Biology Commons^™

Disruption Of Cul3-Mediated Ubiquitination Causes Proximal Tubule Injury And Kidney Fibrosis, Turgay Saritas, Catherina A. Cuevas, Mohammed Z. Ferdaus, Christophe Kuppe, Rafael Kramann, Marcus J. Moeller, Jurgen Floege, Jeffrey Singer, James A. Mccormick

Biology Faculty Publications and Presentations

Cullin 3 (CUL3) is part of the ubiquitin proteasomal system and controls several cellular processes critical for normal organ function including the cell cycle, and Keap1/Nrf2 signaling. Kidney tubule-specific Cul3disruption causes tubulointerstitial fibrosis, but little is known about the mechanisms. Therefore, we tested the hypothesis that dysregulation of the cell cycle and Keap1/Nrf2 pathway play a role in initiating the kidney injury upon Cul3 disruption. Cul3 deletion increased expression of cyclin E and p21, associated with uncontrolled proliferation, DNA damage, and apoptosis, all of which preceded proximal tubule injury. The cdk2-cyclin E inhibitor roscovitine did not prevent the effects …

Cullin-3 Dependent Deregulation Of Actn1 Represents A New Pathogenic Mechanism In Nemaline Myopathy, Jordan Blondelle, Kavya Tallapaka, Jane T. Seto, Majid Ghassemian, Madison Clark, Jenni M. Laitila, Adam Bournazos, Jeffrey Singer, Stephan Lange

Biology Faculty Publications and Presentations

Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness, fiber atrophy, and presence of nemaline bodies within myofibers. However, understanding of the underlying pathomechanisms is lacking. Recently, mutations in KBTBD13, KLHL40, and KLHL41, three substrate adaptors for the E3 ubiquitin ligase Cullin-3, have been associated with early-onset nemaline myopathies. We hypothesized that deregulation of Cullin-3 and its muscle protein substrates may be responsible for disease development. Using Cullin-3–knockout mice, we identified accumulation of non-muscle α-actinins (ACTN1 and ACTN4) in muscles of these mice, which we also observed in patients with mutations in KBTBD13. Our …

Differential Activity Of Coexisting Prochlorococcus Ecotypes, Anne Thompson, Kathleen Kouba

Biology Faculty Publications and Presentations

The abundance and widespread distribution of the unicellular cyanobacterium Prochlorococcus is attributed to its extensive genetic diversity. At least twelve distinct clades, or ecotypes, of Prochlorococcus have been discovered so far, and follow distinct distribution patterns over horizontal and vertical gradients in the oligotrophic ocean. However, multiple ecotypes (and sub-ecotypes) of Prochlorococcus always coexist in varying proportions. While laboratory experiments and genomic analysis suggest that ecotypes contribute differently to biogeochemical cycles, no studies have tested the differential activity of coexisting ecotypes in natural assemblages of Prochlorococcus. Here, we performed DNA stable isotope probing (DNA-SIP) experiments in on-deck incubations of oceanic …

Mitosrnas And Extreme Anoxia Tolerance In Embryos Of The Annual Killifish Austrofundulus Limnaeus, Claire L. Riggs, Steven Cody Woll, Jason Podrabsky

Biology Faculty Publications and Presentations

Embryos of the annual killifish Austrofundulus limnaeus are the most anoxia-tolerant vertebrate. Annual killifish inhabit ephemeral ponds, producing drought and anoxia-tolerant embryos, which allows the species to persist generation after generation. Anoxia tolerance and physiology vary by developmental stage, creating a unique opportunity for comparative study within the species. A recent study of small ncRNA expression in A. limnaeus embryos in response to anoxia and aerobic recovery revealed small ncRNAs with expression patterns that suggest a role in supporting anoxia tolerance. MitosRNAs, small ncRNAs derived from the mitochondrial genome, emerged as an interesting group of these sequences. MitosRNAs derived from …

Small Rna Mgrr Regulates Sensitivity Of Escherichia Fergusonii To Oxidative Stress, Austin Paul Wright

