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.

The number and variety of connectivity estimation methods is likely to continue to grow over the coming decade. Comparisons between methods are necessary to prune this growth to only the most accurate and robust methods. However, the nature of connectivity is elusive with different methods potentially attempting to identify different aspects of connectivity. Commonalities of connectivity definitions across methods upon which base direct comparisons can be difficult to derive. Here, we explicitly define “effective connectivity” using a common set of observation and state equations that are appropriate for three connectivity methods: dynamic causal modeling (DCM), multivariate autoregressive modeling (MAR), and switching linear dynamic systems for fMRI (sLDSf). In addition while deriving this set, we show how many other popular functional and effective connectivity methods are actually simplifications of these equations. We discuss implications of these connections for the practice of using one method to simulate data for another method. After mathematically connecting the three effective connectivity methods, simulated fMRI data with varying numbers of regions and task conditions is generated from the common equation. This simulated data explicitly contains the type of the connectivity that the three models were intended to identify. Each method is applied to the simulated data sets and the accuracy of parameter identification is analyzed. All methods perform above chance levels at identifying correct connectivity parameters. The sLDSf method was superior in parameter estimation accuracy to both DCM and MAR for all types of comparisons.

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.

Background: Carriers of the APOE ε4 allele are at increased risk of developing Alzheimer’s disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE ε4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated.

Methods: Using quantitative mass spectrometry we quantified the plasma levels of total apoE and the individual apoE3 and apoE4 isoforms in 128 cognitively normal APOE ε3/ε4 individuals included in the Arizona APOE cohort. All included individuals had undergone extensive neuropsychological testing and 25 had in addition undergone FDG-PET and MRI to determine CMRgl and regional gray matter volume (GMV).

Results: Our results demonstrated higher apoE4 levels in females versus males and an age-dependent increase in the apoE3 isoform levels in females only. Importantly, a higher relative ratio of apoE4 over apoE3 was associated with GMV loss in the right posterior cingulate and with reduced CMRgl bilaterally in the anterior cingulate and in the right hippocampal area. Additional exploratory analysis revealed several negative associations between total plasma apoE, individual apoE isoform levels, GMV and CMRgl predominantly in the frontal, occipital and temporal areas. Finally, our results indicated only weak associations between apoE plasma levels and cognitive performance which further appear to be affected by sex.

Conclusions: Our study proposes a sex-dependent and age-dependent variation in plasma apoE isoform levels and concludes that peripheral apoE levels are associated with GMV, CMRgl and possibly cognitive performance in cognitively healthy individuals with a genetic predisposition to AD.

The urban heat island (UHI) phenomenon is a significant worldwide problem caused by rapid population growth and associated urbanization. The UHI effect exacerbates heat waves during the summer, increases energy and water consumption, and causes the high risk of heat-related morbidity and mortality. UHI mitigation efforts have increasingly relied on wisely designing the urban residential environment such as using high albedo rooftops, green rooftops, and planting trees and shrubs to provide canopy coverage and shading. Thus, strategically designed residential rooftops and their surrounding landscaping have the potential to translate into significant energy, long-term cost savings, and health benefits. Rooftop albedo, material, color, area, slope, height, aspect and nearby landscaping are factors that potentially contribute. To extract, derive, and analyze these rooftop parameters and outdoor landscaping information, high resolution optical satellite imagery, LIDAR (light detection and ranging) point clouds and thermal imagery are necessary. Using data from the City of Tempe AZ (a 2010 population of 160,000 people), we extracted residential rooftop footprints and rooftop configuration parameters from airborne LIDAR point clouds and QuickBird satellite imagery (2.4 m spatial resolution imagery). Those parameters were analyzed against surface temperature data from the MODIS/ASTER airborne simulator (MASTER). MASTER images provided fine resolution (7 m) surface temperature data for residential areas during daytime and night time. Utilizing these data, ordinary least squares (OLS) regression was used to evaluate the relationships between residential building rooftops and their surface temperature in urban environment. The results showed that daytime rooftop temperature was closely related to rooftop spectral attributes, aspect, slope, and surrounding trees. Night time temperature was only influenced by rooftop spectral attributes and slope.

