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Aquatic vertebrates that emerge onto land to spawn, feed, or evade aquatic predators must return to the water to avoid dehydration or asphyxiation. How do such aquatic organisms determine their location on land? Do particular behaviors facilitate a safe return to the aquatic realm? In this study, we asked: will

Aquatic vertebrates that emerge onto land to spawn, feed, or evade aquatic predators must return to the water to avoid dehydration or asphyxiation. How do such aquatic organisms determine their location on land? Do particular behaviors facilitate a safe return to the aquatic realm? In this study, we asked: will fully-aquatic mosquitofish (Gambusia affinis) stranded on a slope modulate locomotor behavior according to body position to facilitate movement back into the water? To address this question, mosquitofish (n = 53) were placed in four positions relative to an artificial slope (30° inclination) and their responses to stranding were recorded, categorized, and quantified.

We found that mosquitofish may remain immobile for up to three minutes after being stranded and then initiate either a “roll” or a “leap”. During a roll, mass is destabilized to trigger a downslope tumble; during a leap, the fish jumps up, above the substrate. When mosquitofish are oriented with the long axis of the body at 90° to the slope, they almost always (97%) initiate a roll. A roll is an energetically inexpensive way to move back into the water from a cross-slope body orientation because potential energy is converted back into kinetic energy. When placed with their heads toward the apex of the slope, most mosquitofish (>50%) produce a tail-flip jump to leap into ballistic flight. Because a tail-flip generates a caudually-oriented flight trajectory, this locomotor movement will effectively propel a fish downhill when the head is oriented up-slope. However, because the mass of the body is elevated against gravity, leaps require more mechanical work than rolls. We suggest that mosquitofish use the otolith-vestibular system to sense body position and generate a behavior that is “matched” to their orientation on a slope, thereby increasing the probability of a safe return to the water, relative to the energy expended.

ContributorsBoumis, Robert J. (Author) / Ferry, Lara (Author) / Pace, Cinnamon M. (Author) / Gibb, Alice C. (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2014-08-27
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Background: Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD) - a high-fat, low-carbohydrate treatment for medically refractory epilepsy

Background: Malignant brain tumors affect people of all ages and are the second leading cause of cancer deaths in children. While current treatments are effective and improve survival, there remains a substantial need for more efficacious therapeutic modalities. The ketogenic diet (KD) - a high-fat, low-carbohydrate treatment for medically refractory epilepsy - has been suggested as an alternative strategy to inhibit tumor growth by altering intrinsic metabolism, especially by inducing glycopenia.

Methods: Here, we examined the effects of an experimental KD on a mouse model of glioma, and compared patterns of gene expression in tumors vs. normal brain from animals fed either a KD or a standard diet.

Results: Animals received intracranial injections of bioluminescent GL261-luc cells and tumor growth was followed in vivo. KD treatment significantly reduced the rate of tumor growth and prolonged survival. Further, the KD reduced reactive oxygen species (ROS) production in tumor cells. Gene expression profiling demonstrated that the KD induces an overall reversion to expression patterns seen in non-tumor specimens. Notably, genes involved in modulating ROS levels and oxidative stress were altered, including those encoding cyclooxygenase 2, glutathione peroxidases 3 and 7, and periredoxin 4.

Conclusions: Our data demonstrate that the KD improves survivability in our mouse model of glioma, and suggests that the mechanisms accounting for this protective effect likely involve complex alterations in cellular metabolism beyond simply a reduction in glucose.

ContributorsStafford, Phillip (Author) / Abdelwahab, Mohammed G. (Author) / Kim, Do Young (Author) / Preul, Mark C. (Author) / Rho, Jong M. (Author) / Scheck, Adrienne C. (Author) / Biodesign Institute (Contributor)
Created2010-09-10
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Description

Vitamin D receptor (VDR) is a substrate for modification with small ubiquitin-like modifier (SUMO). To further assess the role of reversible SUMOylation within the vitamin D hormonal response, we evaluated the effects of sentrin/SUMO-specific proteases (SENPs) that can function to remove small ubiquitin-like modifier (SUMO) from target proteins upon the

Vitamin D receptor (VDR) is a substrate for modification with small ubiquitin-like modifier (SUMO). To further assess the role of reversible SUMOylation within the vitamin D hormonal response, we evaluated the effects of sentrin/SUMO-specific proteases (SENPs) that can function to remove small ubiquitin-like modifier (SUMO) from target proteins upon the activities of VDR and related receptors. We report that SENP1 and SENP2 strikingly potentiate ligand-mediated transactivation of VDR and also its heterodimeric partner, retinoid X receptor (RXRα) with depletion of cellular SENP1 significantly diminishing the hormonal responsiveness of the endogenous vitamin D target gene CYP24A1. We find that SENP-directed modulation of VDR activity is cell line-dependent, achieving potent modulatory effects in Caco-2 and HEK-293 cells, while in MCF-7 cells the vitamin D signal is unaffected by any tested SENP. In support of their function as novel modulators of the vitamin D hormonal pathway we demonstrate that both SENP1 and SENP2 can interact with VDR and reverse its modification with SUMO2. In a preliminary analysis we identify lysine 91, a residue known to be critical for formation and DNA binding of the VDR-RXR heterodimer, as a minor SUMO acceptor site within VDR. In combination, our results support a repressor function for SUMOylation of VDR and reveal SENPs as a novel class of VDR/RXR co-regulatory protein that significantly modulate the vitamin D response and which could also have important impact upon the functionality of both RXR-containing homo and heterodimers.

ContributorsLee, Wai-Ping (Author) / Jena, Sarita (Author) / Doherty, Declan (Author) / Ventakesh, Jaganathan (Author) / Schimdt, Joachim (Author) / Furmick, Julie (Author) / Widener, Tim (Author) / Lemau, Jana (Author) / Jurutka, Peter (Author) / Thompson, Paul D. (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2014-02-20
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Description

Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione), a high-value ketocarotenoid with a broad range of applications in food, feed, nutraceutical, and pharmaceutical industries, has been gaining great attention from science and the public in recent years. The green microalgae Haematococcus pluvialis and Chlorella zofingiensis represent the most promising producers of natural astaxanthin. Although H. pluvialis

Astaxanthin (3,3′-dihydroxy-β,β-carotene-4,4′-dione), a high-value ketocarotenoid with a broad range of applications in food, feed, nutraceutical, and pharmaceutical industries, has been gaining great attention from science and the public in recent years. The green microalgae Haematococcus pluvialis and Chlorella zofingiensis represent the most promising producers of natural astaxanthin. Although H. pluvialis possesses the highest intracellular astaxanthin content and is now believed to be a good producer of astaxanthin, it has intrinsic shortcomings such as slow growth rate, low biomass yield, and a high light requirement. In contrast, C. zofingiensis grows fast phototrophically, heterotrophically and mixtrophically, is easy to be cultured and scaled up both indoors and outdoors, and can achieve ultrahigh cell densities. These robust biotechnological traits provide C. zofingiensis with high potential to be a better organism than H. pluvialis for mass astaxanthin production. This review aims to provide an overview of the biology and industrial potential of C. zofingiensis as an alternative astaxanthin producer. The path forward for further expansion of the astaxanthin production from C. zofingiensis with respect to both challenges and opportunities is also discussed.

ContributorsLiu, Jin (Author) / Sun, Zheng (Author) / Gerken, Henri (Author) / Liu, Zheng (Author) / Jiang, Yue (Author) / Chen, Feng (Author) / New College of Interdisciplinary Arts and Sciences (Contributor)
Created2014-06-10
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Description

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight.

