Digital Commons Network^™

Targeted Enrichment Of Ancient Pathogens Yielding The Ppcp1 Plasmid Of Yersinia Pestis From Victims Of The Black Death, Verena J. Schuenemann, Kristen Bos, Sharon Dewitte, Hendrik N. Poinar, Sarah Schmedes, Joslyn Jamieson, Alissa Mittnik, Stephen Forrest, Brian K. Coombes, James W. Wood, David J.D. Earn, William White, Johannes Krause, Hendrik N. Poinar

Faculty Publications

Although investigations of medieval plague victims have identified Yersinia pestis as the putative etiologic agent of the pandemic, methodological limitations have prevented large-scale genomic investigations to evaluate changes in the pathogen's virulence over time. We screened over 100 skeletal remains from Black Death victims of the East Smithfield mass burial site (1348–1350, London, England). Recent methods of DNA enrichment coupled with high-throughput DNA sequencing subsequently permitted reconstruction of ten full human mitochondrial genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at high coverage. Comparisons of molecular damage profiles between endogenous human and Y. pestis DNA confirmed …

Aebp2 As An Epigenetic Regulator For Neural Crest Cells, Hana Kim, Keunsoo Kang, Muhammad B. Ekram, Tae Young Roh, Joomyeong Kim

Faculty Publications

Aebp2 is a potential targeting protein for the mammalian Polycomb Repression Complex 2 (PRC2). We generated a mutant mouse line disrupting the transcription of Aebp2 to investigate its in vivo roles. Aebp2-mutant homozygotes were embryonic lethal while heterozygotes survived to adulthood with fertility. In developing mouse embryos, Aebp2 is expressed mainly within cells of neural crest origin. In addition, many heterozygotes display a set of phenotypes, enlarged colon and hypopigmentation, similar to those observed in human patients with Hirschsprung's disease and Waardenburg syndrome. These phenotypes are usually caused by the absence of the neural crest-derived ganglia in hindguts and melanocytes. …

The Regulation Of Skeletal Muscle Protein Turnover During The Progression Of Cancer Cachexia In The ApcMin/+ Mouse, James P. White, John W. Baynes, Stephen L. Welle, Matthew C. Kostek, Lydia E. Matesic, Shuichi Sato, James A. Carson

Faculty Publications

Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+) mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the Apc(Min/+) mouse is not known. Cachexia progression was studied in Apc(Min/+) mice that were either weight stable (WS) or had initial (≤5%), intermediate (6-19%), or extreme (≥20%) body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight …

Stimulant Reduction Intervention Using Dosed Exercise (Stride) - Ctn 0037: Study Protocol For A Randomized Controlled Trial, Madhukar H. Trivedi, Tracy L. Greer, Bruce D. Grannemann, Timothy S. Church, Eugene Somoza, Steven N. Blair, Jose Szapocznik, Mark Stoutenberg, Chad Rethorst, Diane Warden, Kolette M. Ring, Robrina Walker, David W. Morris, Andrzej S. Kosinski, Tiffany Kyle, Bess H. Marcus, Becca Crowell, Neal Oden, Edward Nunes

Faculty Publications

Background: There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these …

Highly Efficient Extraction Of Phenolic Compounds By Use Of Magnetic Room Temperature Ionic Liquids For Environmental Remediation, Ning Deng, Min Li, Lijie Zhao, Chengfei Lu, Sergio L. De Rooy, Isiah M. Warner

Faculty Publications

A hydrophobic magnetic room temperature ionic liquid (MRTIL), trihexyltetradecylphosphonium tetrachloroferrate(III) ([3C 6PC 14][FeCl 4]), was synthesized from trihexyltetradecylphosphonium chloride and FeCl 3·6H 2O. This MRTIL was investigated as a possible separation agent for solvent extraction of phenolic compounds from aqueous solution. Due to its strong paramagnetism, [3C 6PC 14][FeCl 4] responds to an external neodymium magnet, which was employed in the design of a novel magnetic extraction technique. The conditions for extraction, including extraction time, volume ratio between MRTIL and aqueous phase, pH of aqueous solution, and structures of phenolic compounds were investigated and optimized. The magnetic extraction of phenols …