This study examines the spatial and temporal patterns of the surface urban heat island (SUHI) intensity in the Phoenix metropolitan area and the relationship with land use land cover (LULC) change between 2000 and 2014. The objective is to identify specific regions in Phoenix that have been increasingly heated and cooled to further understand how LULC change influences the SUHI intensity. The data employed include MODerate-resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) 8-day composite June imagery, and classified LULC maps generated using 2000 and 2014 Landsat imagery. Results show that the regions that experienced the most significant LST changes during the study period are primarily on the outskirts of the Phoenix metropolitan area for both daytime and nighttime. The conversion to urban, residential, and impervious surfaces from all other LULC types has been identified as the primary cause of the UHI effect in Phoenix. Vegetation cover has been shown to significantly lower LST for both daytime and nighttime due to its strong cooling effect by producing more latent heat flux and less sensible heat flux. We suggest that urban planners, decision-makers, and city managers formulate new policies and regulations that encourage residential, commercial, and industrial developers to include more vegetation when planning new construction.

This paper reviews how remotely sensed data have been used to understand the impact of urbanization on global environmental change. We describe how these studies can support the policy and science communities’ increasing need for detailed and up-to-date information on the multiple dimensions of cities, including their social, biological, physical, and infrastructural characteristics. Because the interactions between urban and surrounding areas are complex, a synoptic and spatial view offered from remote sensing is integral to measuring, modeling, and understanding these relationships. Here we focus on three themes in urban remote sensing science: mapping, indices, and modeling. For mapping we describe the data sources, methods, and limitations of mapping urban boundaries, land use and land cover, population, temperature, and air quality. Second, we described how spectral information is manipulated to create comparative biophysical, social, and spatial indices of the urban environment. Finally, we focus how the mapped information and indices are used as inputs or parameters in models that measure changes in climate, hydrology, land use, and economics.

Background: We introduced a hypometabolic convergence index (HCI) to characterize in a single measurement the extent to which a person’s fluorodeoxyglucose positron emission tomogram (FDG PET) corresponds to that in Alzheimer’s disease (AD). Apolipoprotein E ε4 (APOE ε4) gene dose is associated with three levels of risk for late-onset AD. We explored the association between gene dose and HCI in cognitively normal ε4 homozygotes, heterozygotes, and non-carriers.

Methods: An algorithm was used to characterize and compare AD-related HCIs in cognitively normal individuals, including 36 ε4 homozygotes, 46 heterozygotes, and 78 non-carriers.

Results: These three groups differed significantly in their HCIs (ANOVA, p = 0.004), and there was a significant association between HCIs and gene dose (linear trend, p = 0.001).

Conclusions: The HCI is associated with three levels of genetic risk for late-onset AD. This supports the possibility of using a single FDG PET measurement to help in the preclinical detection and tracking of AD.

Deforestation in Myanmar has recently attracted much attention worldwide. This study examined spatio-temporal patterns of deforestation and forest carbon flux in Myanmar from 2001 to 2010 and environmental impacts at the regional scale using land products of the Moderate Resolution Imaging Spectroradiometer (MODIS). The results suggest that the total deforestation area in Myanmar was 21,178.8 km², with an annual deforestation rate of 0.81%, and that the total forest carbon release was 20.06 million tons, with an annual rate of 0.37%. Mangrove forests had the highest deforestation and carbon release rates, and deciduous forests had both the largest deforestation area and largest amount of carbon release. During the study period, the south and southwestern regions of Myanmar, especially Ayeyarwady and Rakhine, were deforestation hotspots (i.e., the highest deforestation and carbon release rates occurred in these regions). Deforestation caused significant carbon release, reduced evapotranspiration (ET), and increased land surface temperatures (LSTs) in deforested areas in Myanmar during the study period. Constructive policy recommendations are put forward based on these research results.