Life Sciences Commons^™

Nullomer Derived Anticancer Peptides (Nullops): Differential Lethal Effects On Normal And Cancer Cells In Vitro, Abdelkrim Alileche, Jayita Goswami, William Bourland, Mike Davis, Greg Hampikian

Biology Faculty Publications and Presentations

We demonstrate the first use of the nullomer (absent sequences) approach to drug discovery and development. Nullomers are the shortest absent sequences determined in a species, or group of species. By identifying the shortest absent peptide sequences from the NCBI databases, we screened several potential anti-cancer peptides. In order to improve cell penetration and solubility we added short poly arginine tails (5Rs), and initially solubilized the peptides in1M trehalose. The results for one of the absent sequences 9R (RRRRRNWMWC), and its scrambled version 9S1R (RRRRRWCMNW) are reported here. We refer to these peptides derived from nullomers as PolyArgNulloPs. A control …

When Dna Won't Work, Rick Visser, Greg Hampikian

Biology Faculty Publications and Presentations

Within the criminal justice system, DNA (deoxyribonucleic acid) evidence has often been heralded as the gold standard of forensic science. In a 2009 U.S. Supreme Court decision, Chief Justice Roberts wrote that "DNA testing has an unparalleled ability both to exonerate the wrongly convicted and to identify the guilty. It has the potential to significantly improve both the criminal justice system and police investigative practices." The phrases “unparalleled ability” and “significantly improve” reflect the high standard that DNA has attained in both forensic science and the entire criminal justice system.

Forensic DNA technology has a major advantage over other forensic …

Phylogeny Of A Neotropical Clade In The Gesneriaceae: More Tales Of Convergent Evolution, John L. Clark, Minde M. Funke, Aaron M. Duffy, James F. Smith

Biology Faculty Publications and Presentations

The Gesneriaceae is a family known for convergent evolution of complex floral forms. As a result, defining genera and resolving evolutionary relationships among such genera using morphological data alone has been challenging and often does not accurately reflect monophyletic lineages. The tribe Episcieae is the most diverse within Neotropical Gesneriaceae in terms of its number of species and morphological diversity. As a result, defining genera using floral characters has been historically troublesome. Here we investigate relationships among genera of the tribe using an array of chloroplast DNA, nuclear ribosomal genes, and low-copy nuclear genes to provide resolution for the monophyly …

Identification Of An Amino-Terminal Fragment Of Apolipoprotein E4 That Localizes To Neurofibrillary Tangles Of The Alzheimer’S Disease Brain, Troy T. Rohn, Lindsey W. Catlin, Kendra G. Coonse, Jeffrey W. Habig

Biology Faculty Publications and Presentations

Although the risk factor for harboring the apolipoprotein E4 (apoE4) allele in late-onset Alzheimer’s disease (AD) is well known, the mechanism by which apoE4 contributes to AD pathogenesis has yet to be clarified. Preferential cleavage of the ApoE4 isoform relative to other polymorphic forms appears to be significant, as the resulting fragments are associated with hallmarks of AD. To examine the possible role of apoE4 proteolysis in AD, we designed a site-directed antibody directed at position D172, which would yield a predicted amino-terminal fragment previously identified in AD brain extracts. Western blot analysis utilizing this novel antibody, termed the amino-terminal …

Directional Selection Causes Decanalization In A Group I Ribozyme, Eric J. Hayden, Christian Weikert, Andreas Wagner

Eric J. Hayden

A canalized genotype is robust to environmental or genetic perturbations. Canalization is expected to result from stabilizing selection on a well-adapted phenotype. Decanalization, the loss of robustness, might follow periods of directional selection toward a new optimum. The evolutionary forces causing decanalization are still unknown, in part because it is difficult to determine the fitness effects of mutations in populations of organisms with complex genotypes and phenotypes. Here, we report direct experimental measurements of robustness in a system with a simple genotype and phenotype, the catalytic activity of an RNA enzyme. We find that the robustness of a population of …

Landscape Of Transcription In Human Cells, Jainab Khatun

Biology Faculty Publications and Presentations

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell’s regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, …

Oncostatin M Promotes Mammary Tumor Metastasis To Bone And Osteolytic Bone Degradation, Celeste Bolin, Ken Tawara, Caleb Sutherland, Jeff Redshaw, Patrick S. Aranda, Jim Moselhy, Robin Anderson, Cheryl Jorcyk

Biology Faculty Publications and Presentations

Oncostatin M (OSM) is an interleukin-6 (IL-6) family cytokine that has been implicated in a number of biological processes including inflammation, hematopoiesis, immune responses, development, and bone homeostasis. Recent evidence suggests that OSM may promote breast tumor invasion and metastasis. We investigated the role of OSM in the formation of bone metastases in vivo using the 4T1.2 mouse mammary tumor model in which OSM expression was knocked down using shRNA (4T1.2-OSM). 4T1.2-OSM cells were injected orthotopically into Balb/c mice, resulting in a greater than 97% decrease in spontaneous metastasis to bone compared to control cells. Intratibial injection of these same …

An Integrated Encyclopedia Of Dna Elements In The Human Genome, Jainab Khatun

Biology Faculty Publications and Presentations

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence …

Long Noncoding Rnas Are Rarely Translated In Two Human Cell Lines, Jainab Khatun, Brian Risk, Morgan Giddings

