Biology Commons^™

Development And Implementation Of Natural Killer Cell Simultaneous Adcc And Direct Killing Assay, Maia M.C. Bennett-Boehm, Anna Mahr, Alexander Regan, Sean T. Hartwell, Isabelle Weber, Arriana Blackmon, Cami Bisson, Angela Ngoc Truong, Bella Circo, Jaden Nienhueser, Donald Rogers, Nathan Booher, Nithya Rajagopalan, Jacob W.S. Martens, Paul Denton

Biology Faculty Publications

Assays to quantify natural killer (NK) cell killing efficacy have traditionally focused on assessing either direct killing or antibody dependent cell-mediated cytotoxicity (ADCC) independently. Due to the probability that immunotherapeutic interventions affect NK cell-mediated direct killing and NK cell-mediated ADCC differently, we developed an assay with the capacity to measure NK cell-mediated direct killing and ADCC simultaneously with cells from the same human donor. Specifically, this design allows for a single NK cell population to be split into several experimental conditions (e.g., direct killing, ADCC), thus controlling for potential confounders associated with human-to-human variation when assessing immunotherapy impacts. Our Natural …

Impact Of A Tlr9 Agonist And Broadly Neutralizing Antibodies On Hiv-1 Persistence: The Randomized Phase 2a Titan Trial, Jesper D. Gunst, Jesper Falkesgaard Højen, Marie H. Pahus, Miriam Rosás-Umbert, Birgitte Stiksrud, James Mcmahon, Paul Denton, Henrik Nielsen, Isik S. Johansen, Thomas Benfield, Steffen Leth, Jan Gerstoft, Lars Østergaard, Mariane H. Schleimann, Rikke Olesen, Henrik Støvring, Line K. Vibholm, Nia Weis, Anne M. Dyrhol-Riise, Karen B.H. Pedersen, Jillian S.Y. Lau, Dennis C. Copertino, Noemi Linden, Tan T. Huynh, Victor Ramos, Rl Brad Jones, Sharon R. Lewin, Martin Tolstrup, Thomas A. Rasmussen, Michel C. Nussenzweig, Marina Caskey, Dag Henrik Reikvam, Ole Schmeltz Søgaard

Biology Faculty Publications

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to …

Sialylation And Fucosylation Modulate Inflammasome-Activating Eif2 Signaling And Microbial Translocation During Hiv Infection, Leila B. Giron, Ceylan E. Tanes, Mariane H. Schleimann, Phillip A. Engen, Lisa M. Mattei, Altizel Anzurez, Mohammad Damra, Huanjia Zhang, Kyle Bittinger, Frederic Bushman, Andrew Kossenkov, Paul Denton, Hiroaki Tateno, Ali Keshavarizian, Mohamed Abdel-Mohsen, Alan L. Landay

Biology Faculty Publications

An emerging paradigm suggests that gut glycosylation is a key force in maintaining the homeostatic relationship between the gut and its microbiota. Nevertheless, it is unclear how gut glycosylation contributes to the HIV-associated microbial translocation and inflammation that persist despite viral suppression and contribute to the development of several comorbidities. We examined terminal ileum, right colon, and sigmoid colon biopsies from HIV-infected virally-suppressed individuals and found that gut glycomic patterns are associated with distinct microbial compositions and differential levels of chronic inflammation and HIV persistence. In particular, high levels of the pro-inflammatory hypo-sialylated T-antigen glycans and low levels of the …

Administration Of Broadly Neutralizing Anti-Hiv-1 Antibodies At Art Initiation Maintains Long-Term Cd8+ T Cell Immunity, Miriam Rosás-Umbert, Jesper D. Gunst, Marie H. Pahus, Rikke Olesen, Mariane H. Schleimann, Paul W. Denton, Victor Ramos, Adam R. Ward, Natalie N. Kinloch, Dennis C. Copertino, Tuixent Escribà, Anuska Llano, Zabrina L. Brumme, R. Brad Jones, Beatriz Mothe, Christian Brander, Julie Fox, Michel C. Nussenzweig, Sarah Fidler, Marina Caskey, Martin Tolstrup, Ole S. Søgaard

Biology Faculty Publications

In simian-human immunodeficiency virus (SHIV)-infected non-human primates, broadly neutralizing antibodies (bNAbs) against the virus appear to stimulate T cell immunity. To determine whether this phenomenon also occurs in humans we measured HIV-1-specific cellular immunity longitudinally in individuals with HIV-1 starting antiviral therapy (ART) with or without adjunctive bNAb 3BNC117 treatment. Using the activation-induced marker (AIM) assay and interferon-γ release, we observe that frequencies of Pol- and Gag-specific CD8+ T cells, as well as Gag-induced interferon-γ responses, are significantly higher among individuals that received adjunctive 3BNC117 compared to ART-alone at 3 and 12 months after starting ART. The observed changes in …

Early Intervention With 3bnc117 And Romidepsin At Antiretroviral Treatment Initiation In People With Hiv-1: A Phase 1b/2a, Randomized Trial, Jesper D. Gunst, Marie H. Pahus, Miriam Rosás-Umbert, I-Na Lu, Thomas Benfield, Henrik Nielsen, Isik S. Johansen, Rajesh Mohey, Lars Østergaard, Vibeke Klastrup, Maryam Khan, Mariane H. Schleimann, Rikke Olesen, Henrik Støvring, Paul W. Denton, Natalie N. Kinloch, Dennis C. Copertino, Adam R. Ward, Winiffer D. Conce Alberto, Silke D. Nielsen, Maria C. Puertas, Victor Ramos, Jacqueline D. Reeves, Christos J. Petropoulos, Javier Martinez-Picado, Zabrina L. Brumme, R. Brad Jones, Julie Fox, Martin Tolstrup, Michel C. Nussenzweig, Marina Caskey, Sarah Fidler, Ole S. Søgaard

Biology Faculty Publications

Attempts to reduce the human immunodeficiency virus type 1 (HIV-1) reservoir and induce antiretroviral therapy (ART)-free virologic control have largely been unsuccessful. In this phase 1b/2a, open-label, randomized controlled trial using a four-group factorial design, we investigated whether early intervention in newly diagnosed people with HIV-1 with a monoclonal anti-HIV-1 antibody with a CD4-binding site, 3BNC117, followed by a histone deacetylase inhibitor, romidepsin, shortly after ART initiation altered the course of HIV-1 infection (NCT03041012). The trial was undertaken in five hospitals in Denmark and two hospitals in the United Kingdom. The coprimary endpoints were analysis of initial virus …

Cd169 (Siglec-1) As A Robust Human Cell Biomarker Of Toll-Like Receptor 9 Agonist Immunotherapy, Stine Sofie Frank Lende, Marie H. Pahus, Ida Monrad, Rikka Olesen, Anna Mahr, Line K. Vibholm, Lars Østergaard, Ole Schmeltz Søgaard, Anna Halling Folkmar Andersen, Paul Denton, Martin Tolstrup

Biology Faculty Publications

Immunotherapy is a promising therapeutic area in cancer and chronic viral infections. An important component of immunotherapy in these contexts is the activation of innate immunity. Here we investigate the potential for CD169 (Siglec 1) expression on monocytes to serve as a robust biomarker for activation of innate immunity and, particular, as a proxy for IFN-α production. Specifically, we investigated the effects of Toll-like receptor 9 agonism with MGN1703 (lefitolimod) across experimental conditions ex vivo, in humanized mice, and in clinical trial participants. Ex vivo we observed that the percentage of classical monocytes expressing CD169 increased dramatically from …

Helminth Products Modulate Innate Immune Recognition Of Nucleic Acids In Systemic Lupus Erythematosus, Laura B. Dall, Bent Deleuran, Lars Østergaard, Maibritt Mardahl, Paul Denton, Peter Nejsum

Biology Faculty Publications

Aim

Methods

Modest De Novo Reactivation Of Single Hiv-1 Proviruses In Peripheral Cd4+ T Cells By Romidepsin, Anne Sofie Kjaer, Steffen Leth, Christina V. Konrad, Jesper D. Gunst, Rasmus Nymann, Lars Østergaard, Ole S. Søgaard, Mariane H. Schleimann, Martin Tolstrup, Paul Denton

