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Sample records for influences antigenic variation

  1. Characterization of a Novel Antisense RNA in the Major Pilin Locus of Neisseria meningitidis Influencing Antigenic Variation

    PubMed Central

    Tan, Felicia Y. Y.; Wörmann, Mirka E.; Tang, Christoph M.

    2015-01-01

    ABSTRACT Expression of type four pili (Tfp) is essential for virulence in Neisseria meningitidis. Pili mediate adhesion, bacterial aggregation, and DNA uptake. In N. meningitidis, the major pilin subunit is encoded by the pilE gene. In some strains, PilE is subject to phase and antigenic variation, which can alter Tfp properties and together offer a possible mechanism of immune escape. Pilin expression and antigenic variation can be modulated in response to environmental cues; however, the precise mechanisms of such regulation remain unclear. We identified a promoter in the pilE locus, 3′ of the pilE coding sequence, on the antisense (AS) strand which is conserved in meningococci. We show that this promoter directs transcription of an AS RNA that is expressed during specific growth phases and in response to salt stress. Furthermore, we demonstrate that the transcript encompasses sequences complementary to the entire pilE coding sequence and 5′ untranslated region. AS RNAs can regulate the gene on the sense strand by altering transcript stability or translation. However, by using Northern blotting, quantitative reverse transcription-PCR (RT-PCR), and Western blotting, we found no significant AS RNA-dependent changes in pilE transcript or protein level. Instead, our data indicate that the AS RNA influences pilin antigenic variation. This work provides further insights into the complex regulation of pilin expression and variation in pathogenic Neisseria. IMPORTANCE Pathogenic Neisseria spp. express type four pili (Tfp) which are important for adhesion, aggregation and transformation. Some strains of N. meningitidis are able to vary the sequence of the major subunit (PilE) of the Tfp. The mechanisms underlying this variation are not fully defined, but the process requires several noncoding elements that are found adjacent to the pilE gene. In this work, we identified a cis-encoded RNA antisense to pilE in N. meningitidis. By using Northern blotting and RT

  2. Antigenic variation in African trypanosomes

    PubMed Central

    Horn, David

    2014-01-01

    Studies on Variant Surface Glycoproteins (VSGs) and antigenic variation in the African trypanosome, Trypanosoma brucei, have yielded a remarkable range of novel and important insights. The features first identified in T. brucei extend from unique to conserved-among-trypanosomatids to conserved-among-eukaryotes. Consequently, much of what we now know about trypanosomatid biology and much of the technology available has its origin in studies related to VSGs. T. brucei is now probably the most advanced early branched eukaryote in terms of experimental tractability and can be approached as a pathogen, as a model for studies on fundamental processes, as a model for studies on eukaryotic evolution or often all of the above. In terms of antigenic variation itself, substantial progress has been made in understanding the expression and switching of the VSG coat, while outstanding questions continue to stimulate innovative new approaches. There are large numbers of VSG genes in the genome but only one is expressed at a time, always immediately adjacent to a telomere. DNA repair processes allow a new VSG to be copied into the single transcribed locus. A coordinated transcriptional switch can also allow a new VSG gene to be activated without any detectable change in the DNA sequence, thereby maintaining singular expression, also known as allelic exclusion. I review the story behind VSGs; the genes, their expression and switching, their central role in T. brucei virulence, the discoveries that emerged along the way and the persistent questions relating to allelic exclusion in particular. PMID:24859277

  3. Antigenic variation: Molecular and genetic mechanisms of relapsing disease

    SciTech Connect

    Cruse, J.M.; Lewis, R.E.

    1987-01-01

    This book contains 10 chapters. They are: Contemporary Concepts of Antigenic Variation; Antigenic Variation in the Influenza Viruses; Mechanisms of Escape of Visna Lentiviruses from Immunological Control; A Review of Antigenic Variation by the Equine Infectious Anemia Virus; Biologic and Molecular Variations in AIDS Retrovirus Isolates; Rabies Virus Infection: Genetic Mutations and the Impact on Viral Pathogenicity and Immunity; Immunobiology of Relapsing Fever; Antigenic Variation in African Trypanosomes; Antigenic Variation and Antigenic Diversity in Malaria; and Mechanisms of Immune Evasion in Schistosomiasis.

  4. Antigenic variation in the intestinal parasite Giardia lamblia.

    PubMed

    Gargantini, Pablo Rubén; Serradell, Marianela Del Carmen; Ríos, Diego Nicolás; Tenaglia, Albano Heraldo; Luján, Hugo Daniel

    2016-08-01

    Giardia lamblia trophozoites undergo antigenic variation, where one member of the Variant-specific Surface Protein (VSP) family is expressed on the surface of proliferating trophozoites and periodically replaced by another one. Two main questions have challenged researchers since antigenic switching was discovered in Giardia: What are the mechanisms involved? How are they influenced by other cellular processes or by the environment? Two molecular mechanisms have been proposed, both involving small non-coding RNAs. Here we postulate that (a) chromatin remodeling, triggered by environmental factors, also plays an important role in selecting the VSP that will be expressed and (b) the particular VSP structure may not only protect the parasite in the small intestine but also signal the need to exchange the existing VSP for another. PMID:27177351

  5. Mosaic VSGs and the Scale of Trypanosoma brucei Antigenic Variation

    PubMed Central

    Hall, James P. J.; Wang, Huanhuan; Barry, J. David

    2013-01-01

    A main determinant of prolonged Trypanosoma brucei infection and transmission and success of the parasite is the interplay between host acquired immunity and antigenic variation of the parasite variant surface glycoprotein (VSG) coat. About 0.1% of trypanosome divisions produce a switch to a different VSG through differential expression of an archive of hundreds of silent VSG genes and pseudogenes, but the patterns and extent of the trypanosome diversity phenotype, particularly in chronic infection, are unclear. We applied longitudinal VSG cDNA sequencing to estimate variant richness and test whether pseudogenes contribute to antigenic variation. We show that individual growth peaks can contain at least 15 distinct variants, are estimated computationally to comprise many more, and that antigenically distinct ‘mosaic’ VSGs arise from segmental gene conversion between donor VSG genes or pseudogenes. The potential for trypanosome antigenic variation is probably much greater than VSG archive size; mosaic VSGs are core to antigenic variation and chronic infection. PMID:23853603

  6. DNA Double-Strand Breaks and Telomeres Play Important Roles in Trypanosoma brucei Antigenic Variation

    PubMed Central

    2015-01-01

    Human-infecting microbial pathogens all face a serious problem of elimination by the host immune response. Antigenic variation is an effective immune evasion mechanism where the pathogen regularly switches its major surface antigen. In many cases, the major surface antigen is encoded by genes from the same gene family, and its expression is strictly monoallelic. Among pathogens that undergo antigenic variation, Trypanosoma brucei (a kinetoplastid), which causes human African trypanosomiasis, Plasmodium falciparum (an apicomplexan), which causes malaria, Pneumocystis jirovecii (a fungus), which causes pneumonia, and Borrelia burgdorferi (a bacterium), which causes Lyme disease, also express their major surface antigens from loci next to the telomere. Except for Plasmodium, DNA recombination-mediated gene conversion is a major pathway for surface antigen switching in these pathogens. In the last decade, more sophisticated molecular and genetic tools have been developed in T. brucei, and our knowledge of functions of DNA recombination in antigenic variation has been greatly advanced. VSG is the major surface antigen in T. brucei. In subtelomeric VSG expression sites (ESs), VSG genes invariably are flanked by a long stretch of upstream 70-bp repeats. Recent studies have shown that DNA double-strand breaks (DSBs), particularly those in 70-bp repeats in the active ES, are a natural potent trigger for antigenic variation in T. brucei. In addition, telomere proteins can influence VSG switching by reducing the DSB amount at subtelomeric regions. These findings will be summarized and their implications will be discussed in this review. PMID:25576484

  7. Antigenic variation with a twist--the Borrelia story.

    PubMed

    Norris, Steven J

    2006-06-01

    A common mechanism of immune evasion in pathogenic bacteria and protozoa is antigenic variation, in which genetic or epigenetic changes result in rapid, sequential shifts in a surface-exposed antigen. In this issue of Molecular Microbiology, Dai et al. provide the most complete description to date of the vlp/vsp antigenic variation system of the relapsing fever spirochaete, Borrelia hermsii. This elaborate, plasmid-encoded system involves an expression site that can acquire either variable large protein (vlp) or variable small protein (vsp) surface lipoprotein genes from 59 different archival copies. The archival vlp and vsp genes are arranged in clusters on at least five different plasmids. Gene conversion occurs through recombination events at upstream homology sequences (UHS) found in each gene copy, and at downstream homology sequences (DHS) found periodically among the vlp/vsp archival genes. Previous studies have shown that antigenic variation in relapsing fever Borrelia not only permits the evasion of host antibody responses, but can also result in changes in neurotropism and other pathogenic properties. The vlsE antigenic variation locus of Lyme disease spirochaetes, although similar in sequence to the relapsing fever vlp genes, has evolved a completely different antigenic variation mechanism involving segmental recombination from a contiguous array of vls silent cassettes. These two systems thus appear to represent divergence from a common precursor followed by functional convergence to create two distinct antigenic variation processes. PMID:16796669

  8. DNA Recombination Strategies During Antigenic Variation in the African Trypanosome.

    PubMed

    McCulloch, Richard; Morrison, Liam J; Hall, James P J

    2015-04-01

    Survival of the African trypanosome in its mammalian hosts has led to the evolution of antigenic variation, a process for evasion of adaptive immunity that has independently evolved in many other viral, bacterial and eukaryotic pathogens. The essential features of trypanosome antigenic variation have been understood for many years and comprise a dense, protective Variant Surface Glycoprotein (VSG) coat, which can be changed by recombination-based and transcription-based processes that focus on telomeric VSG gene transcription sites. However, it is only recently that the scale of this process has been truly appreciated. Genome sequencing of Trypanosoma brucei has revealed a massive archive of >1000 VSG genes, the huge majority of which are functionally impaired but are used to generate far greater numbers of VSG coats through segmental gene conversion. This chapter will discuss the implications of such VSG diversity for immune evasion by antigenic variation, and will consider how this expressed diversity can arise, drawing on a growing body of work that has begun to examine the proteins and sequences through which VSG switching is catalyzed. Most studies of trypanosome antigenic variation have focused on T. brucei, the causative agent of human sleeping sickness. Other work has begun to look at antigenic variation in animal-infective trypanosomes, and we will compare the findings that are emerging, as well as consider how antigenic variation relates to the dynamics of host-trypanosome interaction. PMID:26104717

  9. Microbial antigenic variation mediated by homologous DNA recombination.

    PubMed

    Vink, Cornelis; Rudenko, Gloria; Seifert, H Steven

    2012-09-01

    Pathogenic microorganisms employ numerous molecular strategies in order to delay or circumvent recognition by the immune system of their host. One of the most widely used strategies of immune evasion is antigenic variation, in which immunogenic molecules expressed on the surface of a microorganism are continuously modified. As a consequence, the host is forced to constantly adapt its humoral immune response against this pathogen. An antigenic change thus provides the microorganism with an opportunity to persist and/or replicate within the host (population) for an extended period of time or to effectively infect a previously infected host. In most cases, antigenic variation is caused by genetic processes that lead to the modification of the amino acid sequence of a particular antigen or to alterations in the expression of biosynthesis genes that induce changes in the expression of a variant antigen. Here, we will review antigenic variation systems that rely on homologous DNA recombination and that are found in a wide range of cellular, human pathogens, including bacteria (such as Neisseria spp., Borrelia spp., Treponema pallidum, and Mycoplasma spp.), fungi (such as Pneumocystis carinii) and parasites (such as the African trypanosome Trypanosoma brucei). Specifically, the various DNA recombination-based antigenic variation systems will be discussed with a focus on the employed mechanisms of recombination, the DNA substrates, and the enzymatic machinery involved. PMID:22212019

  10. Immunogenetic Mechanisms Driving Norovirus GII.4 Antigenic Variation

    PubMed Central

    Donaldson, Eric F.; Corti, Davide; Swanstrom, Jesica; Debbink, Kari; Lanzavecchia, Antonio; Baric, Ralph S.

    2012-01-01

    Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs) characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs). Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987–1997), contemporary (2004–2009), and broad (1987–2009). NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped. Amino acids 294–298 and 368–372 were required for binding NVB 114, 111 and 43.9 mAbs. Amino acids 393–395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation. These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease. Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing epitopes

  11. Colony morphology variation of Burkholderia pseudomallei is associated with antigenic variation and O-polysaccharide modification.

