ASU Scholarship Showcase

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.

From cells to societies, several general principles arise again and again that facilitate cooperation and suppress conflict. In this study, I describe three general principles of cooperation and how they operate across systems including human sharing, cooperation in animal and insect societies and the massively large-scale cooperation that occurs in our multicellular bodies. The first principle is that of Walk Away: that cooperation is enhanced when individuals can leave uncooperative partners. The second principle is that resource sharing is often based on the need of the recipient (i.e., need-based transfers) rather than on strict account-keeping. And the last principle is that effective scaling up of cooperation requires increasingly sophisticated and costly cheater suppression mechanisms. By comparing how these principles operate across systems, we can better understand the constraints on cooperation. This can facilitate the discovery of novel ways to enhance cooperation and suppress cheating in its many forms, from social exploitation to cancer.

Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates.

Several Zika virus (ZIKV) vaccine candidates have recently been described which use inactivated whole virus, DNA or RNA that express the virus’ Envelope (E) glycoprotein as the antigen. These were successful in stimulating production of virus-targeted antibodies that protected animals against ZIKV challenges, but their use potentially will predispose vaccinated individuals to infection by the related Dengue virus (DENV). We have devised a virus like particle (VLP) carrier based on the hepatitis B core antigen (HBcAg) that displays the ZIKV E protein domain III (zDIII), and shown that it can be produced quickly and easily purified in large quantities from Nicotiana benthamiana plants. HBcAg-zDIII VLPs are shown to be highly immunogenic, as two doses elicited potent humoral and cellular responses in mice that exceed the threshold correlated with protective immunity against multiple strains of Zika virus. Notably, HBcAg-zDIII VLPs-elicited antibodies did not enhance the infection of DENV in Fc gamma receptor-expressing cells, offsetting the concern of ZIKV vaccines inducing cross-reactive antibodies and sensitizing people to subsequent DENV infection. Thus, our zDIII-based vaccine offers improved safety and lower cost production than other current alternatives, with equivalent effectiveness.

Background: Centralized silos of genomic data are architecturally easier to initially design, develop and deploy than distributed models. However, as interoperability pains in EHR/EMR, HIE and other collaboration-centric life sciences domains have taught us, the core challenge of networking genomics systems is not in the construction of individual silos, but the interoperability of those deployments in a manner embracing the heterogeneous needs, terms and infrastructure of collaborating parties. This article demonstrates the adaptation of BitTorrent to private collaboration networks in an authenticated, authorized and encrypted manner while retaining the same characteristics of standard BitTorrent.

Results: The BitTorious portal was sucessfully used to manage many concurrent domestic Bittorrent clients across the United States: exchanging genomics data payloads in excess of 500GiB using the uTorrent client software on Linux, OSX and Windows platforms. Individual nodes were sporadically interrupted to verify the resilience of the system to outages of a single client node as well as recovery of nodes resuming operation on intermittent Internet connections.

Conclusions: The authorization-based extension of Bittorrent and accompanying BitTorious reference tracker and user management web portal provide a free, standards-based, general purpose and extensible data distribution system for large ‘omics collaborations.

Background: Our publication of the BitTorious portal [1] demonstrated the ability to create a privatized distributed data warehouse of sufficient magnitude for real-world bioinformatics studies using minimal changes to the standard BitTorrent tracker protocol. In this second phase, we release a new server-side specification to accept anonymous philantropic storage donations by the general public, wherein a small portion of each user’s local disk may be used for archival of scientific data. We have implementated the server-side announcement and control portions of this BitTorrent extension into v3.0.0 of the BitTorious portal, upon which compatible clients may be built.

Results: Automated test cases for the BitTorious Volunteer extensions have been added to the portal’s v3.0.0 release, supporting validation of the “peer affinity” concept and announcement protocol introduced by this specification. Additionally, a separate reference implementation of affinity calculation has been provided in C++ for informaticians wishing to integrate into libtorrent-based projects.

Conclusions: The BitTorrent “affinity” extensions as provided in the BitTorious portal reference implementation allow data publishers to crowdsource the extreme storage prerequisites for research in “big data” fields. With sufficient awareness and adoption of BitTorious Volunteer-based clients by the general public, the BitTorious portal may be able to provide peta-scale storage resources to the scientific community at relatively insignificant financial cost.

The Gratton effect, the observation that the size of the Stroop effect is larger following a congruent trial compared to an incongruent trial, is one pivotal observation in support of the conflict-monitoring hypothesis. Previous reports have demonstrated that non-conflict components, such as feature binding, also contribute to this effect. Critically, Schmidt and De Houwer (2011) report a flanker task and a button-press Stroop task suggesting that there is no conflict adaptation in the Gratton effect; it is entirely caused by feature binding. The current investigation attempts to replicate and extend this important finding across two experiments using a canonical four-choice Stroop task with vocal responses. In contrast to Schmidt and De Houwer, we observe reliable conflict adaptation after controlling for feature binding. We argue that the overall strength of conflict is critical for determining whether a conflict adaptation component will remain in the Gratton effect after explaining binding components.

The Writing Pal (W-Pal) is an intelligent tutoring system (ITS) designed to provide students with explicit writing strategy instruction and practice. W-Pal includes a suite of educational games developed to increase writing engagement and provide opportunities to practice writing strategies. In this study, first (L1) (n = 26) and second (L2) language (n = 16) students interacted with W-Pal over eight sessions. We collected students’ daily self- reports of engagement, motivation, and perceptions of performance, as well as their reported game attitudes (difficulty, helpfulness for learning, and enjoyment). Results indicated that, for all students, interactions with W-Pal led to increases in writing performance and more positive attitudes towards the system (engagement, motivation, and perceived performance). For L1 students, game difficulty was a significant predictor of boredom; however, for the L2 students, game enjoyment predicted both their motivation and perceived writing improvement. Notably, the L2 students’ game ratings accounted for more variance in these daily reports than did the ratings of L1 students. This study suggests that L1 and L2 students experience similar benefits offered by game-based strategy practice in an ITS. Further, the link between game attitudes and overall daily perceptions of training may be stronger for L2 students than L1 students.

Rapid identification of facial expressions can profoundly affect social interactions, yet most research to date has focused on static rather than dynamic expressions. In four experiments, we show that when a non-expressive face becomes expressive, happiness is detected more rapidly anger. When the change occurs peripheral to the focus of attention, however, dynamic anger is better detected when it appears in the left visual field (LVF), whereas dynamic happiness is better detected in the right visual field (RVF), consistent with hemispheric differences in the processing of approach- and avoidance-relevant stimuli. The central advantage for happiness is nevertheless the more robust effect, persisting even when information of either high or low spatial frequency is eliminated. Indeed, a survey of past research on the visual search for emotional expressions finds better support for a happiness detection advantage, and the explanation may lie in the coevolution of the signal and the receiver.

Mexican Americans are one of the largest and fastest growing ethnic groups in the United States, yet we have limited knowledge regarding changes (i.e., developmental trajectories) in cultural orientation based upon their exposure to the Mexican American and mainstream cultures. We examined the parallel trajectories of Mexican American and mainstream cultural values in a sample of 749 Mexican American adolescents (49% female) across assessments during the fifth grade (approximately 11 years of age), the seventh grade (approximately 13 years of age) and the tenth grade (approximately 16 years of age). We expected that these values would change over this developmental period and this longitudinal approach is more appropriate than the often used median split classification to identify distinct types of acculturation. We found four distinct acculturation trajectory groups: two trajectory groups that were increasing slightly with age in the endorsement of mainstream cultural values, one of which was relatively stable in Mexican American cultural values while the other was declining in their endorsement of these values; and two trajectory groups that were declining substantially with age in their endorsement of mainstream cultural values, one of which was also declining in Mexican American cultural values and the other which was stable in these values. These four trajectory groups differed in expected ways on a number of theoretically related cultural variables, but were not highly consistent with the median split classifications. The findings highlight the need to utilize longitudinal data to examine the developmental changes of Mexican American individual’s adaptation to the ethnic and mainstream culture in order to understand more fully the processes of acculturation and enculturation.