230 Works

Data from: Identification of candidate risk factor genes for human idelalisib toxicity using a collaborative cross approach

Merrie Mosedale, Yanwei Cai, J. Scott Eaddy, Robert Corty, Manisha Nautiyal, Paul B. Watkins & William Valdar
Idelalisib is a phosphatidylinositol 3-kinase inhibitor highly selective for the delta isoform that has shown good efficacy in treating chronic lymphocytic leukemia and follicular lymphoma. In clinical trials, however, idelalisib was associated with rare, but potentially serious liver and lung toxicities. In this study, we used the Collaborative Cross (CC) mouse population to identify genetic factors associated with the drug response that may inform risk management strategies for idelalisib in humans. Eight (8) male mice...

Data from: A logical model of homology for comparative biology

Paula Mabee, James Balhoff, Wasila Dahdul, Hilmar Lapp, Christopher Mungall & Todd Vision
There is a growing body of research on the evolution of anatomy in a wide variety of organisms. Discoveries in this field could be greatly accelerated by computational methods and resources that enable these findings to be compared across different studies and different organisms and linked with the genes responsible for anatomical modifications. Homology is a key concept in comparative anatomy; two important types are historical homology (the similarity of organisms due to common ancestry)...

Interactive effects of previous and current thermal conditions on gene expression in Manduca sexta

Meggan A Alston, Jeeyun Lee, M. Elizabeth Moore, Joel G Kingsolver & Christopher S Willett
High temperatures can negatively impact performance and survival of organisms, particularly ectotherms. While an organism’s response to high temperature stress clearly depends on current thermal conditions, its response may also be affected by the temporal pattern and duration of past temperature exposures. We used RNA sequencing of Manduca sexta larvae fat body tissue to evaluate how diurnal temperature fluctuations during development affected gene expression both independently and in conjunction with subsequent heat stress. Additionally, we...

Data from: Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis

James F. Howard, Vera Bril, Ted M. Burns, Renato Mantegazza, Malgorzata Bilinska, Andrzej Szczudlik, Said Beydoun, Francisco Javier Rodriguez De Rivera Garrido, Fredrik Piehl, Mariarosa Rottoli, Philip Van Damme, Tuan Vu, Amelia Evoli, Miriam Freimer, Tahseen Mozaffar, E. Sally Ward, Torsten Dreier, Peter Ulrichts, Katrien Verschueren, Antonio Guglietta, Hans De Haard, Nicolas Leupin & Jan J. G. M. Verschuuren
Objective: To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment. Methods: A phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or...

Data from: Hybridization in the Drosophila melanogaster subgroup: incomplete isolation among the three species of the yakuba complex

David A. Turissini, Geoffrey Liu, Jean R. David & Daniel R. Matute
In the Drosophila melanogaster subgroup, the yakuba species complex, D. yakuba, D. santomea and D. teissieri have identical mitochondrial genomes in spite of nuclear differentiation. The first two species can be readily hybridized in the laboratory, and produce fertile females and sterile males. They also form hybrids in natural conditions. Nonetheless, the third species, D. teissieri, was thought to be unable to produce hybrids with either D. yakuba or D. santomea. This in turn posed...

Unique bacterial composition and assembly in a parasitic plant

Connor Fitzpatrick & Adam Schneider
How plant-associated microbiota are shaped by, and potentially contribute to the unique ecology and heterotrophic life history of parasitic plants is relatively unknown. Here, we investigate the leaf and root bacterial communities associated with the root holoparasite Orobanche hederae and its host plant Hedera spp. We sequenced the V4 region of the 16S rRNA gene from DNA extracted from leaf and root samples of naturally growing populations of Orobanche and infected and uninfected Hedera. Root...

Data from: Population genetic structure between Yap and Palau for the coral Acropora hyacinthus

Annick Cros, Robert J. Toonen, Sarah W. Davies & Stephen A. Karl
Information on connectivity is becoming increasingly in demand as marine protected areas are being designed as an integral part of a network to protect marine resources at the ecosystem level. Larval dispersal and population structure, however, remain very difficult to assess. Here, we tested the predictions of a detailed oceanographic connectivity model of larval dispersal and coral recruitment within Palau and between Palau and Yap, which was developed to support the review of the existing...

