Life Sciences Commons^™

Multivariate Adaptive Shrinkage Improves Cross-Population Transcriptome Prediction And Association Studies In Underrepresented Populations, Daniel Araujo, Chris Nguyen, Xiaowei Hu, Anna V. Mikhaylova, Christopher R. Gignoux, Kristin Ardlie, Kent D. Taylor, Peter Durda, Yongmei Liu, George Papanicolaou, Michael H. Cho, Stephen S. Rich, Jerome I. Rotter, Nhlbi Topmed Consortium, Hae Kyung Im, Ani Manichaikul, Heather Wheeler

Biology: Faculty Publications and Other Works

Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized that methods that leverage shared regulatory effects across different conditions, in this case, across different populations, may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWASs) using different methods (elastic net, joint-tissue imputation [JTI], matrix expression quantitative trait loci [Matrix eQTL], multivariate adaptive shrinkage in R [MASHR], and transcriptome-integrated genetic association resource [TIGAR]) and tested their out-of-sample transcriptome prediction accuracy …

Miocene Phytolith And Diatom Dataset From 10.3myo Diatomite Formation, Fernley, Nevada, Usa, Jacopo Niccolò Cerasoni, Megan C. O'Toole, Richa Patel, Yoel E. Stuart

Biology: Faculty Publications and Other Works

Phytoliths are opal silica particles formed within plant tissues. Diatoms are aquatic, single-celled photosynthetic algae with silica skeletons. Phytolith and diatom morphotypes vary depending on local environmental and climatic conditions and because their silicate structures preserve well, the study of phytolith and diatom morphotypes can be used to better understand paleoclimatic and paleoenvironmental dynamics and changes. This article presents original data from an 820cm-deep stratigraphy excavated at the Hazen diatomite deposits, a high-elevation desert paleolake in the Fernley District, Northern Nevada, USA. The site has been studied for an assemblage of fossilized threespine stickleback, Gasterosteus doryssus, that reveal adaptive …

Improving Focality And Consistency In Micromagnetic Stimulation, Hui Ye, Vincent Hall, Jenna Hendee

Biology: Faculty Publications and Other Works

The novel micromagnetic stimulation (μMS) technology aims to provide high resolution on neuronal targets. However, consistency of neural activation could be compromised by a lack of surgical accuracy, biological variation, and human errors in operation. We have recently modeled the activation of an unmyelinated axon by a circular micro-coil. Although the coil could activate the axon, its performance sometimes lacked focality and consistency. The site of axonal activation could shift by several experimental factors, including the reversal of the coil current, displacement of the coil, and changes in the intensity of the stimulation. Current clinical practice with transcranial magnetic stimulation …

Egestion Rates Of Microplastic Fibres In Fish Scaled To In Situ Concentration And Fish Density, Loren Hou, Rachel Mcneish, Timothy Hoellein

Biology: Faculty Publications and Other Works

Microplastics (particles <5 >mm) are commonly found in aquatic organisms across taxonomic groups and ecosystems. However, the egestion rate of microplastics from aquatic organisms and how egestion rates compare to other rates of microplastic movement in the environment are sparsely documented.We fed microplastic fibres to round gobies (Neogobius melanostomus), an abundant, invasive species in the Laurentian Great Lakes. We conducted two trials where round gobies were fed microplastic-containing food either a single time (1 day) or every day over 7 days.There was no difference in microplastic egestion rates from the 1 day or 7 day feeding trials, suggesting no impact of …

Genetic And Environmental Variation Impact Transferability Of Polygenic Risk Scores, Daniel S. Araújo, Heather E. Wheeler

Biology: Faculty Publications and Other Works

Even when polygenic risk scores (PRSs) are trained in African ancestral populations, Kamiza and colleagues showed that genetic and environmental variation within sub-Saharan African populations impacts prediction performance, highlighting the challenges of clinical implementation of PRSs for risk assessment.