ContributorsBarrila, Jennifer (Author) / Ott, C. Mark (Author) / LeBlanc, Carly (Author) / Mehta, Satish K. (Author) / Crabbe, Aurelie (Author) / Stafford, Phillip (Author) / Pierson, Duane L. (Author) / Nickerson, Cheryl (Author) / ASU Biodesign Center Immunotherapy, Vaccines and Virotherapy (Contributor) / Biodesign Institute (Contributor)
Created2016-12-08
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Description

There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide microarrays can do this through antibody signatures (immunosignatures). Unfortunately, printed

There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide microarrays can do this through antibody signatures (immunosignatures). Unfortunately, printed microarrays are not scalable. Here we demonstrate a platform based on fabricating microarrays (~10 M peptides per slide, 330,000 peptides per assay) on silicon wafers using equipment common to semiconductor manufacturing. The potential of these microarrays for comprehensive health monitoring is verified through the simultaneous detection and classification of six different infectious diseases and six different cancers. Besides diagnostics, these high-density peptide chips have numerous other applications both in health care and elsewhere.

ContributorsLegutki, Joseph Barten (Author) / Zhao, Zhan-Gong (Author) / Greving, Matt (Author) / Woodbury, Neal (Author) / Johnston, Stephen (Author) / Stafford, Phillip (Author) / Biodesign Institute (Contributor)
Created2014-09-03
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Description

This study investigates the presence of dynamical patterns of interpersonal coordination in extended deceptive conversations across multimodal channels of behavior. Using a novel "devil’s advocate" paradigm, we experimentally elicited deception and truth across topics in which conversational partners either agreed or disagreed, and where one partner was surreptitiously asked to

This study investigates the presence of dynamical patterns of interpersonal coordination in extended deceptive conversations across multimodal channels of behavior. Using a novel "devil’s advocate" paradigm, we experimentally elicited deception and truth across topics in which conversational partners either agreed or disagreed, and where one partner was surreptitiously asked to argue an opinion opposite of what he or she really believed. We focus on interpersonal coordination as an emergent behavioral signal that captures interdependencies between conversational partners, both as the coupling of head movements over the span of milliseconds, measured via a windowed lagged cross correlation (WLCC) technique, and more global temporal dependencies across speech rate, using cross recurrence quantification analysis (CRQA). Moreover, we considered how interpersonal coordination might be shaped by strategic, adaptive conversational goals associated with deception. We found that deceptive conversations displayed more structured speech rate and higher head movement coordination, the latter with a peak in deceptive disagreement conversations. Together the results allow us to posit an adaptive account, whereby interpersonal coordination is not beholden to any single functional explanation, but can strategically adapt to diverse conversational demands.

Created2017-06-02
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Lack of biodiversity data is a major impediment to prioritizing sites for species representation. Because comprehensive species data are not available in any planning area, planners often use surrogates (such as vegetation communities, or mapped occurrences of a well-inventoried taxon) to prioritize sites. We propose and demonstrate the effectiveness of

Lack of biodiversity data is a major impediment to prioritizing sites for species representation. Because comprehensive species data are not available in any planning area, planners often use surrogates (such as vegetation communities, or mapped occurrences of a well-inventoried taxon) to prioritize sites. We propose and demonstrate the effectiveness of predicted rarity-weighted richness (PRWR) as a surrogate in situations where species inventories may be available for a portion of the planning area. Use of PRWR as a surrogate involves several steps. First, rarity-weighted richness (RWR) is calculated from species inventories for a q% subset of sites. Then random forest models are used to model RWR as a function of freely available environmental variables for that q% subset. This function is then used to calculate PRWR for all sites (including those for which no species inventories are available), and PRWR is used to prioritize all sites. We tested PRWR on plant and bird datasets, using the species accumulation index to measure efficiency of PRWR. Sites with the highest PRWR represented species with median efficiency of 56% (range 32%–77% across six datasets) when q = 20%, and with median efficiency of 39% (range 20%–63%) when q = 10%. An efficiency of 56% means that selecting sites in order of PRWR rank was 56% as effective as having full knowledge of species distributions in PRWR's ability to improve on the number of species represented in the same number of randomly selected sites. Our results suggest that PRWR may be able to help prioritize sites to represent species if a planner has species inventories for 10%–20% of the sites in the planning area.