Biology Faculty Publications and Presentations

Data from the Encyclopedia of DNA Elements (ENCODE) project show over 9640 human genome loci classified as long noncoding RNAs (lncRNAs), yet only ~100 have been deeply characterized to determine their role in the cell. To measure the protein-coding output from these RNAs, we jointly analyzed two recent data sets produced in the ENCODE project: tandem mass spectrometry (MS/MS) data mapping expressed peptides to their encoding genomic loci, and RNA-seq data generated by ENCODE in long polyA+ and polyA– fractions in the cell lines K562 and GM12878. We used the machinelearning algorithm RuleFit3 to regress the peptide data against RNA …

Predicting Occupancy Of Wintering Migratory Birds: Is Microhabitat Information Necessary?, Christopher J. W. Mcclure, Brian W. Rolek, Geoffrey E. Hill

Biology Faculty Publications and Presentations

Information regarding microhabitat, here defined as small-scale vegetation structure, is often useful in predicting use of habitat by birds. Quantifying microhabitat, however, is expensive and labor intensive compared to assessment of habitat at a larger scale, possibly from remotely sensed imagery. To assess the importance of microhabitat information in constructing predictive models of habitat occupancy, we compared occupancy models built on the basis of macro- and microhabitat together and separately. We based our models on counts of wintering migratory bird species and vegetation surveys within Tuskegee National Forest, Alabama, completed during winter 2009. Models built from macrohabitat data only outperformed …

The Effect Of Human Activities And Their Associated Noise On Ungulate Behavior, Casey L. Brown, Amanda R. Hardy, Jesse R. Barber, Kurt M. Fristrup, Kevin R. Crooks, Lisa M. Angeloni

Biology Faculty Publications and Presentations

Background: The effect of anthropogenic noise on terrestrial wildlife is a relatively new area of study with broad ranging management implications. Noise has been identified as a disturbance that has the potential to induce behavioral responses in animals similar to those associated with predation risk. This study investigated potential impacts of a variety of human activities and their associated noise on the behavior of elk (Cervus elaphus) and pronghorn (Antilocapra americana) along a transportation corridor in Grand Teton National Park.

Methodology/Principal Findings: We conducted roadside scan surveys and focal observations of ungulate behavior while concurrently recording …

Shorter Migration Distances Associated With Higher Winter Temperatures Suggest A Mechanism For Advancing Nesting Phenology Of American Kestrels Falco Sparverius, Julie A. Heath, Karen Steenhof, Mark A. Foster

Biology Faculty Publications and Presentations

Global climate change has affected avian migration patterns and nesting phenology. Changes in one phase of a bird's cycle will most likely affect other stages, but few studies focus simultaneously on multiple life-history events. We used western North American ringing records and Christmas Bird Counts to examine whether changes in migration patterns were concordant with advancing American kestrel Falco sparverius nesting phenology. Consistent with previous findings, male kestrels migrated shorter distances than female kestrels, and kestrels nesting in southern latitudes migrated shorter distances than kestrels nesting in more northern areas. In addition, kestrel migration distance decreased significantly from 1960 to …

Morphology And Phylogeny Of A New Woodruffiid Ciliate, Etoschophrya Inornata Sp. N. (Ciliophora, Colpodea, Platyophryida), With An Account On Evolution Of Platyophryids, William A. Bourland, Greg Hampikian, Peter Vďačný

Biology Faculty Publications and Presentations

We studied the morphology, morphometry, resting cysts and molecular phylogeny of a new woodruffiid ciliate, Etoschophrya inornata, from ephemeral puddles and two lacustrine habitats in Idaho, North-west USA. Up to now, the genus Etoschophrya has included a single species, Etoschophrya oscillatoriophaga, from which our new form is distinguished by (i) the absence of interkinetal cortical granules and, consequently, the absence of extrusible red material in methyl green-pyronin stains, (ii) usually ≥5 adoral membranelles vs. usually four, (iii) greater length and length/width ratio, (iv) prominent cortical furrows vs. inconspicuous and (v) adaptation to non-saline semi-terrestrial and lacustrine habitats in …

Novel Mouse Mammary Cell Lines For In Vivo Bioluminescence Imaging (Bli) Of Bone Metastasis, Celeste Bolin, Caleb Sutherland, Ken Tawara, Jim Moselhy, Cheryl Jorcyk

Biology Faculty Publications and Presentations

Background

Tumor cell lines that can be tracked in vivo during tumorigenesis and metastasis provide vital tools for studying the specific cellular mechanisms that mediate these processes as well as investigating therapeutic targets to inhibit them. The goal of this study was to engineer imageable mouse mammary tumor cell lines with discrete propensities to metastasize to bone in vivo. Two novel luciferase expressing cell lines were developed and characterized for use in the study of breast cancer metastasis to bone in a syngeneic mouse model.

Results

The 4T1.2 luc3 and 66c14 luc2 cell lines were shown to have high …

Nuclear Ribosomal Internal Transcribed Spacer (Its) Region As A Universal Dna Barcode Marker For Fungi, Eric Tretter, Yan Wang, Eric M. Johnson, Merlin M. White

Biology Faculty Publications and Presentations

Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding …