The First World War (1914-1918) introduced the world to the horrors of warfare on an industrial scale. But it also gave rise to the one of the most dynamic and active anti-war movements of the 20th century. This research explores the activities of the local Pacific Northwest anti-war movement during World War I. National resistance to the militarist and imperialist policies of the United States peaked during the war period, and the Seattle anti-war movement provides a fascinating case study of how socialists, anarchists, labor unions and pacifists organized a robust anti-war movement. Using a wide variety of contemporary local newspapers, letters, activist memoirs and labor union meeting minutes, this study weaves together the story of Seattle’s radical and pacifist organizations during the First World War. This study finds that despite aggressive persecution from the Federal government, conservative labor unions and pro-war business interests, the Seattle anti-war coalition continued to offer active and radical resistance to militarist policies up until the end of the war.

We are interested in the effects of naturally secreted defensins on viral replication. Defensins are small, cysteine-rich, antimicrobial peptides produced by the innate immune system. Although most studies of defensins have focused on their antimicrobial activity, we have shown in vitro that growth of enteric mouse adenovirus 2 (MAdV-2) is unexpectedly enhanced by defensins. Since this observation was made using purified defensins, we sought to determine if naturally secreted defensins also enhance enteric viral infection. Mouse defensins are exclusively produced by Paneth cells (PCs) in the small intestine. As isolated PCs are not culturable, we utilize a novel 3D small intestinal organoid model, which allows us to grow primary small intestinal epithelial cells in culture. The organoid lumen is topologically equivalent to the apical side of the small intestine. Thus, to mimic oral infection, I directly microinjected the virus into the organoid lumen. I first demonstrated that MAdV-2 replicates in wild-type organoids. Then, I compared the growth of MAdV-2 in wild-type organoids to growth in knockout organoids that do not produce functional defensins. I found that, consistent with the enhanced infection, replication was accelerated in the wild-type organoids as measured by plaque forming units. To confirm these results, and to examine any effect of defensins on viral tropism, I created and characterized a fluorescently tagged construct of MAdV-2, in which I fused green fluorescent protein (GFP) to a minor capsid protein. After microinjection, more green cells were observed in the wild-type organoids. Enteric viruses are routinely exposed to defensins during natural infection. Therefore, the observed enhancement of MAdV-2 may represent a novel mechanism by which enteric viruses hijack a host defense peptide and use it to augment their own infection. Future studies will look at enhancement of other enteric viruses and use additional models with altered levels of defensin expression.

Placental mammals (Eutheria) are one of the most ecologically diverse and dominant groups of terrestrial vertebrates alive today. However, prior to the Cretaceous-Paleogene (K-Pg) mass extinction event 66 million years ago (m.y.), two groups of mammals known as multituberculates and metatherians (group including marsupials) were far more successful in terms of number of species (species richness) and relative abundance. Substantial paleontological research has been conducted on the recovery of mammals immediately after the K-Pg mass extinction and their major diversification 5-10 million years later, but relatively little is known about the transition from recovery to diversification in the intervening interval. Recent research suggests that ca. 65 to 64.8 m.y. the placental radiation began, but whether this is an artifact of sampling or a meaningful evolutionary trend remains somewhat unclear. Here, I add to our knowledge of this important interval in mammalian evolution by describing and analyzing a new sample of fossils from the upper Tullock Formation of northeastern Montana, USA. The data set consists of over 70 isolated fossil teeth from the Horsethief Canyon 1 Locality, nearly doubling the size of the previously known sample. I identified each specimen to at least family level based on morphology and dimensions. Using the resulting identifications, I quantified the species richness and relative abundance of the major mammal groups: Multituberculata, Metatheria, “archaic ungulates,” Primates, “insectivorans,” Triisodontidae, Creodonta, Taeniodonta, and Pantodonta. Species richness was greatest for “archaic ungulates,” with more than 10 species, and lowest for metatherians, with 0 species. Primates had a relative abundance of ~55%, “archaic ungulates” ~27%, Multituberculates ~16%, and “insectivorans” ~1.6%. These results corroborate previous research implicating this time period as the beginning of placental radiation and takeover, and help illuminate patterns of decline and diversification during this critical chapter in mammalian history.

