32nd Hayes Graduate Research Forum (March, 2018)

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https://kb.osu.edu/handle/1811/81903

Arts
1st place: Truett, Joshua
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2nd place: Trevor, Caitlyn
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3rd place: Reymore, Lindsey
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Biological Sciences
1st place: Modak, Debadrita
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2nd place: Crowe, Kelly
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3rd place: Schwebach, Christopher
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Business
1st place: Ge, Shan
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2nd place: Costello, John
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3rd place: Zane, Daniel
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Education and Human Ecology
1st place: Bhaktha, Nivedita
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2nd place: Smith, Kirsten
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3rd place: Groom, Leiah

Engineering
1st place: Cui, Yixiao
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2nd place: Nguyen, B. Audrey
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3rd place: Laszakovits, Juliana
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FAES
1st place: Robertson, Katie
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2nd place: Lee, Seungjun
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3rd place: Dubrow, Geoffrey

Humanities
1st place: Lang, Kathryn
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2nd place: Young, Nathan
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3rd place: Alex, Stacey
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Math and Physical Sciences
1st place: Eder, Grace
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2nd place: Khan, Gabriel
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3rd place: King, Michalea
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Health Sciences
1st place: Altabtbaei, Khaled
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2nd place: Bonneville, Russell
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3rd place: Zwolski, Christin
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Social and Behavioral Sciences
1st place: Shatzer, Hannah
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2nd place: Cole, Mary
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3rd place: Plate, Andre
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Poster Division: Arts, Humanities, and Social Sciences
1st place: Hannum, Mackenzie
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2nd place: Keller-Hamilton, Brittney
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3rd place: McDonough-Caplan, Heather
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Poster Division: Biological Sciences
1st place: Yoseph, Rim
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2nd place: Webb, Lindsay
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3rd place: Mrdjen, Igor
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Poster Division: Engineering, Math, and Physical Sciences
1st place: Presley, Kayla
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2nd place: Gustin, Vance
3rd place: Duvvuri, Krishnaja
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Expedited Extraction of 2D Bone Porosity Descriptors from 3D Micro-CT and Serial Section Images
(2018-03) Cole, Mary; Stout, Samuel
Anthropologists have extensively studied how physical activity changes the shape of the bones used for those behaviors (Ruff et al., 2006). When mechanical demand changes from an optimal level, bone is formed or resorbed (removed) until it restores the balance of bone meeting mechanical needs. Bone forms on surfaces where demand is increased, and bone is resorbed on surfaces where demand is decreased (Lanyon, 1982). The cross-sectional shapes of limb bones in particular have been broadly tracked across fossil and archaeological populations to detect trends in bone strength associated with the evolution of bipedalism, transition to agriculture, division of labor, roughness of terrain, and tool use (30+ studies reviewed in Ruff and Larsen, 2014). The relationship between mechanical demand and bone shape becomes more complicated when anthropologists examine the internal structures of bone tissue. The cortical "walls" of bone are perforated with hundreds (in the rib) to thousands (in the femur) of canal systems known as vascular pores, which carry the blood vessels that supply bone cells (Agnew and Stout, 2012, Cole, 2014). Vascular pores form through a mechanically-stimulated process of bone turnover called "remodeling", which involves osteoclast cells tunneling into bone tissue, and osteoblast cells filling in all of this tunnel except a central pore (Burr and Akkus 2014). Remodeling is triggered under three circumstances: 1) mechanical demand decreases, so pores form to remove "excess" bone, 2) mechanical demand increases, damaging the bone, so the microscopically cracked tissue is removed through remodeling, or 3) the cellular processes underlying remodeling become de-sensitized and dis-regulated with age, leading to increased porosity beyond what is mechanically stimulated (Agnew and Bolte, 2012, Burr and Akkus, 2014). Since these contradictory mechanical stimuli can all lead to porosity, anthropologists have sought to untangle the relationship between mechanical demand and pore number, shape, and location. Age-associated increases in porosity are also a key marker of bone fragility – decreased bone strength and increased fracture risk – both in archaeological (e.g. Cho and Stout, 2002) and modern populations (e.g. Yeni et al., 1997). At least 76% of the reduction in cortical strength with age results from porosity (McCalden et al., 2003). This is because vascular pores are stress concentrators where microscopic cracks can initiate and then propagate into a spontaneous fracture (Reilly and Currey, 1999, Ebacher et al., 2007). One in three women and one in five men over the age of 50 will experience at least one fracture due to severe bone loss (osteoporosis) (Melton et al., 1992, 1998, Kanis et al., 2000). Traditionally, anthropologists have examined porosity by cutting a ~100 micrometer thick cross-section of a bone. The cross-sections of pore systems