Data from: Evolution of a mating preference for a dual-utility trait used in intrasexual competition in genetically monogamous populations

Caitlin A. Stern & Maria R. Servedio
The selection pressures by which mating preferences for ornamental traits can evolve in genetically monogamous mating systems remain understudied. Empirical evidence from several taxa supports the prevalence of dual-utility traits, defined as traits used both as armaments in intersexual selection and ornaments in intrasexual selection, as well as the importance of intrasexual resource competition for the evolution of female ornamentation. Here, we study whether mating preferences for traits used in intrasexual resource competition can evolve...

Data from: Non-adaptive female pursuit of extra-pair copulations can evolve through hitchhiking

Nan Lyu, Maria R. Servedio & Yue-Hua Sun
Mounting evidence has indicated that engaging in extra-pair copulations (EPCs) might be maladaptive or detrimental to females. It is unclear why such non-adaptive female behavior evolves. In this study, we test two hypotheses about the evolution of female EPC behavior using population genetic models. First, we find that both male preference for allocating extra-effort to seek EPCs and female pursuit behavior without costs can be maintained and remain polymorphic in a population via frequency dependent...

Data from: Using trait and phylogenetic diversity to evaluate the generality of the stress-dominance hypothesis in eastern North American tree communities

Jessica R. Coyle, Fletcher W. Halliday, Bianca E. Lopez, Kyle A. Palmquist, Peter A. Wilfahrt & Allen H. Hurlbert
The stress-dominance hypothesis (SDH) is a model of community assembly predicting that the relative importance of environmental filtering increases and competition decreases along a gradient of increasing environmental stress. Tests of the SDH at limited spatial scales have thus far demonstrated equivocal support and no prior study has assessed the generality of the SDH at continental scales. We examined over 53 000 tree communities spanning the eastern United States to determine whether functional trait variation...

Data from: Natural soil microbes alter flowering phenology and the intensity of selection on flowering time in a wild Arabidopsis relative

Maggie R. Wagner, Derek S. Lundberg, Devin Coleman-Derr, Susannah G. Tringe, Jeffery L. Dangl & Thomas Mitchell-Olds
Plant phenology is known to depend on many different environmental variables, but soil microbial communities have rarely been acknowledged as possible drivers of flowering time. Here, we tested separately the effects of four naturally occurring soil microbiomes and their constituent soil chemistries on flowering phenology and reproductive fitness of Boechera stricta, a wild relative of Arabidopsis. Flowering time was sensitive to both microbes and the abiotic properties of different soils; varying soil microbiota also altered...

Data from: Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

Dmitry Shungin, Wei Q. Deng, Tibor V. Varga, Jian'an Luan, Evelin Mihailov, Andres Metspalu, Andrew P. Morris, Nita G. Forouhi, Cecilia Lindgren, Patrik K. E. Magnusson, Nancy L. Pedersen, Göran Hallmans, Audrey Y. Chu, Anne E. Justice, Mariaelisa Graff, Thomas W. Winkler, Lynda M. Rose, Claudia Langenberg, L. Adrienne Cupples, Paul M. Ridker, Nicholas J. Wareham, Ken K. Ong, Ruth J. F. Loos, Daniel I. Chasman, Erik Ingelsson … & Paul W. Franks
Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G·E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between variance effects (Pv), G·E interaction effects (with smoking and physical activity), and marginal genetic effects (Pm). Correlations between Pv and Pm were stronger for SNPs with established marginal effects (Spearman's ρ=0.401 for triglycerides, and ρ=0.236 for BMI) compared...

Data from: Wolbachia in the Drosophila yakuba complex: pervasive frequency variation and weak cytoplasmic incompatibility, but no apparent effect on reproductive isolation

Brandon S. Cooper, Paul S. Ginsberg, Michael Turelli & Daniel R. Matute
Three hybridizing species-the clade ((Drosophila yakuba, D. santomea), D. teissieri) -comprise the yakuba complex in the D. melanogaster subgroup. Their ranges overlap on Bioko and São Tomé, islands off west Africa. All three species are infected with Wolbachia, maternally inherited, endosymbiotic bacteria, best known for manipulating host reproduction to favor infected females. Previous analyses reported no cytoplasmic incompatibility (CI) in these species. However, we discovered that Wolbachia from each species cause intra- and interspecific CI....