Biology Faculty Publications

A cure for human immunodeficiency virus (HIV-1) is restricted by the continued presence of a latent reservoir of memory CD4+ T cells with proviruses integrated into their DNA despite suppressive antiretroviral therapy (ART). A predominant strategy currently pursued in HIV-1 cure-related research is the “kick and kill” approach, where latency reversal agents (LRAs) are used to reactivate transcription from integrated proviruses. The premise of this approach is that “kicking” latent virus out of hiding allows the host immune system to recognize and kill infected cells. Clinical trials investigating the efficacy of LRAs, such as romidepsin, have shown that these interventions …

The Size And Culturability Of Patient-Generated Sars-Cov-2 Aerosol, Joshua L. Santarpia, Vicki L. Herrera, Danielle N. Rivera, Shanna Ratnesar-Shumate, St. Patrick Reid, Daniel N. Ackerman, Paul Denton, Jacob W.S. Martens, Ying Fan, Nicholas Conoan, Michael V. Callahan, James V. Lawler, David M. Brett-Major, John J. Lowe

Biology Faculty Publications

Background

Aerosol transmission of COVID-19 is the subject of ongoing policy debate. Characterizing aerosol produced by people with COVID-19 is critical to understanding the role of aerosols in transmission.

Objective

We investigated the presence of virus in size-fractioned aerosols from six COVID-19 patients admitted into mixed acuity wards in April of 2020.

Methods

Size-fractionated aerosol samples and aerosol size distributions were collected from COVID-19 positive patients. Aerosol samples were analyzed for viral RNA, positive samples were cultured in Vero E6 cells. Serial RT-PCR of cells indicated samples where viral replication was likely occurring. Viral presence was also investigated by western …

Predicting Cognitive Rehabilitation Needs In Patients With Central Nervous System Infections Using Montreal Cognitive Assessment, Matilde Ørum, Merete Storgaard, Paul Denton, Trine Hyrup Mogensen, Christina Kjærgaard Højbjerg, Mathilde Pedersen, Jesper Damsgaard Gunst

Biology Faculty Publications

Cognitive impairments are reported in some patients with central nervous system (CNS) infections after discharge. Our objectives were to evaluate the prevalence of CNS patients in need of rehabilitation after discharge and to assess whether the Montreal Cognitive Assessment (MoCA) could be used as a screening tool to identify these patients. CNS patients admitted during a 2-year study period were included. The need for rehabilitation was assessed by physicians with the aid of an occupational therapy assessment, after which a MoCA was performed. The prevalence of needing rehabilitation was 58% among CNS patients. An abnormal MoCA score < 26 was the only variable strongly associated with higher odds of needing rehabilitation. In 42% of the CNS patients in need of rehabilitation, the MoCA score was ≥ 26, and most of these patients were aged 16 to 43 years (young adults). There is a need for rehabilitation among CNS patients after discharge. As a screening tool, MoCA was able to identify patients in need of rehabilitation. In young adults, MoCA scores were often normal despite a need for rehabilitation. Thus, MoCA cannot stand alone as a screening tool for identifying young adults in need of rehabilitation following CNS infection.

Poor Compliance With An Antibiotic Directive—A Call For Intensified Monitoring, Frederik Novak, Jens T. Hørlück, Jacob D. Redder, Paul Denton, Merete Storgaard

Biology Faculty Publications

Background

In April 2017, the Central Denmark Region Antibiotic Stewardship Committee issued a directive to reduce the general use of piperacillin-tazobactam and prescribe narrow-spectrum antibiotics for mild and moderate pneumonia. The directive was distributed to all regional hospital clinicians.

Methods

Electronic medical records were used to obtain de-identified details of all antibiotics administered (together with diagnosis codes) to all in-hospital patients (pre-directive and post-directive) in the nine regional hospitals. Average moving range statistical process control charts were used to analyze pre-directive and post-directive variation in antibiotic usage patterns.

Results

Upon the distribution of the directive, a period of decline of …

Comparable Human Reconstitution Following Cesium-137 Versus X-Ray Irradiation Preconditioning In Immunodeficient Nog Mice, Anna Halling Folkmar Andersen, Stine Sofie Frank Nielsen, Rikka Olesen, Jakob Le Fèvre Harslund, Ole S. Søgaard, Lars Østergaard, Paul Denton, Martin Tolstrup

Biology Faculty Publications

Humanized mouse models are used extensively in research involving human pathogens and diseases. However, most of these models require preconditioning. Radio-active sources have been used routinely for this purpose but safety issues have motivated researchers to transition to chemical or X-ray based preconditioning. In this study, we directly compare 350 kV X-ray and Cs-137 low-dose precondition of NOG mice before human stem cell transplantation. Based on flow cytometry data, we found that engraftment of human cells into the mouse bone marrow was similar between radiation sources. Likewise, human engraftment in the peripheral blood was comparable between Cs-137 and three different …

Gene-Based Clustering Algorithms: Comparison Between Denclue, Fuzzy-C, And Birch, Martin C. Nwadiugwu

Interdisciplinary Informatics Faculty Publications

The current study seeks to compare 3 clustering algorithms that can be used in gene-based bioinformatics research to understand disease networks, protein-protein interaction networks, and gene expression data. Denclue, Fuzzy-C, and Balanced Iterative and Clustering using Hierarchies (BIRCH) were the 3 gene-based clustering algorithms selected. These algorithms were explored in relation to the subfield of bioinformatics that analyzes omics data, which include but are not limited to genomics, proteomics, metagenomics, transcriptomics, and metabolomics data. The objective was to compare the efficacy of the 3 algorithms and determine their strength and drawbacks. Result of the review showed that unlike Denclue and …

Humanized Nog Mice For Intravaginal Hiv Exposure And Treatment Of Hiv Infection, Anna Halling Folkmar Andersen, Stine Sofie Frank Nielsen, Rikka Olesen, Katharine Mack, Frederik Dagnæs-Hansen, N. Uldbjerg, Lars Østergaard, Ole S. Søgaard, Paul Denton, Martin Tolstrup

Biology Faculty Publications

Humanized mice provide a sophisticated platform to study human immunodeficiency virus (HIV) virology and to test antiviral drugs. This protocol describes the establishment of a human immune system in adult NOG mice. Here, we explain all the practical steps from isolation of umbilical cord blood derived human CD34+ cells and their subsequent intravenous transplantation into the mice, to the manipulation of the model through HIV infection, combination antiretroviral therapy (cART), and blood sampling. Approximately 75,000 hCD34+ cells are injected intravenously into the mice and the level of human chimerism, also known as humanization, in the peripheral blood is estimated longitudinally …

Structure Of The 5′ Untranslated Region Of Enteroviral Genomic Rna, Bejan Mahmud, Christopher M. Horn, William E. Tapprich

Biology Faculty Publications

Enteroviral RNA genomes share a long, highly structured 5= untranslated region (5= UTR) containing a type I internal ribosome entry site (IRES). The 5= UTR is composed of stably folded RNA domains connected by unstructured RNA regions. Proper folding and functioning of the 5= UTR underlies the efficiency of viral replication and also determines viral virulence. We have characterized the structure of 5= UTR genomic RNA from coxsackievirus B3 using selective 2=-hydroxyl acylation analyzed by primer extension (SHAPE) and base-specific chemical probes in solution. Our results revealed novel structural features, including realignment of major domains, newly identified long-range interactions, and …

Resolving The Genetic Paradox Of Invasions: Preadapted Genomes And Postintroduction Hybridization Of Bigheaded Carps In The Mississippi River Basin, Jun Wang, Sarah Gaughan, James T. Lamer, Cao Deng, Wanting Hu, Michael Wachholtz, Shishang Qin, Hu Nie, Xiaolin Liao, Qufei Ling, Weitao Li, Lifeng Zhu, Louis Bernatchez, Chenghui Wang, Guoqing Lu

Biology Faculty Publications

The genetic paradox of biological invasions is complex and multifaceted. In particular, the relative role of disparate propagule sources and genetic adaptation through postintroduction hybridization has remained largely unexplored. To add resolution to this paradox, we investigate the genetic architecture responsible for the invasion of two invasive Asian carp species, bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix) (bigheaded carps) that experience extensive hybridization in the Mississippi River Basin (MRB). We sequenced the genomes of bighead and silver carps (~1.08G bp and ~1.15G bp, respectively) and their hybrids collected from the MRB. We found moderate‐to‐high …