on this slice of bone are then counted and measured (Agnew and Stout, 2012) However, pore networks are highly complex in three-dimensions, frequently splitting, merging, and branching at varied angles. In two-dimensional cross-section, pore shapes and numbers are distorted (Stout et al., 1999; Bell et al. 2001). Traditional histological slide preparation also involves grinding away several hundred micrometers of structural information between adjacent cross-sections, making it impossible to accurately reconstruct and follow pore structures as they change along a bone (Cho, 2012). Consequently, previous studies have not agreed on how pores respond in number, size, and orientation to different mechanical demands in different bone types or regions (reviewed in Stout et al. 1999 and Gocha and Agnew 2016). Additionally, manual selection and measurement of hundreds to thousands of individual pores is time-intensive (Agnew and Stout 2012, Cole 2014). This presentation will demonstrate two new automated or near-automated techniques that extract two-dimensional pore measurements from exactly adjacent slices of bone, without a loss of three-dimensional information. The sample consisted of adjacent regions of the midshaft of a cadaveric right-side fourth rib from a 72 year old human female. The first technique, high-resolution micro-computed tomography, involved scanning a 1 cm long rib segment using a Skyscan 1172-D High Resolution Desk-Top Micro-CT. Pore spaces were automatically extracted in three-dimensional space through the Segmentation Editor of AvizoFire 8.1 and exported as series of two-dimensional slices. Each slice represented an adjacent region of the bone length, with thickness 4.88 µm. The second technique, reconstruction from serial sections, involved decalcification in 14% EDTA and freezing cryostat serial sectioning of an immediately adjacent 1 mm long rib segment. Due to the thinness of each serial section (30 µm), pore spaces were empty with distinct boundaries, facilitating automated extraction of the majority of pores through thresholding of pixel intensity, particle size, and particle circularity in ImageJ, and near-automated extraction of section boundaries and the few remaining pores by adjusting wand tool pixel value tolerance. Both microCT and serial section image sequences were loaded into ImageJ, which reported descriptive statistics for pore number, area, and circularity. Average sectional pore mean area and percent porosity were similar between micro-CT (mean area = 0.00560 +/- 0.00262 mm2; % porosity = 5.59 +/- 0.05%) and histological technique (mean area = 0.00444 +/- 0.000771 mm2; % porosity = 5.71 +/- 1.9%). Micro-CT serial sections on average reported fewer, more circular pores (130 +/- 6.58 pores; 0.877 +/- 0.0132 circularity) than histological technique (167 +/- 8.98 pores; 0.709 +/- 0.050 circularity), as micro-CT can better incorporate tissue separating or edging pores. Both techniques preserve three-dimensional structural information and minimize sample processing time. For both methods, adjacent serial sections can also be interpolated to reconstruct the three-dimensional structure of the pore network.
Generalized Aggressive Periodontitis - A Periodontal Chimera
(2018-03) Altabtbaei, Khaled; Kumar, Purnima
Objectives: Periodontitis is a disease of the surrounding tissues of the tooth (periodontium) in which the destruction leads to weakening of the tooth support and eventual tooth loss. Approximately 46% of adults in the US suffer from this disease.1 The current classification of periodontal diseases and conditions recognizes 3 forms of periodontitis: Chronic periodontitis (CP), Localized Aggressive Periodontitis (LAP), and Generalized Aggressive Periodontitis (GAP). All three are inflammatory conditions that are microbial in nature. GAP is considered the most destructive of the three conditions due to its rapid destruction of the periodontium and its wide distribution in the mouth. Previous close-ended approaches to examine the bacterial constituents of the 3 diseases were equivocal, however, the consensus is that CP and GAP are considered polymicrobial in nature, while LAP is attributed to a mono-infection of the bacterial species Aggregatibacter actinomycetemcomitans.2 Since evidence is emerging that taxonomically distinct periodontal biofilms are functionally congruent, the present investigation sought to characterize the functional potential within the subgingival bacteria of CP, GAP and LAP. Methods: Subgingival plaque samples were collected from deep and shallow sites of 25 patients with CP, 17 with GAP, and 17 with LAP. Whole-genome shotgun DNA sequencing was used to characterize the functions encoded in these microbial communities. Sequences were analyzed using the MG-RAST pipeline for subsystem classification, and Kraken for taxonomic identification. Organismal diversity and functional abundances were compared between groups using dissimilarity indices, differential abundance metrics and network analysis. Results: 11.5 million sequences per sample contributed to 5973 functionally annotated genes. Principal coordinate analysis revealed distinct clustering of the three diseases based on community membership, structure and functional potential (p<0.05, ANOSIM). GAP separated the distances between LAP and CP, concordant with concept of a mixed infection of the two diseases. GAP and CP had similar functions of fermentation, phage transfer, while GAP and LAP had similar virulence factors. Taxonomic analysis revealed the polymicrobial nature of all three conditions. Network analysis showed similar inter-bacterial interaction networks between GAP and LAP, with similar membership of Treponema denticola, Filifactor alocis, Tannerella forsythia and Porphyromonadaceae Spp. Implications: This is the first time that the three disease entities are shown to exist as a continuum rather than discrete disease entities. This paradigm shift in has major implications on the classification of disease. That is, the aggressive but localized nature of LAP is globalized to the entire periodontal tissues by the superimposition of CP. Moreover, these findings cast doubt on current empirical treatment protocols for GAP that follow closely the protocols made for LAP. Finally, the breadth of the microbial members in LAP extend beyond the single bacteria species which greatly expands our understanding of the disease.