    PubMed

    Wikraiphat, Chanthiwa; Saiprom, Natnaree; Tandhavanant, Sarunporn; Heiss, Christian; Azadi, Parastoo; Wongsuvan, Gumphol; Tuanyok, Apichai; Holden, Matthew T G; Burtnick, Mary N; Brett, Paul J; Peacock, Sharon J; Chantratita, Narisara

    2015-05-01

    Burkholderia pseudomallei is a CDC tier 1 select agent that causes melioidosis, a severe disease in humans and animals. Persistent infections are common, and there is currently no vaccine available. Lipopolysaccharide (LPS) is a potential vaccine candidate. B. pseudomallei expresses three serologically distinct LPS types. The predominant O-polysaccharide (OPS) is an unbranched heteropolymer with repeating d-glucose and 6-deoxy-l-talose residues in which the 6-deoxy-l-talose residues are variably replaced with O-acetyl and O-methyl modifications. We observed that primary clinical B. pseudomallei isolates with mucoid and nonmucoid colony morphologies from the same sample expressed different antigenic types distinguishable using an LPS-specific monoclonal antibody (MAb). MAb-reactive (nonmucoid) and nonreactive (mucoid) strains from the same patient exhibited identical LPS banding patterns by silver staining and indistinguishable genotypes. We hypothesized that LPS antigenic variation reflected modification of the OPS moieties. Mutagenesis of three genes involved in LPS synthesis was performed in B. pseudomallei K96243. Loss of MAb reactivity was observed in both wbiA (encoding a 2-O-acetyltransferase) and wbiD (putative methyl transferase) mutants. The structural characteristics of the OPS moieties from isogenic nonmucoid strain 4095a and mucoid strain 4095c were further investigated. Utilizing nuclear magnetic resonance (NMR) spectroscopy, we found that B. pseudomallei 4095a and 4095c OPS antigens exhibited substitution patterns that differed from the prototypic OPS structure. Specifically, 4095a lacked 4-O-acetylation, while 4095c lacked both 4-O-acetylation and 2-O-methylation. Our studies indicate that B. pseudomallei OPS undergoes antigenic variation and suggest that the 9D5 MAb recognizes a conformational epitope that is influenced by both O-acetyl and O-methyl substitution patterns. PMID:25776750

  12. Analysis of antigenic variation in equine 2 influenza A viruses.

    PubMed

    Hinshaw, V S; Naeve, C W; Webster, R G; Douglas, A; Skehel, J J; Bryans, J

    1983-01-01

    Influenza outbreaks involving viruses of the H3N8 subtype (equine 2) often occur in vaccinated horses. For this reason, a series of influenza viruses of the H3N8 subtype were examined to determine if antigenic variation could be detected in isolates during the period 1963-81. Antigenic analyses with post-infection ferret sera and monoclonal antibodies showed that the haemagglutinins of recent isolates were antigenically distinguishable from the prototype A/eq/Miami/1/63 and that antigenically distinguishable groups of equine 2 viruses co-circulate in the horse population. Based on these studies, it is recommended that a recent equine strain, A/equine/Fontainebleu/1/79 or A/equine/Kentucky/1/81, serve as an additional prototype strain for this subtype.Antigenic variation in equine 2 viruses may be of epidemiological significance, yet the overall conservation of these strains makes it unlikely that vaccine failures can be attributed solely to antigenic changes in these viruses. A sufficiently potent vaccine, containing a current representative of the most prevalent equine 2 strain, may improve the protection afforded by equine vaccines. PMID:6601538

  13. Genetic diversity and antigenicity variation of Babesia bovis merozoite surface antigen-1 (MSA-1) in Thailand.

    PubMed

    Tattiyapong, Muncharee; Sivakumar, Thillaiampalam; Takemae, Hitoshi; Simking, Pacharathon; Jittapalapong, Sathaporn; Igarashi, Ikuo; Yokoyama, Naoaki

    2016-07-01

    Babesia bovis, an intraerythrocytic protozoan parasite, causes severe clinical disease in cattle worldwide. The genetic diversity of parasite antigens often results in different immune profiles in infected animals, hindering efforts to develop immune control methodologies against the B. bovis infection. In this study, we analyzed the genetic diversity of the merozoite surface antigen-1 (msa-1) gene using 162 B. bovis-positive blood DNA samples sourced from cattle populations reared in different geographical regions of Thailand. The identity scores shared among 93 msa-1 gene sequences isolated by PCR amplification were 43.5-100%, and the similarity values among the translated amino acid sequences were 42.8-100%. Of 23 total clades detected in our phylogenetic analysis, Thai msa-1 gene sequences occurred in 18 clades; seven among them were composed of sequences exclusively from Thailand. To investigate differential antigenicity of isolated MSA-1 proteins, we expressed and purified eight recombinant MSA-1 (rMSA-1) proteins, including an rMSA-1 from B. bovis Texas (T2Bo) strain and seven rMSA-1 proteins based on the Thai msa-1 sequences. When these antigens were analyzed in a western blot assay, anti-T2Bo cattle serum strongly reacted with the rMSA-1 from T2Bo, as well as with three other rMSA-1 proteins that shared 54.9-68.4% sequence similarity with T2Bo MSA-1. In contrast, no or weak reactivity was observed for the remaining rMSA-1 proteins, which shared low sequence similarity (35.0-39.7%) with T2Bo MSA-1. While demonstrating the high genetic diversity of the B. bovis msa-1 gene in Thailand, the present findings suggest that the genetic diversity results in antigenicity variations among the MSA-1 antigens of B. bovis in Thailand. PMID:27101782

  14. Bloodstream form Trypanosome plasma membrane proteins: antigenic variation and invariant antigens.

    PubMed

    Schwede, Angela; Carrington, Mark

    2010-12-01

    Trypanosoma brucei is exposed to the adaptive immune system and complement in the blood of its mammalian hosts. The aim of this review is to analyse the role and regulation of the proteins present on the external face of the plasma membrane in the long-term persistence of an infection and transmission. In particular, the following are addressed: (1) antigenic variation of the variant surface glycoprotein (VSG), (2) the formation of an effective VSG barrier shielding invariant surface proteins, and (3) the rapid uptake of VSG antibody complexes combined with degradation of the immunoglobulin and recycling of the VSG. PMID:20109254

  15. Genetic analysis of a Treponema phagedenis locus encoding antigenic lipoproteins with potential for antigenic variation.

    PubMed

    Mushtaq, Mamoona; Bongcam-Rudloff, Erik; Loftsdottir, Heidur; Pringle, Märit; Segerman, Bo; Zuerner, Richard; Rosander, Anna

    2016-06-30

    Digital dermatitis (DD) is a painful and debilitating claw disease in cattle. Spirochetes of the genus Treponema are found in high numbers in the lesions and are likely to be involved in the pathogenesis. The occurrence of Treponema phagedenis in DD lesions, especially near the interface of healthy and diseased tissue, suggests that this species contributes to the development and/or progression of the lesions. In this study we characterized a genetic locus in T. phagedenis that contains coding regions for three antigenic proteins, PrrA, VpsA, and VpsB. Comparative analysis of homologous loci from fifteen strains suggests that prrA may be transposed into or out of this locus. Alterations in the copy number of TA repeats within the putative promoter region may regulate VpsA/B expression. The vpsA and prrA genes occur in allelic variants in different T. phagedenis isolates and may provide one explanation for the antigenic variation observed in T. phagedenis DD isolates. PMID:27259832

  16. Potentially conflicting selective forces that shape the vls antigenic variation system in Borrelia burgdorferi

    PubMed Central

    Zhou, Wei; Brisson, Dustin

    2014-01-01

    Changing environmental conditions present an evolutionary challenge for all organisms. The environment of microbial pathogens, including the adaptive immune responses of the infected host, changes rapidly and is lethal to the pathogen lineages that cannot quickly adapt. The dynamic immune environment creates strong selective pressures favoring microbial pathogen lineages with antigenic variation systems that maximize the antigenic divergence among expressed antigenic variants. However, divergence among expressed antigens may be constrained by other molecular features such as the efficient expression of functional proteins. We computationally examined potential conflicting selection pressures on antigenic variation systems using the vls antigenic variation system in Borrelia burgdorferi as a model system. The vls system alters the sequence of the expressed antigen by recombining gene fragments from unexpressed but divergent ‘cassettes’ into the expression site, vlsE. The in silico analysis of natural and altered cassettes from seven lineages in the B. burgdorferi sensu lato species complex revealed that sites that are polymorphic among unexpressed cassettes, as well as the insertion/deletion mutations, are organized to maximize divergence among the expressed antigens within the constraints of translational ability and high translational efficiency. This study provides empirical evidence that conflicting selection pressures on antigenic variation systems can limit the potential antigenic divergence in order to maintain proper molecular function. PMID:24837669

  17. Mini-review: Strategies for Variation and Evolution of Bacterial Antigens

    PubMed Central

    Foley, Janet

    2015-01-01

    Across the eubacteria, antigenic variation has emerged as a strategy to evade host immunity. However, phenotypic variation in some of these antigens also allows the bacteria to exploit variable host niches as well. The specific mechanisms are not shared-derived characters although there is considerable convergent evolution and numerous commonalities reflecting considerations of natural selection and biochemical restraints. Unlike in viruses, mechanisms of antigenic variation in most bacteria involve larger DNA movement such as gene conversion or DNA rearrangement, although some antigens vary due to point mutations or modified transcriptional regulation. The convergent evolution that promotes antigenic variation integrates various evolutionary forces: these include mutations underlying variant production; drift which could remove alleles especially early in infection or during life history phases in arthropod vectors (when the bacterial population size goes through a bottleneck); selection not only for any particular variant but also for the mechanism for the production of variants (i.e., selection for mutability); and overcoming negative selection against variant production. This review highlights the complexities of drivers of antigenic variation, in particular extending evaluation beyond the commonly cited theory of immune evasion. A deeper understanding of the diversity of purpose and mechanisms of antigenic variation in bacteria will contribute to greater insight into bacterial pathogenesis, ecology and coevolution with hosts. PMID:26288700

  18. Renibacterium salmoninarum p57 antigenic variation is restricted in geographic distribution and correlated with genomic markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The 57 kDa protein (p57) is an important diagnostic antigen that is implicated in the pathogenesis of salmonid bacterial kidney disease. Little is known about the nature and extent of antigenic variation in p57. Previously, we reported that p57 produced by Renibacterium salmoninarum Strain 684 conta...

  19. Antigen

    MedlinePlus

    An antigen is any substance that causes your immune system to produce antibodies against it. This means your immune ... and is trying to fight it off. An antigen may be a substance from the environment, such ...

  20. Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control

    PubMed Central

    Glover, Lucy; Hutchinson, Sebastian; Alsford, Sam; McCulloch, Richard; Field, Mark C; Horn, David

    2013-01-01

    African trypanosomes are lethal human and animal parasites that use antigenic variation for evasion of host adaptive immunity. To facilitate antigenic variation, trypanosomes dedicate approximately one third of their nuclear genome, including many minichromosomes, and possibly all sub-telomeres, to variant surface glycoprotein (VSG) genes and associated sequences. Antigenic variation requires transcription of a single VSG by RNA polymerase I (Pol-I), with silencing of other VSGs, and periodic switching of the expressed gene, typically via DNA recombination with duplicative translocation of a new VSG to the active site. Thus, telomeric location, epigenetic controls and monoallelic transcription by Pol-I at an extranucleolar site are prominent features of VSGs and their expression, with telomeres, chromatin structure and nuclear organization all making vitally important contributions to monoallelic VSG expression control and switching. We discuss VSG transcription, recombination and replication control within this chromosomal and sub-nuclear context. PMID:24047558

  1. Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells.