Impacts Of Hiv Cure Interventions On Viral Reservoirs In Tissues, Paul W. Denton, Ole S. Søgaard, Martin Tolstrup

Biology Faculty Publications

HIV reservoirs persist in infected individuals despite combination antiretroviral therapy and can be identified in secondary lymphoid tissues, in intestinal tissues, in the central nervous system as well as in blood. Clinical trials have begun to explore effects of small molecule interventions to perturb the latent viral infection, but only limited information is available regarding the impacts of HIV cure-related clinical interventions on viral reservoirs found in tissues. Of the 14 HIV cure-related clinical trials since 2012 that have evaluated the effects of small molecule interventions in vivo, four trials have examined the impacts of the interventions in peripheral …

Contextual Fear Learning And Memory Differ Between Stress Coping Styles In Zebrafish, Matthew R. Baker, Ryan Y. Wong

Biology Faculty Publications

Animals frequently overcome stressors and the ability to learn and recall these salient experiences is essential to an individual’s survival. As part of an animal’s stress coping style, behavioral and physiological responses to stressors are often consistent across contexts and time. However, we are only beginning to understand how cognitive traits can be biased by different coping styles. Here we investigate learning and memory differences in zebrafish (Danio rerio) displaying proactive and reactive stress coping styles. We assessed learning rate and memory duration using an associative fear conditioning paradigm that trained zebrafish to associate a context with exposure to a …

Tlr9 Agonist Mgn1703 Enhances B Cell Differentiation And Function In Lymph Nodes, Mariane H. Schleimann, Maria-Louise Kobberø, Line K. Vibholm, Katherine Kjær, Leila B. Giron, Kathleen Busman-Sahay, Chi Ngai Chan, Michael Nekorchuk, Manuel Schmidt, Burghardt Wittig, Tine E. Damsgaard, Peter Ahlburg, Michel B. Hellfritzsch, Kaja Zuwala, Frederik H. Rothemejer, Rikke Olesen, Phillipp Schommers, Florian Klein, Harsh Dweep, Andrew Kossenkov, Jens R. Nyengaard, Jacob D. Estes, Mohamed Abdel-Mohsen, Lars Østergaard, Ole S. Søgaard, Paul W. Denton

Biology Faculty Publications

Background

TLR9 agonists are being developed as immunotherapy against malignancies and infections. TLR9 is primarily expressed in B cells and plasmacytoid dendritic cells (pDCs). TLR9 signalling may be critically important for B cell activity in lymph nodes but little is known about the in vivo impact of TLR9 agonism on human lymph node B cells. As a pre-defined sub-study within our clinical trial investigating TLR9 agonist MGN1703 (lefitolimod) treatment in the context of developing HIV cure strategies (NCT02443935), we assessed TLR9 agonist-mediated effects in lymph nodes.

Methods

Participants received MGN1703 for 24 weeks concurrent with antiretroviral therapy. Seven …

Differences In Stress Reactivity Between Zebrafish With Alternative Stress Coping Styles, Ryan Y. Wong, Jeffrey French, Jacalyn B. Russ

Biology Faculty Publications

Animals experience stress in a variety of contexts and the behavioural and neuroendocrine responses to stress can vary among conspecifics. The responses across stressors often covary within an individual and are consistently different between individuals, which represent distinct stress coping styles (e.g. proactive and reactive). While studies have identified differences in peak glucocorticoid levels, less is known about how cortisol levels differ between stress coping styles at other time points of the glucocorticoid stress response. Here we quantified whole-body cortisol levels and stress-related behaviours (e.g. depth preference, movement) at time points representing the rise and recovery periods of the stress …

Burning And Mowing Similarly Increase Prairie Plant Production In The Spring, But Not Due To Increased Soil Temperatures, Timothy L. Dickson