Dissertations and Theses

Non-coding small RNAs (sRNAs) are integral to post-transcriptional gene regulation in bacteria. The function of an sRNA is dependent on both secondary structure and the sequence of its unstructured seed region. The sRNA seed region typically base-pairs with target mRNAs to down-regulate the expression of target genes by blocking the ribosome-binding site or by promoting RNase-mediated degradation of the sRNA-mRNA complex. sRNAs have also been shown to increase expression of target genes by releasing RNA secondary structures that block ribosome-binding sites. Selective pressure to maintain sRNA function conserves the sequence of the sRNA seed region, but mutations in mRNA sequences …

Accumulation And Transmission Dynamics Of A Naturally-Occurring Mtdna Deletion In Caenorhabditis Briggsae, Jennifer Anne Sullins

Dissertations and Theses

Maintaining mitochondrial genome sequence integrity is essential for preserving normal mitochondrial function. Several human diseases have been associated with heteroplasmic mitochondrial genome mutations, but few genetic systems can simultaneously represent pathogenic mitochondrial genome evolution and inheritance. The nematode Caenorhabditis briggsae is one such model. Natural C. briggsae isolates are globally-distributed and phylogenetically grouped into three distinct clades, with isolates exhibiting varying levels of a large-scale mtDNA deletion, nad5∆. Furthermore, a small subset of clade II isolates exhibits putative compensatory mutations that may reduce the risk of deletion formation and accumulation in those populations. In this thesis, the author characterizes the …

Dynamics Of Prochlorococcus Diversity And Photoacclimation During Short-Term Shifts In Water Column Stratification At Station Aloha, Anne W. Thompson, Ger Van Den Engh, Nathan A. Ahlgren, Kathleen Kouba, Samantha Ward, Samuel T. Wilson, David M. Karl

Biology Faculty Publications and Presentations

The cyanobacterium Prochlorococcus is the dominant phototroph in surface waters of the vast oligotrophic oceans, the foundation of marine food webs, and an important component of global biogeochemical cycles. The prominence of Prochlorococcus across the environmental gradients of the open ocean is attributed to its extensive genetic diversity and flexible chlorophyll physiology, enabling light capture over a wide range of intensities. What remains unknown is the balance between temporal dynamics of genetic diversity and chlorophyll physiology in the ability of Prochlorococcus to respond to a variety of short (approximately 1 day) and longer (months to year) changes in the environment. …

Dual Gain And Loss Of Cullin 3 Function Mediates Familial Hyperkalemic Hypertension, Ryan J. Cornelius, Chang Zhang, Kayla J. Erspamer, Larry N. Agbor, Curt D. Sigmund, Jeffrey Singer, Chao-Ling Yang, David H. Ellison

Biology Faculty Publications and Presentations

Familial hyperkalemic hypertension is caused by mutations in with-no-lysine kinases (WNKs) or in proteins that mediate their degradation, kelch-like 3 (KLHL3) and cullin 3 (CUL3). Although the mechanisms by which WNK and KLHL3 mutations cause the disease are now clear, the effects of the disease-causing CUL3Δ403-459 mutation remain controversial. Possible mechanisms, including hyperneddylation, altered ubiquitin ligase activity, decreased association with the COP9 signalosome (CSN), and increased association with and degradation of KLHL3 have all been postulated. Here, we systematically evaluated the effects of Cul3Δ403-459 using cultured kidney cells. We first identified that the catalytically active CSN subunit jun activation domain-binding …

Small Noncoding Rna Profiles Along Alternative Developmental Trajectories In An Annual Killifish, Amie L. Romney, Jason E. Podrabsky

Biology Faculty Publications and Presentations

Embryonic development of Austrofundulus limnaeus can occur along two phenotypic trajectories that are physiologically and biochemically distinct. Phenotype appears to be influenced by maternal provisioning based on the observation that young females produce predominately non-diapausing embryos and older females produce mostly diapausing embryos. Embryonic incubation temperature can override this pattern and alter trajectory. We hypothesized that temperature-induced phenotypic plasticity may be regulated by post-transcriptional modification via noncoding RNAs. As a first step to exploring this possibility, RNA-seq was used to generate transcriptomic profiles of small noncoding RNAs in embryos developing along the two alternative trajectories. We find distinct profiles of …