The Incidence of Second Anterior Cruciate Ligament Injury in Young Athletes is not Influenced by Time to Return to Sport
(2018-03) Zwolski, Christin; Schmitt, Laura
Purpose/Hypothesis: The incidence of second anterior cruciate ligament (ACL) injury among the population of young athletes is reported to be as high as 30%. Time between ACL reconstruction (ACLR) and return to sport (RTS) has been considered as a factor in second injury risk, particularly for patients who achieve RTS prior to 6 months. The purpose of this study was to investigate the effect of time between ACLR and RTS on incidence of 2nd ACL injury. The tested hypothesis was that incidence of 2nd ACL injury among young, athletic participants would not be influenced by time to RTS or patient-reported function following primary ACLR. Subjects: 184 participants (mean age=16.8±3.0 years) who underwent ACLR, completed rehabilitation, and were medically cleared to RTS. Methods: All subjects participated in a longitudinal study on outcomes following ACLR. Subjects were enrolled in the study within 4 weeks of their medical clearance to RTS. At this time, each subject completed the International Knee Documentation Committee (IKDC) Survey, the Knee injury and Osteoarthritis Outcome Score (KOOS) and was grouped into an early RTS group (<6 months post-operative (PO)) (n=19), an average RTS group (6-9 months PO)(n=106), and a late RTS group (≥9 months PO)(n=63). Subjects were then tracked for 24 months to record the incidence of a second ACL injury to either the involved limb or contralateral limb. One-way ANOVA was used to identify differences in demographics and patient-reported outcomes among the groups. Crude incidence of 2nd ACL injury was identified within each group and chi-squared analyses were used to determine the difference in proportion of 2nd ACL injuries between groups. Results: No significant differences in age (p=0.40), height (p=0.65) or weight (p=0.92) existed among the groups. At time of RTS, no differences between the early RTS, average RTS and late RTS groups were seen in patient-reported function on the IKDC (84.9±10.8, 90.5±9.5, 88.7±10.9; p= 0.08) and all KOOS subscales (p=0.05-0.41). With respect to 2nd ACL injury, there were no group differences (p=0.716) in the proportion of patients within each group who suffered a 2nd ACL injury within 24 months of RTS date (26.3% (5/19) of patients in the early RTS group, 18.9% (20/106) in the average RTS group and 22.2% (14/63) in the late RTS group). Conclusion: In accordance with our hypothesis, length of time between ACLR and RTS had no influence on incidence of second ACL injury among a population of young athletes after ACLR. Furthermore, patient-reported function at time of RTS was similar among groups, regardless of time between ACLR and RTS. Clinical Relevance: In the months between primary ACLR and RTS, factors aside from time, such as functional performance, movement patterns, psychological readiness and achievement of RTS testing, may require more attention for prevention of second ACL injury. Particularly among young athletes, further research is necessary to determine the optimization of this time in order to address the high incidence of second ACL injury.
Signal quality affects audiovisual speech integration in cochlear implant users and normal-hearing listeners
(2018-03) Shatzer, Hannah; Pitt, Mark
Human communication often includes the use of visual speech cues to understand an auditory speech signal, with cues from both modalities combined through the process of audiovisual integration. Cochlear implant users, with an impoverished auditory signal, tend to rely more heavily upon visual speech cues and would therefore show stronger weighting of the more reliable visual signal and enhanced suppression of early auditory cortex activity. The current study sought to test these predictions for both cochlear implant (CI) users and normal hearing (NH) listeners to assess the degree of visual influence with vary degrees of auditory and visual reliability. Postlingually deafened CI users and age-matched NH controls participated in an audiovisual phoneme identification task with electroencephalography (EEG) recording. Auditory tokens (/aba/, /aga/, /awa/) were presented at a signal-to-noise ratio (SNR) above or below a participant's predetermined threshold and paired with clear blurred videos of mouth movements that were either congruent or incongruent with the auditory token. Participants identified the consonant they heard with a button press. Behavioral and event-related potential (ERP) results suggest an early influence of reliable visual information on auditory cortex for both groups, though the effect is stronger for NH controls. The NH participants also demonstrated that auditory and visual signal quality interact in the suppression of auditory-evoked potentials, though effects were not observed in CI users. This implies that NH perceivers are more sensitive to differences in acoustic quality, and thus experience more variable effects of visual speech on AV processing than CI users.
Deriving a high-resolution record of Greenland glacier discharge
(2018-03) King, Michalea; Howat, Ian
Ice mass loss from the Greenland Ice Sheet is a major contributor to present-day sea level rise. Some of this mass is lost through the calving of ice from marine-terminating outlet glaciers. This research documents changes in speed and velocity for a large collection of glaciers by assimilating modeled and remotely sensed data. These data are used to derive continuous time series of solid ice discharge for every major glacier in Greenland over the 2000-2016 period. Combined, these records provide a single cumulative time series of the total dynamic ice loss of the GrIS, and reveal a marked seasonality superimposed on long-term trends. These data will allow us to identify regions of the ice sheet most vulnerable to change, and better understand how seasonal variability in ice flux contributes to overall glacier mass-balance, and the health of the ice sheet going forward.
Value Added Products from Feedstock Chemicals: Cobalt Catalyzed Asymmetric Hydroboration of 2-Alkyl-1,3-Dienes
(2018-03) Duvvuri, Krishnaja; RajanBabu, T. V.
Olefins, one of the most abundantly obtained class of feedstocks from the petroleum refining industry, are starting carbon units for many of the processes used to produce value-added chemicals in the pharmaceutical, agrochemical and polymer industry. However, many of these processes are often limited with harsh reaction conditions, poor yields and low selectivities. Organic chemists have long been trying to address the unmet challenges in this field; to simultaneously activate and functionalize olefins under mild reaction conditions, with the desired level of precision and selectivity, in order to access high value-added molecules from cheap and abundant lower alkenes. By employing transition metal catalysts as powerful tools, we sought to address olefin functionalization, more specifically carbon-boron bond forming reactions, which could provide a powerful means to access a broad range of advanced, highly functionalized target molecules of interest to medicinal chemistry and related areas. We sought to develop a highly efficient catalytic protocol using the earth abundant metal, cobalt, linked to suitable ligands, to achieve the hydroboration of unactivated olefins to obtain organo-borane products with desired level of yield and selectivity. The operationally simple, yet unprecedented reactions we discovered expand the realm of hydrofunctionalizations to provide direct access to a number of boranes, of interest in organic synthesis.