Modern frogs and toads (Anura) are environmentally sensitive vertebrates that are often viewed as bellwether taxa for the modern biodiversity crisis. As such, one would expect that they did not fare well in the Cretaceous-Paleogene (K-Pg) mass extinction event (ca. 66 million years ago) that killed off the non-avian dinosaurs. However, relative to other taxa, little is known about Late Cretaceous and early Paleogene anurans or how they fared in the K-Pg event. I have documented temporal changes in anuran diversity leading up to and across the K-Pg boundary, based on the vertebrate microfossil assemblages in the Hell Creek and Tullock formations in Garfield County, Montana. These geologic formations span approximately the last two million years of the Cretaceous and the first one million years of the Paleogene. I have identified known anuran species and distinct morphotypes, which likely represent unnamed species, from more than 200 isolated fossil anuran jaws and hip bones. Initial results, based on maxillae, show an increase in anuran species richness from 9 morphospecies in the lower Hell Creek Formation to 17 morphospecies in the middle of the formation. Then, species richness drops before the K-Pg boundary down to 9 morphotypes in the upper Hell Creek Formation. Anuran fossils are relatively scarce after the K-Pg boundary: the lower middle Tullock Formation includes one species that locally survived the mass extinction and one apparent immigrant taxon. Later in the middle Tullock Formation, I document only one unnamed immigrant taxon. These results parallel pre-K-Pg declines in some vertebrate taxa (e.g., mammals) from this study area but contrast with the high survivorship of more fully aquatic lissamphibians (e.g., salamanders). I hypothesize that the high levels of extinction suffered by anurans at the K-Pg boundary may be due to the greater vulnerability of their more terrestrial life habit.  My research aims to bring a greater understanding to the timing and mechanisims of one of the most important events in the history of terrestrial life (the K-Pg mass extinction), and possibly give insite into the current biodiversity crisis effecting extant amphibians.

Teledermatology is a clinical service program hosted by the VA Puget Sound to deliver expert dermatology care to underserved and rural veterans in the Pacific Northwest Region. During the four years since program inception, 25,830 consultations were completed on 13,249 unique Veterans resulting in the diagnosis and treatment of 23,332 conditions. The aim is to evaluate and improve Teledermatology processes and outcomes, rendering them non-inferior to face-to-face encounters with the few board-certified dermatologists in the VA healthcare system. Melanoma care is complex, requiring secure handoffs from primary care to dermatologists, general surgeons, surgical oncologists and other specialists, often in different locations. Dropped or missed handoffs risk allowing tumors to invade and spread; a system that safely focuses care in the primary care team might achieve better outcomes. The VA Teledermatology program educates and trains primary care providers to perform surgical procedures. The purpose of this study was to measure the uptake of the surgical education and assess its safety and benefit in reducing the amount of travel miles and time to receive care. 185 veterans identified as having malignant melanomas or severely dysplastic nevi between July 1, 2009 and June 30, 2013, met criteria for analysis. Of 361 surgical procedures performed for diagnosis and treatment 191 (53%) were performed by primary care clinicians with 1.95% biopsy complication rate compared to 3.33% for the equivalent procedure performed by dermatologists, general surgeons or specialty surgeons and a 5.41% wide-local excision complication rate compared to 12.12% and 9.38% for dermatologists and general surgeons respectively. These results show that a significant fraction of surgical procedures for diagnosis and treatment of malignant melanoma and severely dysplastic nevi can be safely performed in rural clinics by trained primary care providers. Future studies set will focus on the timelines for care and longitudinal follow up for outcomes.

