Life Sciences Commons^™

Dicer1 Syndrome: Dicer1 Mutations In Rare Cancers, Jake C. Robertson, Cheryl L. Jorcyk, Julia Thom Oxford

Biology Faculty Publications and Presentations

DICER1 syndrome is a rare genetic disorder that predisposes individuals to multiple cancer types. Through mutations of the gene encoding the endoribonuclease, Dicer, DICER1 syndrome disrupts the biogenesis and processing of miRNAs with subsequent disruption in control of gene expression. Since the first description of DICER1 syndrome, case reports have documented novel germline mutations of the DICER1 gene in patients with cancers as well as second site mutations that alter the function of the Dicer protein expressed. Here, we present a review of mutations in the DICER1 gene, the respective protein sequence changes, and clinical manifestations of DICER1 syndrome. Directions …

Allele Frequencies Of 15 Str Loci (Identifiler™ Kit) In Basque-Americans, Jason Besecker, Gianluca Peri, Michael Davis, Josu Zubizarreta, Greg Hampikian

Biology Faculty Publications and Presentations

Individuals with Basque ancestry form a historically and culturally important minority of the population of the western United States. Allele frequencies for the 15 autosomal STRs in the AmpFlSTR^® Identifiler^® PCR Amplification Kit (Applied Biosystems) from 156 unrelated self-identified Basque individuals born in the United States are presented. Allele frequencies were used to calculate parameters commonly used in genetics and forensics including power of discrimination (PD), power of exclusion (PE), polymorphic information content (PIC), and expected heterozygosity (He). The sample population was also compared with the European Basque population and the major American ethnicities.

Beyond The Matrix: The Many Non-Ecm Ligands For Integrins, Bryce Lafoya, Jordan A. Munroe, Alison Miyamoto, Michael A. Detweiler, Jacob J. Crow, Tana Gazdik, Allan R. Albig

Biology Faculty Publications and Presentations

The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM), and to a lesser degree, as coordinators of leukocyte adhesion to the endothelium. These canonical activities are indispensable; however, there is also a wide variety of integrin functions mediated by non-ECM ligands that transcend the traditional roles of integrins. Some of these unorthodox roles involve cell-cell interactions and are engaged to support immune functions such as leukocyte transmigration, recognition of opsonization factors, and stimulation of neutrophil extracellular traps. Other cell-cell interactions mediated by integrins include hematopoietic stem cell …

A Comparison Of Resveratrol And Other Polyphenolic Compounds On Notch Activation And Endothelial Cell Activity, Bryce Lafoya, Jordan A. Munroe, Allan R. Albig

Biology Faculty Publications and Presentations

Resveratrol is a polyphenolic compound produced by plants which makes its way into the human diet through plant-based foods. It has been shown to provide many health benefits, helping to ward of age-related diseases and promoting cardiovascular health. Additionally, resveratrol is a potent activator of the Notch signaling pathway. While resveratrol receives the most attention as a polyphenolic nutraceutical, other compounds with similar structures may be more potent regulators of specific cellular processes. Here, we compare resveratrol, apigenin, chrysin, genistein, luteolin, myricetin, piceatannol, pterostilbene, and quercetin for their ability to regulate Notch signaling. In addition, we compare the ability of …

Case Report: Coincidental Inclusion In A 17-Locus Y-Str Mixture, Wrongful Conviction And Exoneration, Greg Hampikian, Gianluca Peri, Shih-Shiang Lo, Mon-Hwa Chin, Kuo-Lan Liu

Biology Faculty Publications and Presentations

We report the case of a suspect (Suspect-3) who was convicted (and later exonerated) of participating in the multiple-attacker rape of two women. The forensic evidence against him was his inclusion in a 17-marker Y-STR mixture isolated from semen on one victim’s clothing. The DNA inclusion produced a match statistic with a combined probability of inclusion of 1 in 741, and a Likelihood Ratio of 3296. While the defense team was told that Suspect-3 was included in the semen DNA mixture, they were not told that all of the Y-STR alleles could also be explained by just the other two …

Evaluation Of Micro-Gps Receivers For Tracking Small-Bodied Mammals, Laura A. Mcmahon, Janet L. Rachlow, Lisa A. Shipley, Jennifer S. Forbey, Timothy R. Johnson, Peter J. Olsoy

Biology Faculty Publications and Presentations

GPS telemetry markedly enhances the temporal and spatial resolution of animal location data, and recent advances in micro-GPS receivers permit their deployment on small mammals. One such technological advance, snapshot technology, allows for improved battery life by reducing the time to first fix via postponing recovery of satellite ephemeris (satellite location) data and processing of locations. However, no previous work has employed snapshot technology for small, terrestrial mammals. We evaluated performance of two types of micro-GPS (< 20 g) receivers (traditional and snapshot) on a small, semi-fossorial lagomorph, the pygmy rabbit (Brachylagus idahoensis), to understand how GPS errors might influence fine-scale assessments of space use and habitat selection. During stationary tests, microtopography (i.e., …

Endoplasmic Reticulum Stress And Unfolded Protein Response In Cartilage Pathophysiology; Contributing Factors To Apoptosis And Osteoarthritis, Alexandria Hughes, Alexandra E. Oxford, Ken Tawara, Cheryl L. Jorcyk, Julia Thom Oxford

Biology Faculty Publications and Presentations

Chondrocytes of the growth plate undergo apoptosis during the process of endochondral ossification, as well as during the progression of osteoarthritis. Although the regulation of this process is not completely understood, alterations in the precisely orchestrated programmed cell death during development can have catastrophic results, as exemplified by several chondrodystrophies which are frequently accompanied by early onset osteoarthritis. Understanding the mechanisms that underlie chondrocyte apoptosis during endochondral ossification in the growth plate has the potential to impact the development of therapeutic applications for chondrodystrophies and associated early onset osteoarthritis. In recent years, several chondrodysplasias and collagenopathies have been recognized as …

Effects Of Delayed Nsaid Administration After Experimental Eccentric Contraction Injury – A Cellular And Proteomics Study, Laura Bond

Biology Faculty Publications and Presentations

Background

Acute muscle injuries are exceedingly common and non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed to reduce the associated inflammation, swelling and pain that peak 1–2 days post-injury. While prophylactic use or early administration of NSAIDs has been shown to delay muscle regeneration and contribute to loss of muscle strength after healing, little is known about the effects of delayed NSAID use. Further, NSAID use following non-penetrating injury has been associated with increased risk and severity of infection, including that due to group A streptococcus, though the mechanisms remain to be elucidated. The present study investigated the effects of delayed …

Earlier Nesting By Generalist Predatory Bird Is Associated With Human Responses To Climate Change, Shawn H. Smith, Karen Steenhof, Christopher J.W. Mcclure, Julie A. Heath

Biology Faculty Publications and Presentations

1. Warming temperatures cause temporal changes in growing seasons and prey abundance that drive earlier breeding by birds, especially dietary specialists within homogeneous habitat. Less is known about how generalists respond to climate-associated shifts in growing seasons or prey phenology, which may occur at different rates across land cover types.
2. We studied whether breeding phenology of a generalist predator, the American kestrel (Falco sparverius), was associated with shifts in growing seasons and, presumably, prey abundance, in a mosaic of non-irrigated shrub/grasslands and irrigated crops/pastures. We examined the relationship between remotely-sensed normalized difference vegetation index (NDVI) and abundance of small …

The Effect Of Nullomer-Derived Peptides 9r, 9s1r And 124r On The Nci-60 Panel And Normal Cell Lines, Abdelkrim Alileche, Greg Hampikian

Biology Faculty Publications and Presentations

Background: Nullomer peptides are the smallest sequences absent from databases of natural proteins. We first began compiling a list of absent 5-amino acid strings in 2006 (1). We report here the effects of Nullomer-derived peptides 9R, 9S1R and 124R on the NCI-60 panel, derived from human cancers of 9 organs (kidney, ovary, skin melanoma, lung, brain, lung, colon, prostate and the hematopoietic system), and four normal cell lines (endothelial HUVEC, skin fibroblasts BJ, colon epithelial FHC and normal prostate RWPE-1).

