ASU Scholarship Showcase

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.

We investigate near-field radiative heat transfer between Indium Tin Oxide (ITO) nanowire arrays which behave as type 1 and 2 hyperbolic metamaterials. Using spatial dispersion dependent effective medium theory to model the dielectric function of the nanowires, the impact of filling fraction on the heat transfer is analyzed. Depending on the filling fraction, it is possible to achieve both types of hyperbolic modes. At 150 nm vacuum gap, the heat transfer between the nanowires with 0.5 filling fraction can be 11 times higher than that between two bulk ITOs. For vacuum gaps less than 150 nm the heat transfer increases as the filling fraction decreases. Results obtained from this study will facilitate applications of ITO nanowires as hyperbolic metamaterials for energy systems.

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.

In this letter, we study the near-field radiative heat transfer between two metamaterial substrates coated with silicon carbide (SiC) thin films. It is known that metamaterials can enhance the near-field heat transfer over ordinary materials due to excitation of magnetic plasmons associated with s polarization, while strong surface phonon polariton exists for SiC. By careful tuning of the optical properties of metamaterial, it is possible to excite electrical and magnetic resonances for the metamaterial and surface phonon polaritons for SiC at different spectral regions, resulting in the enhanced heat transfer. The effect of the SiC film thickness at different vacuum gaps is investigated. Results obtained from this study will be beneficial for application of thin film coatings for energy harvesting.

A film-coupled metamaterial structure is numerically investigated for enhancing the light absorption in an ultrathin photovoltaic layer of crystalline gallium arsenide (GaAs). The top subwavelength concave grating and the bottom metallic film could not only effectively trap light with the help of wave interference and magnetic resonance effects excited above the bandgap, but also practically serve as electrical contacts for photon-generated charge collection. The energy absorbed by the active layer is greatly enhanced with the help of the film-coupled metamaterial structure, resulting in significant improvement on the short-circuit current density by three times over a free-standing GaAs layer at the same thickness. The performance of the proposed light trapping structure is demonstrated to be little affected by the grating ridge width considering the geometric tolerance during fabrication. The optical absorption at oblique incidences also shows direction-insensitive behavior, which is highly desired for efficiently converting off-normal sunlight to electricity. The results would facilitate the development of next-generation ultrathin solar cells with lower cost and higher efficiency.

We know very little about how soil-borne pollutants such as selenium (Se) can impact pollinators, even though Se has contaminated soils and plants in areas where insect pollination can be critical to the functioning of both agricultural and natural ecosystems. Se can be biotransferred throughout the food web, but few studies have examined its effects on the insects that feed on Se-accumulating plants, particularly pollinators. In laboratory bioassays, we used proboscis extension reflex (PER) and taste perception to determine if the presence of Se affected the gustatory response of honey bee (Apis mellifera L., Hymenoptera: Apidae) foragers. Antennae and proboscises were stimulated with both organic (selenomethionine) and inorganic (selenate) forms of Se that commonly occur in Se-accumulating plants. Methionine was also tested. Each compound was dissolved in 1 M sucrose at 5 concentrations, with sucrose alone as a control. Antennal stimulation with selenomethionine and methionine reduced PER at higher concentrations. Selenate did not reduce gustatory behaviors. Two hours after being fed the treatments, bees were tested for sucrose response threshold. Bees fed selenate responded less to sucrose stimulation. Mortality was higher in bees chronically dosed with selenate compared with a single dose. Selenomethionine did not increase mortality except at the highest concentration. Methionine did not significantly impact survival. Our study has shown that bees fed selenate were less responsive to sucrose, which may lead to a reduction in incoming floral resources needed to support coworkers and larvae in the field. If honey bees forage on nectar containing Se (particularly selenate), reductions in population numbers may occur due to direct toxicity. Given that honey bees are willing to consume food resources containing Se and may not avoid Se compounds in the plant tissues on which they are foraging, they may suffer similar adverse effects as seen in other insect guilds.

Octopamine plays an important role in many behaviors in invertebrates. It acts via binding to G protein coupled receptors located on the plasma membrane of responsive cells. Several distinct subtypes of octopamine receptors have been found in invertebrates, yet little is known about the expression pattern of these different receptor subtypes and how each subtype may contribute to different behaviors. One honey bee (Apis mellifera) octopamine receptor, AmOA1, was recently cloned and characterized. Here we continue to characterize the AmOA1 receptor by investigating its distribution in the honey bee brain. We used two independent antibodies produced against two distinct peptides in the carboxyl-terminus to study the distribution of the AmOA1 receptor in the honey bee brain. We found that both anti-AmOA1 antibodies revealed labeling of cell body clusters throughout the brain and within the following brain neuropils: the antennal lobes; the calyces, pedunculus, vertical (alpha, gamma) and medial (beta) lobes of the mushroom body; the optic lobes; the subesophageal ganglion; and the central complex. Double immunofluorescence staining using anti-GABA and anti-AmOA1 receptor antibodies revealed that a population of inhibitory GABAergic local interneurons in the antennal lobes express the AmOA1 receptor in the cell bodies, axons and their endings in the glomeruli. In the mushroom bodies, AmOA1 receptors are expressed in a subpopulation of inhibitory GABAergic feedback neurons that ends in the visual (outer half of basal ring and collar regions) and olfactory (lip and inner basal ring region) calyx neuropils, as well as in the collar and lip zones of the vertical and medial lobes. The data suggest that one effect of octopamine via AmOA1 in the antennal lobe and mushroom body is to modulate inhibitory neurons.

Neural representations of odors are subject to computations that involve sequentially convergent and divergent anatomical connections across different areas of the brains in both mammals and insects. Furthermore, in both mammals and insects higher order brain areas are connected via feedback connections. In order to understand the transformations and interactions that this connectivity make possible, an ideal experiment would compare neural responses across different, sequential processing levels. Here we present results of recordings from a first order olfactory neuropile – the antennal lobe (AL) – and a higher order multimodal integration and learning center – the mushroom body (MB) – in the honey bee brain. We recorded projection neurons (PN) of the AL and extrinsic neurons (EN) of the MB, which provide the outputs from the two neuropils. Recordings at each level were made in different animals in some experiments and simultaneously in the same animal in others. We presented two odors and their mixture to compare odor response dynamics as well as classification speed and accuracy at each neural processing level. Surprisingly, the EN ensemble significantly starts separating odor stimuli rapidly and before the PN ensemble has reached significant separation. Furthermore the EN ensemble at the MB output reaches a maximum separation of odors between 84–120 ms after odor onset, which is 26 to 133 ms faster than the maximum separation at the AL output ensemble two synapses earlier in processing. It is likely that a subset of very fast PNs, which respond before the ENs, may initiate the rapid EN ensemble response. We suggest therefore that the timing of the EN ensemble activity would allow retroactive integration of its signal into the ongoing computation of the AL via centrifugal feedback.

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.