During the Late Cretaceous (100 to 66 million years ago), most mammals were relatively small (< 200 g) and occupied very few ecological niches. Didelphodon vorax was the largest mammal of that time period (~1.7 kg). Thus, study of Didelphodon vorax is key to understanding the range of mammal evolution during the Late Cretaceous. Although a significant amount of research has been conducted on this species, it has exclusively focused on cranial elements, specifically dentition and rare skull fragments. From these elements, researchers have hypothesized Didelphodon had a semiaquatic habit and bulbous premolars for a shell-crushing diet. However, a major limitation of these hypotheses is that they have not been tested with postcranial data. I describe parts of a disarticulated but associated partial skull and skeleton of Didelphodon vorax. The fossils were excavated from a locality called Marshoupial in the Late Cretaceous-age Hell Creek Formation in McCone County, Montana. Specifically, I compared the morphology and dimensions of the hands and feet to those of extant marsupials (e.g., Didelphis virginiana). I have determined that the hand and foot elements preserved at the Marshoupial locality include two distal metacarpals, one distal metatarsal, one complete proximal phalanx (digit III or IV), one distal phalanx, one proximal phalanx (digit II or V), and three intermediate phalanges. From these elements, I infer the locomotion, habitat, and body size of Didelphodon vorax to better understand the ecology of this species. In preliminary observations, Didelphodon vorax is larger than Didelphis virginiana (1.9–6.0 kg) and the shape of its distal phalanx (ungual flexor protruding anteriorly, broad profile in dorsal view) resembles that of aquatic extant mammals. If this interpretation of Didelphodon vorax is confirmed, it would suggest some Late Cretaceous mammals were more ecologically diverse than previously thought.

The Mesozoic Era (250–66 million years ago) was a significant interval in Earth’s history when the supercontinent Pangaea broke apart into the continents we know today, allowing continental biotas to evolve independently from one another. Throughout this era, vertebrates diversified into many of the major groups known today. Although there has been much research on the vertebrate fauna of this era from many parts of the world, the Mesozoic vertebrate fossil record of Africa is still poorly known. In 2008, a team of paleontologists from the University of California, Berkeley, the University of Washington, and the University of Utah collected large volumes of fossiliferous sediment (~1,000 lbs) from a Late Jurassic locality (Jema-5) near Addis Ababa in Ethiopia. Our team of undergraduates has begun to process, sort, and identify vertebrate microfossils from these fossiliferous sediment samples. We are in the preliminary stages of our project, but previous workers have recorded a diversity of cartilaginous and bony fish, such as hybodont sharks, guitarfish (Rhinobatos), lungfish (Asioceratodus tiguidensis), and primitive ray-finned fish (Lepidotes, Pycnodus) from nearby localities. Other aquatic vertebrates and terrestrial vertebrates have also been identified from this area, including pleurodiran and cryptodiran turtles, crocodyliforms, ornithiscian and theropod dinosaurs, and primitive mammals. We aim to (1) develop a faunal list from this locality; (2) add to our understanding of vertebrate diversity in Ethiopia during the Late Jurassic; (3) better constrain the age of the fossil locality within the latter half of the Mesozoic; and (4) shed light on vertebrate evolution from a critical area and time in Earth’s history.