    PubMed

    Nassif, X; Lowy, J; Stenberg, P; O'Gaora, P; Ganji, A; So, M

    1993-05-01

    Pili have been shown to play an essential role in the adhesion of Neisseria meningitidis to epithelial cells. However, among piliated strains, both inter- and intrastrain variability exist with respect to their degree of adhesion to epithelial cells in vitro (Virji et al., 1992). This suggests that factors other than the presence of pili per se are involved in this process. The N. meningitidis pilin subunit undergoes extensive antigenic variation. Piliated low- and high-adhesive derivatives of the same N. meningitidis strain were selected and the nucleotide sequence of the pilin gene expressed in each was determined. The highly adhesive derivatives had the same pilin sequence. The alleles encoding the pilin subunit of the low-adhesive derivatives were completely different from the one found in the high-adhesive isolates. Using polyclonal antibodies raised against one hyperadhesive variant, it was confirmed that the low-adhesive piliated derivatives expressed pilin variants antigenically different from the highly adhesive strains. The role of antigenic variation in the adhesive process of N. meningitidis was confirmed by performing allelic exchanges of the pilE locus between low- and high-adhesive isolates. Antigenic variation has been considered a means by which virulent bacteria evade the host immune system. This work provides genetic proof that a bacterial pathogen, N. meningitidis, can use antigenic variation to modulate their degree of virulence. PMID:8332064

  2. Factors influencing variation in dentist service rates.

    PubMed

    Grembowski, D; Milgrom, P; Fiset, L

    1990-01-01

    In the previous article, we calculated dentist service rates for 200 general dentists based on a homogeneous, well-educated, upper-middle-class population of patients. Wide variations in the rates were detected. In this analysis, factors influencing variation in the rates were identified. Variation in rates for categories of dental services was explained by practice characteristics, patient exposure to fluoridated water supplies, and non-price competition in the dental market. Rates were greatest in large, busy practices in markets with high fees. Older practices consistently had lower rates across services. As a whole, these variables explained between 5 and 30 percent of the variation in the rates. PMID:2118182

  3. DNA Binding by the Meningococcal RdgC Protein, Associated with Pilin Antigenic Variation

    PubMed Central

    Moore, Timothy; Sharples, Gary J.; Lloyd, Robert G.

    2004-01-01

    The RdgC protein of Neisseria gonorrhoeae is required for efficient pilin antigenic variation, although its precise role has yet to be established. We demonstrate that the nearly identical RdgC from Neisseria meningitidis binds DNA with little specificity for sequence or structure, like the Escherichia coli protein. We also show that neither protein is able to constrain torsional tension in relaxed DNA. These data exclude several possible roles for RdgC in pilin antigenic variation and suggest that RdgC performs a similar function in both E. coli and the Neisseria spp. PMID:14729716

  4. Influenza A Virus Hemagglutinin Antibody Escape Promotes Neuraminidase Antigenic Variation and Drug Resistance

    PubMed Central

    Hensley, Scott E.; Das, Suman R.; Gibbs, James S.; Bailey, Adam L.; Schmidt, Loren M.; Bennink, Jack R.; Yewdell, Jonathan W.

    2011-01-01

    Drugs inhibiting the influenza A virus (IAV) neuraminidase (NA) are the cornerstone of anti-IAV chemotherapy and prophylaxis in man. Drug-resistant mutations in NA arise frequently in human isolates, limiting the therapeutic application of NA inhibitors. Here, we show that antibody-driven antigenic variation in one domain of the H1 hemagglutinin Sa site leads to compensatory mutations in NA, resulting in NA antigenic variation and acquisition of drug resistance. These findings indicate that influenza A virus resistance to NA inhibitors can potentially arise from antibody driven HA escape, confounding analysis of influenza NA evolution in nature. PMID:21364978

  5. Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern

    PubMed Central

    Recker, Mario; Buckee, Caroline O.; Serazin, Andrew; Kyes, Sue; Pinches, Robert; Christodoulou, Zóe; Springer, Amy L.; Gupta, Sunetra; Newbold, Chris I.

    2011-01-01

    Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection. PMID:21408201

  6. 'Nothing is permanent but change'- antigenic variation in persistent bacterial pathogens.

    PubMed

    Palmer, Guy H; Bankhead, Troy; Lukehart, Sheila A

    2009-12-01

    Pathogens persist in immunocompetent mammalian hosts using various strategies, including evasion of immune effectors by antigenic variation. Among highly antigenically variant bacteria, gene conversion is used to generate novel expressed variants from otherwise silent donor sequences. Recombination using oligonucleotide segments from multiple donors is a combinatorial mechanism that tremendously expands the variant repertoire, allowing thousands of variants to be generated from a relatively small donor pool. Three bacterial pathogens, each encoded by a small genome (< 1.2 Mb), illustrate this variant generating capacity and its role in persistent infection. Borrelia burgdorferi VlsE diversity is encoded and expressed on a linear plasmid required for persistence and recent experiments have demonstrated that VlsE recombination is necessary for persistence in the immunocompetent host. In contrast, both Treponema pallidum TprK and Anaplasma marginale Msp2 expression sites and donors are chromosomally encoded. Both T. pallidum and A. marginale generate antigenic variants in vivo in individual hosts and studies at the population level reveal marked strain diversity in the variant repertoire that may underlie pathogen strain structure and the capacity for re-infection and heterologous strain superinfection. Here, we review gene conversion in bacterial antigenic variation and discuss the short- and long-term selective pressures that shape the variant repertoire. PMID:19709057

  7. Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections.

    PubMed Central

    Deitsch, K W; Moxon, E R; Wellems, T E

    1997-01-01

    Pathogenic microbes have evolved highly sophisticated mechanisms for colonizing host tissues and evading or deflecting assault by the immune response. The ability of these microbes to avoid clearance prolongs infection, thereby promoting their long-term survival within individual hosts and, through transmission, between hosts. Many pathogens are capable of extensive antigenic changes in the face of the multiple constitutive and dynamic components of host immune defenses. As a result, highly diverse populations that have widely different virulence properties can arise from a single infecting organism (clone). In this review, we consider the molecular and genetic features of antigenic variation and corresponding host-parasite interactions of different pathogenic bacterial, fungal, and protozoan microorganisms. The host and microbial molecules involved in these interactions often determine the adhesive, invasive, and antigenic properties of the infecting organisms and can dramatically affect the virulence and pathobiology of individual infections. Pathogens capable of such antigenic variation exhibit mechanisms of rapid mutability in confined chromosomal regions containing specialized genes designated contingency genes. The mechanisms of hypermutability of contingency genes are common to a variety of bacterial and eukaryotic pathogens and include promoter alterations, reading-frame shifts, gene conversion events, genomic rearrangements, and point mutations. PMID:9293182

  8. Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation

    PubMed Central

    Devlin, Rebecca; Marques, Catarina A; Paape, Daniel; Prorocic, Marko; Zurita-Leal, Andrea C; Campbell, Samantha J; Lapsley, Craig; Dickens, Nicholas; McCulloch, Richard

    2016-01-01

    Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating – a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility. DOI: http://dx.doi.org/10.7554/eLife.12765.001 PMID:27228154

  9. Renibacterium salmoninarum p57 antigenic variation is restricted in geographic distribution and correlated with genomic markers.

    PubMed

    Wiens, Gregory D; Dale, Ole Bendik

    2009-02-12

    The 57 kDa protein (p57) is an important diagnostic antigen that is implicated in the pathogenesis of salmonid bacterial kidney disease. Little is known about the nature and extent of antigenic variation in p57. Previously, we reported that p57 produced by Renibacterium salmoninarum Strain 684 contains a mutation that disrupts monoclonal antibody (MAb) 4C11 binding. In the present study, we examined MAb binding to a panel of 23 additional R. salmoninarum isolates obtained from diverse geographic locations to examine the prevalence of this variant and whether additional variability exists within other p57 epitopes. Six p57-specific MAbs (4C11, 4D3, 3H1, 4H8, 4D10 and 1A1) were used to probe dot and western blots to determine the relative expression, size and cellular association of p57. Full-length p57 was produced by all isolates, and for each isolate, the protein was associated with the bacterial cell surface. The epitopes recognized by 4 MAbs, 4D3, 4H8, 3H1 and 1A1, were conserved among all strains tested. The 4C11 epitope was absent in 5 of 8 strains originating from Norway, while the 4D10 epitope was partially disrupted in one isolate from British Columbia, Canada. The 5 Norwegian antigenic-variant strains appeared to be clonally related as they shared the following characteristics: one tandem repeat in the ETRA locus, a Sequovar-4 16-23S rRNA intervening DNA sequence, a larger XhoI fragment in the msa1 5' region, and absent msa3 gene. These results indicate that limited antigenic and genomic variation exists between strains and this variation appears geographically restricted in distribution. PMID:19326793

  10. Evaluation of the Importance of VlsE Antigenic Variation for the Enzootic Cycle of Borrelia burgdorferi

    PubMed Central

    Rogovskyy, Artem S.; Casselli, Timothy; Tourand, Yvonne; Jones, Cami R.; Owen, Jeb P.; Mason, Kathleen L.; Scoles, Glen A.; Bankhead, Troy

    2015-01-01

    Efficient acquisition and transmission of Borrelia burgdorferi by the tick vector, and the ability to persistently infect both vector and host, are important elements for the life cycle of the Lyme disease pathogen. Previous work has provided strong evidence implicating the significance of the vls locus for B. burgdorferi persistence. However, studies involving vls mutant clones have thus far only utilized in vitro-grown or host-adapted spirochetes and laboratory strains of mice. Additionally, the effects of vls mutation on tick acquisition and transmission has not yet been tested. Thus, the importance of VlsE antigenic variation for persistent infection of the natural reservoir host, and for the B. burgdorferi enzootic life cycle in general, has not been examined to date. In the current work, Ixodes scapularis and Peromyscus maniculatus were infected with different vls mutant clones to study the importance of the vls locus for the enzootic cycle of the Lyme disease pathogen. The findings highlight the significance of the vls system for long-term infection of the natural reservoir host, and show that VlsE antigenic variability is advantageous for efficient tick acquisition of B. burgdorferi from the mammalian reservoir. The data also indicate that the adaptation state of infecting spirochetes influences B. burgdorferi avoidance from host antibodies, which may be in part due to its respective VlsE expression levels. Overall, the current findings provide the most direct evidence on the importance of VlsE for the enzootic cycle of Lyme disease spirochetes, and underscore the significance of VlsE antigenic variation for maintaining B. burgdorferi in nature. PMID:25893989

  11. Evaluation of the Importance of VlsE Antigenic Variation for the Enzootic Cycle of Borrelia burgdorferi.

    PubMed

    Rogovskyy, Artem S; Casselli, Timothy; Tourand, Yvonne; Jones, Cami R; Owen, Jeb P; Mason, Kathleen L; Scoles, Glen A; Bankhead, Troy

    2015-01-01

    Efficient acquisition and transmission of Borrelia burgdorferi by the tick vector, and the ability to persistently infect both vector and host, are important elements for the life cycle of the Lyme disease pathogen. Previous work has provided strong evidence implicating the significance of the vls locus for B. burgdorferi persistence. However, studies involving vls mutant clones have thus far only utilized in vitro-grown or host-adapted spirochetes and laboratory strains of mice. Additionally, the effects of vls mutation on tick acquisition and transmission has not yet been tested. Thus, the importance of VlsE antigenic variation for persistent infection of the natural reservoir host, and for the B. burgdorferi enzootic life cycle in general, has not been examined to date. In the current work, Ixodes scapularis and Peromyscus maniculatus were infected with different vls mutant clones to study the importance of the vls locus for the enzootic cycle of the Lyme disease pathogen. The findings highlight the significance of the vls system for long-term infection of the natural reservoir host, and show that VlsE antigenic variability is advantageous for efficient tick acquisition of B. burgdorferi from the mammalian reservoir. The data also indicate that the adaptation state of infecting spirochetes influences B. burgdorferi avoidance from host antibodies, which may be in part due to its respective VlsE expression levels. Overall, the current findings provide the most direct evidence on the importance of VlsE for the enzootic cycle of Lyme disease spirochetes, and underscore the significance of VlsE antigenic variation for maintaining B. burgdorferi in nature. PMID:25893989

  12. Antigenic variation among equine H 3 N 8 influenza virus hemagglutinins.

    PubMed

    Ozaki, H; Shimizu-Nei, A; Sugita, S; Sugiura, T; Imagawa, H; Kida, H

    2001-02-01

    To provide information on the antigenic variation of the hemagglutinins (HA) among equine H 3 influenza viruses, 26 strains isolated from horses in different areas in the world during the 1963-1996 period were analyzed using a panel of monoclonal antibodies recognizing at least 7 distinct epitopes on the H 3 HA molecule of the prototype strain A/equine/Miami/1/63 (H 3 N 8). The reactivity patterns of the virus strains with the panel indicate that antigenic drift of the HA has occurred with the year of isolation, but less extensively than that of human H 3 N 2 influenza virus isolates, and different antigenic variants co-circulate. To assess immunogenicity of the viruses, antisera from mice vaccinated with each of the 7 representative inactivated viruses were examined by neutralization and hemagglutination-inhibition tests. These results emphasize the importance of monitoring the antigenic drift in equine influenza virus strains and to introduce current isolates into vaccine. On the basis of the present results, equine influenza vaccine strain A/equine/Tokyo/2/71 (H 3 N 8) was replaced with A/equine/La Plata/1/93 (H 3 N 8) in 1996 in Japan. The present results of the antigenic analysis of the 26 strains supported the results of a phylogenetic analysis, that viruses belonging to each of the Eurasian and American equine influenza lineages have independently evolved. However, the current vaccine in Japan consists of two American H 3 N 8 strains; A/equine/Kentucky/1/81 and A/equine/La Plata/1/93. It is also therefore recommended that a representative Eurasian strain should be included as a replacement of A/equine/Kentucky/1/81. PMID:11276582