Displacement Of The Transcription Factor B Reader Domain During Transcription Initiation, Stefan Dexl, Robert Reichelt, Katharina Kraatz, Sarah Schulz, Dina Grohmann, Michael S. Bartlett, Michael Thomm

Biology Faculty Publications and Presentations

Transcription initiation by archaeal RNA polymerase (RNAP) and eukaryotic RNAP II requires the general transcription factor (TF) B/ IIB. Structural analyses of eukaryotic transcription initiation complexes locate the B-reader domain of TFIIB in close proximity to the active site of RNAP II. Here, we present the first crosslinking mapping data that describe the dynamic transitions of an archaeal TFB to provide evidence for structural rearrangements within the transcription complex during transition from initiation to early elongation phase of transcription. Using a highly specific UV-inducible crosslinking system based on the unnatural amino acid para-benzoyl-phenylalanine allowed us to analyze contacts of …

Impact Of Suburban Landscape Features On Gene Flow Of The Model Invasive Grass, Brachypodium Sylvaticum, Tina Marie Arredondo

Dissertations and Theses

Rapid range expansion of newly invasive species provides a unique opportunity for studying patterns of dispersal and gene flow. In this thesis, I examined the effect of landscape features on gene flow in the invasive grass Brachypodium sylvaticum at the edge of its expanding range. I used genome-wide Single Nucleotide Polymorphism (SNP) surveys of individuals from 22 locations in the Clackamas Watershed in the Portland, Oregon metropolitan region to assess genetic diversity and structure, to identify putative source populations, and to conduct landscape genetic analyses. Resistance surfaces were created for each landscape feature, using ResistanceGA to optimize resistance parameters. My …

The Limitations Of Dna Interstrand Cross-Link Repair In Escherichia Coli, Jessica Michelle Cole

Dissertations and Theses

DNA interstrand cross-links are a form of genomic damage that cause a block to replication and transcription of DNA in cells and cause lethality if unrepaired. Chemical agents that induce cross-links are particularly effective at inactivating rapidly dividing cells and, because of this, have been used to treat hyperproliferative skin disorders such as psoriasis as well as a variety of cancers. However, evidence for the removal of cross-links from DNA as well as resistance to cross-link-based chemotherapy suggests the existence of a cellular repair mechanism. Characterizing the pathways involved in DNA interstrand cross-link repair has been challenging due to the …

Follow The Rain? Environmental Drivers Of Tyrannus Migration Across The New World, Maggie P. Macpherson, Alex E. Jahn, Michael T. Murphy, Daniel H. Kim, Victor R. Cueto, Diego T. Tuero, Elliot D. Hill

Biology Faculty Publications and Presentations

Predictable seasonal changes in resources are thought to drive the timing of annual animal migrations; however, we currently understand little about which environmental cues or resources are tracked by different migratory bird species across the planet. Understanding which environmental cues or resources birds track in multiple migratory systems is a prerequisite to developing generalizable conservation plans for migratory birds in a changing global environment. Within the New World, climatic differences experienced by Nearctic–Neotropical migratory (NNM; i.e. breed in North America and spend the nonbreeding period in the Neotropics) and Neotropical austral migratory (NAM; i.e. breed and spend the nonbreeding period …

Comparative Genetic And Genomic Analysis Of The Novel Fusellovirus Sulfolobus Spindle-Shaped Virus 10, David Andrew Goodman

Dissertations and Theses

Viruses that infect thermophilic Archaea are unique in both their structure and genetic makeup. The lemon-shaped fuselloviruses - which infect members of the order Sulfolobales, growing optimally at 80º C and pH 3 - are some of the most ubiquitous and best studied viruses of the thermoacidophilic Archaea. They provide a malleable and useful genetic tool for probing into the functions of their host, as well as the host responses to infection. Nonetheless, much about these viruses remains to be learned to further understand their morphological, genetic, and life cycle characteristics.