Accelerating Peripheral Nerve Regeneration Using Electrical Stimulation Of Selected Power Spectral Densities, Wei-Ming Yu, Madelyn Mccullen, Vincent Chiun-Fan Chen

Biology: Faculty Publications and Other Works

Peripheral nerve injuries are common consequences of extremity trauma or chronic compression with a prevalence of 43.8 per 1 million people (on average) reported in the United States annually, accompanied by a yearly increase in cost of care. Patients suffering from these injuries require surgical procedures and rehabilitative strategies to reinforce their extensive recovery. Several studies have found that the application of electrical stimulation can accelerate peripheral nerve regeneration, thus shortening the time of peripheral nerve growth and reducing the cost of care (Willand et al., 2016). The electrical stimulation paradigms that effectively enhanced functional recovery in most studies employed …

Evolution Of Static Allometry And Constraint On Evolutionary Allometry In A Fossil Stickleback, Kjetil L. Voje, Michael A. Bell, Yoel E. Stuart

Biology: Faculty Publications and Other Works

Allometric scaling describes the relationship of trait size to body size within and among taxa. The slope of the population-level regression of trait size against body size (i.e. static allometry) is typically invariant among closely related populations and species. Such invariance is commonly interpreted to reflect a combination of developmental and selective constraints that delimit a phenotypic space into which evolution could proceed most easily. Thus, understanding how allometric relationships do eventually evolve is important to understanding phenotypic diversification. In a lineage of fossil Threespine Stickleback (Gasterosteus doryssus), we investigated the evolvability of static allometric slopes for nine traits (five …

Attempting Genetic Inference From Directional Asymmetry During Convergent Hindlimb Reduction In Squamates, Samantha Swank, Ethan Elazegui, Sophia Janidlo, Thomas J. Sanger, Michael A. Bell, Yoel E. Stuart

Biology: Faculty Publications and Other Works

Loss and reduction in paired appendages are common in vertebrate evolution. How often does such convergent evolution depend on similar developmental and genetic pathways? For example, many populations of the threespine stickleback and ninespine stickleback (Gasterosteidae) have independently evolved pelvic reduction, usually based on independent mutations that caused reduced Pitx1 expression. Reduced Pitx1 expression has also been implicated in pelvic reduction in manatees. Thus, hindlimb reduction stemming from reduced Pitx1 expression has arisen independently in groups that diverged tens to hundreds of millions of years ago, suggesting a potential for repeated use of Pitx1 across vertebrates. Notably, hindlimb reduction based …

Combining Gwas And Population Genomic Analyses To Characterize Coevolution In A Legume-Rhizobia Symbiosis, Brendan Epstein, Liana T. Burghardt, Katy D. Heath, Michael A. Grillo, Adam Kostanecki, Toumas Hämälä, Nevin D. Young, Peter Tiffin

Biology: Faculty Publications and Other Works

The mutualism between legumes and rhizobia is clearly the product of past coevolution. However, the nature of ongoing evolution between these partners is less clear. To characterize the nature of recent coevolution between legumes and rhizobia, we used population genomic analysis to characterize selection on functionally annotated symbiosis genes as well as on symbiosis gene candidates identified through a two-species association analysis. For the association analysis, we inoculated each of 202 accessions of the legume host Medicago truncatula with a community of 88 Sinorhizobia (Ensifer) meliloti strains. Multistrain inoculation, which better reflects the ecological reality of rhizobial selection in nature …

Gut Dysbiosis In Cutaneous T-Cell Lymphoma Is Characterized By Shifts In Relative Abundances Of Specific Bacterial Taxa And Decreased Diversity In More Advanced Disease, Madeline J. Hooper, T.M. Lewitt, Y. Pang, F.L. Veon, G.E Chlipala, L. Feferman, S.J. Green, D. Sweeney, K.T. Bagnowski, Michael B. Burns, P.C. Seed, J. Choi, J. Guitart, X.A. Zhou