At the Cretaceous-Paleogene (K-Pg) boundary, approximately 66 million years ago, a major mass extinction event eliminated up to 75% of all species on the planet. Considerable debate surrounds the cause of this extinction. Was the extraterrestrial bolide impact at the K-Pg boundary the sole cause? Or were ecosystems already deteriorating prior to the impact? In non-marine ecosystems, dinosaurs (except birds), lizards, metatherian mammals, and sharks and rays (Chondrichthyes) suffered the greatest levels of extinction. Chondrichthyans have received little research attention relative to other taxonomic groups. Here, I investigated the fossil record of freshwater chondrichthyans through the Hell Creek Formation in eastern Montana. The formation is ~90 meters thick, divided into lower, upper and middle parts, and spans the last two million years of the Cretaceous. I examined 12 vertebrate microfossil assemblages through the section, identifying teeth, dermal denticles, and vertebrae of freshwater sharks and rays to the genus level. I used this dataset to estimate generic richness and relative abundance trends leading up to the K-Pg boundary. My richness results show that one genus of ray occurs through the entire section. From the lower to middle parts of the section, sharks increase from one to five genera and then drop back down to one genus in the upper part of the section. This pattern temporally correlates with a minor rise and fall, respectively, in sea level of the Western Interior Seaway. Alternatively, this pattern may reflect differences in sampling intensity and site availability through the Hell Creek Formation. I will test the latter hypothesis using rarefaction analysis, which compensates for differences in sampling intensity. Results will help me determine whether these trends are a true glimpse into the shifting biogeographic ranges of non-marine cartilaginous fish communities of the latest Cretaceous or an artifact of variable sampling through the section.

The fossils of the Cabbage Patch beds of western Montana record over five million years of mammalian evolution leading up to and across the Oligocene-Miocene boundary (23 million years ago [Ma]). This boundary marks the advent of many modern mammalian families. This evolutionary event may have been driven by the climatic and environmental changes of the time. Prior studies of these deposits have identified three faunal divisions occurring chronologically within the beds. To test whether faunal change was correlated with climatic or environmental change in our study area, we quantified the number of mammalian families and their relative abundance in the two oldest divisions of the Cabbage Patch beds (28-25 Ma), and compared this record with the record of habitat change and fossil preservation biases. A preliminary analysis of 495 microfossil specimens from five well-sampled different rock layers in these two divisions shows no change in the number of families throughout the time span; however, temporal shifts in relative abundances of families likely reflect differences in habitat and fossil preservation. Despite potential preservational biases, turnover in mammalian taxa occurs between the older and the younger layers. For example, mouse-deer, interpreted as forest specialists, are very abundant in the oldest layers but absent in the younger layers suggesting their local extinction. Conversely, gophers, native to more open, drier habitats, occur in the younger layers but are absent from the older ones. Together, these data provide circumstantial evidence of changing environments in our study area. These preliminary findings increase our understanding of habitat change and preservation bias in the two oldest divisions of the Cabbage Patch beds. We are currently improving the taxonomic resolution (from family to genus level) of our dataset to provide a more detailed view of changes in regional mammalian diversity during this critical interval in mammalian evolution.

Malaria is an infectious disease caused by various species of the Plasmodium parasite which affects an estimated 207 million individuals, resulting in approximately 627,000 deaths per year. While this disease is primarily prevalent in developing nations, over half of the world’s population is at risk for malaria. Among existing malaria drugs, primaquine is uniquely effective against late-stage Plasmodium gametocytes and liver hypnozoites; however, it is dangerous to patients who are G6PD deficient. G6PD deficiency is caused primarily by point mutations in the Glucose-6-Phosphate Dehydrogenase (G6PD) protein—an enzyme that catalyzes the formation of NAPDH (a reducing agent) in the Pentose Phosphate Pathway. This condition affects around 400,000 individuals worldwide, most of whom live in areas at risk for malaria. Screening for G6PD deficiency is not readily available in many of these at risk areas and thus complicates treatment of malaria with primaquine. Therefore, screening for compounds that stabilize mutant forms of G6PD may yield potential candidates that can be used in combination with primaquine for a new therapeutic regimen. In a screen of ~100,000 compounds, 71 compounds were found to have stabilizing effects on mutant G6PD R454H (Andalus). Screening was done with a standard biochemical assay that measured enzyme activity through the detection of reaction product, NADPH (detected by fluorescence). Additional biochemical assays and studies on these 71 hits will follow to assess the mechanism and extent to which these compounds increase mutant G6PD Andalus activity. Candidate compounds that make it through these follow up experiments will then be tested with other G6PD mutants in search of a stabilizer of multiple G6PD mutants.