ASU Scholarship Showcase

Background:
Ketogenic diets are high fat and low carbohydrate or very low carbohydrate diets, which render high production of ketones upon consumption known as nutritional ketosis (NK). Ketosis is also produced during fasting periods, which is known as fasting ketosis (FK). Recently, the combinations of NK and FK, as well as NK alone, have been used as resources for weight loss management and treatment of epilepsy.

Methods:
A crossover study design was applied to 11 healthy individuals, who maintained moderately sedentary lifestyle, and consumed three types of diet randomly assigned over a three-week period. All participants completed the diets in a randomized and counterbalanced fashion. Each weekly diet protocol included three phases: Phase 1 - A mixed diet with ratio of fat: (carbohydrate + protein) by mass of 0.18 or the equivalence of 29% energy from fat from Day 1 to Day 5. Phase 2- A mixed or a high-fat diet with ratio of fat: (carbohydrate + protein) by mass of approximately 0.18, 1.63, or 3.80 on Day 6 or the equivalence of 29%, 79%, or 90% energy from fat, respectively. Phase 3 - A fasting diet with no calorie intake on Day 7. Caloric intake from diets on Day 1 to Day 6 was equal to each individual’s energy expenditure. On Day 7, ketone buildup from FK was measured.

Results:
A statistically significant effect of Phase 2 (Day 6) diet was found on FK of Day 7, as indicated by repeated analysis of variance (ANOVA), F(2,20) = 6.73, p < 0.0058. Using a Fisher LDS pair-wise comparison, higher significant levels of acetone buildup were found for diets with 79% fat content and 90% fat content vs. 29% fat content (with p = 0.00159**, and 0.04435**, respectively), with no significant difference between diets with 79% fat content and 90% fat content. In addition, independent of the diet, a significantly higher ketone buildup capability of subjects with higher resting energy expenditure (R[superscript 2] = 0.92), and lower body mass index (R[superscript 2] = 0.71) was observed during FK.

Although insulin resistance in skeletal muscle is well-characterized, the role of circulating whole blood in the metabolic syndrome phenotype is not well understood. We set out to test the hypothesis that genes involved in inflammation, insulin signaling and mitochondrial function would be altered in expression in the whole blood of individuals with metabolic syndrome. We further wanted to examine whether similar relationships that we have found previously in skeletal muscle exist in peripheral whole blood cells. All subjects (n=184) were Latino descent from the Arizona Insulin Resistance registry. Subjects were classified based on the metabolic syndrome phenotype according to the National Cholesterol Education Program’s Adult Treatment Panel III. Of the 184 Latino subjects in the study, 74 were classified with the metabolic syndrome and 110 were without. Whole blood gene expression profiling was performed using the Agilent 4x44K Whole Human Genome Microarray. Whole blood microarray analysis identified 1,432 probes that were altered in expression ≥1.2 fold and P<0.05 after Benjamini-Hochberg in the metabolic syndrome subjects. KEGG pathway analysis revealed significant enrichment for pathways including ribosome, oxidative phosphorylation and MAPK signaling (all Benjamini-Hochberg P<0.05). Whole blood mRNA expression changes observed in the microarray data were confirmed by quantitative RT-PCR. Transcription factor binding motif enrichment analysis revealed E2F1, ELK1, NF-kappaB, STAT1 and STAT3 significantly enriched after Bonferroni correction (all P<0.05). The results of the present study demonstrate that whole blood is a useful tissue for studying the metabolic syndrome and its underlying insulin resistance although the relationship between blood and skeletal muscle differs.

Many drugs are effective in the early stage of treatment, but patients develop drug resistance after a certain period of treatment, causing failure of the therapy. An important example is Herceptin, a popular monoclonal antibody drug for breast cancer by specifically targeting human epidermal growth factor receptor 2 (Her2). Here we demonstrate a quantitative binding kinetics analysis of drug-target interactions to investigate the molecular scale origin of drug resistance. Using a surface plasmon resonance imaging, we measured the in situ Herceptin-Her2 binding kinetics in single intact cancer cells for the first time, and observed significantly weakened Herceptin-Her2 interactions in Herceptin-resistant cells, compared to those in Herceptin-sensitive cells. We further showed that the steric hindrance of Mucin-4, a membrane protein, was responsible for the altered drug-receptor binding. This effect of a third molecule on drug-receptor interactions cannot be studied using traditional purified protein methods, demonstrating the importance of the present intact cell-based binding kinetics analysis.

Quantifying the interactions of bacteria with external ligands is fundamental to the understanding of pathogenesis, antibiotic resistance, immune evasion, and mechanism of antimicrobial action. Due to inherent cell-to-cell heterogeneity in a microbial population, each bacterium interacts differently with its environment. This large variability is washed out in bulk assays, and there is a need of techniques that can quantify interactions of bacteria with ligands at the single bacterium level. In this work, we present a label-free and real-time plasmonic imaging technique to measure the binding kinetics of ligand interactions with single bacteria, and perform statistical analysis of the heterogeneity. Using the technique, we have studied interactions of antibodies with single Escherichia coli O157:H7 cells and demonstrated a capability of determining the binding kinetic constants of single live bacteria with ligands, and quantify heterogeneity in a microbial population.

