ASU Scholarship Showcase

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.

What relationships can be understood between resilience and vulnerability in social-ecological systems? In particular, what vulnerabilities are exacerbated or ameliorated by different sets of social practices associated with water management? These questions have been examined primarily through the study of contemporary or recent historic cases. Archaeology extends scientific observation beyond all social memory and can thus illuminate interactions occurring over centuries or millennia. We examined trade-offs of resilience and vulnerability in the changing social, technological, and environmental contexts of three long-term, pre-Hispanic sequences in the U.S. Southwest: the Mimbres area in southwestern New Mexico (AD 650–1450), the Zuni area in northern New Mexico (AD 850–1540), and the Hohokam area in central Arizona (AD 700–1450). In all three arid landscapes, people relied on agricultural systems that depended on physical and social infrastructure that diverted adequate water to agricultural soils. However, investments in infrastructure varied across the cases, as did local environmental conditions. Zuni farming employed a variety of small-scale water control strategies, including centuries of reliance on small runoff agricultural systems; Mimbres fields were primarily watered by small-scale canals feeding floodplain fields; and the Hohokam area had the largest canal system in pre-Hispanic North America. The cases also vary in their historical trajectories: at Zuni, population and resource use remained comparatively stable over centuries, extending into the historic period; in the Mimbres and Hohokam areas, there were major demographic and environmental transformations. Comparisons across these cases thus allow an understanding of factors that promote vulnerability and influence resilience in specific contexts.

Neural progenitor cells (NPCs) derived from human pluripotent stem cells (hPSCs) are a multipotent cell population that is capable of nearly indefinite expansion and subsequent differentiation into the various neuronal and supporting cell types that comprise the CNS. However, current protocols for differentiating NPCs toward neuronal lineages result in a mixture of neurons from various regions of the CNS. In this study, we determined that endogenous WNT signaling is a primary contributor to the heterogeneity observed in NPC cultures and neuronal differentiation. Furthermore, exogenous manipulation of WNT signaling during neural differentiation, through either activation or inhibition, reduces this heterogeneity in NPC cultures, thereby promoting the formation of regionally homogeneous NPC and neuronal cultures. The ability to manipulate WNT signaling to generate regionally specific NPCs and neurons will be useful for studying human neural development and will greatly enhance the translational potential of hPSCs for neural-related therapies.

The threat of West Nile virus (WNV) epidemics with increasingly severe neuroinvasive infections demands the development and licensing of effective vaccines. To date, vaccine candidates based on inactivated, live-attenuated, or chimeric virus, and viral DNA and WNV protein subunits have been developed. Some have been approved for veterinary use or are under clinical investigation, yet no vaccine has been licensed for human use. Reaching the milestone of a commercialized human vaccine, however, may largely depend on the economics of vaccine production. Analysis suggests that currently only novel low-cost production technologies would allow vaccination to outcompete the cost of surveillance and clinical treatment. Here, we review progress using plants to address the economic challenges of WNV vaccine production. The advantages of plants as hosts for vaccine production in cost, speed and scalability, especially those of viral vector-based transient expression systems, are discussed. The progress in developing WNV subunit vaccines in plants is reviewed within the context of their expression, characterization, downstream processing, and immunogenicity in animal models. The development of vaccines based on enveloped and non-enveloped virus-like particles is also discussed. These advancements suggest that plants may provide a production platform that offers potent, safe and affordable human vaccines against WNV.

Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and retained the ability to differentiate into cells representative of the three germ layers.

Nonsense-mediated RNA decay (NMD) is a highly conserved pathway that selectively degrades specific subsets of RNA transcripts. Here, we provide evidence that NMD regulates early human developmental cell fate. We found that NMD factors tend to be expressed at higher levels in human pluripotent cells than in differentiated cells, raising the possibility that NMD must be downregulated to permit differentiation. Loss- and gain-of-function experiments in human embryonic stem cells (hESCs) demonstrated that, indeed, NMD downregulation is essential for efficient generation of definitive endoderm. RNA-seq analysis identified NMD target transcripts induced when NMD is suppressed in hESCs, including many encoding signaling components. This led us to test the role of TGF-β and BMP signaling, which we found NMD acts through to influence definitive endoderm versus mesoderm fate. Our results suggest that selective RNA decay is critical for specifying the developmental fate of specific human embryonic cell lineages.

Previously, our group engineered a plant-derived monoclonal antibody (MAb) (pHu-E16) that efficiently treated West Nile virus (WNV) infection in mice. In this study, we developed several pHu-E16 variants to improve its efficacy. These variants included a single-chain variable fragment (scFv) of pHu-E16 fused to the heavy chain (HC) constant domains (CH1-3) of human IgG (pHu-E16scFv-CH1-3) and a tetravalent molecule (Tetra pHu-E16) assembled from pHu-E16scFv-CH1-3 with a second pHu-E16scFv fused to the light chain (LC) constant region. pHu-E16scFv-CH1-3 and Tetra pHu-E16 were efficiently expressed and assembled in plants. To assess the impact of differences in N-linked glycosylation on pHu-E16 variant assembly and function, we expressed additional pHu-E16 variants with various combinations of HC and LC components.