Oxygen Sensing Electrospun Nanofibers for Biological Applications
(2018-03) Presley, Kayla; Lannutti, John
Incorporation of luminescent oxygen-sensitive molecules into electrospun polymeric nanofibers can create a sensor with linear Stern-Volmer behavior and a rapid response time. This overcomes several issues associated with traditional polymer film-based sensors. Nevertheless, disadvantages remain that could limit use in biological applications: photobleaching, excitation wavelengths that poorly penetrate tissue, and difficulties associated with delivery. This work attempts to address each of these issues. Systematic studies on long-term photobleaching have examined the effect of specific parameters (i.e., porphyrin content) on decreases in sensor brightness and oxygen-sensitivity. While the ultraviolet and visible excitation wavelengths exhibit poor tissue penetration, near-infrared (NIR) light much more easily penetrates tissue due to decreased scattering and absorbance by tissue chromophores. The ability to achieve NIR-activated oxygen sensing in electrospun bilayer and core-shell nanofibers has been demonstrated by using upconverting particles to locally stimulate oxygen-sensitive molecules. Finally, concerns associated with delivery have been addressed by utilizing the same sensing components in the form of polymeric core-shell particles.
A Novel Mechanism of Human Plastin Regulation
(2018-03) Schwebach, Christopher; Kudryashov, Dmitri
The actin cytoskeleton is a vast network intricately regulated by numerous actin-binding proteins. Plastins are one family of these actin-binding proteins that non-covalently crosslink actin into bundles and contribute to a variety of cellular processes including cell migration and invasion. Plastin2 (PLS2) is expressed in hematopoietic cells and contributes to the activation, migration, and invasion of these cells and is also ectopically expressed in ~70% of epithelial cancers contributing to their metastatic capabilities. Actin bundling is achieved upon binding of two actin-binding domains (ABD1 and ABD2) to actin filaments. Our recently published data show that the ABDs are not functionally equal. ABD1 is the primary, low affinity domain whereas ABD2 is the secondary regulated domain. We have used a variety of biochemical, fluorescent, and microscopic techniques to determine the nature of the ABD1 – ABD2 interaction. We found that ABD2 binds actin with a low nanomolar affinity and can nucleate new filaments, properties not observed with full-length PLS2. Intriguingly, we observed that ABD1 is able to inhibit actin nucleation by ABD2 when introduced in trans and that the domains bind each other with a high affinity. In addition, we characterized ABD1 mutations that disrupt the ABD1/2 interaction and found that ABD1 binding actin releases the inhibition of ABD2. These data support a novel mode of plastin regulation where ABD1 allosterically inhibits ABD2. Upon ABD1-actin binding and upon phosphorylation, ABD2 inhibition is released allowing bundling.
Assessment of extended-stage small cell lung cancer tumor heterogeneity from rapid research autopsy
(2018-03) Bonneville, Russell, III; Roychowdhury, Sameek
Extended-stage small cell lung cancer (ES-SCLC) is a highly lethal neuroendocrine cancer arising from the bronchial epithelium, with 2-year survival rates less than 10%. SCLC initially exhibits high sensitivity to standard-of-care chemotherapy. However, relapse occurs almost universally, characterized by high resistance to second-line chemotherapy and a median survival of 5 months. Tumor heterogeneity is thought to contribute to the evolution of treatment-resistant clones and delayed relapse in SCLC, but this has been difficult to characterize due to lack of available tumor tissues. Consequently, very little is known of the evolution of SCLC through metastasis and chemotherapy. Through rapid research autopsy, whole exome sequencing, and bioinformatics analysis, we describe the tumor heterogeneity present within two patients with metastatic, relapsed SCLC. We demonstrate that analysis of tumor heterogeneity permits reconstruction of paths of tumor metastasis, along with the determination of site-specific influences on clonal dynamics. Our results suggest a model of relapsed ES-SCLC heterogeneity in which genetic diversity develops in the lung early in relapse, followed by co-metastasis of multiple clones and Darwinian selection of specific subclones at metastatic sites. Mutational signature analysis reflected DNA damage from both tobacco smoking and platinum-based chemotherapy, suggesting a potential role of chemotherapy given for initial SCLC onset in promotion of genetic diversity in relapsed SCLC.
The Silent Voices of Gifted, Black Males
(2018-03) Smith, Kirsten; Moore, James L., III
This qualitative study used social capital theory, label theory, and institutional theory as the interpretive lens to examine the achievement attitudes, gifted identification, racial identity development, beliefs, and behaviors of gifted, Black male high school students in select high schools at a large, urban school district in the Midwest. The primary objectives of the study were to: (a) understand the school experiences of gifted, Black male students in today's urban public schools; (b) expand the theoretical and scientific knowledge on the social, cultural, and racial implications on the achievement of gifted, Black male high school students; (c) pinpoint the factors that most positively and negatively shape the academic success of gifted, Black students who attend urban schools; and (d) contribute to current research to advance teachers, administrators, and school counselors understanding of gifted, Black students who attend urban schools. The sample comprised sixteen gifted, Black male students, from grades 10th to 12th. Five themes emerged from the larger study with academic achievement being the focus of this paper. Recommendations for school personnel, parents, and students are discussed.
