Life Sciences Commons^™

Administration Of Panobinostat Is Associated With Increased Il-17a Mrna In The Intestinal Epithelium Of Hiv-1 Patients, Ane Bjerg Christensen, Anders Dige, Johan Vad-Nielsen, Christel R. Brinkmann, Mia Bendix, Lars Østergaard, Martin Tolstrup, Ole S. Søgaard, Thomas A. Rasmussen, Jens Randel Nyengaard, Jørgen Agnholt, Paul W. Denton

Biology Faculty Publications

Intestinal CD4+ T cell depletion is rapid and profound during early HIV-1 infection.This leads to a compromised mucosal barrier that prompts chronic systemic inflammation.The preferential loss of intestinal T helper 17 (Th17) cells in HIV-1 disease is a driver of the damage within the mucosal barrier and of disease progression.Thus, understanding the effects of new therapeutic strategies in the intestines has high priority. Histone deacetylase (HDAC) inhibitors (e.g., panobinostat) are actively under investigation as potential latency reversing agents in HIV eradication studies. These drugs have broad effects that go beyond reactivating virus, including modulation of immune pathways. We examined colonic …

Conserved Molecular Underpinnings And Characterization Of A Role For Caveolin-1 In The Tumor Microenvironment Of Mature T-Cell Lymphomas, Tyler A. Herek, Timothy D. Shew, Heather N. Spurgin, Christine E. Cutucache

Biology Faculty Publications

Neoplasms of extra-thymic T-cell origin represent a rare and difficult population characterized by poor clinical outcome, aggressive presentation, and poorly defined molecular characteristics. Much work has been done to gain greater insights into distinguishing features among malignant subtypes, but there also exists a need to identify unifying characteristics to assist in rapid diagnosis and subsequent potential treatment. Herein, we investigated gene expression data of five different mature T-cell lymphoma subtypes (n = 187) and found 21 genes to be up- and down-regulated across all malignancies in comparison to healthy CD4+ and CD8+ T-cell controls (n = 52). From these results, …

Clinically Available Medicines Demonstrating Anti-Toxoplasma Activity, Andrew J. Neville, Sydney J. Zach, Xiaofang Wang, Joshua L. Larson, Abigail K. Judge, Lisa A. Davis, Jonathan L. Vennerstrom, Paul H. Davis

Biology Faculty Publications

Toxoplasma gondii is an apicomplexan parasite of humans and other mammals, including livestock and companion animals. While chemotherapeutic regimens, including pyrimethamine and sulfadiazine regimens, ameliorate acute or recrudescent disease such as toxoplasmic encephalitis or ocular toxoplasmosis, these drugs are often toxic to the host. Moreover, no approved options are available to treat infected women who are pregnant. Lastly, no drug regimen has shown the ability to eradicate the chronic stage of infection, which is characterized by chemoresistant intracellular cysts that persist for the life of the host. In an effort to promote additional chemotherapeutic options, we now evaluate clinically available …

The Depsipeptide Romidepsin Reverses Hiv-1 Latency In Vivo, Ole S. Søgaard, Mette E. Graversen, Steffen Leth, Rikke Olesen, Christel R. Brinkmann, Sara K. Nissen, Anne Sofie Kjaer, Mariane H. Schleimann, Paul W. Denton, William J. Hey-Cunningham, Giuseppe Pantaleo, Kim Krogsgaard, Maja Sommerfelt, Remi Fromentin, Nicolas Chomont, Thomas A. Rasmussen, Lars Østergaard, Martin Tolstrup

Biology Faculty Publications

Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription …

Transcriptomic Variation Of Hepatopancreas Reveals The Energy Metabolism And Biological Processes Associated With Molting In Chinese Mitten Crab, Eriocheir Sinensis, Shu Huang, Jun Wang, Wucheng Yue, Jiao Chen, Sarah Gaughan, Weiqun Lu, Guoqing Lu, Chenghui Wang

Biology Faculty Publications

Molting is a critical developmental process for crustaceans, yet the underlying molecular mechanism is unknown. In this study, we used RNA-Seq to investigate transcriptomic profiles of the hepatopancreas and identified differentially expressed genes at four molting stages of Chinese mitten crab (Eriocheir sinensis). A total of 97,398 transcripts were assembled, with 31,900 transcripts annotated. Transcriptomic comparison revealed 1,189 genes differentially expressed amongst different molting stages. We observed a pattern associated with energy metabolism and physiological responses during a molting cycle. In specific, differentially expressed genes enriched in postmolt were linked to energy consumption whereas genes enriched in intermolt were related …

Can The Results Of Biodiversity-Ecosystem Productivity Studies Be Translated To Bioenergy Production?, Timothy L. Dickson, Katherine L. Gross