Data from: Further development of the Assessment of Military Multitasking Performance: iterative reliability testing

Margaret M. Weightman, Karen L. McCulloch, Mary V. Radomski, Marsha Finkelstein, Amy S. Cecchini, Leslie F. Davidson, Kristin J. Heaton, Laurel B. Smith & Matthew R. Scherer
The Assessment of Military Multitasking Performance (AMMP) is a battery of functional dual-tasks and multitasks based on military activities that target known sensorimotor, cognitive, and exertional vulnerabilities after concussion/mild traumatic brain injury (mTBI). The AMMP was developed to help address known limitations in post concussive return to duty assessment and decision making. Once validated, the AMMP is intended for use in combination with other metrics to inform duty-readiness decisions in Active Duty Service Members following...

Data from: Transitions between phases of genomic differentiation during stick-insect speciation

Rüdiger Riesch, Moritz Muschick, Dorothea Lindtke, Romain Villoutreix, Aaron A. Comeault, Timothy E. Farkas, Kay Lucek, Elizabeth Hellen, Víctor Soria-Carrasco, Stuart R. Dennis, Clarissa F. De Carvalho, Rebecca J. Safran, Cristina P. Sandoval, Jeff Feder, Regine Gries, Bernard J. Crespi, Gerhard Gries, Zach Gompert & Patrik Nosil
Speciation can involve a transition from a few genetic loci that are resistant to gene flow to genome-wide differentiation. However, only limited data exist concerning this transition and the factors promoting it. Here, we study phases of speciation using data from >100 populations of 11 species of Timema stick insects. Consistent with early phases of genic speciation, adaptive colour-pattern loci reside in localized genetic regions of accentuated differentiation between populations experiencing gene flow. Transitions to...

Data from: Genetic by environmental variation but no local adaptation in oysters (Crassostrea virginica)

A. Randall Hughes, Torrance C. Hanley, James E. Byers, Jonathan H. Grabowski, Jennafer C. Malek, Micahel F. Piehler, David L. Kimbro & Michael F. Piehler
Functional trait variation within and across populations can strongly influence population, community, and ecosystem processes, but the relative contributions of genetic vs. environmental factors to this variation are often not clear, potentially complicating conservation and restoration efforts. For example, local adaptation, a particular type of genetic by environmental (G*E) interaction in which the fitness of a population in its own habitat is greater than in other habitats, is often invoked in management practices, even in...

Data from: Upper atmosphere heating from ocean-generated acoustic wave energy

Daniel C. Bowman & Jonathan M. Lees
Colliding sea surface waves generate the ocean microbarom, an acoustic signal that may transmit significant energy to the upper atmosphere. Previous estimates of acoustic energy flux from the ocean microbarom and mountain/wind interactions are on the order of 0.01 to 1 mW/m2, heating the thermosphere by tens of degrees Kelvin per day. We captured up going ocean microbarom waves with a balloon borne infrasound microphone; the maximum acoustic energy flux was approximately 0.05 mW/m2. This...

Data from: Mainland size variation informs predictive models of exceptional insular body size change in rodents

Paul A. P. Durst & V. Louise Roth
The tendency for island populations of mammalian taxa to diverge in body size from their mainland counterparts consistently in particular directions is both impressive for its regularity and, especially among rodents, troublesome for its exceptions. However, previous studies have largely ignored mainland body size variation, treating size differences of any magnitude as equally noteworthy. Here, we use distributions of mainland population body sizes to identify island populations as ‘extremely’ big or small, and we compare...

Data from: Habitat context influences nitrogen removal by restored oyster reefs

Ashley R. Smyth, Michael F. Piehler & Jonathan H. Grabowski
1. Like many ecosystem functions in marine and terrestrial environments, nutrient processing varies dramatically over small spatial scales, making efforts to apply findings within and across ecosystems challenging. In estuaries, information on the influence of habitat context on sediment nutrient cycling is lacking even though this is an important estuarine function with high societal value. 2. We collected triplicate intact sediment cores from restored oyster reefs located in different habitat contexts (adjacent to salt marshes,...