Biology Faculty Publications

Burning and mowing are two of the most common grassland disturbances across millions of hectares worldwide, but uncertainty remains about when and why these disturbances increase plant production. One of the main hypotheses for increased plant production is that disturbances increase soil temperature in the early growing season and thereby increase plant growth. I tested this hypothesis using a multi‐decade study of the frequency (annual or quadrennial) and season (spring, summer, or autumn) of reconstructed tallgrass prairie burning and mowing. To determine plant production, I measured aboveground biomass during three periods of the 2015 growing season: (1) prior to mid‐May; …

Bulldozing The Stem Silos In Omaha: While Engaging P-12 Teachers And Building Campus Stem Excellence, Neal Grandgenett, Christine Cutucache, William Tapprich, Brian Dorn

Biology Faculty Publications

It has been said that all universities “do STEM these days”, but what exactly does it take to “do STEM” well? Questions commonly heard on a university campus these days include: “What is the STEM context for inquiry?”, “Should P-16 STEM be a campus priority?”, “How can a campus break down departmental silos for interdisciplinary workforce development?” In many ways STEM represents, at its core, an interdisciplinary approach and workforce development context to learning, that rigorously engages the core concepts of science, technology, engineering, and mathematics (Tsupros, N., Kohler, R. and Hallinen, J., 2009; National Science and Technology Council, 2018). …

Postfledging Habitat Selection And Survival Of Henslow’S Sparrow: Management Implications For A Critical Life Stage, Aaron C. Young, W. Andrew Cox, John P. Mccarty, L. Lareesa Wolfenbarger

Biology Faculty Publications

Conserving populations of species that rely on rare habitat requires that managers understand which habitat characteristics will best support population growth across multiple life stages. For songbirds, management is most often aimed at nesting adult habitat associations. However, habitat that meets adult requirements may not be similarly suited to requirements for other life stages. Henslow’s Sparrow (Centronyx henslowii) is a tallgrass prairie songbird listed as threatened or endangered in 13 states. We examined survival and habitat selection of Henslow’s Sparrow during the postfledging period. During the nesting seasons in 2015 and 2016, we attached radio transmitters to 46 nestlings in …

Cognitive Processes That Indirectly Affect Olfactory Dysfunction In Parkinson's Disease, Attakias T. Mertens, Jonathan B. Santo, Katerina Markopoulou, Bruce A. Chase

Biology Faculty Publications

Introduction
Accurate early diagnosis of Parkinson's disease is hampered by its long prodromal period and the variable manifestations of its motor symptoms. While olfactory dysfunction can occur before motor-symptom onset and serve as a non-disease-specific diagnostic aid, its underlying causes are incompletely understood.

Methods
Correlation analyses, univariate density estimates, ANOVA and regression evaluated relationships between scores on the Montreal Cognitive Assessment and Hopkins Verbal Learning Test and those on the University of Pennsylvania Smell Identification Test in 1280 Parkinson's Progression Markers Initiative subjects placed into five diagnostic categories. Structural equation modeling identified cognitive measures having significant indirect effects on olfactory-function-test …

Ne Stem 4u Afterschool Intervention Leads To Gains In Stem Content Knowledge For Middle School Youth, Christine E. Cutucache, Taylor Boham, Jamie Luhr, Amie Sommers, Nikolaus Stevenson, Erkko Sointu, Kati Mäkitalo‐Siegl, Sirpa Kärkkäinen, Teemu Valtonen, Neal Grandgenett, William Tapprich

Biology Faculty Publications

Afterschool interventions in STEM are linked to learning gains during the school day. These opportunities engage and excite students about STEM concepts since they observe a more hands-on, project-oriented approach. Often these opportunities for afterschool interventions are infrequent in nature and leave gaps for students in their maturation and understanding. Herein we describe the first report of an afterschool intervention, named NE STEM 4U, targeting socioeconomically disadvantaged middle school youth via a twice weekly, year-long intervention, studied across two years. We assessed the impact of this program on i.) short-term, individual student gains in STEM content knowledge and ii.) delivery …

Derivatives Of A Benzoquinone Acyl Hydrazone With Activity Against Toxoplasma Gondii, A. G. Sanford, T. T. Schulze, L. P. Potluri, G. F. Watson, E. B. Darner, S. J. Zach, R. M. Hemsley, A. I. Wallick, R. C. Warner, S. A. Charman, X. Wang, J. L. Vennerstrom, P. H. Davis