Methods: NCI-60 cancer cell panel and four normal cell lines were cultured in vitro in RPMI1640 supplemented with 10% Hyclone …

Understanding Tradeoffs Between Food And Predation Risks In A Specialist Mammalian Herbivore, Jamie L. Utz, Lisa A. Shipley, Janet L. Rachlow, Tamara Johnstone-Yellin, Meghan Camp, Jennifer Sorenson Forbey

Biology Faculty Publications and Presentations

Understanding habitat use by animals requires understanding the simultaneous tradeoffs between food and predation risk within a landscape. Quantifying the synergy between patches that provide quality food and those that are safe from predators at a scale relevant to a foraging animal could better reveal the parameters that influence habitat selection. To understand more thoroughly how animals select habitat components, we investigated tradeoffs between diet quality and predation risk in a species endemic to sagebrush Artemisia spp. communities in North America, the pygmy rabbitBrachylagus idahoensis. This species is a rare example of a specialist herbivore that relies almost entirely …

Early-Onset Alzheimer’S: Should You Worry?, Troy Rohn

Biology Faculty Publications and Presentations

You have forgotten where you put your car keys, or you can’t seem to remember the name of your colleague you saw in the grocery store the other day. You fear the worst, that maybe these are signs of Alzheimer’s disease.

Proteolytic Cleavage Of Apolipoprotein E In The Down Syndrome Brain, Ryan J. Day, Katie L. Mccarty, Kayla E. Ockerse, Elizabeth Head, Troy T. Rohn

Biology Faculty Publications and Presentations

Down syndrome (DS) is one of the most common genetic causes of intellectual disability and is characterized by a number of behavioral as well as cognitive symptoms. Many of the neuropathological features of early-onset Alzheimer’s disease (AD) including senile plaques and neurofibrillary tangles (NFTs) are also present in people with DS as a result of triplication of the amyloid precursor gene on chromosome 21. Evidence suggests that harboring one or both apolipoprotein E4 (APOE4) alleles may increase the risk for AD due to the proteolytic cleavage of apoE4 and a subsequent loss of function. To investigate a role …

Selection Of Food Patches By Sympatric Herbivores In Response To Concealment And Distance From A Refuge, Miranda M. Crowell, Lisa A. Shipley, Meghan J. Camp, Janet L. Rachlow, Jennifer S. Forbey, Timothy R. Johnson

Biology Faculty Publications and Presentations

Small herbivores face risks of predation while foraging and are often forced to trade off food quality for safety. Life history, behaviour, and habitat of predator and prey can influence these trade-offs. We compared how two sympatric rabbits (pygmy rabbit, Brachylagus idahoensis; mountain cottontail, Sylvilagus nuttallii) that differ in size, use of burrows, and habitat specialization in the sagebrush-steppe of western North America respond to amount and orientation of concealment cover and proximity to burrow refuges when selecting food patches. We predicted that both rabbit species would prefer food patches that offered greater concealment and food patches that …

Magp2 Controls Notch Via Interactions With Rgd Binding Integrins: Identification Of A Novel Ecm-Integrin-Notch Signaling Axis, Peter Deford, Kasey Brown, Rae Lee Richards, Aric King, Kristin Newburn, Katherine Westover, Allan R. Albig

Biology Faculty Publications and Presentations

Canonical Notch signaling involves Notch receptor activation via interaction with cell surface bound Notch ligand. Recent findings also indicate that Notch signaling may be modulated by cross-talk with other signaling mechanisms. The ECM protein MAGP2 was previously shown to regulate Notch in a cell type dependent manner, although the molecular details of this interaction have not been dissected. Here, we report that MAGP2 cell type specific control of Notch is independent of individual Notch receptor-ligand combinations but dependent on interaction with RGD binding integrins. Overexpressed MAGP2 was found to suppress transcriptional activity from the Notch responsive Hes1 promoter activity in …