Removal of Algal Toxins by Potassium Permanganate: Incorporating Competition from Natural Water Constituents
(2018-03) Laszakovits, Juliana; MacKay, Allison
In recent years, the increased occurrence and severity of harmful algal blooms has threatened public health. These blooms are capable of producing a number of toxins including microcystins, cylindrospermopsin, and saxitoxin. These toxins can enter drinking water treatment plants and if not effectively removed, they pose a serious threat to human health. The work here investigated the efficacy of permanganate as a treatment strategy. We report rate constants of 272 ± 23 M-1 s-1 for the reaction between permanganate and microcystin-LR, 0.26 ± 0.05 M-1 s-1 for the reaction between permanganate and cylindrospermopsin, and estimate a maximum rate constant of 2.7 ± 0.2 M-1 s¬-1 for the reaction between permanganate and saxitoxin based on chemical analogs. We conclude that permanganate only shows potential to remove microcystins. No pH or alkalinity dependence on the rate of reaction between microcystin-LR and permanganate was observed; a temperature dependence, however, was observed and can be characterized by an activation energy of 16 ± 5 kJ mol-1. The competition posed by cyanobacterial cells was quantified by an apparent second order rate constant of 2.5 ± 0.3 x 10-6 L μg-chl-a-1 s-1. From this apparent second order rate constant, it was concluded that cyanobacterial cells are not efficient scavengers of permanganate. The competition posed by dissolved organic matter (DOM) was quantified by an apparent second order rate constant of 8.8 ± 3.1 x 10-5 L mg-C-1 s-1. Neither DOM source type nor electron donating capacity was observed to impact the rate of reaction between DOM and permanganate. DOM was concluded to efficiently scavenge permanganate and we forward that this should be considered in permanganate dosing calculations.
Drinking Water Exposure to Cyanotoxins in a Two-Staged Model of Liver Cancer Promotion
(2018-03) Mrdjen, Igor; Lee, Jiyoung
Microcystins (MCs) are hepatotoxins produced by over 40 cyanobacterial species found in harmful algal blooms (HABs) reported in fresh waterbodies worldwide. MC-LR, the most common and potent congener of MC can readily be found in eutrophic freshwater, including western Lake Erie. Exposure to MCs and other cyanobacterial hepatotoxins have previously been linked to promotion of liver carcinogenesis and increased liver cancer incidence in pre-clinical and epidemiologic studies. In this pilot study, we hypothesized that chronic ingestion of purified MC-LR (via drinking water) or a complex bioactive mixture, extracted from Microcystis aeruginosa (Lysate), would promote liver cancer development in mice. Three groups of C3H/HeJ mice received one intraperitoneal (i.p.) injection of diethylnitrosamine (DEN, cancer initiator) at 3 weeks of age. Three weeks later we administered ad libitum drinking water exposure to either 1) pure water, 2) water with MC-LR (10 µg/L), 3) water with Lysate (10 µg/L total MC). Exposure concentrations were based on potentially environmentally relevant levels, such as previously established US EPA recreational water MC guidelines. Over the course of the study, mouse weights, amount of food and water consumption were not impacted by toxin ingestion. Upon analysis, we found no significant differences in the number of gross and histopathologic liver lesion counts across treatment groups. However, the proportion of lesions classified as hepatocellular carcinomas in the MC-LR group (44%; p= 0.02) and Lysate (56%; p=0.0073) were significantly higher compared to the pure water group (13%). Mice ingested with Lysate also had a significantly increased mortality (35.6%; p=0.0009), compared to the other groups, over the course of the study. This study uses a exposure model analogous to real-world exposure and avoids stress associated with traditional intraperitoneal and gavage methods. Here, we note the cancer promoting effects of combinatorial exposures to multiple MCs and bioactive compounds of cyanobacterial cells, and mortality associated with chronic relatively low-dose exposure to MCs.
Resolving the mechanism of adhesion mediated by Protocadherin-1, a non-clustered delta-1 protocadherin
(2018-03) Modak, Debadrita; Sotomayor, Marcos
Cadherins form a large family of calcium-dependent cell adhesion proteins involved in cell differentiation, tissue morphogenesis and neuronal connectivity. Non-clustered δ1-protocadherins form a cadherin subgroup with seven extracellular cadherin (EC) repeats and cytoplasmic domains distinct from classical cadherins. The non-clustered δ1 proteins mediate homophilic adhesion and have been implicated in various diseases including asthma, autism, Alzheimer's and cancer. However, how δ1-protocadherins use their extracellular domain to mediate adhesion is unknown. Here we present the first X-ray crystal structure of a δ1-protocadherin member (Protocadherin-1) involved in asthma. Protocadherin-1 (PCDH1) is a δ1-protocadherin expressed mainly in the airway epithelium, skin keratinocytes, and lungs. The structure revealed binding modes that involve antiparallel overlap of multiple EC repeats. Mutagenesis, binding assays and other biochemical experiments tested the modes of adhesion as predicted from the structure. Overall, our studies reveal the molecular mechanism of adhesion mediated by PCDH1EC1-4 and shed light on its role in maintaining epithelial integrity, the loss of which causes asthma. Further, this mode of adhesion is relevant for other δ1-protocadherins too as they are highly similar in sequence.