Biology Faculty Publications

Toxoplasma gondii is an obligate intracellular parasite with global incidence. The acute infection, toxoplasmosis, is treatable but current regimens have poor host tolerance and no cure has been found for latent infections. This work builds upon a previous high throughput screen which identified benzoquinone acyl hydrazone (KG8) as the most promising compound; KG8 displayed potent in vitro activity against T. gondii but only marginal in vivoefficacy in a T. gondii animal model. To define the potential of this new lead compound, we now describe a baseline structure-activity relationship for this chemotype. Several derivatives displayed IC50's comparable …

Recruitment, Survival, And Parasitism Of Monarch Butterflies (Danaus Plexippus) In Milkweed Gardens And Conservation Areas, Emily A. Geest, L. Lareesa Wolfenbarger, John P. Mccarty

Biology Faculty Publications

Monarch butterflies (Danaus plexippus) are suffering from declining populations and conservationists have encouraged planting milkweed gardens in urban and suburban landscapes to help offset habitat loss across the breeding range. The effectiveness of gardens as a conservation strategy depends on their ability to attract ovipositing adults and the survival of monarch larvae in these gardens. Larvae are susceptible to a variety of predators as well as to parasitism by a tachinid fly (Lespesia archippivora) and a protozoan parasite (Ophryocystis elektroscirrha) which cause lethal or sublethal effects, yet the severity of these risks in gardens …

Life Science Undergraduate Mentors In Ne Stem 4u Significantly Outperform Their Peers In Critical Thinking Skills, Kari L. Nelson, Claudia M. Rauter, Christine E. Cutucache

Biology Faculty Publications

The development of critical thinking skills in recent college graduates is keenly requested by employers year after year. Moreover, improving these skills can help students to better question and analyze data. Consequently, we aimed to implement a training program that would add to the critical thinking skills of undergraduate students: Nebraska Science, Technology, Engineering, and Math 4U (NE STEM 4U). In this program, undergraduates provide outreach, mentoring, and science, technology, engineering, and mathematics (STEM) education to K–8 students. To determine the impacts of serving as an undergraduate mentor in this program on critical thinking, we compared undergraduate mentors (intervention group) …

Interferon Priming Is Essential For Human Cd34+ Cell-Derived Plasmacytoid Dendritic Cell Maturation And Function, A. Lausten, R. O. Bak, C. Krapp, L. Kjær, J. H. Egedahl, C. C. Petersen, S. Pillai, H. Q. Tang, N. Uldbjerg, M. Porteus, N. R. Roan, M. Nyegaard, Paul W. Denton, M. R. Jakobsen

Biology Faculty Publications

Plasmacytoid dendritic cells (pDC) are essential for immune competence. Here we show that pDC precursor differentiated from human CD34+ hematopoietic stem and progenitor cells (HSPC) has low surface expression of pDC markers, and has limited induction of type I interferon (IFN) and IL-6 upon TLR7 and TLR9 agonists treatment; by contrast, cGAS or RIG-I agonists-mediated activation is not altered. Importantly, after priming with type I and II IFN, these precursor pDCs attain a phenotype and functional activity similar to that of peripheral blood-derived pDCs. Data from CRISPR/Cas9-mediated genome editing of HSPCs further show that HSPC-pDCs with genetic modifications can be …

Repeatability And Reliability Of Exploratory Behavior In Proactive And Reactive Zebrafsh, Danio Rerio, Matthew R. Baker, Alexander C. Goodman, Jonathan B. Santo, Ryan Y. Wong

Biology Faculty Publications

Behavioral responses to novel situations often vary and can belong to a suite of correlated behaviors. Characteristic behaviors of different personality types (e.g. stress coping styles) are generally consistent across contexts and time. Here, we compare the repeatability and reliability of exploratory behaviors between zebrafsh strains selectively bred to display contrasting behavioral responses to stressors that represent the proactive-reactive axis. Specifically, we measure exploratory behavior of individual fish in an open field test over five weeks. We quantified the stationary time, average swimming speed and time spent by a fish in the center area. We found a number of strain …