Created2016-10-27
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Description

One of the gravest dangers facing cancer patients is an extended symptom-free lull between tumor initiation and the first diagnosis. Detection of tumors is critical for effective intervention. Using the body’s immune system to detect and amplify tumor-specific signals may enable detection of cancer using an inexpensive immunoassay. Immunosignatures are

One of the gravest dangers facing cancer patients is an extended symptom-free lull between tumor initiation and the first diagnosis. Detection of tumors is critical for effective intervention. Using the body’s immune system to detect and amplify tumor-specific signals may enable detection of cancer using an inexpensive immunoassay. Immunosignatures are one such assay: they provide a map of antibody interactions with random-sequence peptides. They enable detection of disease-specific patterns using classic train/test methods. However, to date, very little effort has gone into extracting information from the sequence of peptides that interact with disease-specific antibodies. Because it is difficult to represent all possible antigen peptides in a microarray format, we chose to synthesize only 330,000 peptides on a single immunosignature microarray. The 330,000 random-sequence peptides on the microarray represent 83% of all tetramers and 27% of all pentamers, creating an unbiased but substantial gap in the coverage of total sequence space. We therefore chose to examine many relatively short motifs from these random-sequence peptides. Time-variant analysis of recurrent subsequences provided a means to dissect amino acid sequences from the peptides while simultaneously retaining the antibody–peptide binding intensities. We first used a simple experiment in which monoclonal antibodies with known linear epitopes were exposed to these random-sequence peptides, and their binding intensities were used to create our algorithm. We then demonstrated the performance of the proposed algorithm by examining immunosignatures from patients with Glioblastoma multiformae (GBM), an aggressive form of brain cancer. Eight different frameshift targets were identified from the random-sequence peptides using this technique. If immune-reactive antigens can be identified using a relatively simple immune assay, it might enable a diagnostic test with sufficient sensitivity to detect tumors in a clinically useful way.

Created2015-06-18
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Description

Through the mathematical study of two models we quantify some of the theories of co-development and co-existence of focused groups in the social sciences. This work attempts to develop the mathematical framework behind the social sciences of community formation. By using well developed theories and concepts from ecology and epidemiology

Through the mathematical study of two models we quantify some of the theories of co-development and co-existence of focused groups in the social sciences. This work attempts to develop the mathematical framework behind the social sciences of community formation. By using well developed theories and concepts from ecology and epidemiology we hope to extend the theoretical framework of organizing and self-organizing social groups and communities, including terrorist groups. The main goal of our work is to gain insight into the role of recruitment and retention in the formation and survival of social organizations. Understanding the underlining mechanisms of the spread of ideologies under competition is a fundamental component of this work. Here contacts between core and non-core individuals extend beyond its physical meaning to include indirect interaction and spread of ideas through phone conversations, emails, media sources and other similar mean.

This work focuses on the dynamics of formation of interest groups, either ideological, economical or ecological and thus we explore the questions such as, how do interest groups initiate and co-develop by interacting within a common environment and how do they sustain themselves? Our results show that building and maintaining the core group is essential for the existence and survival of an extreme ideology. Our research also indicates that in the absence of competitive ability (i.e., ability to take from the other core group or share prospective members) the social organization or group that is more committed to its group ideology and manages to strike the right balance between investment in recruitment and retention will prevail. Thus under no cross interaction between two social groups a single trade-off (of these efforts) can support only a single organization. The more efforts that an organization implements to recruit and retain its members the more effective it will be in transmitting the ideology to other vulnerable individuals and thus converting them to believers.

Created2013-09-11