  13. Antigen nature and complexity influence human antibody light chain usage and specificity.

    PubMed

    Smith, Kenneth; Shah, Hemangi; Muther, Jennifer J; Duke, Angie L; Haley, Kathleen; James, Judith A

    2016-05-27

    Human antibodies consist of a heavy chain and one of two possible light chains, kappa (κ) or lambda (λ). Here we tested how these two possible light chains influence the overall antibody response to polysaccharide and protein antigens by measuring light chain usage in human monoclonal antibodies from antibody secreting cells obtained following vaccination with Pneumovax23. Remarkably, we found that individuals displayed restricted light chain usage to certain serotypes and that lambda antibodies have different specificities and modes of cross-reactivity than kappa antibodies. Thus, at both the monoclonal (7 kappa, no lambda) and serum levels (145μg/mL kappa, 2.82μg/mL lambda), antibodies to cell wall polysaccharide were nearly always kappa. The pneumococcal reference serum 007sp was analyzed for light chain usage to 12 pneumococcal serotypes for which it is well characterized. Similar to results at the monoclonal level, certain serotypes tended to favor one of the light chains (14 and 19A, lambda; 6A and 23F, kappa). We also explored differences in light chain usage at the serum level to a variety of antigens. We examined serum antibodies to diphtheria toxin mutant CRM197 and Epstein-Barr virus protein EBNA-1. These responses tended to be kappa dominant (average kappa-to-lambda ratios of 4.52 and 9.72 respectively). Responses to the influenza vaccine were more balanced with kappa-to-lambda ratio averages having slight strain variations: seasonal H1N1, 1.1; H3N2, 0.96; B, 0.91. We conclude that antigens with limited epitopes tend to produce antibodies with restricted light chain usage and that in most individuals, antibodies with lambda light chains have specificities different and complementary to kappa-containing antibodies. PMID:27113164

  14. Genome-wide genetic and transcriptomic investigation of variation in antibody response to dietary antigens.

    PubMed

    Rubicz, Rohina; Yolken, Robert; Alaedini, Armin; Drigalenko, Eugene; Charlesworth, Jac C; Carless, Melanie A; Severance, Emily G; Krivogorsky, Bogdana; Dyer, Thomas D; Kent, Jack W; Curran, Joanne E; Johnson, Matthew P; Cole, Shelley A; Almasy, Laura; Moses, Eric K; Blangero, John; Göring, Harald H H

    2014-07-01

    Increased immunoglobulin G (IgG) response to dietary antigens can be associated with gastrointestinal dysfunction and autoimmunity. The underlying processes contributing to these adverse reactions remain largely unknown, and it is likely that genetic factors play a role. Here, we estimate heritability and attempt to localize genetic factors influencing IgG antibody levels against food-derived antigens using an integrative genomics approach. IgG antibody levels were determined by ELISA in >1,300 Mexican Americans for the following food antigens: wheat gliadin; bovine casein; and two forms of bovine serum albumin (BSA-a and BSA-b). Pedigree-based variance components methods were used to estimate additive genetic heritability (h(2) ), perform genome-wide association analyses, and identify transcriptional signatures (based on 19,858 transcripts from peripheral blood lymphocytes). Heritability estimates were significant for all traits (0.15-0.53), and shared environment (based on shared residency among study participants) was significant for casein (0.09) and BSA-a (0.33). Genome-wide significant evidence of association was obtained only for antibody to gliadin (P = 8.57 × 10(-8) ), mapping to the human leukocyte antigen II region, with HLA-DRA and BTNL2 as the best candidate genes. Lack of association of known celiac disease risk alleles HLA-DQ2.5 and -DQ8 with antigliadin antibodies in the studied population suggests a separate genetic etiology. Significant transcriptional signatures were found for all IgG levels except BSA-b. These results demonstrate that individual genetic differences contribute to food antigen antibody measures in this population. Further investigations may elucidate the underlying immunological processes involved. PMID:24962563

  15. Spleen-Dependent Regulation of Antigenic Variation in Malaria Parasites: Plasmodium knowlesi SICAvar Expression Profiles in Splenic and Asplenic Hosts

    PubMed Central

    Lapp, Stacey A.; Korir-Morrison, Cindy; Jiang, Jianlin; Bai, Yaohui; Corredor, Vladimir; Galinski, Mary R.

    2013-01-01

    Background Antigenic variation by malaria parasites was first described in Plasmodium knowlesi, which infects humans and macaque monkeys, and subsequently in P. falciparum, the most virulent human parasite. The schizont-infected cell agglutination (SICA) variant proteins encoded by the SICAvar multigene family in P. knowlesi, and Erythrocyte Membrane Protein-1 (EMP-1) antigens encoded by the var multigene family in P. falciparum, are expressed at the surface of infected erythrocytes, are associated with virulence, and serve as determinants of naturally acquired immunity. A parental P. knowlesi clone, Pk1(A+), and a related progeny clone, Pk1(B+)1+, derived by an in vivo induced variant antigen switch, were defined by the expression of distinct SICA variant protein doublets of 210/190 and 205/200 kDa, respectively. Passage of SICA[+] infected erythrocytes through splenectomized rhesus monkeys results in the SICA[-] phenotype, defined by the lack of surface expression and agglutination with variant specific antisera. Principal Findings We have investigated SICAvar RNA and protein expression in Pk1(A+), Pk1(B+)1+, and SICA[-] parasites. The Pk1(A+) and Pk1(B+)1+ parasites express different distinct SICAvar transcript and protein repertoires. By comparison, SICA[-] parasites are characterized by a vast reduction in SICAvar RNA expression, the lack of full-length SICAvar transcript signals on northern blots, and correspondingly, the absence of any SICA protein detected by mass spectrometry. Significance SICA protein expression may be under transcriptional as well as post-transcriptional control, and we show for the first time that the spleen, an organ central to blood-stage immunity in malaria, exerts an influence on these processes. Furthermore, proteomics has enabled the first in-depth characterization of SICA[+] protein phenotypes and we show that the in vivo switch from Pk1(A+) to Pk1(B+)1+ parasites resulted in a complete change in SICA profiles. These results

  16. Seasonal and Physiological Variations of Phlebotomus papatasi Salivary Gland Antigens in Central Iran

    PubMed Central

    Hosseini-Vasoukolaei, Nasibeh; Mahmoudi, Ahmad-Reza; Khamesipour, Ali; Yaghoobi-Ershadi, Mohammad Reza; Kamhawi, Shaden; Valenzuela, Jesus G.; Arandian, Mohammad Hossein; Mirhendi, Hossein; Emami, Shaghayegh; Saeidi, Zahra; Idali, Farah; Jafari, Reza; Jeddi-Tehrani, Mahmood; Akhavan, Amir Ahmad

    2016-01-01

    Background: Sand fly saliva helps parasite establishment and induce immune responses in vertebrate hosts. In the current study, we investigated the modulation of Phlebotomus papatasi salivary gland antigen expression by seasonal and biological factors. Methods: Sand flies were grouped according to physiological stages such as unfed, fed, semi-gravid, gravid, parous, nulliparous, infected or non-infected with Leishmania major and based on the season in which they were collected. Salivary gland antigens (SGAs) were analyzed using SDS-PAGE and the antibody response against SGAs in Rhombomys opimus was determined by ELISA and Western blot. Results: The highest protein content was found in the salivary glands of unfed sand flies. The saliva content was higher in parous compared to nulliparous, in summer compared to spring, and in Leishmania-infected compared to non-infected flies. The salivary gland lysate (SGL) electrophoretic pattern variations were observed among sand flies with various physiological stages particularly from 4–9 protein bands of 14–70 kDa. The SGL of unfed and gravid flies had extra protein bands compared to fed and semi-gravid sand flies. There was missing protein bands in SGL of parous compared to nulliparous; and in summer compared to spring collected flies. Rhombomys opimus serum reacted strongly with an antigenic band of around 28 kDa in the SGL of all sand fly groups. Conclusion: Certain biological and environmental characteristics of wild populations of vector sand flies affect the protein content and antigenicity of saliva. This might have an important implication in the design of vector-based vaccines. PMID:27047970

  17. Variation in the structural subunit and basal protein antigens of Bacteroides nodosus fimbriae.

    PubMed Central

    Anderson, B J; Kristo, C L; Egerton, J R; Mattick, J S

    1986-01-01

    The fimbriae of Bacteroides nodosus play a major role in protective immunity against ovine footrot and are an important determinant in the serological classification system that divides field isolates into at least eight serogroups and 16 serotypes. Purified fimbriae contain two polypeptide antigens, the structural subunit of the fimbrial strand (molecular weight about 17,000) and a basal protein (molecular weight about 80,000), both of which exhibit structural variation. Fimbriae were prepared from all prototype strains, as well as from a number of other isolates representative of each of the B. nodosus serotypes, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Substantial variation was observed in the electrophoretic mobility of the fimbrial subunits from the prototypes of each of the eight serogroups. With the exception of serogroup H, which is an unusual case, the apparent molecular weights of the fimbrial subunits ranged from about 16,500 in serogroup D to 19,000 in serogroup F (serotype 1); in serogroup A, B, C and E, the apparent molecular weights were clustered in the range of 17,000 to 17,500, whereas serogroup G was about 18,500. Serogroup H fimbriae appeared to consist of two smaller polypeptides, which in the prototype (H1) had apparent molecular weights of about 6,000 and 10,000 and which seem to have arisen as a consequence of an internal proteolytic nick in the original subunit. Electrophoretic variation in the fimbrial subunit was also observed between different serotypes, although with the exceptions of serogroups F and H, this was not as pronounced as between the serogroups. Examination of a number of isolates classified within the same serotypes showed that some variation, although minor, also occurred at this level. The basal antigen exhibited significant variation at all levels of the serotypic hierarchy in a manner apparently unrelated to the classification system. Among the range of isolates examined, the apparent

  18. Antigenic variation of TprK facilitates development of secondary syphilis.

    PubMed

    Reid, Tara B; Molini, Barbara J; Fernandez, Mark C; Lukehart, Sheila A

    2014-12-01

    Although primary syphilis lesions heal spontaneously, the infection is chronic, with subsequent clinical stages. Healing of the primary chancre occurs as antibodies against outer membrane antigens facilitate opsonophagocytosis of the bacteria by activated macrophages. TprK is an outer membrane protein that undergoes antigenic variation at 7 variable regions, and variants are selected by immune pressure. We hypothesized that individual TprK variants escape immune clearance and seed new disseminated lesions to cause secondary syphilis. As in human syphilis, infected rabbits may develop disseminated secondary skin lesions. This study explores the nature of secondary syphilis, specifically, the contribution of antigenic variation to the development of secondary lesions. Our data from the rabbit model show that the odds of secondary lesions containing predominately TprK variant treponemes is 3.3 times higher than the odds of finding TprK variants in disseminated primary lesions (odds ratio [OR] = 3.3 [95% confidence interval {CI}, 0.98 to 11.0]; P = 0.055) and that 96% of TprK variant secondary lesions are likely seeded by single treponemes. Analysis of antibody responses demonstrates significantly higher antibody titers to tprK variable region sequences found in the inoculum compared to reactivity to tprK variant sequences found in newly arising secondary lesions. This suggests that tprK variants escape the initial immune response raised against the V regions expressed in the inoculum. These data further support a role for TprK in immune evasion and suggest that the ability of TprK variants to persist despite a robust immune response is instrumental in the development of later stages of syphilis. PMID:25225245

  19. Antigenic Variation of TprK Facilitates Development of Secondary Syphilis

    PubMed Central

    Reid, Tara B.; Molini, Barbara J.; Fernandez, Mark C.