In order to investigate these aspects of these …

Water Flow And Biofilm Cover Influence Environmental Dna Detection In Recirculating Streams, Arial Shogren, Jennifer L. Tank, Scott P. Egan, Olivia August, Emma J. Rosi, Brittany R. Hanrahan, Mark A. Renshaw, Crysta A. Gantz, Diogo Bolster

Environmental Science and Management Faculty Publications and Presentations

The increasing use of environmental DNA (eDNA) for determination of species presence in aquatic ecosystems is an invaluable technique for both ecology as a field and for the management of aquatic ecosystems. We examined the degradation dynamics of fish eDNA using an experimental array of recirculating streams, also using a “nested” primer assay to estimate degradation among eDNA fragment sizes. We introduced eDNA into streams with a range of water velocities (0.1–0.8 m s–1) and substrate biofilm coverage (0–100%) and monitored eDNA concentrations over time (∼10 d) to assess how biophysical conditions influence eDNA persistence. We found that the presence …

Assembly And Analysis Of Unmapped Genome Sequence Reads Reveal Novel Sequence And Variation In Dogs, Lindsay Adrian Holden, Meharji Arumilli, Marjo K. Hytönen, Sruthi Hundi, Jarkko Salojärvi, Kim H. Brown, Hannes Lohi

Biology Faculty Publications and Presentations

Dogs are excellent animal models for human disease. They have extensive veterinary histories, pedigrees, and a unique genetic system due to breeding practices. Despite these advantages, one factor limiting their usefulness is the canine genome reference (CGR) which was assembled using a single purebred Boxer. Although a common practice, this results in many high-quality reads remaining unmapped. To address this whole-genome sequence data from three breeds, Border Collie (n = 26), Bearded Collie (n = 7), and Entlebucher Sennenhund (n = 8), were analyzed to identify novel, non- CGR genomic contigs using the previously validated pseudo-de novo assembly pipeline. We …

Comparative Genetic And Genomic Analysis Of The Novel Fusellovirus Sulfolobus Spindle-Shaped Virus 10, David Andrew Goodman, Kenneth M. Stedman

Biology Faculty Publications and Presentations

Viruses that infect thermophilic Archaea are unique in both their structure and genetic makeup. The lemon-shaped fuselloviruses—which infect members of the order Sulfolobales, growing optimally at 80 C and pH 3—are some of the most ubiquitous and best studied viruses of the thermoacidophilic Archaea. Nonetheless, much remains to be learned about these viruses. In order to investigate fusellovirus evolution, we have isolated and characterized a novel fusellovirus, Sulfolobus spindle-shaped virus 10 (formerly SSV-L1). Comparative genomic analyses highlight significant similarity with both SSV8 and SSV9, as well as conservation of promoter elements within the Fuselloviridae. SSV10 encodes five ORFs with no …

Completion Of Dna Replication In Escherichia Coli, Brian Michael Wendel

Dissertations and Theses

To maintain genomic integrity, all cells must accurately duplicate their genetic material in order to provide intact and complete copies to each daughter cell following cell division. Successful inheritance of chromosomal information without changing even a single nucleotide requires accurate and robust DNA replication. This requires that cells tightly control replication initiation from the origin(s), processive elongation of the replisome, and the completion of DNA replication by resolving convergent replication forks ensuring that each sequence is duplicated without alteration. Unlike initiation and elongation, the process by which replication forks converge and are resolved into two discrete, inheritable DNA molecules is …

Maternal Angiotensinogen Genotype And Fetal Sex Impact Uteroplacental Function And The Developmental Origins Of Stress-Induced Hypertension, Jessica Faith Hebert

Dissertations and Theses

Fetal growth restriction (FGR) is a common and potentially life-threatening complication that affects 5-10% of human pregnancies. Maternal genetic predisposition and fetal male sex are known risk factors, but the underlying mechanisms are unknown. To study a known maternal genetic risk factor and the impact of fetal sex, we employed a published transgenic (TG) mouse model, which was designed to mimic a common human angiotensinogen (AGT) promoter variant associated with a 20% increase in circulating AGT levels. We hypothesized that TG dams would deliver growth restricted pups and that the underlying mechanism would be related to differences in maternal uterine …

Sexually Dimorphic Patterns Of Cell Proliferation In The Brain Are Linked To Seasonal Life-History Transitions In Red-Sided Garter Snakes, Deborah Lutterschmidt, Ashley R. Lucas, Ritta A. Karam, Vicky T. Nguyen, Meghann R. Rasmussen

