration and capacity building. These insights drawn from the ECBR demonstrate that biosphere reserves are indeed learning sites for sustainable development and that this case is exemplary in illustrating the challenges, but more importantly, the opportunities that arise when ensuring parallel care and respect for people and ecosystems through the model of transboundary protected areas around the world.

Protected areas are a cornerstone of biodiversity conservation, and increasingly, conservation science is integrating ecological and social considerations in park management. Indeed, both social and ecological factors need to be considered to understand processes that lead to changes in environmental conditions. Here, we use a social-ecological systems lens to examine changes in governance through time in an extensive regional protected area network, the Great Barrier Reef Marine Park. We studied the peer-reviewed and nonpeer-reviewed literature to develop an understanding of governance of the Great Barrier Reef Marine Park and its management changes through time. In particular, we examined how interacting and changing property rights, as designated by the evolving marine protected area network and other institutional changes (e.g., fisheries management), defined multiple goods and ecosystem services and altered who could benefit from them.

The rezoning of the Great Barrier Reef Marine Park in 2004 substantially altered the types and distribution of property rights and associated benefits from ecosystem goods and services. Initially, common-pool resources were enjoyed as common and private benefits at the expense of public goods (overexploited fisheries and reduced biodiversity and ecosystem health). The rezoning redefined the available goods and benefits and who could benefit, prioritizing public goods and benefits (i.e., biodiversity conservation), and inducing private costs (through reduced fishing). We also found that the original conceptualization of the step-wise progression of property rights from user to owner oversimplifies property rights based on its division into operational and collective-choice rule-making levels. Instead, we suggest that a diversity of available management tools implemented simultaneously can result in interactions that are seldom fully captured by the original conceptualization of the bundling of property rights. Understanding the complexities associated with overlapping property rights and multiple goods and ecosystem services, particularly within large-scale systems, can help elucidate the source and nature of some of the governance challenges that large protected areas are facing.