    2014-01-01

    Although primary syphilis lesions heal spontaneously, the infection is chronic, with subsequent clinical stages. Healing of the primary chancre occurs as antibodies against outer membrane antigens facilitate opsonophagocytosis of the bacteria by activated macrophages. TprK is an outer membrane protein that undergoes antigenic variation at 7 variable regions, and variants are selected by immune pressure. We hypothesized that individual TprK variants escape immune clearance and seed new disseminated lesions to cause secondary syphilis. As in human syphilis, infected rabbits may develop disseminated secondary skin lesions. This study explores the nature of secondary syphilis, specifically, the contribution of antigenic variation to the development of secondary lesions. Our data from the rabbit model show that the odds of secondary lesions containing predominately TprK variant treponemes is 3.3 times higher than the odds of finding TprK variants in disseminated primary lesions (odds ratio [OR] = 3.3 [95% confidence interval {CI}, 0.98 to 11.0]; P = 0.055) and that 96% of TprK variant secondary lesions are likely seeded by single treponemes. Analysis of antibody responses demonstrates significantly higher antibody titers to tprK variable region sequences found in the inoculum compared to reactivity to tprK variant sequences found in newly arising secondary lesions. This suggests that tprK variants escape the initial immune response raised against the V regions expressed in the inoculum. These data further support a role for TprK in immune evasion and suggest that the ability of TprK variants to persist despite a robust immune response is instrumental in the development of later stages of syphilis. PMID:25225245

  20. Genomic and antigenic variations of porcine reproductive and respiratory syndrome virus major envelope GP5 glycoprotein.

    PubMed Central

    Pirzadeh, B; Gagnon, C A; Dea, S

    1998-01-01

    The objective of the present study was to evaluate the importance of genomic and antigenic variations which may have affected the major envelope glycoprotein GP5 of porcine reproductive and respiratory syndrome virus (PRRSV) isolates responsible for outbreaks in Quebec and Ontario, in comparison with the modified-live U.S. vaccine strain (MLV) and the European prototype strain from Lelystad (LV). Nucleotide sequence analyses of the open reading frame (ORF)5 genes showed that all of the isolates studied were heterogenous, amino acid (aa) identities varied from 88 to 99% with the MLV strain, and between 51 and 54% with the LV strain. The aa substitutions were randomly scattered across the protein, although one region between residues 26 and 39 was found to correspond to a hypervariable region which involved 0 to 3 potential N-glycosylation sites. The ORF5 encoded products of 5 of these isolates, including the MLV and LV strains, were expressed in E. coli as recombinant proteins fused to the glutathione S-transferase (GST) protein and used to raise hyperimmune anti-ORF5 sera in rabbits. The reactivity patterns of strain-specific hyperimmune anti-ORF5 sera and a panel of 4 monoclonal antibodies directed against the ORF5 gene product of the Quebec IAF-Klop strain of PRRSV, indicated that GP5 of field isolates also underwent antigenic variations. The data suggest that neutralizing epitopes, independent of conformation and glycosylation, are also associated with antigenic variability of the GP5 of PRRSV. PMID:9684045

  1. Mismatch correction modulates mutation frequency and pilus phase and antigenic variation in Neisseria gonorrhoeae.

    PubMed

    Criss, Alison K; Bonney, Kevin M; Chang, Rhoda A; Duffin, Paul M; LeCuyer, Brian E; Seifert, H Steven

    2010-01-01

    The mismatch correction (MMC) system repairs DNA mismatches and single nucleotide insertions or deletions postreplication. To test the functions of MMC in the obligate human pathogen Neisseria gonorrhoeae, homologues of the core MMC genes mutS and mutL were inactivated in strain FA1090. No mutH homologue was found in the FA1090 genome, suggesting that gonococcal MMC is not methyl directed. MMC mutants were compared to a mutant in uvrD, the helicase that functions with MMC in Escherichia coli. Inactivation of MMC or uvrD increased spontaneous resistance to rifampin and nalidixic acid, and MMC/uvrD double mutants exhibited higher mutation frequencies than any single mutant. Loss of MMC marginally enhanced the transformation efficiency of DNA carrying a single nucleotide mismatch but not that of DNA with a 1-kb insertion. Unlike the exquisite UV sensitivity of the uvrD mutant, inactivating MMC did not affect survival after UV irradiation. MMC and uvrD mutants exhibited increased PilC-dependent pilus phase variation. mutS-deficient gonococci underwent an increased frequency of pilin antigenic variation, whereas uvrD had no effect. Recombination tracts in the mutS pilin variants were longer than in parental gonococci but utilized the same donor pilS loci. These results show that gonococcal MMC repairs mismatches and small insertion/deletions in DNA and also affects the recombination events underlying pilin antigenic variation. The differential effects of MMC and uvrD in gonococci unexpectedly reveal that MMC can function independently of uvrD in this human-specific pathogen. PMID:19854909

  2. The Plasmodium falciparum STEVOR Multigene Family Mediates Antigenic Variation of the Infected Erythrocyte

    PubMed Central

    Niang, Makhtar; Yan Yam, Xue; Preiser, Peter Rainer

    2009-01-01

    Modifications of the Plasmodium falciparum–infected red blood cell (iRBC) surface have been linked to parasite-associated pathology. Such modifications enable the parasite to establish long-lasting chronic infection by evading antibody mediate immune recognition and splenic clearance. With the exception of the well-demonstrated roles of var-encoded PfEMP1 in virulence and immune evasion, the biological significance of other variant surface antigens (rif and stevor) is largely unknown. While PfEMP1 and RIFIN have been located on the iRBC surface, recent studies have located STEVOR at the iRBC membrane where it may be exposed on the erythrocyte surface. To investigate the role of STEVOR in more detail, we have developed antibodies against two putative STEVOR proteins and used a combination of indirect immunofluorescence assays (IFA), live IFA, flow cytometry, as well as agglutination assays, which enable us to demonstrate that STEVOR is clonally variant at the surface of schizont stage parasites. Crucially, expression of different STEVOR on the surface of the iRBC changes the antigenic property of the parasite. Taken together, our data for the first time demonstrate that STEVOR plays a role in creating antigenic diversity of schizont stage parasites, thereby adding additional complexity to the immunogenic properties of the iRBC. Furthermore, it clearly demonstrates that to obtain a complete understanding of how parasite-induced pathology is linked to variation on the surface of the iRBC, focusing the interactions of multiple multigene families needs to be considered. PMID:19229319

  3. Influence of human leukocyte antigen matching on liver allograft survival and rejection: "the dualistic effect".

    PubMed

    Donaldson, P; Underhill, J; Doherty, D; Hayllar, K; Calne, R; Tan, K C; O'Grady, J; Wight, D; Portmann, B; Williams, R

    1993-06-01

    To date only one published large series of human leukocyte antigen matching and liver allograft survival exists, and considerable confusion has arisen about the advantage or disadvantage of human leukocyte antigen matching. In the present study we have reinvestigated the relationship between human leukocyte antigen mismatch and graft survival in 466 first liver allografts, seeking to clarify the relationship between human leukocyte antigen and both acute rejection and the vanishing bile duct syndrome. In view of current criticism regarding the accuracy of serological tissue typing for human leukocyte antigen-DR, we have used both classic serology and restriction fragment length polymorphism analysis to ensure the accurate assignment of recipient DR types. In addition, we have used polymerase chain reaction amplification and allele-specific and sequence-specific oligonucleotide probes to retest the hypothesis that human leukocyte antigen class II matching may increase susceptibility to the vanishing bile duct syndrome. One-year graft survival was significantly lower in patients with zero or two human leukocyte antigen-A mismatches (52% and 63%, respectively) than in those with one human leukocyte antigen--A mismatch (69%) (p = 0.016 and p = 0.018). A similar effect of B mismatching was observed, with a 1-yr graft survival of 73% for those with one compared with 60% for those with two human leukocyte antigen-B mismatches. In contrast no correlation was found between DR mismatch and graft survival. Human leukocyte antigen class I matching appears to influence graft survival largely through the occurrence of acute rejection and the development of the vanishing bile duct syndrome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8514248

  4. Telomere Length Affects the Frequency and Mechanism of Antigenic Variation in Trypanosoma brucei

    PubMed Central

    Hovel-Miner, Galadriel A.; Boothroyd, Catharine E.; Mugnier, Monica; Dreesen, Oliver; Cross, George A. M.; Papavasiliou, F. Nina

    2012-01-01

    Trypanosoma brucei is a master of antigenic variation and immune response evasion. Utilizing a genomic repertoire of more than 1000 Variant Surface Glycoprotein-encoding genes (VSGs), T. brucei can change its protein coat by “switching” from the expression of one VSG to another. Each active VSG is monoallelically expressed from only one of approximately 15 subtelomeric sites. Switching VSG expression occurs by three predominant mechanisms, arguably the most significant of which is the non-reciprocal exchange of VSG containing DNA by duplicative gene conversion (GC). How T. brucei orchestrates its complex switching mechanisms remains to be elucidated. Recent work has demonstrated that an exogenous DNA break in the active site could initiate a GC based switch, yet the source of the switch-initiating DNA lesion under natural conditions is still unknown. Here we investigated the hypothesis that telomere length directly affects VSG switching. We demonstrate that telomerase deficient strains with short telomeres switch more frequently than genetically identical strains with long telomeres and that, when the telomere is short, switching preferentially occurs by GC. Our data supports the hypothesis that a short telomere at the active VSG expression site results in an increase in subtelomeric DNA breaks, which can initiate GC based switching. In addition to their significance for T. brucei and telomere biology, the findings presented here have implications for the many diverse pathogens that organize their antigenic genes in subtelomeric regions. PMID:22952449

  5. Genetic Mechanism of Human Neutrophil Antigen 2 Deficiency and Expression Variations

    PubMed Central

    Li, Yunfang; Mair, David C.; Schuller, Randy M.; Li, Ling; Wu, Jianming

    2015-01-01

    Human neutrophil antigen 2 (HNA-2) deficiency is a common phenotype as 3–5% humans do not express HNA-2. HNA-2 is coded by CD177 gene that associates with human myeloproliferative disorders. HNA-2 deficient individuals are prone to produce HNA-2 alloantibodies that cause a number of disorders including transfusion-related acute lung injury and immune neutropenia. In addition, the percentages of HNA-2 positive neutrophils vary significantly among individuals and HNA-2 expression variations play a role in human diseases such as myelodysplastic syndrome, chronic myelogenous leukemia, and gastric cancer. The underlying genetic mechanism of HNA-2 deficiency and expression variations has remained a mystery. In this study, we identified a novel CD177 nonsense single nucleotide polymorphism (SNP 829A>T) that creates a stop codon within the CD177 coding region. We found that all 829TT homozygous individuals were HNA-2 deficient. In addition, the SNP 829A>T genotypes were significantly associated with the percentage of HNA-2 positive neutrophils. Transfection experiments confirmed that HNA-2 expression was absent on cells expressing the CD177 SNP 829T allele. Our data clearly demonstrate that the CD177 SNP 829A>T is the primary genetic determinant for HNA-2 deficiency and expression variations. The mechanistic delineation of HNA-2 genetics will enable the development of genetic tests for diagnosis and prognosis of HNA-2-related human diseases. PMID:26024230

  6. Sir2 Paralogues Cooperate to Regulate Virulence Genes and Antigenic Variation in Plasmodium falciparum

    PubMed Central

    Duraisingh, Manoj T; Voss, Till S; Ralph, Stuart A; Hommel, Mirja; Duffy, Michael F; da Silva, Liliana Mancio; Scherf, Artur; Ivens, Alasdair; Speed, Terence P; Beeson, James G; Cowman, Alan F

    2009-01-01

    Cytoadherance of Plasmodium falciparum-infected erythrocytes in the brain, organs and peripheral microvasculature is linked to morbidity and mortality associated with severe malaria. Parasite-derived P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) molecules displayed on the erythrocyte surface are responsible for cytoadherance and undergo antigenic variation in the course of an infection. Antigenic variation of PfEMP1 is achieved by in situ switching and mutually exclusive transcription of the var gene family, a process that is controlled by epigenetic mechanisms. Here we report characterisation of the P. falciparum silent information regulator's A and B (PfSir2A and PfSir2B) and their involvement in mutual exclusion and silencing of the var gene repertoire. Analysis of P. falciparum parasites lacking either PfSir2A or PfSir2B shows that these NAD+-dependent histone deacetylases are required for silencing of different var gene subsets classified by their conserved promoter type. We also demonstrate that in the absence of either of these molecules mutually exclusive expression of var genes breaks down. We show that var gene silencing originates within the promoter and PfSir2 paralogues are involved in cis spreading of silenced chromatin into adjacent regions. Furthermore, parasites lacking PfSir2A but not PfSir2B have considerably longer telomeric repeats, demonstrating a role for this molecule in telomeric end protection. This work highlights the pivotal but distinct role for both PfSir2 paralogues in epigenetic silencing of P. falciparum virulence genes and the control of pathogenicity of malaria infection. PMID:19402747

  7. Variations in O-antigen biosynthesis and O-acetylation associated with altered phage sensitivity in Escherichia coli 4s.