Lame Duck CEOs' Horizons: Evidence from CEO Retirement and Loan Maturity
(2018-03) Ge, Shan; Weisbach, Michael; Erel, Isil; Ben-David, Itzhak
CEOs who know they will leave office in the near future are likely to have shorter horizons than other CEOs, and thus are likely to focus on short-term payoffs or decrease their effort. To detect shorter horizons, I focus on the maturities of firms' new loans, since this decision has an observable time dimension. I find that as CEOs approach retirement, maturities of new loans shorten, but are just long enough for more loans to mature soon after CEOs retire. The shorter maturities lead to lower loan spreads. Departing CEOs appear to care less about firms' refinancing risk after their departure, but more about interest savings before their departure. I also find that firms near CEOs' retirement decrease acquisitions. Such firms also hold more cash, presumably due to fewer activities requiring liquidity and CEOs' effort before retirement. Results on loan maturities, acquisitions and cash all hold, when instrumenting for CEOs' departure using departure probabilities based on industry and CEOs' age.
Undocumented Latinx Comics: Resisting the Biopolitical Nation
(2018-03) Alex, Stacey; Martinez-Cruz, Paloma
Because undocumented subjects are widely excluded or essentialized, this article asks how and why the comics form has become an effective vehicle for narratives that portray undocumented Latinx people as agents of resistance and change. I narrow my scope to Latinx creators whose representation of undocumented people is informed by having at one time been undocumented or by having undocumented family. While these kinds of works are not necessarily better equipped to foreground agency, their connection to undocumented people may provide a greater potential to remain anchored in their experiences and perspectives. Objects of study include the zine, Rosita se asusta/Rosita Gets Scared by Vicko Alvarez and El viaje más caro/The Most Costly Journey.
Biomechanical impact of the sclera on corneal deformation response to an air-puff: a finite-element study
(2018-03) Nguyen, Boihoan Audrey; Roberts, Cynthia J.
Purpose: Glaucoma is the leading cause of irreversible blindness worldwide and results from the death of retinal ganglion cells [1-8]. Altered mechanical properties of the sclera – the white part of the eye – have been implicated in the pathogenesis of glaucoma [1-5, 7]. To our knowledge, a method for the clinical evaluation of scleral properties has yet to be devised. We have sought to address this deficiency using a commercially-available non-contact tonometer and an inverse finite-element analysis. Methods: Human donor eyes were obtained from a local eye bank and mounted in a rigid fixture. One eye from each pair had the sclera undergo a stiffening treatment, with the contralateral eye serving as a control. A CorVis ST non-contact tonometer was used to load the eye at several levels of intraocular pressure (IOP) and quantify the resulting deformation behavior. The CorVis ST utilizes a high-speed camera and image analysis software to output dynamic deformation response parameters of the cornea – the clear part of the eye – during air-puff loading. An axisymmetric model of the whole eye was created using the average dimensions for the adult human eye. The ocular tissues were modeled as hyperelastic and nearly incompressible, with material properties based on literature values [10-12]. The eye is naturally under tension while loaded by intraocular pressure [8, 9]. Therefore, the unloaded state of the eye was first estimated and assumed to represent a stress-free state. The IOP was then applied to induced the residually stressed state. Finally, the eye was loaded by simulating the air-puff generated by the CorVis ST non-contact tonometer. The intraocular pressure and scleral material properties were varied between simulations to determine their influence on the cornea's deformation response during air-puff loading. The maximum rearward displacement of the corneal apex was recorded for each IOP-mechanical property pairing for comparison with experimental findings. Results and Discussion: For each value of IOP tested, it was shown that increasing the ratio of scleral to corneal stiffness resulted in decreasing maximum apical displacement of the cornea. The model demonstrated that the stiffer the sclera was, the higher the apparent stiffness of the whole eye – normally interpreted as reflecting only the stiffness of the cornea. Additionally, the model showed that increasing the IOP while keeping all other factors constant resulted in decreasing maximum apical displacement, which is consistent with literature reports. The trends shown in the finite-element analysis were also observed in the experimental results from human donor eyes. Implications: The finite element model presented in this study demonstrates that scleral material properties have an important impact on the biomechanical deformation response of the cornea in air-puff induced deformation. Namely, the stiffer the sclera, the greater will be the limitation on corneal deformation. This may have important clinical implications. Often in the clinic, the observed biomechanical deformation response of the cornea is attributed solely to the material properties of the cornea. However, it is clear in the finite-element analysis that the maximum apical displacement of the same cornea varies significantly with varying scleral properties. This suggests that that the observed biomechanical response to an air puff may be used to deduce the IOP as well as the mechanical properties of the cornea and sclera. Obtaining these additional parameters from a current clinical diagnostic modality will lead to improved diagnostic capabilities for glaucoma.