Biology Faculty Publications and Presentations

Seasonal rhythms in physiology and behavior are widespread across diverse taxonomic groups and may be mediated by seasonal changes in neurogenesis, including cell proliferation, migration, and differentiation. We examined if cell proliferation in the brain is associated with the seasonal life-history transition from spring breeding to migration and summer foraging in a free-ranging population of red-sided garter snakes (Thamnophis sirtalis) in Manitoba, Canada. We used the thymidine analog 5-bromo-2′-deoxyuridine (BrdU) to label newly proliferated cells within the brain of adult snakes collected from the den during the mating season or from a road located along their migratory route. …

Interplay Of Transcription Factor E And Spt4/5 During Transcription Initiation In Pyrococcus Furiosus, Kimberly Kay Sheffield

Dissertations and Theses

Transcription, the first step in gene expression, is a highly regulated process which relies on a multi-protein complex to occur. Among these proteins are transcription factors, including initiation and elongation factors, which play differing roles in early and late stages of transcription. The mechanisms of transition from transcription initiation to elongation are not well understood in archaea, nor are the structures of the transcription factors involved. For transcription to occur in vitro, transcription factors TATA binding protein (TBP) and Transcription Factor B (TFB) are sufficient to allow RNA polymerase (RNAP) to synthesize RNA from template DNA. Another factor, Transcription …

Fungal Endophytes In A Seed-Free Host: New Species That Demonstrate Unique Community Dynamics, Brett Steven Younginger

Dissertations and Theses

Fungal endophytes are highly diverse, cryptic plant endosymbionts that form asymptomatic infections within host tissue. They represent a large fraction of the millions of undescribed fungal taxa on our planet with some demonstrating mutualistic benefits to their hosts including herbivore and pathogen defense and abiotic stress tolerance. Other endophytes are latent saprotrophs or pathogens, awaiting host plant senescence to begin alternative stages of their life cycles. Most, however, are likely plant commensals with no observable benefits to their hosts while under study. Yet, when considering the context-dependence that may determine plant resistance to pathogen attack, the consortium of endophytes present …

Understanding The Impacts Of Urbanization On The Avian Community Of Portland Oregon And Evaluation Of The Portland Oregon Backyard Habitat Certification Program, Andrew Daniel Gibbs

Dissertations and Theses

Over fifty percent of humans live in cities. The environmental cost of this is massive, as is the potential for utilizing privately held yards as an integral part of conservation in urban areas. The Backyard Habitat Certification Program (BHCP) in Portland, Oregon, was established to reduce invasive plants, support wildlife, and promote conservation. The program involves > 3000 yards certified at three tiers. While onsite inspections are required to verify compliance, there has never been an assessment of the value of these yards to wildlife. Chapter 1 examined the relationships between the urban landscape and bird distributions outside of yards. Chapter …

Investigating The Role Of Genomic Variation In Susceptibility To Environmental Chemicals Across Populations, Lindsay Adrian Holden

Dissertations and Theses

No two individuals are identical. This is true at the genetic level and at the phenotypic level. One of the traits that varies between populations is toxicant susceptibility: some individuals are sensitive to the effects of environmental chemical exposure, and others are resistant. This body of work aims to address the impact of genomic copy number variants (CNV)--large (>1 Kb) duplications or deletions across the genome--on the toxicant-susceptibility phenotype.

Herein copy number variants were characterized across three commonly used laboratory strains of zebrafish (Danio rerio) and mRNA expression phenotypes were identified in the same strains. It was found that …

Interstrand Crosslink Resistance In Escherichia Coli, Jedidiah D. Acott, Jessica M. Cole, Charmain Courcelle, Justin Courcelle

Student Research Symposium

8-methoxypsoralen is a photoactivated DNA-intercalating agent, which after absorbing two high-energy UVA photons, covalently binds pyrimidine bases on both DNA strands, to form an interstrand crosslink (ICL). These lesions completely block replication and transcription, and are widely used in chemotherapies; yet the mechanism by which they are processed remains poorly understood. In 1985, Ahmed and Holland reported an Escherichia coli mutant demonstrating hyper-resistance to ICL-inducing agents. The mutation was mapped to 57.2 minutes on the chromosome, and potentially encoded a 55-kDa protein that was induced as part of the SOS response. Although these genes remain unidentified, hscA and hscB map …

