ASU Scholarship Showcase

We recommend using backward design to develop course-based undergraduate research experiences (CUREs). The defining hallmark of CUREs is that students in a formal lab course explore research questions with unknown answers that are broadly relevant outside the course. Because CUREs lead to novel research findings, they represent a unique course design challenge, as the dual nature of these courses requires course designers to consider two distinct, but complementary, sets of goals for the CURE: 1) scientific discovery milestones (i.e., research goals) and 2) student learning in cognitive, psychomotor, and affective domains (i.e., pedagogical goals). As more undergraduate laboratory courses are re-imagined as CUREs, how do we thoughtfully design these courses to effectively meet both sets of goals? In this Perspectives article, we explore this question and outline recommendations for using backward design in CURE development.

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.

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.

Women who start college in one of the natural or physical sciences leave in greater proportions than their male peers. The reasons for this difference are complex, and one possible contributing factor is the social environment women experience in the classroom. Using social network analysis, we explore how gender influences the confidence that college-level biology students have in each other’s mastery of biology. Results reveal that males are more likely than females to be named by peers as being knowledgeable about the course content. This effect increases as the term progresses, and persists even after controlling for class performance and outspokenness. The bias in nominations is specifically due to males over-nominating their male peers relative to their performance. The over-nomination of male peers is commensurate with an overestimation of male grades by 0.57 points on a 4 point grade scale, indicating a strong male bias among males when assessing their classmates. Females, in contrast, nominated equitably based on student performance rather than gender, suggesting they lacked gender biases in filling out these surveys. These trends persist across eleven surveys taken in three different iterations of the same Biology course. In every class, the most renowned students are always male. This favoring of males by peers could influence student self-confidence, and thus persistence in this STEM discipline.

The U.S. scientific research community does not reflect America's diversity. Hispanics, African Americans, and Native Americans made up 31% of the general population in 2010, but they represented only 18 and 7% of science, technology, engineering, and mathematics (STEM) bachelor's and doctoral degrees, respectively, and 6% of STEM faculty members (National Science Foundation [NSF], 2013). Equity in the scientific research community is important for a variety of reasons; a diverse community of researchers can minimize the negative influence of bias in scientific reasoning, because people from different backgrounds approach a problem from different perspectives and can raise awareness regarding biases (Intemann, 2009). Additionally, by failing to be attentive to equity, we may exclude some of the best and brightest scientific minds and limit the pool of possible scientists (Intemann, 2009). Given this need for equity, how can our scientific research community become more inclusive?

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 Dawn Framing Camera (FC) has imaged the northern hemisphere of the Asteroid (4) Vesta at high spatial resolution and coverage. This study represents the first investigation of the overall geology of the northern hemisphere (22–90°N, quadrangles Av-1, 2, 3, 4 and 5) using these unique Dawn mission observations. We have compiled a morphologic map and performed crater size–frequency distribution (CSFD) measurements to date the geologic units. The hemisphere is characterized by a heavily cratered surface with a few highly subdued basins up to ∼200 km in diameter. The most widespread unit is a plateau (cratered highland unit), similar to, although of lower elevation than the equatorial Vestalia Terra plateau. Large-scale troughs and ridges have regionally affected the surface. Between ∼180°E and ∼270°E, these tectonic features are well developed and related to the south pole Veneneia impact (Saturnalia Fossae trough unit), elsewhere on the hemisphere they are rare and subdued (Saturnalia Fossae cratered unit). In these pre-Rheasilvia units we observed an unexpectedly high frequency of impact craters up to ∼10 km in diameter, whose formation could in part be related to the Rheasilvia basin-forming event. The Rheasilvia impact has potentially affected the northern hemisphere also with S–N small-scale lineations, but without covering it with an ejecta blanket. Post-Rheasilvia impact craters are small (<60 km in diameter) and show a wide range of degradation states due to impact gardening and mass wasting processes. Where fresh, they display an ejecta blanket, bright rays and slope movements on walls. In places, crater rims have dark material ejecta and some crater floors are covered by ponded material interpreted as impact melt.

Oppia Quadrangle Av-10 (288–360°E, ±22°) is a junction of key geologic features that preserve a rough history of Asteroid (4) Vesta and serves as a case study of using geologic mapping to define a relative geologic timescale. Clear filter images, stereo-derived topography, slope maps, and multispectral color-ratio images from the Framing Camera on NASA’s Dawn spacecraft served as basemaps to create a geologic map and investigate the spatial and temporal relationships of the local stratigraphy. Geologic mapping reveals the oldest map unit within Av-10 is the cratered highlands terrain which possibly represents original crustal material on Vesta that was then excavated by one or more impacts to form the basin Feralia Planitia. Saturnalia Fossae and Divalia Fossae ridge and trough terrains intersect the wall of Feralia Planitia indicating that this impact basin is older than both the Veneneia and Rheasilvia impact structures, representing Pre-Veneneian crustal material. Two of the youngest geologic features in Av-10 are Lepida (∼45 km diameter) and Oppia (∼40 km diameter) impact craters that formed on the northern and southern wall of Feralia Planitia and each cross-cuts a trough terrain. The ejecta blanket of Oppia is mapped as ‘dark mantle’ material because it appears dark orange in the Framing Camera ‘Clementine-type’ color-ratio image and has a diffuse, gradational contact distributed to the south across the rim of Rheasilvia. Mapping of surface material that appears light orange in color in the Framing Camera ‘Clementine-type’ color-ratio image as ‘light mantle material’ supports previous interpretations of an impact ejecta origin. Some light mantle deposits are easily traced to nearby source craters, but other deposits may represent distal ejecta deposits (emplaced >5 crater radii away) in a microgravity environment.

The Quadrangles Av-11 and Av-12 on Vesta are located at the northern rim of the giant Rheasilvia south polar impact basin. The primary geologic units in Av-11 and Av-12 include material from the Rheasilvia impact basin formation, smooth material and different types of impact crater structures (such as bimodal craters, dark and bright crater ray material and dark ejecta material). Av-11 and Av-12 exhibit almost the full range of mass wasting features observed on Vesta, such as slump blocks, spur-and-gully morphologies and landslides within craters. Processes of collapse, slope instability and seismically triggered events force material to slump down crater walls or scarps and produce landslides or rotational slump blocks. The spur-and-gully morphology that is known to form on Mars is also observed on Vesta; however, on Vesta this morphology formed under dry conditions.