The impact of outdoor advertising on adolescent tobacco use: Exposures at home and school
(2018-03) Keller-Hamilton, Brittney; Ferketich, Amy
Purpose: Prevalence of tobacco use among adolescents has remained stagnant since 2011.1 Major predictors of adolescent tobacco initiation are density of tobacco retailers near adolescents’ homes and schools. Further, adolescents who visit tobacco retailers most often, and are therefore exposed to tobacco product advertisements within the stores, are more likely to initiate tobacco use. An important gap in the literature is that we do not know whether the amount of tobacco product advertising on store exteriors affects adolescent tobacco use. We hypothesize that greater levels of exterior advertising at tobacco retailers around adolescents’ homes and schools will be associated with higher odds of tobacco use. Research methods: A cohort of adolescent males ages 11-16 (N=1220) from urban and Appalachian Ohio were recruited in 2015 and 2016 and followed for one year. Ever use of any tobacco product was assessed at baseline and follow-up via self-report. Participants’ home and school addresses were also geocoded and spatially joined to census tracts. For the counties where the participants resided, fieldworkers conducted audits on a random sample of tobacco retailers (N=212) during the summer of 2016. These fieldworkers collected comprehensive information about retailers’ tobacco marketing, including the count and size of exterior tobacco advertisements. Exterior advertising scores based on count and size of exterior advertisements were calculated for each audited store. Median advertising scores were calculated by store type and then applied to all retailers of the same type in participants’ home and school census tracts. These median scores were summed to compute a total exterior advertising score per census tract. Odds of cigarette, electronic cigarette, or smokeless tobacco initiation at follow-up by density of tobacco retailers (i.e., sum of retailers per census tract) and amount of exterior advertising (i.e., sum of exterior advertising scores per census tract) in home and school census tracts were estimated using survey-weighted logistic regression. Due to linearity violations, density of retailers and exterior advertising score per census tract were modeled using weighted tertiles (low, medium, and high exposure levels). Adjusted, complete case analyses controlled for race, age, parental tobacco use, urban/Appalachian status, parental education, and census tract-level poverty. Due to small cluster sizes and low intraclass correlation coefficients, multi-level models were not used.5 Findings: Crude analyses revealed that odds of cigarette initiation were higher among participants living in census tracts with the highest retailer density compared to participants living in census tracts with the lowest retailer density (OR = 2.39; 95% confidence interval [CI]: 1.14, 5.02). Similarly, participants living in census tracts with high exterior advertising scores had greater odds of cigarette initiation than participants living in census tracts with low exterior advertising scores (OR = 2.71; 95% CI: 1.31, 5.59). In the adjusted analyses, participants living in census tracts with high exterior advertising scores still had greater odds of cigarette initiation compared to participants living in census tracts with low exterior advertising scores (OR=2.27; 95% CI: 1.11, 4.62). Neither retailer density nor exterior advertising score in school census tracts were associated with incident use of tobacco products. Implications: This study is the first to demonstrate that quantity of exterior advertising in home census tracts is associated with greater odds of cigarette initiation among adolescents, even after controlling for several potential confounders of the association. Community- and individual-level tobacco control interventions should consider this as an important risk factor for adolescent tobacco use. Finally, policies to reduce the burden of exterior advertising at the census-tract level are worthy of exploration.
Nodes of Ranvier are Incompletely Repaired and Continually Disrupted after Traumatic Spinal Cord Injury
(2018-03) Yoseph, Rim; McTigue, Dana
Approximately 17,500 new cases of spinal cord injuries (SCI) are reported in the US each year, yet less than 1% of patients experience complete neurological recovery. This is due to the limited ability of injured spinal cord axons to regenerate and reform functional circuits. Novel treatments have emerged that increase sprouting of spared axons through the lesion after SCI; however, many of these axons remain unmyelinated or experience suboptimal remyelination. Thus, strategies that enhance the endogenous ability of the injured cord to remyelinate spared axons are critical to achieving clinically relevant functional recovery after SCI. Oligodendrocytes (OLs), the myelinating cells of the central nervous system (CNS), ensheath axons to ensure timely signal conduction. After myelinating OLs die or retract their processes following injury, oligodendrocyte progenitor cells (OPCs) proliferate and migrate to the lesion where they differentiate into mature OLs. Spontaneous regeneration of OLs persists for months after SCI, suggesting that endogenous OLs continuously attempt to remyelinate spared axons. However, remyelination of spared axons is often incomplete or limited in function. Rapid, saltatory conduction of signals along myelinated axons requires the establishment of discreet domains of structural proteins and ion channels within and around the Node of Ranvier. In healthy, myelinated CNS axons, nodes of Ranvier are highly organized and include the paranodal protein, Caspr, flanked by juxtaparanodal K+ channels (Kv1.2). Nav 1.6 voltage-gated Na+ channels are also clustered in the Node of Ranvier to support regeneration of signals. However, OL death disrupts the organization of these proteins, resulting in compromised signal propagation, aberrant excitability patterns, and neuronal dysfunction. Evidence from a mouse model of multiple sclerosis suggests that in demyelinated lesions, there is a Na+ channel subtype switch from the Nav1.6 isoform to Nav1.2, an embryonic isoform that is expressed on pre-myelinated axons. This suggests that Na+ channel subtype switching occurs after demyelination and may underlie impaired remyelination. Currently, structural abnormalities in the node induced by SCI have not been characterized. Understanding nodal pathology after SCI is essential because suboptimal remyelination of spared axons leaves them vulnerable to degeneration. Such degeneration can enhance pathology and impair functional recovery after SCI. The goal of this work was