Aryl Hydrocarbon Receptor Activation By Tcdd Modulates Expression Of Extracellular Matrix Remodeling Genes During Experimental Liver Fibrosis, Cheri L. Lamb, Giovan Cholico, Daniel E. Perkins, Michael T. Fewkes, Julia T. Oxford, Trevor J. Lujan, Erica E. Morrill, Kristen A. Mitchell

Biology Faculty Publications and Presentations

The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl₄).However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl₄-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for …

Modeling Trade-Offs Between Plant Fiber And Toxins: A Framework For Quantifying Risks Perceived By Foraging Herbivores, Meghan J. Camp, Lisa A. Shipley, Timothy R. Johnson, Jennifer Sorenson Forbey, Janet L. Rachlow, Miranda M. Crowell

Biology Faculty Publications and Presentations

When selecting habitats, herbivores must weigh multiple risks, such as predation, starvation, toxicity, and thermal stress, forcing them to make fitness trade-offs. Here, we applied the method of paired comparisons (PC) to investigate how herbivores make trade-offs between habitat features that influence selection of food patches. The method of PC measures utility and the inverse of utility, relative risk, and makes trade-offs and indifferences explicit by forcing animals to make choices between two patches with different types of risks. Using a series of paired-choice experiments to titrate the equivalence curve and find the marginal rate of substitution for one risk …

Caspase-Cleaved Tau Co-Localizes With Early Tangle Markers In The Human Vascular Dementia Brain, Ryan J. Day, Maria J. Mason, Chloe Thomas, Wayne W. Poon, Troy T. Rohn

Troy T. Rohn

Vascular dementia (VaD) is the second most common form of dementia in the United States and is characterized as a cerebral vessel vascular disease that leads to ischemic episodes. Whereas the relationship between caspase-cleaved tau and neurofibrillary tangles (NFTs) in Alzheimer’s disease (AD) has been previously described, whether caspase activation and cleavage of tau occurs in VaD is presently unknown. To investigate a potential role for caspase-cleaved tau in VaD, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing a well-characterized antibody that specifically detects caspase-cleaved tau truncated at Asp⁴²¹. Application of this antibody (TauC3) revealed consistent …

Caspase-Cleaved Tau Co-Localizes With Early Tangle Markers In The Human Vascular Dementia Brain, Ryan J. Day, Maria J. Mason, Chloe Thomas, Wayne W. Poon, Troy T. Rohn

Biology Faculty Publications and Presentations

Vascular dementia (VaD) is the second most common form of dementia in the United States and is characterized as a cerebral vessel vascular disease that leads to ischemic episodes. Whereas the relationship between caspase-cleaved tau and neurofibrillary tangles (NFTs) in Alzheimer’s disease (AD) has been previously described, whether caspase activation and cleavage of tau occurs in VaD is presently unknown. To investigate a potential role for caspase-cleaved tau in VaD, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing a well-characterized antibody that specifically detects caspase-cleaved tau truncated at Asp⁴²¹. Application of this antibody (TauC3) revealed consistent …

Antioxidant Capacity Of Wyoming Big Sagebrush (Artemisia Tridentata Ssp. Wyomingensis) Varies Spatially And Is Not Related To The Presence Of A Sagebrush Dietary Specialist, Xinzhu Pu, Lisa Lam, Kristina Gehlken, Amy C. Ulappa, Janet Rachlow, Jennifer Sorensen Forbey

Biology Faculty Publications and Presentations

Sagebrush (Artemisia spp.) in North America is an abundant native plant species that is ecologically and evolutionarily adapted to have a diverse array of biologically active chemicals. Several of these chemicals, specifically polyphenols, have antioxidant activity that may act as biomarkers of biotic or abiotic stress. This study investigated the spatial variation of antioxidant capacity, as well as the relationship between a mammalian herbivore and antioxidant capacity in Wyoming big sagebrush (Artemisia tridentata wyomingensis). We quantified and compared total polyphenols and antioxidant capacity of leaf extracts from sagebrush plants from different spatial scales and at different levels …

Cyclosporin A Disrupts Notch Signaling And Vascular Lumen Maintenance, Raghav Pandey, Mark A. Botros, Benjamin A. Nacev, Allan R. Albig