The Genome Of The Extremophile Crucifer Thellungiella Parvula, Maheshi Dassanayake, Dong Ha Oh, Jeffrey S. Haas, Alvaro Hernandez, Hyewon Hong, Shahjahan Ali, Dae Jin Yun, Ray A. Bressan, Jian Kang Zhu, Hans J. Bohnert, John M. Cheeseman

Faculty Publications

Thellungiella parvula is related to Arabidopsis thaliana and is endemic to saline, resource-poor habitats, making it a model for the evolution of plant adaptation to extreme environments. Here we present the draft genome for this extremophile species. Exclusively by next generation sequencing, we obtained the de novo assembled genome in 1,496 gap-free contigs, closely approximating the estimated genome size of 140 Mb. We anchored these contigs to seven pseudo chromosomes without the use of maps. We show that short reads can be assembled to a near-complete chromosome level for a eukaryotic species lacking prior genetic information. The sequence identifies a …

Enhancing Arabidopsis Leaf Growth By Engineering The Brassinosteroid Insensitive1 Receptor Kinase, Man Ho Oh, Jindong Sun, Dong Ha Oh, Raymond E. Zielinski, Steven D. Clouse, Steven C. Huber

Faculty Publications

The BRASSINOSTEROID INSENSITIVE1 (BRI1) receptor kinase has recently been shown to possess tyrosine kinase activity, and preventing autophosphorylation of the tyrosine-831 regulatory site by site-directed mutagenesis enhances shoot growth. In this study, we characterized the increased leaf growth of Arabidopsis (Arabidopsis thaliana) plants expressing BRI1(Y831F)-Flag compared with BRI1-Flag (both driven by the native promoter and expressed in the bri1-5 weak allele background) and provide insights into the possible mechanisms involved. On average, relative leaf growth rate was increased 16% in the Y831F plants (in the bri1-5 background), and the gain of function of the Y831F-directed mutant was dominant in the …

Stat5a Expression In Swiss 3t3 Cells Promotes Adipogenesis In Vivo In An Athymic Mice Model System, William C. Stewart, Lisa A. Pearcy, Z. Elizabeth Floyd, Jacqueline M. Stephens

Faculty Publications

Many studies from our laboratories and others have shown that STAT5 expression and activity are increased during adipogenesis of murine and human adipocytes. Ectopic expression of STAT5A in fibroblasts or preadipocytes can confer or enhance adipogenesis. To determine whether STAT5A also plays a role in adipogenesis in vivo, we injected athymic mice with Swiss 3T3 cells expressing an empty pBABE retrovirus, Swiss cells expressing a pBABE retrovirus-containing STAT5A, or 3T3-F442A preadipocytes. Athymic mice injected with either 3T3-F442A cells or Swiss 3T3 cells expressing STAT5A resulted in fat pad formation at the site of injection. However, mice injected with Swiss cells …

Functional Genomics Of Physiological Plasticity And Local Adaptation In Killifish, Andrew Whitehead, Fernando Galvez, Shujun Zhang, Larissa M. Williams, Marjorie F. Oleksiak

Faculty Publications

Evolutionary solutions to the physiological challenges of life in highly variable habitats can span the continuum from evolution of a cosmopolitan plastic phenotype to the evolution of locally adapted phenotypes. Killifish (Fundulus sp.) have evolved both highly plastic and locally adapted phenotypes within different selective contexts, providing a comparative system in which to explore the genomic underpinnings of physiological plasticity and adaptive variation. Importantly, extensive variation exists among populations and species for tolerance to a variety of stressors, and we exploit this variation in comparative studies to yield insights into the genomic basis of evolved phenotypic variation. Notably, species of …

Calophya Latiforceps, A New Species Of Jumping Plant Lice (Hemiptera: Calophyidae) Associated With Schinus Terebinthifolius (Anacardiaceae) In Brazil, D. Burckhardt, J. P. Cuda, V. Manrique, R. Diaz, W. A. Overholt, D. A. Williams, L. R. Christ, M. D. Vitorino

Faculty Publications

Brazilian peppertree, Schinus terebinthifolius Raddi, is a perennial woody plant native to Brazil, Argentina, and Paraguay that is recognized as one of the most invasive weeds in Florida. A new species of leaflet galling psyllid was discovered attacking Brazilian peppertree in Bahia, Brazil in March 2010. In this paper, a formal morphological description of the new psyllid Calophya latiforceps sp. nov. (Hemiptera: Calophyidae) is presented along with molecular evidence confirming new species designation. This previously unknown natural enemy may have potential as a biological control agent for the Brazilian peppertree. Copyright © 2011 BioOne All rights reserved.