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.

A variety of geologic landforms and features are observed within quadrangle Av-13 Tuccia in the southern hemisphere of Vesta. The quadrangle covers parts of the highland Vestalia Terra as well as the floors of the large Rheasilvia and Veneneia impact basins, which results in a substantial elevation difference of more than 40 km between the northern and the southern portions of the quadrangle. Measurements of crater size–frequency distributions within and surrounding the Rheasilvia basin indicate that gravity-driven mass wasting in the interior of the basin has been important, and that the basin has a more ancient formation age than would be expected from the crater density on the basin floor alone. Subsequent to its formation, Rheasilvia was superimposed by several mid-sized impact craters. The most prominent craters are Tuccia, Eusebia, Vibidia, Galeria, and Antonia, whose geology and formation ages are investigated in detail in this work. These impact structures provide a variety of morphologies indicating different sorts of subsequent impact-related or gravity-driven mass wasting processes. Understanding the geologic history of the relatively young craters in the Rheasilvia basin is important in order to understand the even more degraded craters in other regions of Vesta.

As part of systematic global mapping of Vesta using data returned by the Dawn spacecraft, we have produced a geologic map of the north pole quadrangle, Av-1 Albana. Extensive seasonal shadows were present in the north polar region at the time of the Dawn observations, limiting the ability to map morphological features and employ color or spectral data for determination of composition. The major recognizable units present include ancient cratered highlands and younger crater-related units (undivided ejecta, and mass-wasting material on crater floors). The antipode of Vesta’s large southern impact basins, Rheasilvia and Veneneia, lie within or near the Av-1 quadrangle. Therefore it is of particular interest to search for evidence of features of the kind that are found at basin antipodes on other planetary bodies. Albedo markings known as lunar swirls are correlated with basin antipodes and the presence of crustal magnetic anomalies on the Moon, but lighting conditions preclude recognition of such albedo features in images of the antipode of Vesta’s Rheasilvia basin. “Hilly and lineated terrain,” found at the antipodes of large basins on the Moon and Mercury, is not present at the Rheasilvia or Veneneia antipodes. We have identified small-scale linear depressions that may be related to increased fracturing in the Rheasilvia and Veneneia antipodal areas, consistent with impact-induced stresses (Buczkowski, D. et al. [2012b]. Analysis of the large scale troughs on Vesta and correlation to a model of giant impact into a differentiated asteroid. Geol. Soc. of America Annual Meeting. Abstract 152-4; Bowling, T.J. et al. [2013]. J. Geophys. Res. – Planets, 118. http://dx.doi.org/10.1002/jgre.20123). The general high elevation of much of the north polar region could, in part, be a result of uplift caused by the Rheasilvia basin-forming impact, as predicted by numerical modeling (Bowling, T.J. et al. [2013]. J. Geophys. Res. – Planets, 118. http://dx.doi.org/10.1002/jgre.20123). However, stratigraphic and crater size–frequency distribution analysis indicate that the elevated terrain predates the two southern basins and hence is likely a remnant of the ancient vestan crust. The lack of large-scale morphological features at the basin antipodes can be attributed to weakened antipodal constructive interference of seismic waves caused by an oblique impact or by Vesta’s non-spherical shape, or by attenuation of seismic waves because of the physical properties of Vesta’s interior. A first-order analysis of the Dawn global digital elevation model for Vesta indicates that areas of permanent shadow are unlikely to be present in the vicinity of the north pole.

We produced two 1:250,000 scale geologic maps of the adjacent quadrangles Av-6 Gegania and Av-7 Lucaria, located in the equatorial region of (4) Vesta (0–144°E, 22°S to 22°N). The mapping is based on clear and color filter images of the Framing Camera (FC) onboard the Dawn spacecraft, which has captured the entire illuminated surface of Vesta with high spatial resolution (up to ∼20 m/pixel), and on a digital terrain model derived from FC imagery. Besides the geologic mapping itself, a secondary purpose of this work is to investigate one of the most prominent morphological features on Vesta, namely the aggregation of several giant equatorial troughs termed the Divalia Fossae, most probably formed during the Rheasilvia impact near Vesta’s south pole. The up to 465 km long and 22 km wide troughs show height differences of up to 5 km between adjacent troughs and ridges. Another imprint of the Rheasilvia impact is the >350 km long and ∼250 km wide swath of ejecta crossing quadrangle Av-6 Gegania. This lobe shows a distinct appearance in FC color ratios and a high albedo in FC images, indicating a mineralogical similarity to material typically found within the Rheasilvia basin, in particular composed of diogenite-rich howardites. Almost the entire northern half of the mapping area shows the oldest surface, being dominated by upper crustal basaltic material. To the south, increasingly younger formations related to the Rheasilvia impact occur, either indicated by the troughs formed by Rheasilvia or by the Rheasilvia ejecta itself. Only medium sized impact craters with diameters less than 22 km occur within the two mapped quadrangles. Some of the craters exhibit ejecta blankets and/or distinctly dark or bright ejecta material in ejecta rays outside and exposures within the crater, and mass-wasting deposits down crater slopes, forming the youngest surfaces.