Biology Faculty Publications

Biodiversity experiments show that increases in plant diversity can lead to greater biomass production, and some researchers suggest that high diversity plantings should be used for bioenergy production. However, many methods used in past biodiversity experiments are impractical for bioenergy plantings. For example, biodiversity experiments often use intensive management such as hand weeding to maintain low diversity plantings and exclude unplanted species, but this would not be done for bioenergy plantings. Also, biodiversity experiments generally use high seeding densities that would be too expensive for bioenergy plantings. Here we report the effects of biodiversity on biomass production from two studies …

Biodiversity Assessment Among Two Nebraska Prairies: A Comparison Between Traditional And Phylogenetic Diversity Indices, Shelly K. Aust, Dakota L. Ahrendsen, P. Roxanne Kellar

Biology Faculty Publications

Conservation of the evolutionary diversity among organisms should be included in the selection of priority regions for preservation of Earth’s biodiversity. Traditionally, biodiversity has been determined from an assessment of species richness (S), abundance, evenness, rarity, etc. of organisms but not from variation in species’ evolutionary histories. Phylogenetic diversity (PD) measures evolutionary differences between taxa in a community and is gaining acceptance as a biodiversity assessment tool. However, with the increase in the number of ways to calculate PD, end-users and decision-makers are left wondering how metrics compare and what data are needed to calculate various metrics.

Neurotranscriptome Profiles Of Multiple Zebrafish Strains, Ryan Y. Wong, John Godwin

Biology Faculty Publications

Behavioral displays or physiological responses are often influenced by intrinsic and extrinsic mechanisms in the context of the organism's evolutionary history. Understanding differences in transcriptome profiles can give insight into adaptive or pathological responses.We utilize high throughput sequencing (RNA-sequencing) to characterize the neurotranscriptome profiles in both males and females across four strains of zebrafish (Danio rerio). Strains varied by previously documented differences in stress and anxiety-like behavioral responses, and generations removed from wild-caught individuals. Here we describe detailed methodologies and quality controls in generating the rawRNA-sequencing reads that are publically available in NCBI's Gene Expression Omnibus database (GSE61108).

Characterizing The Neurotranscriptomic States In Alternative Stress Coping Styles, Ryan Y. Wong, Melissa S. Lamm, John Godwin

Biology Faculty Publications

Background: Animals experience stress in many contexts and often successfully cope. Individuals exhibiting the proactive versus reactive stress coping styles display qualitatively different behavioral and neuroendocrine responses to stressors. The predisposition to exhibiting a particular coping style is due to genetic and environmental factors. In this study we explore the neurotranscriptomic and gene network biases that are associated with differences between zebrafish (Danio rerio) lines selected for proactive and reactive coping styles and reared in a common garden environment.

Results: Using RNA-sequencing we quantified the basal transcriptomes from the brains of wild-derived zebrafish lines selectively bred to exhibit the proactive …

Genetic Diversity In Oxytocin Ligands And Receptors In New World Monkeys, Dongren Ren, Guoqing Lu, Hideaki Moriyama, Aaryn C. Mustoe, Emily B. Harrison, Jeffrey French

Biology Faculty Publications

Oxytocin (OXT) is an important neurohypophyseal hormone that influences wide spectrum of reproductive and social processes. Eutherian mammals possess a highly conserved sequence of OXT (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly). However, in this study, we sequenced the coding region for OXT in 22 species covering all New World monkeys (NWM) genera and clades, and characterize five OXT variants, including consensus mammalian Leu⁸-OXT, major variant Pro⁸-OXT, and three previously unreported variants: Ala⁸-OXT, Thr⁸-OXT, and Phe²-OXT. Pro⁸-OXT shows clear structural and physicochemical differences from Leu⁸-OXT. We report multiple predicted amino …

Integrating Interactive Computational Modeling In Biology Curricula, Tomáš Helikar, Christine E. Cutucache, Lauren M. Dahlquist, Tyler A. Herek, Joshua J. Larson, Jim A. Rogers

Biology Faculty Publications

While the use of computer tools to simulate complex processes such as computer circuits is normal practice in fields like engineering, the majority of life sciences/biological sciences courses continue to rely on the traditional textbook and memorization approach. To address this issue, we explored the use of the Cell Collective platform as a novel, interactive, and evolving pedagogical tool to foster student engagement, creativity, and higher-level thinking. Cell Collective is a Web-based platform used to create and simulate dynamical models of various biological processes. Students can create models of cells, diseases, or pathways themselves or explore existing models. This technology …

Biodiversity Comparison Among Phylogenetic Diversity Metrics And Between Three North American Prairies, P. Roxanne (Steele) Kellar, Dakota Ahrendsen, Shelly K. Aust, Amanda R. Jones, J. Chris Pires