Biology Faculty Publications and Presentations

Cyclosporin A (CSA) suppresses immune function by blocking the cyclophilin A and calcineurin/NFAT signaling pathways. In addition to immunosuppression, CSA has also been shown to have a wide range of effects in the cardiovascular system including disruption of heart valve development, smooth muscle cell proliferation, and angiogenesis inhibition. Circumstantial evidence has suggested that CSA might control Notch signaling which is also a potent regulator of cardiovascular function. Therefore, the goal of this project was to determine if CSA controls Notch and to dissect the molecular mechanism(s) by which CSA impacts cardiovascular homeostasis. We found that CSA blocked JAG1, but not …

Oncostatin M Binds To Extracellular Matrix In A Bioactive Conformation: Implications For Inflammation And Metastasis, Randall E. Ryan, Bryan Martin, Liliana Mellor, Reed B. Jacob, Ken Tawara, Owen M. Mcdougal, Julia Thom Oxford, Cheryl L. Jorcyk

Biology Faculty Publications and Presentations

Oncostatin M (OSM) is an interleukin-6-like inflammatory cytokine reported to play a role in a number of pathological processes including cancer. Full-length OSM is expressed as a 26 kDa protein that can be proteolytically processed into 24 kDa and 22 kDa forms via removal of C-terminal peptides. In this study, we examined both the ability of OSM to bind to the extracellular matrix (ECM) and the activity of immobilized OSM on human breast carcinoma cells. OSM was observed to bind to ECM proteins collagen types I and XI, laminin, and fibronectin in a pH-dependent fashion, suggesting a role for electrostatic …

Mitigation Effectiveness For Improving Nesting Success Of Greater Sage-Grouse Influenced By Energy Development, Christopher P. Kirol, Andrew L. Sutphin, Laura Bond, Mark R. Fuller, Thomas L. Maechtle

Biology Faculty Publications and Presentations

Sagebrush Artemisia spp. habitats being developed for oil and gas reserves are inhabited by sagebrush obligate species--including the greater sage-grouse Centrocercus urophasianus (sage-grouse) that is currently being considered for protection under the U.S. Endangered Species Act. Numerous studies suggest increasing oil and gas development may exacerbate species extinction risks. Therefore, there is a great need for effective on-site mitigation to reduce impacts to co-occurring wildlife such as sage-grouse. Nesting success is a primary factor in avian productivity and declines in nesting success are also thought to be an important contributor to population declines in sage-grouse. From 2008 to 2011 we …

Fearscapes: Mapping Functional Properties Of Cover For Prey With Terrestrial Lidar, Peter J. Olsoy, Jennifer S. Forbey, Janet L. Rachlow, Jordan D. Nobler, Nancy F. Glenn, Lisa A. Shipley

Biology Faculty Publications and Presentations

Heterogeneous vegetation structure can create a variable landscape of predation risk—a fearscape—that influences the use and selection of habitat by animals. Mapping the functional properties of vegetation that influence predation risk (e.g., concealment and visibility) across landscapes can be challenging. Traditional ground-based measures of predation risk are location specific and limited in spatial resolution. We demonstrate the benefits of terrestrial laser scanning (TLS) to map the properties of vegetation structure that shape fearscapes. We used TLS data to estimate the concealment of prey from multiple vantage points, representing predator sightlines, as well as the visibility of potential predators from the …

The Dilemma Of Foraging Herbivores: Dealing With Food And Fear, Clare Mcarthur, Peter B. Banks, Rudy Boonstra, Jennifer Sorensen Forbey

Biology Faculty Publications and Presentations

For foraging herbivores, both food quality and predation risk vary across the landscape. Animals should avoid low-quality food patches in favour of high-quality ones, and seek safe patches while avoiding risky ones. Herbivores often face the foraging dilemma, however, of choosing between high-quality food in risky places or low-quality food in safe places. Here, we explore how and why the interaction between food quality and predation risk affects foraging decisions of mammalian herbivores, focusing on browsers confronting plant toxins in a landscape of fear. We draw together themes of plant–herbivore and predator–prey interactions, and the roles of animal ecophysiology, behaviour …