Biology: Faculty Publications and Other Works

Background Cutaneous T-cell lymphoma (CTCL) patients often suffer from recurrent skin infections and profound immune dysregulation in advanced disease. The gut microbiome has been recognized to influence cancers and cutaneous conditions; however, it has not yet been studied in CTCL.ObjectivesTo investigate the gut microbiome in patients with CTCL and in healthy controls.MethodsA case-control study was conducted between January 2019 and November 2020 at Northwestern’s busy multidisciplinary CTCL clinic (Chicago, Illinois, USA) utilizing 16S ribosomal RNA gene amplicon sequencing and bioinformatics analyses to characterize the microbiota present in fecal samples of CTCL patients (n = 38) and age-matched healthy controls (n …

Discordant Population Structure Among Rhizobium Divided Genomes And Their Legume Hosts, Alex B. Riley, Michael A. Grillo, Brendan Epstein, Peter Tiffin, Katy D. Heath

Biology: Faculty Publications and Other Works

Symbiosis often occurs between partners with distinct life history characteristics and dispersal mechanisms. Many bacterial symbionts have genomes comprising multiple replicons with distinct rates of evolution and horizontal transmission. Such differences might drive differences in population structure between hosts and symbionts and among the elements of the divided genomes of bacterial symbionts. These differences might, in turn, shape the evolution of symbiotic interactions and bacterial evolution. Here we use whole genome resequencing of a hierarchically structured sample of 191 strains of Sinorhizobium meliloti collected from 21 locations in southern Europe to characterize population structures of this bacterial symbiont, which forms …

(Non)Parallel Developmental Mechanisms In Vertebrate Appendage Reduction And Loss, Samantha Swank, Thomas Sanger, Yoel E. Stuart

Biology: Faculty Publications and Other Works

Appendages have been reduced or lost hundreds of times during vertebrate evolution. This phenotypic convergence may be underlain by shared or different molecular mechanisms in distantly related vertebrate clades. To investigate, we reviewed the developmental and evolutionary literature of appendage reduction and loss in more than a dozen vertebrate genera from fish to mammals. We found that appendage reduction and loss was nearly always driven by modified gene expression as opposed to changes in coding sequences. Moreover, expression of the same genes was repeatedly modified across vertebrate taxa. However, the specific mechanisms by which expression was modified were rarely shared. …

Somatic Inhibition By Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Electric currents can produce quick, reversible control of neural activity. Externally applied electric currents have been used in inhibiting certain ganglion cells in clinical practices. Via electromagnetic induction, a miniature-sized magnetic coil could provide focal stimulation to the ganglion neurons. Here we report that high-frequency stimulation with the miniature coil could reversibly block ganglion cell activity in marine mollusk Aplysia californica, regardless the firing frequency of the neurons, or concentration of potassium ions around the ganglion neurons. Presence of the ganglion sheath has minimal impact on the inhibitory effects of the coil. The inhibitory effect was local to the …

Transcriptome Prediction Performance Across Machine Learning Models And Diverse Ancestries, Paul Chukwuebuka Okoro, Ryan Schubert, Xiuqing Guo, W. Craig Johnson, Jerome I. Rotter, Ina Hoeschele, Yongmei Liu, Hae Kyung Im, Amy Luke, Lara R. Dugas, Heather Wheeler

Biology: Faculty Publications and Other Works

Transcriptome prediction methods such as PrediXcan and FUSION have become popular in complex trait mapping. Most transcriptome prediction models have been trained in European populations using methods that make parametric linear assumptions like the elastic net (EN). To potentially further optimize imputation performance of gene expression across global populations, we built transcriptome prediction models using both linear and non-linear machine learning (ML) algorithms and evaluated their performance in comparison to EN. We trained models using genotype and blood monocyte transcriptome data from the Multi-Ethnic Study of Atherosclerosis (MESA) comprising individuals of African, Hispanic, and European ancestries and tested them using …

Safety Assessment Of Aconitum-Derived Bulleyaconitine A: A 91-Day Oral Toxicity Study And A Tissue Accumulation Study In Rats, Shi Liang Yin, Feng Xu, Hao Wu, Fei Li, Ge Jin, Zu Qian Wu, Ran Meng, Si Man Ma, Fan Zhou, Peter W. Breslin, Chun Fu Wu, Hong Zhang