Arabidopsis Rtnlb1 And Rtnlb2 Reticulon-Like Proteins Regulate Intracellular Trafficking And Activity Of The Fls2 Immune Receptor, Hyoung Yool Lee, Christopher Hyde Bowen, George Viorel Popescu, Hong Gu Kang, Naohiro Kato, Shisong Ma, Savithramma Dinesh-Kumar, Michael Snyder, Sorina Claudia Popescu

Faculty Publications

Receptors localized at the plasma membrane are critical for the recognition of pathogens. The molecular determinants that regulate receptor transport to the plasma membrane are poorly understood. In a screen for proteins that interact with the FLAGELIN-SENSITIVE2 (FLS2) receptor using Arabidopsis thaliana protein microarrays, we identified the reticulon-like protein RTNLB1. We showed that FLS2 interacts in vivo with both RTNLB1 and its homolog RTNLB2 and that a Ser-rich region in the N-terminal tail of RTNLB1 is critical for the interaction with FLS2. Transgenic plants that lack RTNLB1 and RTNLB2 (rtnlb1 rtnlb2) or overexpress RTNLB1 (RTNLB1ox) exhibit reduced activation of FLS2-dependent …

Decoding The Genome With An Integrative Analysis Tool: Combinatorial Crm Decoder, Keunsoo Kang, Joomyeong Kim, Jae Hoon Chung, Daeyoup Lee

Faculty Publications

The identification of genome-wide cis-regulatory modules (CRMs) and characterization of their associated epigenetic features are fundamental steps toward the understanding of gene regulatory networks. Although integrative analysis of available genome-wide information can provide new biological insights, the lack of novel methodologies has become a major bottleneck. Here, we present a comprehensive analysis tool called combinatorial CRM decoder (CCD), which utilizes the publicly available information to identify and characterize genome-wide CRMs in a species of interest. CCD first defines a set of the epigenetic features which is significantly associated with a set of known CRMs as a code called 'trace code', …

Nonadaptive Evolution Of Mitochondrial Genome Size, Bastien Boussau, Jeremy M. Brown, Matthew K. Fujita

Faculty Publications

Genomes vary greatly in size and complexity, and identifying the evolutionary forces that have generated this variation remains a major goal in biology. A controversial proposal is that most changes in genome size are initially deleterious and therefore are linked to episodes of decrease in effective population sizes. Support for this hypothesis comes from large-scale comparative analyses, but vanishes when phylogenetic nonindependence is taken into account. Another approach to test this hypothesis involves analyzing sequence evolution among clades where duplications have recently fixed. Here we show that episodes of fixation of duplications in mitochondrial genomes of the gecko Heteronotia binoei …

Bioactive Properties And Clinical Safety Of A Novel Milk Protein Peptide, Richard B. Kreider, Mike Iosia, Matt Cooke, Geoffrey M. Hudson, Chris Rasmussen, Helen Chen, Olof Mollstedt, Men-Hwei Tsai

Faculty Publications

Background: Milk protein fractions and peptides have been shown to have bioactive properties. This preliminary study examined the potential mechanisms of action and clinical safety of novel milk protein peptide ( MP).

Findings: A novel MP mixture inhibits the tyrosine kinase activity of epidermal growth factor receptor ( EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and insulin receptor (IR) with IC(50) of 9.85 mu M, 7.7 mu M, and 6.18 mu M respectively. In vitro, this multi-kinase inhibitor causes apoptosis in HT-29 colon cancer cells, and in a C. elegans worm study, showed a weak but significant …

Participational Agency, Stephen C. Yanchar

Faculty Publications

Participational agency is presented as a conceptual account of human action, volition, and possibility. Rooted in hermeneutic and narrative traditions, this view differs from other theorizing about agency (and most psychological theorizing in general) in that it makes no effort to explain human action by virtue of reified constructs. As an alternative to traditional theorizing in this area, participational agency is defined as meaningful engagement in the world and treats the experienced meaningfulness of practical human activity as its central feature. The concept of meaningful engagement is clarified through the presentation of four related themes—situated participation, existential concern, dispositional action, …

Socially Induced Ovulation Synchrony And Its Effect On Seabird Population Dynamics, Shandelle M. Henson, J. M. Cushing, James L. Hayward