    PubMed

    Knirel, Yuriy A; Prokhorov, Nikolai S; Shashkov, Alexander S; Ovchinnikova, Olga G; Zdorovenko, Evelina L; Liu, Bin; Kostryukova, Elena S; Larin, Andrey K; Golomidova, Alla K; Letarov, Andrey V

    2015-03-01

    The O polysaccharide of the lipopolysaccharide (O antigen) of Gram-negative bacteria often serves as a receptor for bacteriophages that can make the phage dependent on a given O-antigen type, thus supporting the concept of the adaptive significance of the O-antigen variability in bacteria. The O-antigen layer also modulates interactions of many bacteriophages with their hosts, limiting the access of the viruses to other cell surface receptors. Here we report variations of O-antigen synthesis and structure in an environmental Escherichia coli isolate, 4s, obtained from horse feces, and its mutants selected for resistance to bacteriophage G7C, isolated from the same fecal sample. The 4s O antigen was found to be serologically, structurally, and genetically related to the O antigen of E. coli O22, differing only in side-chain α-D-glucosylation in the former, mediated by a gtr locus on the chromosome. Spontaneous mutations of E. coli 4s occurring with an unusually high frequency affected either O-antigen synthesis or O-acetylation due to the inactivation of the gene encoding the putative glycosyltransferase WclH or the putative acetyltransferase WclK, respectively, by the insertion of IS1-like elements. These mutations induced resistance to bacteriophage G7C and also modified interactions of E. coli 4s with several other bacteriophages conferring either resistance or sensitivity to the host. These findings suggest that O-antigen synthesis and O-acetylation can both ensure the specific recognition of the O-antigen receptor following infection by some phages and provide protection of the host cells against attack by other phages. PMID:25512310

  8. The Use of High-Throughput DNA Sequencing in the Investigation of Antigenic Variation: Application to Neisseria Species

    PubMed Central

    Davies, John K.; Harrison, Paul F.; Lin, Ya-Hsun; Bartley, Stephanie; Khoo, Chen Ai; Seemann, Torsten; Ryan, Catherine S.; Kahler, Charlene M.; Hill, Stuart A.

    2014-01-01

    Antigenic variation occurs in a broad range of species. This process resembles gene conversion in that variant DNA is unidirectionally transferred from partial gene copies (or silent loci) into an expression locus. Previous studies of antigenic variation have involved the amplification and sequencing of individual genes from hundreds of colonies. Using the pilE gene from Neisseria gonorrhoeae we have demonstrated that it is possible to use PCR amplification, followed by high-throughput DNA sequencing and a novel assembly process, to detect individual antigenic variation events. The ability to detect these events was much greater than has previously been possible. In N. gonorrhoeae most silent loci contain multiple partial gene copies. Here we show that there is a bias towards using the copy at the 3′ end of the silent loci (copy 1) as the donor sequence. The pilE gene of N. gonorrhoeae and some strains of Neisseria meningitidis encode class I pilin, but strains of N. meningitidis from clonal complexes 8 and 11 encode a class II pilin. We have confirmed that the class II pili of meningococcal strain FAM18 (clonal complex 11) are non-variable, and this is also true for the class II pili of strain NMB from clonal complex 8. In addition when a gene encoding class I pilin was moved into the meningococcal strain NMB background there was no evidence of antigenic variation. Finally we investigated several members of the opa gene family of N. gonorrhoeae, where it has been suggested that limited variation occurs. Variation was detected in the opaK gene that is located close to pilE, but not at the opaJ gene located elsewhere on the genome. The approach described here promises to dramatically improve studies of the extent and nature of antigenic variation systems in a variety of species. PMID:24466206

  9. Influence of Design Variations on Systems Performance

    NASA Technical Reports Server (NTRS)

    Tumer, Irem Y.; Stone, Robert B.; Huff, Edward M.; Norvig, Peter (Technical Monitor)

    2000-01-01

    High-risk aerospace components have to meet very stringent quality, performance, and safety requirements. Any source of variation is a concern, as it may result in scrap or rework. poor performance, and potentially unsafe flying conditions. The sources of variation during product development, including design, manufacturing, and assembly, and during operation are shown. Sources of static and dynamic variation during development need to be detected accurately in order to prevent failure when the components are placed in operation. The Systems' Health and Safety (SHAS) research at the NASA Ames Research Center addresses the problem of detecting and evaluating the statistical variation in helicopter transmissions. In this work, we focus on the variations caused by design, manufacturing, and assembly of these components, prior to being placed in operation (DMV). In particular, we aim to understand and represent the failure and variation information, and their correlation to performance and safety and feed this information back into the development cycle at an early stage. The feedback of such critical information will assure the development of more reliable components with less rework and scrap. Variations during design and manufacturing are a common source of concern in the development and production of such components. Accounting for these variations, especially those that have the potential to affect performance, is accomplished in a variety ways, including Taguchi methods, FMEA, quality control, statistical process control, and variation risk management. In this work, we start with the assumption that any of these variations can be represented mathematically, and accounted for by using analytical tools incorporating these mathematical representations. In this paper, we concentrate on variations that are introduced during design. Variations introduced during manufacturing are investigated in parallel work.

  10. Use of molecularly cloned avian leukosis virus to study antigenic variation following infection of meat-type chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A molecularly cloned strain of subgroup J avian leukosis virus (ALV-J) termed R5-4 was used to study antigenic variation following infection of meat-type chickens. Chickens were inoculated with R5-4 virus at either 8 days of embryonation or at 1 week of age. Each chicken was housed in a separate is...

  11. Identification of Major Factors Influencing ELISpot-Based Monitoring of Cellular Responses to Antigens from Mycobacterium tuberculosis

    PubMed Central

    Smith, Steven G.; Joosten, Simone A.; Verscheure, Virginie; Pathan, Ansar A.; McShane, Helen; Ottenhoff, Tom H. M.; Dockrell, Hazel M.; Mascart, Françoise

    2009-01-01

    A number of different interferon-γ ELISpot protocols are in use in laboratories studying antigen-specific immune responses. It is therefore unclear how results from different assays compare, and what factors most significantly influence assay outcome. One such difference is that some laboratories use a short in vitro stimulation period of cells before they are transferred to the ELISpot plate; this is commonly done in the case of frozen cells, in order to enhance assay sensitivity. Other differences that may be significant include antibody coating of plates, the use of media with or without serum, the serum source and the number of cells added to the wells. The aim of this paper was to identify which components of the different ELISpot protocols influenced assay sensitivity and inter-laboratory variation. Four laboratories provided protocols for quantifying numbers of interferon-γ spot forming cells in human peripheral blood mononuclear cells stimulated with Mycobacterium tuberculosis derived antigens. The differences in the protocols were compared directly. We found that several sources of variation in assay protocols can be eliminated, for example by avoiding serum supplementation and using AIM-V serum free medium. In addition, the number of cells added to ELISpot wells should also be standardised. Importantly, delays in peripheral blood mononuclear cell processing before stimulation had a marked effect on the number of detectable spot forming cells; processing delay thus should be minimised as well as standardised. Finally, a pre-stimulation culture period improved the sensitivity of the assay, however this effect may be both antigen and donor dependent. In conclusion, small differences in ELISpot protocols in routine use can affect the results obtained and care should be given to conditions selected for use in a given study. A pre-stimulation step may improve the sensitivity of the assay, particularly when cells have been previously frozen. PMID:19956718

  12. Position 156 influences the peptide repertoire and tapasin dependency of human leukocyte antigen B*44 allotypes

    PubMed Central

    Badrinath, Soumya; Saunders, Philippa; Huyton, Trevor; Aufderbeck, Susanne; Hiller, Oliver; Blasczyk, Rainer; Bade-Doeding, Christina

    2012-01-01

    Background Polymorphic differences between donor and recipient human leukocyte antigen class I molecules can result in graft-versus-host disease due to distinct peptide presentation. As part of the peptide-loading complex, tapasin plays an important role in selecting peptides from the pool of potential ligands. Class I polymorphisms can significantly alter the tapasin-mediated interaction with the peptide-loading complex and although most class I allotypes are highly dependent upon tapasin, some are able to load peptides independently of tapasin. Several human leukocyte antigen B*44 allotypes differ exclusively at position 156 (B*44:02156Asp, 44:03156Leu, 44:28156Arg, 44:35156Glu). From these alleles, only the high tapasin-dependency of human leukocyte antigen B*44:02 has been reported. Design and Methods We investigated the influence of position 156 polymorphisms on both the requirement of tapasin for efficient surface expression of each allotype and their peptide features. Genes encoding human leukocyte antigen B*44 variants bearing all possible substitutions at position 156 were lentivirally transduced into human leukocyte antigen class I-negative LCL 721.221 cells and the tapasin-deficient cell line LCL 721.220. Results Exclusively human leukocyte antigen B*44:28156Arg was expressed on the surface of tapasin-deficient cells, suggesting that the remaining B*44/156 variants are highly tapasin-dependent. Our computational analysis suggests that the tapasin-independence of human leukocyte antigen B*44:28156Arg is a result of stabilization of the peptide binding region and generation of a more peptide receptive state. Sequencing of peptides eluted from human leukocyte antigen B*44 molecules by liquid chromatography-electrospray ionization-mass spectrometry (LTQ-Orbitrap) demonstrated that both B*44:02 and B*44:28 share the same overall peptide motif and a certain percentage of their individual peptide repertoires in the presence and/or absence of tapasin

  13. VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes.

    PubMed

    Glover, Lucy; Hutchinson, Sebastian; Alsford, Sam; Horn, David

    2016-06-28

    Allelic exclusion underpins antigenic variation and immune evasion in African trypanosomes. These bloodstream parasites use RNA polymerase-I (pol-I) to transcribe just one telomeric variant surface glycoprotein (VSG) gene at a time, producing superabundant and switchable VSG coats. We identified trypanosome VSG exclusion-1 (VEX1) using a genetic screen for defects in telomere-exclusive expression. VEX1 was sequestered by the active VSG and silencing of other VSGs failed when VEX1 was either ectopically expressed or depleted, indicating positive and negative regulation, respectively. Positive regulation affected VSGs and nontelomeric pol-I-transcribed genes, whereas negative regulation primarily affected VSGs. Negative regulation by VEX1 also affected telomeric pol-I-transcribed reporter constructs, but only when they contained blocks of sequence sharing homology with a pol-I-transcribed locus. We conclude that restricted positive regulation due to VEX1 sequestration, combined with VEX1-dependent, possibly homology-dependent silencing, drives a "winner-takes-all" mechanism of allelic exclusion. PMID:27226299

  14. VSG switching in Trypanosoma brucei: antigenic variation analysed using RNAi in the absence of immune selection

    PubMed Central

    Aitcheson, Niall; Talbot, Suzanne; Shapiro, Jesse; Hughes, Katie; Adkin, Carl; Butt, Thomas; Sheader, Karen; Rudenko, Gloria

    2006-01-01

    Summary Trypanosoma brucei relies on antigenic variation of its Variant Surface Glycoprotein (VSG) coat for survival. We show that VSG switching can be efficiently studied in vitro using VSG RNAi in place of an immune system to select for switch variants. Contrary to models predicting an instant switch after inhibition of VSG synthesis, switching was not induced by VSG RNAi and occurred at a rate of 10−4 per division. We find a highly reproducible hierarchy of VSG activation which appears to be capable of resetting, whereby more than half of the switch events over 12 experiments were to one of two VSGs. We characterised switched clones according to switch mechanism using marker genes in the active VSG expression site (ES). Transcriptional switches between ESs were the preferred switching mechanism, whereby at least 10 of the 17 ESs identified in T. brucei 427 can be functionally active in vitro. We could specifically select for switches mediated by DNA rearrangements by inducing VSG RNAi in the presence of drug selection for the active ES. Most of the preferentially activated VSGs could be activated by multiple mechanisms. This VSG RNAi based procedure provides a rapid and powerful means for analysing VSG switching in African trypanosomes entirely in vitro. PMID:16135228

  15. VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes

    PubMed Central

    Glover, Lucy; Hutchinson, Sebastian; Horn, David

    2016-01-01

    Allelic exclusion underpins antigenic variation and immune evasion in African trypanosomes. These bloodstream parasites use RNA polymerase-I (pol-I) to transcribe just one telomeric variant surface glycoprotein (VSG) gene at a time, producing superabundant and switchable VSG coats. We identified trypanosome VSG exclusion-1 (VEX1) using a genetic screen for defects in telomere-exclusive expression. VEX1 was sequestered by the active VSG and silencing of other VSGs failed when VEX1 was either ectopically expressed or depleted, indicating positive and negative regulation, respectively. Positive regulation affected VSGs and nontelomeric pol-I–transcribed genes, whereas negative regulation primarily affected VSGs. Negative regulation by VEX1 also affected telomeric pol-I–transcribed reporter constructs, but only when they contained blocks of sequence sharing homology with a pol-I–transcribed locus. We conclude that restricted positive regulation due to VEX1 sequestration, combined with VEX1-dependent, possibly homology-dependent silencing, drives a “winner-takes-all” mechanism of allelic exclusion. PMID:27226299

  16. Immunoglobulin VH clan and family identity predicts variable domain structure and may influence antigen binding.

    PubMed Central

    Kirkham, P M; Mortari, F; Newton, J A; Schroeder, H W

    1992-01-01

    Mammalian immunoglobulin VH families can be grouped into three distinct clans based upon sequence conservation in two of the three framework (FR) intervals. Through replacement/silent site substitution analysis, molecular modeling and mathematical evaluation of known immunoglobulin crystal structures, we demonstrate that this conservation reflects preservation of protein sequence and structure. Each clan contains a characteristic FR 1 interval that is solvent-exposed and structurally separated from the antigen binding site. Families within a clan contain their own unique FR 3 interval that is capable of either influencing the conformation of the antigen binding site or interacting directly with antigen. Our results provide a structural context for theories that address differential use of VH families in the immune response. Images PMID:1537339

  17. Cytoplasmic genetic variation and extensive cytonuclear interactions influence natural variation in the metabolome

    PubMed Central

    Joseph, Bindu; Corwin, Jason A; Li, Baohua; Atwell, Suzi; Kliebenstein, Daniel J

    2013-01-01

    Understanding genome to phenotype linkages has been greatly enabled by genomic sequencing. However, most genome analysis is typically confined to the nuclear genome. We conducted a metabolomic QTL analysis on a reciprocal RIL population structured to examine how variation in the organelle genomes affects phenotypic variation. This showed that the cytoplasmic variation had effects similar to, if not larger than, the largest individual nuclear locus. Inclusion of cytoplasmic variation into the genetic model greatly increased the explained phenotypic variation. Cytoplasmic genetic variation was a central hub in the epistatic network controlling the plant metabolome. This epistatic influence manifested such that the cytoplasmic background could alter or hide pairwise epistasis between nuclear loci. Thus, cytoplasmic genetic variation plays a central role in controlling natural variation in metabolomic networks. This suggests that cytoplasmic genomes must be included in any future analysis of natural variation. DOI: http://dx.doi.org/10.7554/eLife.00776.001 PMID:24150750

  18. Pathogenicity, Transmission and Antigenic Variation of H5N1 Highly Pathogenic Avian Influenza Viruses

    PubMed Central

    Jiao, Peirong; Song, Hui; Liu, Xiaoke; Song, Yafen; Cui, Jin; Wu, Siyu; Ye, Jiaqi; Qu, Nanan; Zhang, Tiemin; Liao, Ming

    2016-01-01

    necessary to conduct continuously epidemiological survey and study the pathogenicity and antigenic variation of avian influenza in Southern China. PMID:27199961

  19. Variation of expression defects in cell surface 190-kDa protein antigen of Streptococcus mutans.

    PubMed

    Lapirattanakul, Jinthana; Nomura, Ryota; Matsumoto-Nakano, Michiyo; Srisatjaluk, Ratchapin; Ooshima, Takashi; Nakano, Kazuhiko

    2015-05-01

    Streptococcus mutans, which consists of four serotypes, c, e, f, and k, possesses a 190-kDa cell surface protein antigen (PA) for initial tooth adhesion. We used Western blot analysis to determine PA expression in 750 S. mutans isolates from 150 subjects and found a significantly higher prevalence of the isolates with PA expression defects in serotypes f and k compared to serotypes c and e. Moreover, the defect patterns could be classified into three types; no PA expression on whole bacterial cells and in their supernatant samples (Type N1), PA expression mainly seen in supernatant samples (Type N2), and only low expression of PA in the samples of whole bacterial cells (Type W). The underlying reasons for the defects were mutations in the gene encoding PA as well as in the transcriptional processing of this gene for Type N1, defects in the sortase gene for Type N2, and low mRNA expression of PA for Type W. Since cellular hydrophobicity and phagocytosis susceptibility of the PA-defective isolates were significantly lower than those of the normal expression isolates, the potential implication of such defective isolates in systemic diseases involving bacteremia other than dental caries was suggested. Additionally, multilocus sequence typing was utilized to characterize S. mutans clones that represented a proportion of isolates with PA defects of 65-100%. Therefore, we described the molecular basis for variation defects in PA expression of S. mutans. Furthermore, we also emphasized the strong association between PA expression defects and serotypes f and k as well as the clonal relationships among these isolates. PMID:25792295

  20. Antigenic variation in Treponema pallidum: TprK sequence diversity accumulates in response to immune pressure during experimental syphilis1

    PubMed Central

    Giacani, Lorenzo; Molini, Barbara J.; Kim, Eric Y.; Godornes, B. Charmie; Leader, B. Troy; Tantalo, Lauren C.; Centurion-Lara, Arturo; Lukehart, Sheila A.

    2010-01-01

    Pathogens that cause chronic infections often employ antigenic variation to evade the immune response and persist in the host. In Treponema pallidum (T. pallidum), the causative agent of syphilis, the TprK antigen undergoes variation of seven variable regions (V1-V7) by nonreciprocal recombination of silent donor cassettes with the tprK expression site. These V regions are the targets of the host humoral immune response during experimental infection. The present study addresses the causal role of the acquired immune response in the selection of TprK variants in two ways: 1) by investigating TprK variants arising in immunocompetent vs immunosuppressed hosts, and 2) by investigating the effect of prior specific immunization on selection of TprK variants during infection. V region diversity, particularly in V6, accumulates more rapidly in immunocompetent rabbits than in pharmacologically immunosuppressed rabbits (treated with weekly injections of methylprednisolone acetate). In a complementary experiment, rabbits pre-immunized with V6 region synthetic peptides had more rapid accumulation of V6 variant treponemes than control rabbits. These studies demonstrate that the host immune response selects against specific TprK epitopes expressed on T. pallidum, resulting in immune selection of new TprK variants during infection, confirming a role for antigenic variation in syphilis. PMID:20190145

  1. Dietary influences over proliferating cell nuclear antigen expression in the locust midgut.

    PubMed

    Zudaire, E; Simpson, S J; Illa, I; Montuenga, L M

    2004-06-01

    We have studied the influence of variations in dietary protein (P) and digestible carbohydrate (C), the quantity of food eaten, and insect age during the fifth instar on the expression of the proliferating cell nuclear antigen (PCNA) in the epithelial cells of the midgut (with special reference to the midgut caeca) in the African migratory locust, Locusta migratoria. Densitometric analysis of PCNA-immunostained cells was used as an indirect measure of the levels of expression of PCNA, and a PCNA cellular index (PCNA-I) was obtained. Measurements of the DNA content of the cells have also been carried out by means of microdensitometry of Feulgen-stained, thick sections of midgut. A comparison between the PCNA nuclear level and the DNA content was performed. The PCNA levels were significantly different among the cells of the five regions studied: caeca, anterior ventricle, medial ventricle, posterior ventricle and ampullae of the Malpighian tubules. We have studied in more detail the region with highest PCNA-I, i.e. the caeca. The quality and the quantity of food eaten under ad libitum conditions were highly correlated with both the PCNA and DNA levels in the caeca cells. Locusts fed a diet with a close to optimal P:C content (P 21%, C 21%) showed the highest PCNA and DNA content. In locusts fed a food that also contained a 1:1 ratio of P to C but was diluted three-fold by addition of indigestible cellulose (P 7%, C 7%), a compensatory increase in consumption was critical to maintaining PCNA levels. Our measurements also showed that the nuclear DNA content of the mature and differentiated epithelial cells was several-fold higher than the levels in the undifferentiated stem cells of the regenerative nests. These results, combined with the low number of mitotic figures found in the regenerative nests of the caeca and the marked variation in PCNA levels among groups, suggest that some type of DNA endoreduplication process may be taking place. Our data also indicate that

  2. Influence of time and number of antigen encounters on memory CD8 T cell development.

    PubMed

    Martin, Matthew D; Badovinac, Vladimir P

    2014-08-01

    CD8 T cells are an important part of the adaptive immune system providing protection against intracellular bacteria, viruses, and protozoa. After infection and/or vaccination, increased numbers of antigen-specific CD8 T cells remain as a memory population that is capable of responding and providing enhanced protection during reinfection. Experimental studies indicate that while memory CD8 T cells can be maintained for great lengths of time, their properties change with time after infection and/or vaccination. However, the full scope of these changes and what effects they have on memory CD8 T cell function remain unknown. In addition, memory CD8 T cells can encounter antigen multiple times through either reinfection or prime-boost vaccine strategies designed to increase numbers of protective memory CD8 T cells. Importantly, recent studies suggest that memory CD8 T cell development following infection and/or vaccination is influenced by the number of times they have encountered cognate antigen. Since protection offered by memory CD8 T cells in response to infection depends on both the numbers and quality (functional characteristics) at the time of pathogen re-encounter, a thorough understanding of how time and antigen stimulation history impacts memory CD8 T cell properties is critical for the design of vaccines aimed at establishing populations of long-lived, protective memory CD8 T cells. PMID:24825776

  3. Comparative Investigation of the Genomic Regions Involved in Antigenic Variation of the TprK Antigen among Treponemal Species, Subspecies, and Strains

    PubMed Central

    Brandt, Stephanie L.; Puray-Chavez, Maritza; Reid, Tara Brinck; Godornes, Charmie; Molini, Barbara J.; Benzler, Martin; Hartig, Jörg S.; Lukehart, Sheila A.; Centurion-Lara, Arturo

    2012-01-01

    Although the three Treponema pallidum subspecies (T. pallidum subsp. pallidum, T. pallidum subsp. pertenue, and T. pallidum subsp. endemicum), Treponema paraluiscuniculi, and the unclassified Fribourg-Blanc treponeme cause clinically distinct diseases, these pathogens are genetically and antigenically highly related and are able to cause persistent infection. Recent evidence suggests that the putative surface-exposed variable antigen TprK plays an important role in both treponemal immune evasion and persistence. tprK heterogeneity is generated by nonreciprocal gene conversion between the tprK expression site and donor sites. Although each of the above-mentioned species and subspecies has a functional tprK antigenic variation system, it is still unclear why the level of expression and the rate at which tprK diversifies during infection can differ significantly among isolates. To identify genomic differences that might affect the generation and expression of TprK variants among these pathogens, we performed comparative sequence analysis of the donor sites, as well as the tprK expression sites, among eight T. pallidum subsp. pallidum isolates (Nichols Gen, Nichols Sea, Chicago, Sea81-4, Dal-1, Street14, UW104, and UW126), three T. pallidum subsp. pertenue isolates (Gauthier, CDC2, and Samoa D), one T. pallidum subsp. endemicum isolate (Iraq B), the unclassified Fribourg-Blanc isolate, and the Cuniculi A strain of T. paraluiscuniculi. Synteny and sequence conservation, as well as deletions and insertions, were found in the regions harboring the donor sites. These data suggest that the tprK recombination system is harbored within dynamic genomic regions and that genomic differences might be an important key to explain discrepancies in generation and expression of tprK variants among these Treponema isolates. PMID:22661689

  4. Comparative investigation of the genomic regions involved in antigenic variation of the TprK antigen among treponemal species, subspecies, and strains.