The First Successful Use Of A Low Stringency Familial Match In A French Criminal Investigation, Emmanuel Pham-Hoai, Frank Crispino, Greg Hampikian

Biology Faculty Publications and Presentations

We describe how a very simple application of familial searching resolved a decade-old, high-profile rape/murder in France. This was the first use of familial searching in a criminal case using the French STR DNA database, which contains approximately 1,800,000 profiles. When an unknown forensic profile (18 loci) was searched against the French arrestee/offender database using CODIS configured for a low stringency search, a single low stringency match was identified. This profile was attributed to the father of the man suspected to be the source of the semen recovered from the murder victim Elodie Kulik. The identification was confirmed using Y-chromosome …

Immunogenicity Of A West Nile Virus Diii-Cholera Toxin A2/B Chimera After Intranasal Delivery, Juliette K. Tinker, Jie Yan, Reece J. Knippel, Panos Panayiotou, Kenneth A. Cornell

Biology Faculty Publications and Presentations

West Nile virus (WNV) causes potentially fatal neuroinvasive disease and persists at endemic levels in many parts of the world. Despite advances in our understanding of WNV pathogenesis, there remains a significant need for a human vaccine. The domain III (DIII) region of the WNV envelope protein contains epitopes that are the target of neutralizing antibodies. We have constructed a chimeric fusion of the non-toxic cholera toxin (CT) CTA₂/B domains to DIII for investigation as a novel mucosally-delivered WNV vaccine. Purification and assembly of the chimera, as well as receptor-binding and antigen delivery, were verified by western blot, …

Stüve-Wiedemann Syndrome: Lifr And Associated Cytokines In Clinical Course And Etiology, Dawn Mikelonis, Cheryl L. Jorcyk, Ken Tawara, Julia Thom Oxford

Biology Faculty Publications and Presentations

Stüve-Wiedemann syndrome (STWS; OMIM #610559) is a rare bent-bone dysplasia that includes radiologic bone anomalies, respiratory distress, feeding difficulties, and hyperthermic episodes. STWS usually results in infant mortality, yet some STWS patients survive into and, in some cases, beyond adolescence. STWS is caused by a mutation in the leukemia inhibitory factor receptor (LIFR) gene, which is inherited in an autosomally recessive pattern. Most LIFR mutations resulting in STWS are null mutations which cause instability of the mRNA and prevent the formation of LIFR, impairing the signaling pathway. LIFR signaling usually follows the JAK/STAT3 pathway, and is initiated by …

Apolipoprotein E Pathology In Vascular Dementia, Troy T. Rohn, Ryan J. Day, Colin B. Sheffield, Alexander J. Rajic, Wayne W. Poon

Biology Faculty Publications and Presentations

Vascular dementia (VaD) is the second most common form of dementia and is currently defined as a cerebral vessel vascular disease leading to ischemic episodes. Apolipoprotein E (apoE) gene polymorphism has been proposed as a risk factor for VaD, however, to date there are few documented post-mortem studies on apoE pathology in the VaD brain. To investigate a potential role for the apoE protein, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing an antibody that specifically detects the amino-terminal fragment of apoE. Application of this antibody, termed N-terminal, apoE cleavage fragment (nApoECF) revealed consistent labeling within neurofibrillary tangles …

Morphologic And Molecular Description Of Metopus Fuscus Kahl From North America And New Rdna Sequences From Seven Metopids (Armophorea, Metopidae), William A. Bourland, Laura Wendell, Greg Hampikian

Biology Faculty Publications and Presentations

Most species in the large ciliate genus Metopus Claparède & Lachmann, 1858 lack detailed descriptions based on modern morphologic and molecular methods. This lack of data for the vast majority of species hampers application of a morphospecies approach to the taxonomy of Metopus and other armophorids. In this report we redescribe the large species, Metopus fuscus Kahl, 1927 based on in vivo observation, silver impregnation, scanning electron microscopy, and single-cell 18S rDNA sequencing of a freshwater North American (Idaho) population. Metopus fuscus invariably has a perinuclear envelope of endosymbiotic bacteria not found in other species. Unlike the original description of …