Our study revealed that proper pairing of HC and LC was essential for the complete N-glycan processing of antibodies in both plant and animal cells. Associated with their distinct N-glycoforms, pHu-E16, pHu-E16scFv-CH1-3 and Tetra pHu-E16 exhibited differential binding to C1q and specific Fcγ receptors (FcγR). Notably, none of the plant-derived Hu-E16 variants showed antibody-dependent enhancement (ADE) activity in CD32A+ human cells, suggesting the potential of plant-produced antibodies to minimize the adverse effect of ADE. Importantly, all plant-derived MAb variants exhibited at least equivalent in vitro neutralization and in vivo protection in mice compared to mammalian cell-produced Hu-E16. This study demonstrates the capacity of plants to express and assemble a large, complex and functional IgG-like tetravalent mAb variant and also provides insight into the relationship between MAb N-glycosylation, FcγR and C1q binding, and ADE. These new insights may allow the development of safer and cost effective MAb-based therapeutics for flaviviruses, and possibly other pathogens.

Ecological models are a fundamental tool that archaeologists use to clarify our thinking about the processes that generate the archaeological record. Typically, arguments reasoned from a single model are bolstered by observing the consistency of ethnographic data with the argument. This validation of a model establishes that an argument is reasonable. In this paper, we attempt to move beyond validation by comparing the consistency of two arguments reasoned from different models that might explain corporate territorial ownership in a large ethnographic data set. Our results suggest that social dilemmas are an under appreciated mechanism that can drive the evolution of corporate territorial ownership. When social dilemmas emerge, the costs associated with provisioning the public goods of information on resources or, perhaps, common defence create situations in which human foragers gain more by cooperating to recognize corporate ownership rules than they lose. Our results also indicate that societies who share a common cultural history are more likely to recognize corporate ownership, and there is a spatial dynamic in which societies who live near each other are more likely to recognize corporate ownership as the number of near-by groups who recognize ownership increases. Our results have important implications for investigating the coevolution of territorial ownership and the adoption of food production in the archaeological record.

In the decade since Yamanaka and colleagues described methods to reprogram somatic cells into a pluripotent state, human induced pluripotent stem cells (hiPSCs) have demonstrated tremendous promise in numerous disease modeling, drug discovery, and regenerative medicine applications. More recently, the development and refinement of advanced gene transduction and editing technologies have further accelerated the potential of hiPSCs. In this review, we discuss the various gene editing technologies that are being implemented with hiPSCs. Specifically, we describe the emergence of technologies including zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 that can be used to edit the genome at precise locations, and discuss the strengths and weaknesses of each of these technologies. In addition, we present the current applications of these technologies in elucidating the mechanisms of human development and disease, developing novel and effective therapeutic molecules, and engineering cell-based therapies. Finally, we discuss the emerging technological advances in targeted gene editing methods.

The insights in Governing the Commons have provided foundational ideas for commons research in the past 23 years. However, the cases that Elinor Ostrom analyzed have been exposed to new social, economic, and ecological disturbances. What has happened to these cases since the 1980s? We reevaluated one of Ostrom’s case studies, the lobster and groundfishery of Port Lameron, Southwest Nova Scotia (SWNS). Ostrom suggested that the self-governance of this fishery was fragile because the government did not recognize the rights of resource users to organize their own rules. In the Maine lobster fishery, however, the government formalized customary rules and decentralized power to fishing ports. We applied the concepts of feedback, governance mismatches, and the robustness of social-ecological systems to understand the pathway of institutional change in Port Lameron. We revisited the case of Port Lameron using marine harvesters’ accounts collected from participant observation, informal interviews and surveys, and literature on fisheries policy and ecology in SWNS and Maine. We found that the government’s failure to recognize the customary rights of harvesters to organize has weakened feedback between the operational level, where resource users interact with the resource, and the collective-choice level, where agents develop rules to influence the behavior of resource users. This has precipitated governance mismatches, which have led harvesters to believe that the decision-making process is detrimental to their livelihoods. Thus, harvesters rarely participate in decision making and resist regulatory change. In Maine, harvesters can influence decisions through participation, but there is a trade-off. With higher influence in decisions, captains have co-opted the decision-making process. Nevertheless, we suggest that the fisheries of SWNS are more vulnerable to social-ecological change because of weaker feedbacks than in Maine. Finally, we have discussed the potential benefits of polycentricity to both fisheries.