Waking Students Up With Explorations Of Metabolic Dormancy: A Pilot Study Of The Killifish Cure, Emma Goodwin, Daniel E. Zajic, Jason E. Podrabsky, Erin E. Shortlidge

Student Research Symposium

A national goal for education reform is to provide opportunities for all biology undergraduates to participate in research. Traditionally, undergraduates gain research experience by apprenticing in faculty-led research labs; however, only a fraction of undergraduates have access to these opportunities. Course-based Undergraduate Research Experiences (CUREs) are a type of laboratory course where students conduct experiments to answer relevant research questions, thus allowing undergraduates to gain authentic research experience at a large scale. To increase equity in opportunities for biology undergraduates to participate in authentic scientific research at Portland State University (PSU), we have designed and implemented a CURE to pilot …

Unique E3 Ligase Complexes Regulate Levels Of Cyclin E, Katia De Oliveira Rebola, Jeffrey Dean Simger

Student Research Symposium

Cyclin E is an evolutionarily conserved protein whose essential function is to promote the cell cycle transition from G1 to S phase. Cul3 is the main component of the pathway that controls Cyclin E ubiquitination, playing an important role in the normal cell cycle regulation in vivo. The binding between Cul3 and Cyclin E does not occur directly and requires a BTB domain protein to act as a substrate adaptor. The substrate linker responsible for this binding is known as RhoBTB3. Muf1, a largely uncharacterized protein of unknown function, is able to bind to RhoBTB3 directly indicating that it might …

Effect Of Microbes On The Growth And Physiology Of The Dioecious Moss, Ceratodon Purpureus, Caitlin Ann Maraist

Dissertations and Theses

The microorganisms colonizing plants can have a significant effect on host phenotype, mediating such processes as pathogen resistance, stress tolerance, nutrient acquisition, growth, and reproduction. Research regarding plant-microbe interactions has focused almost exclusively on vascular plants, and we know comparatively little about how bryophytes -- including mosses, liverworts, and hornworts -- are influenced by their microbiomes. Ceratodon purpureus is a dioecious, cosmopolitan moss species that exhibits sex-specific fungal communities, yet we do not know whether these microbes have a differential effect on the growth and physiology of male and female genotypes. Using a common-garden design, we reared ten axenic genotypes …

Whence And Whither: Acoustic Variability And Biogeography Of Tarsiers In North Sulawesi, Olivia Clare Kulander

Dissertations and Theses

The morning duet calls of eastern tarsiers (Tarsius spp.) in North Sulawesi were recorded and analyzed to examine the effects of geography and geologic history on their call structure. Tarsius species exhibit interspecifically variable duet calls shown to correlate with species differentiation and distribution. They are distributed across Sulawesi, a biogeographically complex island in the Indonesian archipelago, where tectonic activity and multiple glaciations during the Pleistocene generated and modified barriers to their dispersal and gene flow.

Recordings were made at ten locations from November of 2012 through June of 2014. Two locations were categorized as mainland, while eight island …

Taxonomy Based On Science Is Necessary For Global Conservation, Scott A. Thomson, Richard L. Pyle, Shane T. Ahyong, Miguel Alonso-Zarazaga, Joe Ammirati, Luis A. Ruedas, Multiple Additional Authors

Biology Faculty Publications and Presentations

Taxonomy is a scientific discipline that has provided the universal naming and classification system of biodiversity for centuries and continues effectively to accommodate new knowledge. A recent publication by Garnett and Christidis (Garnett ST, Christidis L. Taxonomy anarchy hampers conservation. Nature. 2017; 546(7656):25±27. https://doi.org/10.1038/546025a) expressed concerns regarding the difficulty that taxonomic changes represent for conservation efforts and proposed the establishment of a system to govern taxonomic changes. Their proposal to "restrict the freedom of taxonomic action" through governing subcommittees that would "review taxonomic papers for compliance" and their assertion that "the scientific community's failure to govern taxonomy threatens the …