Faculty Publications

Spontaneous oscillator synchrony is a form of self-organization in which populations of interacting oscillators ultimately cycle together. This phenomenon occurs in a wide range of physical and biological systems. In rats and humans, oestrous/menstrual cycles synchronize through social stimulation with pheromones acting as synchronizing signals. In previous work, we showed that glaucous-winged gulls (Larus glaucescens) can lay eggs synchronously on an every-other-day schedule, and that synchrony increases with colony density. We posed a discrete-time mathematical model for reproduction during the breeding season based on the hypothesis that pre-ovulatory luteinizing hormone surges synchronize by means of visual, auditory and/or olfactory cues. …

Separation Of River Network–Scale Nitrogen Removal Among The Main Channel And Two Transient Storage Compartments, Robert J. Stewart, Wilfred M. Wollheim, Michael N. Gooseff, Martin A. Briggs, Jennifer M. Jacobs, Bruce J. Peterson, Charles S. Hopkinson

Faculty Publications

Transient storage (TS) zones are important areas of dissolved inorganic nitrogen (DIN) processing in rivers. We assessed sensitivities regarding the relative impact that the main channel (MC), surface TS (STS), and hyporheic TS (HTS) have on network denitrification using a model applied to the Ipswich River in Massachusetts, United States. STS and HTS connectivity and size were parameterized using the results of in situ solute tracer studies in first‐ through fifth‐order reaches. DIN removal was simulated in all compartments for every river grid cell using reactivity derived from Lotic Intersite Nitrogen Experiment (LINX2) studies, hydraulic characteristics, and simulated discharge. Model …

Crystal Structure Of Plasminogen Activator Inhibitor-1 In An Active Conformation With Normal Thermodynamic Stability, Jan K. Jensen, Lawrence C. Thompson, Joel C. Bucci, Poul Nissen, Peter G.W. Gettins, Cynthia B. Peterson, Peter A. Andreasen, J. Preben Morth

Faculty Publications

The serpin plasminogen activator inhibitor-1 (PAI-1) is a crucial regulator in fibrinolysis and tissue remodeling. PAI-1 has been associated with several pathological conditions and is a validated prognostic marker in human cancers. However, structural information about the native inhibitory form of PAI-1 has been elusive because of its inherent conformational instability and rapid conversion to a latent, inactive structure. Here we report the crystal structure of PAI-1 W175F at 2.3 Å resolution as the first model of the metastable native molecule. Structural comparison with a quadruple mutant (14-1B) previously used as representative of the active state uncovered key differences. The …

Racial Differences In Tumor Necrosis Factor-Α-Induced Endothelial Microparticles And Interleukin-6 Production, Michael D. Brown, Deborah L. Feairheller, Sunny R. Thakkar, Praveen Veerabhadrappa, Joon-Young Park

Faculty Publications

African Americans (AA) tend to have heightened systemic inflammation and endothelial dysfunction. Endothelial microparticles (EMP) are released from activated/apoptotic endothelial cells (EC) when stimulated by inflammation. The purpose of our study was to assess EMP responses to inflammatory cytokine (TNF-α) and antioxidant (superoxide dismutase, SOD) conditions in human umbilical vein ECs (HUVECs) obtained from AA and Caucasians. EMPs were measured under four conditions: control (basal), TNF-α, SOD, and TNF-α + SOD. Culture supernatant was collected for EMP analysis by flow cytometry and IL-6 assay by ELISA. IL-6 protein expression was assessed by Western blot. AA HUVECs had greater EMP levels …

Intraspecific Aflatoxin Inhibition In Aspergillus Flavus Is Thigmoregulated, Independent Of Vegetative Compatibility Group And Is Strain Dependent, Changwei Huang, Archana Jha, Rebecca Sweany, Catherine Derobertis, Kenneth E. Damann

Faculty Publications

Biological control of preharvest aflatoxin contamination by atoxigenic stains of Aspergillus flavus has been demonstrated in several crops. The assumption is that some form of competition suppresses the fungus's ability to infect or produce aflatoxin when challenged. Intraspecific aflatoxin inhibition was demonstrated by others. This work investigates the mechanistic basis of that phenomenon. A toxigenic and atoxigenic isolate of A. flavus which exhibited intraspecific aflatoxin inhibition when grown together in suspended disc culture were not inhibited when grown in a filter insert-plate well system separated by a.4 or 3 μm membrane. Toxigenic and atoxigenic conidial mixtures (50:50) placed on both …