Data from: Adaptive introgression from distant Caribbean islands contributed to the diversification of a microendemic adaptive radiation of trophic specialist pupfishes

Christopher H. Martin, Emilie H Richards & Emilie J. Richards
Rapid diversification often involves complex histories of gene flow that leave variable and conflicting signatures of evolutionary relatedness across the genome. Identifying the extent and source of variation in these evolutionary relationships can provide insight into the evolutionary mechanisms involved in rapid radiations. Here we compare the discordant evolutionary relationships associated with species phenotypes across 42 whole genomes from a sympatric adaptive radiation of Cyprinodon pupfishes endemic to San Salvador Island, Bahamas and several outgroup...

Data from: The complex effects of demographic history on the estimation of substitution rate: concatenated gene analysis results in no more than twofold overestimation

Christopher H. Martin, Sebastian Hohna, Jacob E. Crawford, Bruce J. Turner, Emilie J. Richards & Lee H. Simons
Our recent estimation of the divergence time and isolation of Death Valley pupfishes, including the iconic Devil’s Hole pupfish (DHP), rewrote widespread assumptions about this group. These species were previously assumed to be relic populations isolated over millions of years; our genomic analyses indicated recent colonization of Devil’s Hole within the past 105–830 years and frequent gene flow among Death Valley populations [1]. These results understandably attracted substantial attention given the iconic battle for conservation...

Data from: The role of habitat filtering in the leaf economics spectrum and plant susceptibility to pathogen infection

Miranda E. Welsh, James Patrick Cronin & Charles E. Mitchell
The leaf economics spectrum (LES) describes global covariation in the traits of plant leaves. The LES is thought to arise from biophysical constraints and habitat filtering (ecological selection against unfit trait combinations along environmental gradients). However, the role of habitat filtering in generating the LES has not been tested experimentally. If the process of habitat filtering plays a role in generating the LES, the LES could weaken in communities that have yet to be filtered...

Data from: Genetic structure of phenotypic robustness in the Collaborative Cross mouse diallel panel

Paula N. Gonzalez, Mihaela Pavlicev, Philipp Mitteroecker, Fernando Pardo-Manuel De Villena, Richard Spritz, Ralph Marcucio & Benedikt Hallgrimsson
Developmental stability and canalization describe the ability of developmental systems to minimize phenotypic variation in the face of stochastic micro-environmental effects, genetic variation and environmental influences. Canalization is the ability to minimize the effects of genetic or environmental effects, while developmental stability is the ability to minimize the effects of micro-environmental effects within individuals. Despite much attention, the mechanisms that underlie these two components of phenotypic robustness remain unknown. We investigated the genetic structure of...

Data from: The use of functional data analysis to evaluate activity in a spontaneous model of degenerative joint disease associated pain in cats

Margaret E. Gruen, Marcela Alfaro-Córdoba, Andrea E. Thomson, Alicia Worth, Ana-Maria Staicu, B. Duncan X. Lascelles & Alicia C. Worth
Accelerometry is used as an objective measure of physical activity in humans and veterinary species. In cats, one important use of accelerometry is in the study of therapeutics designed to treat degenerative joint disease (DJD) associated pain, where it serves as the most widely applied objective outcome measure. These analyses have commonly used summary measures, calculating the mean activity per-minute over days and comparing between treatment periods. While this technique has been effective, information about...

Data from: Diabetes mellitus, glycemic traits, and cerebrovascular disease: A Mendelian randomization study

Marios Georgakis, Eric Harshfield, Rainer Malik, Nora Franceschini, Claudia Langenberg, Nicholas Wareham, Hugh Markus & Martin Dichgans
Objective: We employed Mendelian randomization (MR) to explore the effects of genetic predisposition to type 2 diabetes (T2D), hyperglycemia, insulin resistance, and β-cell dysfunction on risk of stroke subtypes and related cerebrovascular phenotypes. Methods: We selected instruments for genetic predisposition to T2D (74,124 cases, 824,006 controls), HbA1c levels (n=421,923), fasting glucose levels (n=133,010), insulin resistance (n=108,557), and β-cell dysfunction (n=16,378) based on published genome-wide association studies. Applying two-sample MR, we examined associations with ischemic stroke...

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