to characterize structural abnormalities in/around the Node or Ranvier as an index of functional or suboptimal remyelination. Collectively, we tested the theory that functional remyelination after SCI requires specific arrangement of proteins within and around the Node of Ranvier. Accordingly, the following hypotheses were tested: SCI induces diffuse Kv1.2 and Caspr spreading outside of nodes on spared axons: Adult C57BL/6 mice received a partial T9 vertebral laminectomy, followed by a moderate spinal cord contusion (75 kDyn force, Infinite Horizons device). Mice were transcardially perfused with 4% paraformaldehyde at 7 dpi, 18 dpi, 28 dpi, 10 weeks post injury (wpi), and 6 month post injury (mpi). Spinal cords were collected and stained using immunofluorescence for the presence and distribution of voltage gated potassium channel (Kv1.2) and Caspr. Labeling in the proper order (i.e. Kv1.2 in the juxtaparanode and Caspr in the paranode) indicated nodes and was used to generate an index of functional re-myelination in the injured tissues. Diffuse labeling along spared axons indicated demyelination or suboptimal remyelination. Intact nodes were counted, and profile lengths of Caspr and Kv1.2 were normalized to naïves to evaluate aberrant spreading. Data shows that relative to 7dpi, there are increasingly fewer intact nodes at chronic time points, particularly 6 mpi. At 6 mpi, there is also extensive Caspr dysregulation as far distal as 2 mm from the lesion epicenter. This dysregulation is absent 7 dpi, suggesting, for the first time in SCI research, that spared tissue becomes increasingly inhibitory to myelin repair. SCI causes sodium channel subtype switching in demyelinated/remyelinated axons: Mice received the same injury (75 kDyn force, Infinite Horizons device) and tissues were collected as stated above. Spinal cords were immunolabeled for Nav1.2+Caspr and Nav1.6+Caspr. Sections were analyzed for expression of each sodium channel subtype and its association with paranodal Caspr. Positive Nav1.6 labeling in the Node of Ranvier flanked by positive paranodal Caspr labeling indicated an intact node. PCR and Western blots were also used to determine if expression of each Na+ channel is transcriptionally or translationally regulated. Data confirm that myelinated axons in naïve animals have high Nav1.6 expression and low embryonic Nav1.2 expression. Data also show, for the first time, that Na+ channel switching occurs after SCI and may underlie suboptimal endogenous remyelination. Implications: Dysregulation of structural proteins in the nodal area can contribute to neural dysfunction after SCI. My data provides novel evidence that spared tissue is inhibitory to remeylination. The data suggests that nodal proteins whose dysregulation persist chronically after injury may potentially serve as novel therapeutic targets that can restore functional remyelination and facilitate meaningful clinical recovery for patients. We expect that findings from these studies can be applied to other pathologies whose sequelae are driven by aberrant nodal structure such as stroke, MS, and epilepsy – all of which affect large patient populations.
A Systematic Investigation of Microcystin Accumulation in Vegetables under Agricultural Environments: Potential Effects on Crop Performance and Public Health Risk
(Elsevier, 2018-03) Lee, Seungjun; Lee, Jiyoung
Microcystins (MCs), which are common cyanotoxins in fresh water, are produced in cyanobacterial blooms in eutrophic waters. MCs cause major water quality issues worldwide, and they have been widely studied due to their toxic health effects on humans and animals. Among the toxin exposure routes, exposure through food, especially fresh produce, has been understudied. MCs are stable, so in contaminated irrigation water and soil they can lead to toxin accumulation in crops. The objectives of this study were to investigate the fate of MC in different types of crops (lettuce, carrot, green bean) when irrigated with different levels of MC-LR. The crops were cultivated and exposed to different concentrations of MC-LR (1 μg/L, 5 μg/L, and 10 μg/L), either via drip irrigation around the root areas or spray irrigation, three times a week for four weeks. Samples were collected and homogenized with dry ice, and then the MC-LR was extracted using a methanol and filter method. The toxin level was measured with the MCs-ADDA ELISA assay. Our results demonstrated that the levels of accumulated MC-LR in crops were affected by irrigation type and were dose-dependent. Different type of crops had the different ability to adsorb the MC. Also, MC-LR had a negative impact on growth development of crops. Our results indicate that the remaining MC-LR has stay in the soil after harvest and the toxin may have negative impact on crop growth continuously. Thus, we suggest programs to monitor for the presence of MCs in irrigation water and crops, to protect public health.
Porphyrin-based porous polymers for CO2 capture and conversion
(2018-03) Eder, Grace; McGrier, Psaras
Porous organic polymers (POPs) are a diverse group of two-dimensional (2D) polymeric materials that can be used in many applications including gas storage, catalysis, and optoelectronic devices. The gas storage ability of POPs is of particular interest to the scientific community as researchers investigate ways to sequester atmospheric carbon dioxide (CO2) in order to combat global warming. POPs specially designed for CO2 uptake have been optimized to hold up to 27% CO2 by weight. While storage of CO2 is vital, it cannot be stored indefinitely. Ultimately, CO2 must be converted into other compounds that are useful chemical feedstocks. There are a number of methods for converting CO2 into value-added chemicals, however most require expensive single-use catalysts or other harsh conditions to achieve. Discovery of cheaper, milder, and re-usable methods of CO2 conversion will jump-start the widespread use of this abundant carbon source. Metalloporphyrins are an attractive group of catalysts for a variety of different reactions, which are well studied in porous materials. The purpose of this project is to combine the catalytic ability of metalloporphyrins with the gas uptake capability of POPs to convert CO2 to value-added chemicals with a recyclable catalyst. We have successfully synthesized and characterized the control polymer with non-metallated porphryins. The control polymers show moderately high surface areas up to 700 m2/g based on their N2 uptake. Their CO2 uptake is 4.8% by weight, which is comparable to other porphyrin-based porous polymers. Initial results indicate the porphyrin is able to reduce CO2 by a hydrosilation reaction.

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