Biology 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 …

Exploring The Genotypic And Phenotypic Differences Distinguishing Lactobacillus Jensenii And Lactobacillus Mulieris, Adriana Ene, Swarnali Banerjee, Alan J. Wolfe, Catherine Putonti

Mathematics and Statistics: Faculty Publications and Other Works

Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii are dominant species of the urogenital microbiota. Prior studies suggest that these Lactobacillus species play a significant role in the urobiome of healthy females. In our prior genomic analysis of all publicly available L. jensenii and Lactobacillus mulieris genomes at the time (n = 43), we identified genes unique to these two closely related species. This motivated our further exploration here into their genotypic differences as well as into their phenotypic differences. First, we expanded genome sequence representatives of both species to 61 strains, including publicly available …

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 …

Investigating The Bactericidal Activity Of Lactobacillus Crispatus Cell-Free-Supernatant, Omar Majed Abdul-Rahim

Dissertations

Antimicrobial-resistant (AMR) microorganisms are an increasingly seriousproblem worldwide, accounting for thousands of fatalities annually. The current literature on combating AMR pathogens often centers on commensal microbes such as Lactobacillus species, which are most frequently found in asymptomatic ‘healthy’ patients and are believed to elicit protective effects. In this dissertation, I sought to investigate the protective effect of Lactobacillus crispatus, utilizing our vast collection of clinical isolates. Previous work from our lab had found that cell-free-supernatant (CFS) of L. crispatus is robustly bactericidal, and that this killing activity does not depend on hydrogen peroxide or lactic acid. We identified phenyl-lactic acid …

Elucidating The Function Of An Evolutionarily Conserved Col2Α1 Isoform During Vertebrate Development, Charles Lantz H. Ingersoll

Master's Theses

ABSTRACT

Formation of skeletal structural elements during vertebrate embryogenesis is largely a

conserved evolutionary process that employs numerous conserved genes and pathways. One

critical gene in this process is the highly conserved vertebrate Type II Collagen alpha 1 (col2α1).

It produces multiple splice isoforms that have different functions and expression patterns during

skeletogenesis. Two of the primary isoforms are of great interest; variant 1, the primary

embryonic isoform, and variant 2, a post embryonic isoform. While the more commonly known

post-embryonic isoform has been well studied over the last 30 years, identification of a unique

role for the evolutionarily conserved …

Development And Characterization Of A Tissue-Specific Reporter Line For Monitoring Circadian Clock Transcriptional Activity, Lilyan Mather

Master's Theses

Daily rhythms in physiology and behavior are produced by a circadian system consisting of a central clock located in the brain and peripheral clocks located in various peripheral tissues. Circadian clocks track time of day through the presence of a molecular clock that functions as a transcriptional-translational feedback loop. In the nucleus, the transcription factors CLOCK (CLK) and CYCLE (CYC) activate transcription of clock genes period (per) and timeless (tim). PER and TIM proteins slowly accumulate in the cytoplasm before entering the nucleus, where they inhibit CLK and CYC, and therefore repress their own transcription. Degradation of nuclear PER and …

Comparison Of Feeding Functional Morphology Development In North American Esocids, Cheryl Theile

Master's Theses

Esocidae is a family of freshwater fishes within order Esociformes known for its long, cylindrical bodies, duck-bill snouts, and an impressive number of sharp teeth. There are four species, including two subspecies, in North America with areas of overlap of their geographic distribution. These ambush predators change diets from invertebrate prey to vertebrate prey during their first year of life, and the timing of this shift varies between species. In particular, the sister species Esox lucius (Northern Pike) and Esox masquinongy (Muskellunge) overlap in the upper Midwest, but E. masquinongy transitions to a vertebrate diet sooner in its development than …

Rapid Radiation Of Zeiformes Revealed Through Comparison Of Jaw Morphologies, Jeffrey Peters

Master's Theses

Zeiformes (e.g., Dories, Lookdown dories, Tinselfishes, Oreos) are a deep (1000 m) to mid-water (100 m) marine order of acanthomorph fishes with a circumpolar distribution, and a fossil record extending back to the Late Cretaceous. The order consists of 33 species across six families. The phylogenetic placement of the Zeiformes within Teleostei has been debated, but more recent studies based on both molecular and morphological data place Zeiforms within Paracanthopterygii closely related to Gadiformes. Zeiformes are characterized by anal and dorsal profiles that contain a variable number of fin rays and spines. They are mostly deep bodied, highly compressed fishes …

Biofilms On Plastic Litter: Community Composition And Activity And The Effects On Ecosystem Processes, Raul F. Lazcano

Master's Theses

The rapid increase of plastic production and disposal has resulted in plastic pollution becoming a global problem. In aquatic ecosystems, plastic litter is a substrate for biofilms, but little research has simultaneously assessed the effects of plastic litter on biofilm activity, community composition, and ecosystem processes. Our objectives were to: (1) measure biofilm activity and community composition on plastic litter relative to a natural surface in an urban river and (2) assess the impact of microplastic pollution on ecosystem metabolism and N2 flux in an oligotrophic lake. For objective (1) we incubated three common plastics with distinct physical and chemical …

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.

Il-27 Signaling In The Maintenance Of Intestinal Barrier Following Ethanol Intoxication And Burn Injury, Marisa Luck

Dissertations

Roughly half of burn patients that are hospitalized in the United States each year have detectable blood alcohol levels. Alcohol intoxication at the time of burn injury leads to worse outcomes, including longer hospital stays, increased rates of infection, and death. One of the severe consequences of intoxication and burn injury is the disruption of the gastrointestinal (GI) tract, which houses the largest reservoir of bacteria in the human body. Leakiness of the gut barrier can contribute to inflammation, infection, or sepsis from gut-derived microbes. Interleukin-27 (IL-27) is a cytokine that has shown some beneficial effects in other models of …

A Role For Notch Signaling In Drosophila Spermatogenesis, Adrianna Soriano

Master's Theses

The Notch signaling pathway has diverse functions in male and female gonad development. In Drosophila male embryos, Notch specifies hub cell fate in somatic gonadal precursor cells (SGPs), which are important for maintaining germline stem cells and somatic cyst stem cells throughout the lifetime of adult flies. However, a role for Notch signaling in adult males has only started to emerge recently. Nonetheless, we still don’t understand how the Notch pathway functions to regulate spermatogenesis. Notch has been established to be important for the fertility of multiple systems, including mammals, and must be properly regulated for proper spermatogenesis, but the …

The Evolutionary And Morphological Diversification Of The Subtribe Papionina, Sophie B. Labelle

Master's Theses

Analysis of variation is critical in understanding evolutionary processes. The subtribe Papionina, defined commonly as baboons and their closest relatives, is a highly morphologically diverse group of primates that is useful for the examination of the relationship between variation and evolution. The subtribe is also a valuable behavioral, ecological, and morphological analogy for hominins. This study uses landmark-based cranial geometric morphometric data and multivariate analysis to test whether the pattern of morphological diversification present in Papionina is consistent with genetic drift and/or selection. The study sample consists of six extant genera of Papionin, represented by ~500 individuals collected by Michelle …

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 …

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 …

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 …