Biology Faculty Publications

Protection of Earth’s ecosystems requires identification of geographical areas of greatest biodiversity. Assessment of biodiversity begins with knowledge of the evolutionary histories of species in a geographic area. Multiple phylogenetic diversity (PD) metrics have been developed to describe biodiversity beyond species counts, but sufficient empirical studies, particularly at fine phylogenetic scales, have not been conducted to provide conservation planners with evidence for incorporating PD metrics into selection of priority regions. We review notable studies that are contributing to a growing database of empirical results, we report on the effect of using high-throughput sequencing to estimate the phylogenies used to calculate …

Low-To-Moderate Nitrogen And Phosphorus Concentrations Accelerate Microbially Driven Litter Breakdown Rates, John S. Kominoski, Amy D. Rosemond, Jonathan P. Benstead, Vladislav Gulis, John C. Maerz, David W. P. Manning

Biology Faculty Publications

Particulate organic matter (POM) processing is an important driver of aquatic ecosystem productivity that is sensitive to nutrient enrichment and drives ecosystem carbon (C) loss. Although studies of single concentrations of nitrogen (N) or phosphorus (P) have shown effects at relatively low concentrations, responses of litter breakdown rates along gradients of low‐to‐moderate N and P concentrations are needed to establish likely interdependent effects of dual N and P enrichment on baseline activity in stream ecosystems. We established 25 combinations of dissolved inorganic N (DIN; 55–545 μg/L) and soluble reactive P (SRP; 4–86 μg/L) concentrations with corresponding N:P molar ratios of …

Detrital Stoichiometry As A Critical Nexus For The Effects Of Streamwater Nutrients On Leaf Litter Breakdown Rates, David W. P. Manning, Amy D. Rosemond, John S. Kominoski, Vladislav Gulis, Jonathan P. Benstead, John C. Maerz

Biology Faculty Publications

Nitrogen (N) and phosphorus (P) concentrations are elevated in many freshwater systems, stimulating breakdown rates of terrestrially derived plant litter; however, the relative importance of N and P in driving litter breakdown via microbial and detritivore processing are not fully understood. Here, we determined breakdown rates of two litter species, Acer rubrum (maple) and Rhododendron maximum (rhododendron), before (PRE) and during two years (YR1, YR2) of experimental N and P additions to five streams, and quantified the relative importance of hypothesized factors contributing to breakdown. Treatment streams received a gradient of P additions (low to high soluble reactive phosphorus [SRP]; …

Smoking Accelerates Pancreatic Cancer Progression By Promoting Differentiation Of Mdscs And Inducing Hb-Egf Expression In Macrophages, S. Kumar, M. P. Torres, S. Kaur, S. Rachagani, S. Joshi, S. L. Johansson, N. Momi, M. J. Baine, Christine E. Cutucache, L. M. Smith, T. A. Wyatt, M. Jain, S. S. Joshi, S. K. Batra

Biology Faculty Publications

Smoking is an established risk factor for pancreatic cancer (PC), but late diagnosis limits the evaluation of its mechanistic role in the progression of PC. We used a well-established genetically engineered mouse model (LSL-K-rasG12D) of PC to elucidate the role of smoking during initiation and development of pancreatic intraepithelial neoplasia (PanIN). The 10-week-old floxed mice (K-rasG12D; Pdx-1cre) and their control unfloxed (LSL-K-rasG12D) littermates were exposed to cigarette smoke (total suspended particles: 150 mg/m3) for 20 weeks. Smoke exposure significantly accelerated the development of PanIN lesions in the floxed mice, which correlated with tenfold increase in the expression of cytokeratin19. The …

Facing A Changing World: Thermal Physiology Of American Pikas (Ochotona Princeps), Hans W. Otto, James A. Wilson, Erik A. Beever

Biology Faculty Publications

American pikas (Ochotona princeps) are of concern with respect to warming montane temperatures; however, little information exists regarding their physiological ability to adapt to warming temperatures. Previous studies have shown that pikas have high metabolism and low thermal conductance, which allow survival during cold winters. It has been hypothesized that these characteristics may be detrimental, given the recent warming trends observed in montane ecosystems. We examined resting metabolic rate, surface activity, and den and ambient temperatures (Ta) of pikas in late summer (August 2011 and 2012) at 2 locations in the Rocky Mountains. Resting metabolic rate was calculated to be …

Community Chairs As A Catalyst For Campus Collaboration In Stem, Neal Grandgenett, David Boocker, Hesham Ali, Angela M. Hodge, Brian Dorn, Christine E. Cutucache

Biology Faculty Publications

Strong collaborative partnerships are critical to the ongoing success of any urban or metropolitan university in its efforts to build the science, technology, engineering, and mathematics (STEM) career pathways so critical to our nation. At the University of Nebraska at Omaha, we have established a faculty leadership structure of "community chairs" that work across colleges to support campus priorities. This paper describes UNO’s STEM community chair model, including selected initiatives, impacts, and challenges to date.