Investigation Of Dose Perturbations And The Radiographic Visibility Of Potential Fiducials For Proton Radiation Therapy Of The Prostate, Jessie Y. Huang, Wayne D. Newhauser, X. Ronald Zhu, Andrew K. Lee, Rajat J. Kudchadker

Faculty Publications

Image guidance using implanted fiducial markers is commonly used to ensure accurate and reproducible target positioning in radiation therapy for prostate cancer. The ideal fiducial marker is clearly visible in kV imaging, does not perturb the therapeutic dose in the target volume and does not cause any artifacts on the CT images used for treatment planning. As yet, ideal markers that fully meet all three of these criteria have not been reported. In this study, 12 fiducial markers were evaluated for their potential clinical utility in proton radiation therapy for prostate cancer. In order to identify the good candidates, each …

Human Pathogen Shown To Cause Disease In The Threatened Elkhorn Coral Acropora Palmata, Kathryn Patterson Sutherland, Sameera Shaban, Jessica L. Joyner, James W. Porter, Erin K. Lipp

Faculty Publications

Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS), a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments …

Structural And Biochemical Insights Into The Mechanism Of Fosfomycin Phosphorylation By Fosfomycin Resistance Kinase Foma, Svetlana Pakhomova, Sue G. Bartlett, Pamela A. Doerner, Marcia E. Newcomer

Faculty Publications

We present here the crystal structures of fosfomycin resistance protein (FomA) complexed with MgATP, with ATP and fosfomycin, with MgADP and fosfomycin vanadate, with MgADP and the product of the enzymatic reaction, fosfomycin monophosphate, and with ADP at 1.87, 1.58, 1.85, 1.57, and 1.85 Å resolution, respectively. Structures of these complexes that approximate different reaction steps allowed us to distinguish the catalytically active conformation of ATP and to reconstruct the model of the MgATP•fosfomycin complex. According to the model, the triphosphate tail of the nucleotide is aligned toward the phosphonate moiety of fosfomycin, in contast to the previously published MgAMPPNP …

Transcriptional Analysis Of Lactobacillus Brevis To N-Butanol And Ferulic Acid Responses, James Winkler, Katy Kao

Faculty Publications

BackgroundThe presence of anti-microbial phenolic compounds, such as the model compound ferulic acid, in biomass hydrolysates pose significant challenges to the widespread use of biomass in conjunction with whole cell biocatalysis or fermentation. Currently, these inhibitory compounds must be removed through additional downstream processing or sufficiently diluted to create environments suitable for most industrially important microbial strains. Simultaneously, product toxicity must also be overcome to allow for efficient production of next generation biofuels such as n-butanol, isopropanol, and others from these low cost feedstocks.Methodology and Principal FindingsThis study explores the high ferulic acid and n-butanol tolerance in Lactobacillus brevis, a …

Citalopram Improves Metabolic Risk Factors Among High Hostile Adults: Results Of A Placebo-Controlled Intervention., Thomas W. Karmarck, Matthew F. Muldoon, Stephen B. Manuck, Roger F. Haskett, Jeewon Cheong, Janine D. Flory, Elizabeth Vella

Faculty Publications

Hostility is associated with a number of metabolic risk factors for cardiovascular disease, including waist—hip ratio, glucose, and triglycerides. Along with hostility, many of these measures have also been shown to be associated with reduced central serotonergic function. We have previously reported that a citalopram intervention was successful in reducing hostility by self-report assessment (Kamarck et al., 2009). Here we examine the effects of this serotonergic intervention on metabolic risk factors in the same sample.

