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.

This paper describes a novel method for displaying data obtained by three-dimensional medical imaging, by which the position and orientation of a freely movable screen are optically tracked and used in real time to select the current slice from the data set for presentation. With this method, which we call a “freely moving in-situ medical image”, the screen and imaged data are registered to a common coordinate system in space external to the user, at adjustable scale, and are available for free exploration. The three-dimensional image data occupy empty space, as if an invisible patient is being sliced by the moving screen. A behavioral study using real computed tomography lung vessel data established the superiority of the in situ display over a control condition with the same free exploration, but displaying data on a fixed screen (ex situ), with respect to accuracy in the task of tracing along a vessel and reporting spatial relations between vessel structures. A “freely moving in-situ medical image” display appears from these measures to promote spatial navigation and understanding of medical data.

Essential or enduring understandings are often defined as the underlying core concepts or “big ideas” we’d like our students to remember when much of the course content has been forgotten. The central dogma of molecular biology and how cellular information is stored, used, and conveyed is one of the essential understandings students should retain after a course or unit in molecular biology or genetics. An additional enduring understanding is the relationships between DNA sequence, RNA sequence, mRNA production and processing, and the resulting polypeptide/protein product. A final big idea in molecular biology is the relationship between DNA mutation and polypeptide change. To engage students in these essential understandings in a Genetics course, I have developed a hands-on activity to simulate VDJ recombination. Students use a foldable type activity to splice out regions of a mock kappa light chain gene to generate a DNA sequence for transcription and translation. Students fold the activity several different times in multiple ways to “recombine” and generate several different DNA sequences. They then are asked to construct the corresponding mRNA and polypeptide sequence of each “recombined” DNA sequence and reflect on the products in a write-to-learn activity.

The elongases of very long chain fatty acid (ELOVL or ELO) are essential in the biosynthesis of fatty acids longer than C14. Here, two ELO full-length cDNAs (TmELO1, TmELO2) from the yellow mealworm (Tenebrio molitor L.) were isolated and the functions were characterized. The open reading frame (ORF) lengths of TmELO1 and TmELO2 were 1005 bp and 972 bp, respectively and the corresponding peptide sequences each contained several conserved motifs including the histidine-box motif HXXHH. Phylogenetic analysis demonstrated high similarity with the ELO of Tribolium castaneum and Drosophila melanogaster. Both TmELO genes were expressed at various levels in eggs, 1st and 2nd instar larvae, mature larvae, pupae, male and female adults. Injection of dsTmELO1 but not dsTmELO2 RNA into mature larvae significantly increased mortality although RNAi did not produce any obvious changes in the fatty acid composition in the survivors. Heterologous expression of TmELO genes in yeast revealed that TmELO1 and TmELO2 function to synthesize long chain and very long chain fatty acids.

To investigate dual-process persuasion theories in the context of group decision making, we studied low and high need-for-cognition (NFC) participants within a mock trial study. Participants considered plaintiff and defense expert scientific testimony that varied in argument strength. All participants heard a cross-examination of the experts focusing on peripheral information (e.g., credentials) about the expert, but half were randomly assigned to also hear central information highlighting flaws in the expert’s message (e.g., quality of the research presented by the expert). Participants rendered pre- and post-group-deliberation verdicts, which were considered “scientifically accurate” if the verdicts reflected the strong (versus weak) expert message, and “scientifically inaccurate” if they reflected the weak (versus strong) expert message. For individual participants, we replicated studies testing classic persuasion theories: Factors promoting reliance on central information (i.e., central cross-examination, high NFC) improved verdict accuracy because they sensitized individual participants to the quality discrepancy between the experts’ messages. Interestingly, however, at the group level, the more that scientifically accurate mock jurors discussed peripheral (versus central) information about the experts, the more likely their group was to reach the scientifically accurate verdict. When participants were arguing for the scientifically accurate verdict consistent with the strong expert message, peripheral comments increased their persuasiveness, which made the group more likely to reach the more scientifically accurate verdict.

Specification of PM_2.5 transmission characteristics is important for pollution control and policymaking. We apply higher-order organization of complex networks to identify major potential PM_2.5 contributors and PM_2.5 transport pathways of a network of 189 cities in China. The network we create in this paper consists of major cities in China and contains information on meteorological conditions of wind speed and wind direction, data on geographic distance, mountains, and PM_2.5 concentrations. We aim to reveal PM_2.5 mobility between cities in China. Two major conclusions are revealed through motif analysis of complex networks. First, major potential PM_2.5 pollution contributors are identified for each cluster by one motif, which reflects movements from source to target. Second, transport pathways of PM_2.5 are revealed by another motif, which reflects transmission routes. To our knowledge, this is the first work to apply higher-order network analysis to study PM_2.5 transport.

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.

Health systems are heavily promoting patient portals. However, limited health literacy (HL) can restrict online communication via secure messaging (SM) because patients’ literacy skills must be sufficient to convey and comprehend content while clinicians must encourage and elicit communication from patients and match patients’ literacy level. This paper describes the Employing Computational Linguistics to Improve Patient-Provider Secure Email (ECLIPPSE) study, an interdisciplinary effort bringing together scientists in communication, computational linguistics, and health services to employ computational linguistic methods to (1) create a novel Linguistic Complexity Profile (LCP) to characterize communications of patients and clinicians and demonstrate its validity and (2) examine whether providers accommodate communication needs of patients with limited HL by tailoring their SM responses. We will study >5 million SMs generated by >150,000 ethnically diverse type 2 diabetes patients and >9000 clinicians from two settings: an integrated delivery system and a public (safety net) system. Finally, we will then create an LCP-based automated aid that delivers real-time feedback to clinicians to reduce the linguistic complexity of their SMs. This research will support health systems’ journeys to become health literate healthcare organizations and reduce HL-related disparities in diabetes care.

Background: Previous studies exploring sequence variation in the model legume, Medicago truncatula, relied on mapping short reads to a single reference. However, read-mapping approaches are inadequate to examine large, diverse gene families or to probe variation in repeat-rich or highly divergent genome regions. De novo sequencing and assembly of M. truncatula genomes enables near-comprehensive discovery of structural variants (SVs), analysis of rapidly evolving gene families, and ultimately, construction of a pan-genome.

Results: Genome-wide synteny based on 15 de novo M. truncatula assemblies effectively detected different types of SVs indicating that as much as 22% of the genome is involved in large structural changes, altogether affecting 28% of gene models. A total of 63 million base pairs (Mbp) of novel sequence was discovered, expanding the reference genome space for Medicago by 16%. Pan-genome analysis revealed that 42% (180 Mbp) of genomic sequences is missing in one or more accession, while examination of de novo annotated genes identified 67% (50,700) of all ortholog groups as dispensable – estimates comparable to recent studies in rice, maize and soybean. Rapidly evolving gene families typically associated with biotic interactions and stress response were found to be enriched in the accession-specific gene pool. The nucleotide-binding site leucine-rich repeat (NBS-LRR) family, in particular, harbors the highest level of nucleotide diversity, large effect single nucleotide change, protein diversity, and presence/absence variation. However, the leucine-rich repeat (LRR) and heat shock gene families are disproportionately affected by large effect single nucleotide changes and even higher levels of copy number variation.

Conclusions: Analysis of multiple M. truncatula genomes illustrates the value of de novo assemblies to discover and describe structural variation, something that is often under-estimated when using read-mapping approaches. Comparisons among the de novo assemblies also indicate that different large gene families differ in the architecture of their structural variation.

MALDI-TOF MS profiling has been shown to be a rapid and reliable method to characterize pure cultures of bacteria. Currently, there is keen interest in using this technique to identify bacteria in mixtures. Promising results have been reported with two- or three-isolate model systems using biomarker-based approaches. In this work, we applied MALDI-TOF MS-based methods to a more complex model mixture containing six bacteria. We employed: 1) a biomarker-based approach that has previously been shown to be useful in identification of individual bacteria in pure cultures and simple mixtures and 2) a similarity coefficient-based approach that is routinely and nearly exclusively applied to identification of individual bacteria in pure cultures. Both strategies were developed and evaluated using blind-coded mixtures. With regard to the biomarker-based approach, results showed that most peaks in mixture spectra could be assigned to those found in spectra of each component bacterium; however, peaks shared by two isolates as well as peaks that could not be assigned to any individual component isolate were observed. For two-isolate blind-coded samples, bacteria were correctly identified using both similarity coefficient- and biomarker-based strategies, while for blind-coded samples containing more than two isolates, bacteria were more effectively identified using a biomarker-based strategy.