Biology: Faculty Publications and Other Works

Background: Bulleyaconitine A (BLA) is a diterpenoid alkaloid from the rhizomes of Aconitum bulleyanum Diels and has been clinically used for chronic pain treatment in China for many years. However, the newly reported adverse events of BLA indicated that BLA still has potential safety issues. Materials and Methods: To assess the safety of BLA, analgesic tests, acute toxicity studies, repeated-dose oral toxicity studies, and tissue distribution studies after single and repeated administration of BLA were carried out. Results: Administration of 0.14 mg/kg BLA showed potent analgesic effects in both analgesic tests. In acute toxicity study, the LD50value of BLA was …

Scientism And Secularism: Learning To Respond To A Dangerous Ideology By J. P. Moreland. Wheaton, Il: Crossway, 2018. 224 Pages. Paperback; $16.99. Isbn: 9781433556906., Michael B. Burns, Joseph Vukov

Biology: Faculty Publications and Other Works

No abstract provided.

Adding The Third Dimension To Studies Of Parallel Evolution Of Morphology And Function: An Exploration Based On Parapatric Lake-Stream Stickleback, Grant E. Haines, Yoel E. Stuart, Dieta Hanson, Tania Tasneem, Daniel I. Bolnick, Hans Ce Larsson, Andrew P. Hendry

Biology: Faculty Publications and Other Works

Recent methodological advances have led to a rapid expansion of evolutionary studies employing three-dimensional landmark-based geometric morphometrics (GM). GM methods generally enable researchers to capture and compare complex shape phenotypes, and to quantify their relationship to environmental gradients. However, some recent studies have shown that the common, inexpensive, and relatively rapid two-dimensional GM methods can distort important information and produce misleading results because they cannot capture variation in the depth (Z) dimension. We use micro-CT scanned threespine stickleback (Gasterosteus aculeatus Linnaeus, 1758) from six parapatric lake-stream populations on Vancouver Island, British Columbia, to test whether the loss …

Scale‐Dependent Effects Of Host Patch Traits On Species Composition In A Stickleback Parasite Metacommunity, Daniel I. Bolnick, Emlyn J. Resetarits, Kimberly Ballare, Yoel E. Stuart, William E. Stutz

Biology: Faculty Publications and Other Works

A core goal of ecology is to understand the abiotic and biotic variables that regulate species distributions and community composition. A major obstacle is that the rules governing species distributions can change with spatial scale. Here, we illustrate this point using data from a spatially nested metacommunity of parasites infecting a metapopulation of threespine stickleback fish from 34 lakes on Vancouver Island, British Columbia. Like most parasite metacommunities, the composition of stickleback parasites differs among host individuals within each host population, and differs between host populations. The distribution of each parasite taxon depends, to varying degrees, on individual host traits …

Molecular And Cellular Mechanisms Of Aging In Hematopoietic Stem Cells And Their Niches, Lei Zhang, Ryan Mack, Peter W. Breslin, Jiwang Zhang

Biology: Faculty Publications and Other Works

Aging drives the genetic and epigenetic changes that result in a decline in hematopoietic stem cell (HSC) functioning. Such changes lead to aging-related hematopoietic/immune impairments and hematopoietic disorders. Understanding how such changes are initiated and how they progress will help in the development of medications that could improve the quality life for the elderly and to treat and possibly prevent aging-related hematopoietic diseases. Here, we review the most recent advances in research into HSC aging and discuss the role of HSC-intrinsic events, as well as those that relate to the aging bone marrow niche microenvironment in the overall processes of …

Axonal Blockage With Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility and decreased efficacy during chronic implantation. A magnetic coil of miniature size can mitigate some of these problems, by coating it with biocompatible material for chronic implantation. However, it is unknown if miniature coils could be effective in axonal blockage and, if so, what the underlying mechanisms are. Here we demonstrate that a submillimeter magnetic coil can reversibly block action potentials …

Spatiotemporal Analysis Of Cochlear Nucleus Innervation By Spiral Ganglion Neurons That Serve Distinct Regions Of The Cochlea, Jennifer L. Scheffel, Samiha S. Mohammed, Chloe K. Borcean, Annie J. Parng, Hyun Ju Yoon, Darwin A. Gutierrez, Wei-Ming Yu

Biology: Faculty Publications and Other Works

Cochlear neurons innervate the brainstem cochlear nucleus in a tonotopic fashion according to their sensitivity to different sound frequencies (known as the neuron’s characteristic frequency). It is unclear whether these neurons with distinct characteristic frequencies use different strategies to innervate the cochlear nucleus. Here, we use genetic approaches to differentially label spiral ganglion neurons (SGNs) and their auditory nerve fibers (ANFs) that relay different characteristic frequencies in mice. We found that SGN populations that supply distinct regions of the cochlea employ different cellular strategies to target and innervate neurons in the cochlear nucleus during tonotopic map formation. ANFs that will …

Character Displacement In The Midst Of Substantial Background Evolution In Anolis Lizard Island Populations, Ambika Kamath, Nicholas C. Herrmann, Kiyoko M. Gotanda, Kum C. Shim, Jacob Lafond, Gannon Cottone, Heather Falkner, Todd S. Campbell, Yoel E. Stuart

Biology: Faculty Publications and Other Works

Negative interactions between species can generate divergent selection that causes character displacement. However, other processes cause similar divergence. We use spatial and temporal replication across island populations of Anolis lizards to assess the importance of negative interactions in driving trait shifts. Previous work showed that the establishment of Anolis sagrei on islands drove resident Anolis carolinensis to perch higher and evolve larger toepads. To further test the interaction's causality and predictability, we resurveyed a subset of islands nine years later. Anolis sagrei had established on one island between surveys. We found that A. carolinensis on this island now perch higher …

Inferred Genetic Architecture Underlying Evolution In A Fossil Stickleback Lineage, Yoel E. Stuart, Matthew P. Travis, Michael A. Bell

Biology: Faculty Publications and Other Works

Inferring the genetic architecture of evolution in the fossil record is difficult because genetic crosses are impossible, the acquisition of DNA is usually impossible and phenotype–genotype maps are rarely obvious. However, such inference is valuable because it reveals the genetic basis of microevolutionary change across many more generations than is possible in studies of extant taxa, thereby integrating microevolutionary process and macroevolutionary pattern. Here, we infer the genetic basis of pelvic skeleton reduction in Gasterosteus doryssus, a Miocene stickleback fish from a finely resolved stratigraphic sequence that spans nearly 17,000 years. Reduction in pelvic score, a categorical measure of …

Esociformes: Esocidae, Pikes, And Umbridae (Mudminnows), Frank H. Mccormick, Terry C. Grande, Cheryl Theile, Melvin L. Warren, J. Andrés López, Mark V. H. Wilson, Roger A. Tabor, Julian D. Olden, Lauren M. Kuehne

Biology: Faculty Publications and Other Works

The order Esociformes (Pikes and Mudminnows) comprises two families, Esocidae (Pikes) and Umbridae (Mudminnows). The Pikes are a small Holarctic (Northern Hemisphere) family, that includes large, elongate predators with duckbill-like snouts full of sharp teeth. Popular with sport fishers, the largest Pikes fight fiercely on hook and line. As piscivorous, voracious, ambush predators, the Pikes play an important functional role in the trophic ecology and fish assemblage structure of many aquatic systems, especially in northern lakes. Other esocids, such as the Olympic Mudminnow, Novumbra hubbsi, and Blackfishes, genus Dallia, are interesting because of their tolerance of low dissolved oxygen and …

Abl1, Overexpressed In Hepatocellular Carcinomas, Regulates Expression Of Notch1 And Promotes Development Of Liver Tumors In Mice, Fang Wang, Wei Hou, Lennox Chitsike, Yingchen Xu, Carlee Bettler, Aldeb Perera, Thomas Bank, Scott J. Cotler, Asha Dhanarajan, Mitchell F. Denning, Xianzhong Ding, Peter W. Breslin, Wenan Qiang, Jun Li, Anthony J. Koleske, Wei Qiu

Biology: Faculty Publications and Other Works

Background & Aims

We investigated whether ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) is involved in development of hepatocellular carcinoma (HCC).

Methods

We analyzed clinical and gene expression data from The Cancer Genome Atlas. Albumin-Cre (HepWT) mice and mice with hepatocyte-specific disruption of Abl1 (HepAbl–/– mice) were given hydrodynamic injections of plasmids encoding the Sleeping Beauty transposase and transposons with the MET gene and a catenin β1 gene with an N-terminal truncation, which induces development of liver tumors. Some mice were then gavaged with the ABL1 inhibitor nilotinib or vehicle (control) daily for 4 weeks. We knocked …

Focal Suppression Of Epileptiform Activity In The Hippocampus By A High-Frequency Magnetic Field, Hui Ye, Vincent Chiun-Fan Chen, Jessica Helon, Nicole Apostolopoulos

Biology: Faculty Publications and Other Works

Electric current has been used for epilepsy treatment by targeting specific neural circuitries. Despite its success, direct contact between the electrode and tissue could cause side effects including pain, inflammation, and adverse biological reactions. Magnetic stimulation overcomes these limitations by offering advantages over biocompatibility and operational feasibility. However, the underlying neurological mechanisms of its action are largely unknown. In this work, a magnetic generating system was assembled that included a miniature coil. The coil was positioned above the CA3 area of mouse hippocampal slices. Epileptiform activity (EFA) was induced with low Mg2+/high K+ perfusion or with 100 µM 4-aminopyridine (4-AP). …

Host Patch Traits Have Scale‐Dependent Effects On Diversity In A Stickleback Parasite Metacommunity, Daniel I. Bolnick, Emlyn J. Resetarits, Kimberly Ballare, Yoel E. Stuart, William E. Stutz

Biology: Faculty Publications and Other Works

Many metacommunities are distributed across habitat patches that are themselves aggregated into groups. Perhaps the clearest example of this nested metacommunity structure comes from multi‐species parasite assemblages, which occupy individual hosts that are aggregated into host populations. At both spatial scales, we expect parasite community diversity in a given patch (either individual host or population) to depend on patch characteristics that affect colonization rates and species sorting. But, are these patch effects consistent across spatial scales? Or, do different processes govern the distribution of parasite community diversity among individual hosts, versus among host patches? To answer these questions, we document …

Talking Trash: A Human Problem With Human Solutions, Lauren Wisbrock, Erin Reynolds, Jen Mertins, Anne Schultz, Timothy Hoellein, Lara K. Smetana

Biology: Faculty Publications and Other Works

No abstract provided.

Facilitating Growth Through Frustration: Using Genomics Research In A Course-Based Undergraduate Research Experience, David Lopatto, Jennifer Jemc Mierisch

Biology: Faculty Publications and Other Works

A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students’ learning experience is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable …

Neuromodulation With Electromagnetic Stimulation For Seizure Suppression: From Electrode To Magnetic Coil, Hui Ye, Stephanie Kaszuba

Biology: Faculty Publications and Other Works

Non-invasive brain tissue stimulation with a magnetic coil provides several irreplaceable advantages over that with an implanted electrode, in altering neural activities under pathological situations. We reviewed clinical cases that utilized time-varying magnetic fields for the treatment of epilepsy, and the safety issues related to this practice. Animal models have been developed to foster understanding of the cellular/molecular mechanisms underlying magnetic control of epileptic activity. These mechanisms include (but are not limited to) (1) direct membrane polarization by the magnetic field, (2) depolarization blockade by the deactivation of ion channels, (3) alteration in synaptic transmission, and (4) interruption of ephaptic …