Escherichia Coli Topoisomerase I Is An Iron And Zinc Binding Protein, Jianxin Lu, Wu Wang, Guoqiang Tan, Aaron P. Landry, Peng Yi, Fan Si, Yaguang Ren, Huangen Ding

Faculty Publications

Escherichia coli topoisomerase I (TopA) cleaves and rejoins one strand of double-stranded DNA to relax the negatively supercoiled DNA. Structurally, TopA contains an N-terminal catalytic fragment and a C-terminal zinc-binding region that is required for relaxation of the negatively supercoiled DNA. Here we report that E. coli TopA is an iron and zinc binding protein. The UV-Vis absorption measurements and metal content analyses reveal that TopA purified from E. coli cells grown in the rich LB medium contains both iron and zinc. However, TopA purified from E. coli cells grown in the M9 minimal medium has negligible amounts of zinc …

Detection Of Environmentally Persistent Free Radicals At A Superfund Wood Treating Site, Albert Leo N. Dela Cruz, William Gehling, Slawomir Lomnicki, Robert Cook, Barry Dellinger

Faculty Publications

Environmentally persistent free radicals (EPFRs) have previously been observed in association with combustion-generated particles and airborne PM 2.5 (particulate matter, d < 2.5um). The purpose of this study was to determine if similar radicals were present in soils and sediments at Superfund sites. The site was a former wood treating facility containing pentachlorophenol (PCP) as a major contaminant. Both contaminated and noncontaminated (just outside the contaminated area) soil samples were collected. The samples were subjected to the conventional humic substances (HS) extraction procedure. Electron paramagnetic resonance (EPR) spectroscopy was used to measure the EPFR concentrations and determine their structure for each sample fraction. Analyses revealed a ∼30× higher EPFR concentration in the PCP contaminated soils (20.2 × 10 17 spins/g) than in the noncontaminated soil (0.7 × 10 17 spins/g). Almost 90% of the EPFR signal originated from the minerals/clays/humins fraction. GC-MS analyses revealed ∼6500 ppm of PCP in the contaminated soil samples and none detected in the background samples. Inductively coupled plasma-atomic emission spectrophotometry (ICP-AES) analyses revealed ∼7× higher concentrations of redox-active transition metals, in the contaminated soils than the noncontaminated soil. Vapor phase and liquid phase dosing of the clays/minerals/humins fraction of the soil with PCP resulted in an EPR signal identical to that observed in the contaminated soil, strongly suggesting the observed EPFR is pentachlorophenoxyl radical. Chemisorption and electron transfer from PCP to transition metals and other electron sinks in the soil are proposed to be responsible for EPFR formation. © 2011 American Chemical Society.

A Comprehensive Map Of Mobile Element Insertion Polymorphisms In Humans, Chip Stewart, Deniz Kural, Michael P. Strömberg, Jerilyn A. Walker, Miriam K. Konkel, Adrian M. Stütz, Alexander E. Urban, Fabian Grubert, Hugo Y.K. Lam, Wan Ping Lee, Michele Busby, Amit R. Indap, Erik Garrison, Chad Huff, Jinchuan Xing, Michael P. Snyder, Lynn B. Jorde, Mark A. Batzer, Jan O. Korbel, Gabor T. Marth

Faculty Publications

As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and …

Inhibition Of Neutrophil Apoptosis By Pai-1, Jaroslaw W. Zmijewski, Hong Beom Bae, Jessy S. Deshane, Cynthia B. Peterson, David D. Chaplin, Edward Abraham

Faculty Publications

Increased circulating and tissue levels of plasminogen activator inhibitor 1 (PAI-1) are often present in severe inflammatory states associated with neutrophil activation and accumulation and correlate with poor clinical outcome from many of these conditions. The mechanisms by which PAI-1 contributes to inflammation have not been fully delineated. In the present experiments, we found that addition of PAI-1 to neutrophil cultures diminished the rate of spontaneous and TNFrelated apoptosis-inducing ligand-induced apoptotic cell death. The effects of PAI-1 on cell viability were associated with activation of antiapoptotic signaling pathways, including upregulation of PKB/Akt, Mcl-1, and Bcl-xL. Although urokinase-plasminogen activator receptor, lipoprotein …

Emerging Roles Of Jak-Stat Signaling Pathways In Adipocytes, Allison J. Richard, Jacqueline M. Stephens

Faculty Publications

Twenty years ago, adipocytes were largely considered to be inert energy-storage depots. We now know that fat cells are highly insulin-sensitive with significant endocrine functions. Alterations in adipocyte development or function can contribute to metabolic disease, in particular type 2 diabetes. The current obesity epidemic that plagues many nations provides a strong rationale for understanding basic adipocyte biology. The JAK-STAT signaling pathway mediates the action of a variety of hormones that have profound effects on adipocyte development and function. In addition, adipocytes secrete hormones that utilize this signaling pathway. This review summarizes research on the expression and function of JAKs …