    PubMed

    Giacani, Lorenzo; Brandt, Stephanie L; Puray-Chavez, Maritza; Reid, Tara Brinck; Godornes, Charmie; Molini, Barbara J; Benzler, Martin; Hartig, Jörg S; Lukehart, Sheila A; Centurion-Lara, Arturo

    2012-08-01

    Although the three Treponema pallidum subspecies (T. pallidum subsp. pallidum, T. pallidum subsp. pertenue, and T. pallidum subsp. endemicum), Treponema paraluiscuniculi, and the unclassified Fribourg-Blanc treponeme cause clinically distinct diseases, these pathogens are genetically and antigenically highly related and are able to cause persistent infection. Recent evidence suggests that the putative surface-exposed variable antigen TprK plays an important role in both treponemal immune evasion and persistence. tprK heterogeneity is generated by nonreciprocal gene conversion between the tprK expression site and donor sites. Although each of the above-mentioned species and subspecies has a functional tprK antigenic variation system, it is still unclear why the level of expression and the rate at which tprK diversifies during infection can differ significantly among isolates. To identify genomic differences that might affect the generation and expression of TprK variants among these pathogens, we performed comparative sequence analysis of the donor sites, as well as the tprK expression sites, among eight T. pallidum subsp. pallidum isolates (Nichols Gen, Nichols Sea, Chicago, Sea81-4, Dal-1, Street14, UW104, and UW126), three T. pallidum subsp. pertenue isolates (Gauthier, CDC2, and Samoa D), one T. pallidum subsp. endemicum isolate (Iraq B), the unclassified Fribourg-Blanc isolate, and the Cuniculi A strain of T. paraluiscuniculi. Synteny and sequence conservation, as well as deletions and insertions, were found in the regions harboring the donor sites. These data suggest that the tprK recombination system is harbored within dynamic genomic regions and that genomic differences might be an important key to explain discrepancies in generation and expression of tprK variants among these Treponema isolates. PMID:22661689

  5. Individual Variation in Life History Characteristics Can Influence Extinction Risk

    SciTech Connect

    Jager, H I

    2001-01-01

    The white sturgeon (Acipenser transmontanus) shows great individual variation in the age at maturation. This study examines the consequences of model assumptions about individual variation in the age at maturation on predicted population viability. I considered: (1) the effects of variation in age at maturation alone; (2) the effects of heritability; and (3) the influence of a stable and an altered selective regime. Two selective regimes represented conditions before and after the impoundment of a river, blocking access of anadromous white sturgeon populations to the ocean. In contrast to previous simulation studies, I found that increased individual variation in the age at maturity did not necessarily lead to a higher likelihood of persistence. Individual variation increased the simulated likelihood of persistence when the variation was heritable and the selective regime had changed such that the mean age at maturity was no longer optimal.

  6. Can manipulation of a pelvic tumour influence the serum level of cancer antigen 125 and cancer-associated serum antigen?

    PubMed Central

    Kiekegaard, O.; Mogensen, O.; Mogensen, B.; Ahrons, S.

    1998-01-01

    Cancer antigen 125 (CA 125) and cancer-associated serum antigen (CASA) were measured in 24 women with pelvic masses before and after a gynaecological examination and ultrasonography. CA 125 decreased median 16% after manipulation (P < 0.0001) and CASA decreased median 8% (P = 0.0077). The decline was found in patients with benign tumours as well as in patients with malignant tumours. PMID:9667684

  7. Age-specific genetic and antigenic variations of influenza A viruses in Hong Kong, 2013-2014.

    PubMed

    Cao, Peihua; Wong, Chit-Ming; Chan, Kwok-Hung; Wang, Xiling; Chan, King-Pan; Peiris, Joseph Sriyal Malik; Poon, Leo Lit-Man; Yang, Lin

    2016-01-01

    Age-specific genetic and antigenic variations of influenza viruses have not been documented in tropical and subtropical regions. We implemented a systematic surveillance program in two tertiary hospitals in Hong Kong Island, to collect 112 A(H1N1)pdm09 and 254 A(H3N2) positive specimens from 2013 to 2014. Of these, 56 and 72 were identified as genetic variants of the WHO recommended vaccine composition strains, respectively. A subset of these genetic variants was selected for hemagglutination-inhibition (HI) tests, but none appeared to be antigenic variants of the vaccine composition strains. We also found that genetic and antigenicity variations were similar across sex and age groups of ≤18 yrs, 18 to 65 yrs, and ≥65 yrs. Our findings suggest that none of the age groups led other age groups in genetic evolution of influenza virus A strains. Future studies from different regions and longer study periods are needed to further investigate the age and sex heterogeneity of influenza viruses. PMID:27453320

  8. Age-specific genetic and antigenic variations of influenza A viruses in Hong Kong, 2013–2014

    PubMed Central

    Cao, Peihua; Wong, Chit-Ming; Chan, Kwok-Hung; Wang, Xiling; Chan, King-Pan; Peiris, Joseph Sriyal Malik; Poon, Leo Lit-Man; Yang, Lin

    2016-01-01

    Age-specific genetic and antigenic variations of influenza viruses have not been documented in tropical and subtropical regions. We implemented a systematic surveillance program in two tertiary hospitals in Hong Kong Island, to collect 112 A(H1N1)pdm09 and 254 A(H3N2) positive specimens from 2013 to 2014. Of these, 56 and 72 were identified as genetic variants of the WHO recommended vaccine composition strains, respectively. A subset of these genetic variants was selected for hemagglutination-inhibition (HI) tests, but none appeared to be antigenic variants of the vaccine composition strains. We also found that genetic and antigenicity variations were similar across sex and age groups of ≤18 yrs, 18 to 65 yrs, and ≥65 yrs. Our findings suggest that none of the age groups led other age groups in genetic evolution of influenza virus A strains. Future studies from different regions and longer study periods are needed to further investigate the age and sex heterogeneity of influenza viruses. PMID:27453320

  9. A homologue of the recombination-dependent growth gene, rdgC, is involved in gonococcal pilin antigenic variation.

    PubMed Central

    Mehr, I J; Long, C D; Serkin, C D; Seifert, H S

    2000-01-01

    Neisseria gonorrhoeae pilin undergoes high-frequency changes in primary amino acid sequence that aid in the avoidance of the host immune response and alter pilus expression. The pilin amino acid changes reflect nucleotide changes in the expressed gene, pilE, which result from nonreciprocal recombination reactions with numerous silent loci, pilS. A series of mini-transposon insertions affecting pilin antigenic variation were localized to three genes in one region of the Gc chromosome. Mutational analysis with complementation showed that a Gc gene with sequence similarity to the Escherichia coli rdgC gene is involved in pilus-dependent colony phase variation and in pilin antigenic variation. Furthermore, we show that the Gc rdgC homologue is transcriptionally linked in an operon with a gene encoding a predicted GTPase. The inability to disrupt expression of this gene suggests it is an essential gene (engA, essential neisserial GTPase). While some of the transposon mutations in rdgC and insertions in the 5'-untranslated portion of engA showed a growth defect, all transposon insertions investigated conferred an aberrant cellular morphology. Complementation analysis showed that the growth deficiencies are due to the interruption of RdgC expression and not that of EngA. The requirement of RdgC for efficient pilin variation suggests a role for this protein in specialized DNA recombination reactions. PMID:10655208

  10. Recruitment of PfSET2 by RNA Polymerase II to Variant Antigen Encoding Loci Contributes to Antigenic Variation in P. falciparum

    PubMed Central

    Kwiatkowski, Dacia L.; Pandarinath, Chethan; Dahan-Pasternak, Noa; Dzikowski, Ron; Deitsch, Kirk W.

    2014-01-01

    Histone modifications are important regulators of gene expression in all eukaryotes. In Plasmodium falciparum, these epigenetic marks regulate expression of genes involved in several aspects of host-parasite interactions, including antigenic variation. While the identities and genomic positions of many histone modifications have now been cataloged, how they are targeted to defined genomic regions remains poorly understood. For example, how variant antigen encoding loci (var) are targeted for deposition of unique histone marks is a mystery that continues to perplex the field. Here we describe the recruitment of an ortholog of the histone modifier SET2 to var genes through direct interactions with the C-terminal domain (CTD) of RNA polymerase II. In higher eukaryotes, SET2 is a histone methyltransferase recruited by RNA pol II during mRNA transcription; however, the ortholog in P. falciparum (PfSET2) has an atypical architecture and its role in regulating transcription is unknown. Here we show that PfSET2 binds to the unphosphorylated form of the CTD, a property inconsistent with its recruitment during mRNA synthesis. Further, we show that H3K36me3, the epigenetic mark deposited by PfSET2, is enriched at both active and silent var gene loci, providing additional evidence that its recruitment is not associated with mRNA production. Over-expression of a dominant negative form of PfSET2 designed to disrupt binding to RNA pol II induced rapid var gene expression switching, confirming both the importance of PfSET2 in var gene regulation and a role for RNA pol II in its recruitment. RNA pol II is known to transcribe non-coding RNAs from both active and silent var genes, providing a possible mechanism by which it could recruit PfSET2 to var loci. This work unifies previous reports of histone modifications, the production of ncRNAs, and the promoter activity of var introns into a mechanism that contributes to antigenic variation by malaria parasites. PMID:24391504

  11. Periodic variation in side-chain polarities of T-cell antigenic peptides correlates with their structure and activity.

    PubMed Central

    Cornette, J L; Margalit, H; Berzofsky, J A; DeLisi, C

    1995-01-01

    We present an analysis that synthesizes information on the sequence, structure, and motifs of antigenic peptides, which previously appeared to be in conflict. Fourier analysis of T-cell antigenic peptides indicates a periodic variation in amino acid polarities of 3-3.6 residues per period, suggesting an amphipathic alpha-helical structure. However, the diffraction patterns of major histocompatibility complex (MHC) molecules indicate that their ligands are in an extended non-alpha-helical conformation. We present two mutually consistent structural explanations for the source of the alpha-helical periodicity, based on an observation that the side chains of MHC-bound peptides generally partition with hydrophobic (hydrophilic) side chains pointing into (out of) the cleft. First, an analysis of haplotype-dependent peptide motifs indicates that the locations of their defining residues tend to force a period 3-4 variation in hydrophobicity along the peptide sequence, in a manner consistent with the spacing of pockets in the MHC. Second, recent crystallographic determination of the structure of a peptide bound to a class II MHC molecule reveals an extended but regularly twisted peptide with a rotation angle of about 130 degrees. We show that similar structures with rotation angles of 100-130 degrees are energetically acceptable and also span the length of the MHC cleft. These results provide a sound physical chemical and structural basis for the existence of a haplotype-independent antigenic motif which can be particularly important in limiting the search time for antigenic peptides. Images Fig. 3 PMID:7667297

  12. An in vivo experimental model to determine antigenic variations among infectious bursal disease viruses.

    PubMed

    Durairaj, Vijay; Linnemann, Erich; Icard, Alan H; Williams, Susan M; Sellers, Holly S; Mundt, Egbert

    2013-08-01

    Infectious bursal disease virus (IBDV) is a double-stranded RNA virus causing infectious bursal disease in chickens. IBDV undergoes antigenic drift, so characterizing the antigenicity of IBDV plays an important role for identification and selection of vaccine candidates. In this study, an in vivo experimental model was developed to differentiate a new antigenic variant of IBDV. To this end, a hyper-immune serum to IBDV E/Del-type virus was generated in specific pathogen-free chickens and a standard volume of the hyper-immune serum was serially diluted and injected in specific pathogen-free birds via intravenous, subcutaneous, or intramuscular routes. The chickens were bled at different time points in order to evaluate the dynamics of virus neutralization titres. Based on the results, chickens were injected with different serum dilutions by the subcutaneous route. Twenty-four hours later, chickens were bled and then challenged with 100 median chicken infectious doses of the E/Del virus and a new IBDV variant. Chickens were euthanized at 7 days post infection and the bursa of Fabricius was removed for microscopic evaluation to determine the bursal lesion score. The determined virus neutralization titre along with the bursal lesion score was used to determine the breakthrough titre in the in vivo chicken model. Based on the data obtained, an antigenic subtype of IBDV was identified and determined to be different from E/Del. This model is a sensitive model for determination of IBDV antigenicity of non-tissue culture adapted IBDV. PMID:23662946

  13. Sequence variations in the Boophilus microplus Bm86 locus and implications for immunoprotection in cattle vaccinated with this antigen.

    PubMed

    García-García, J C; Gonzalez, I L; González, D M; Valdés, M; Méndez, L; Lamberti, J; D'Agostino, B; Citroni, D; Fragoso, H; Ortiz, M; Rodríguez, M; de la Fuente, J

    1999-11-01

    Cattle tick infestations constitute a major problem for the cattle industry in tropical and subtropical regions of the world. Traditional control methods have been only partially successful, hampered by the selection of chemical-resistant tick populations. The Boophilus microplus Bm86 protein was isolated from tick gut epithelial cells and shown to induce a protective response against tick infestations in vaccinated cattle. Vaccine preparations including the recombinant Bm86 are used to control cattle tick infestations in the field as an alternative measure to reduce the losses produced by this ectoparasite. The principle for the immunological control of tick infestations relies on a polyclonal antibody response against the target antigen and, therefore, should be difficult to select for tick-resistant populations. However, sequence variations in the Bm86 locus, among other factors, could affect the effectiveness of Bm86-containing vaccines. In the present study we have addressed this issue, employing data obtained with B. microplus strains from Australia, Mexico, Cuba, Argentina and Venezuela. The results showed a tendency in the inverse correlation between the efficacy of the vaccination with Bm86 and the sequence variations in the Bm86 locus (R2 = 0.7). The mutation fixation index in the Bm86 locus was calculated and shown to be between 0.02 and 0.1 amino acids per year. Possible implications of these findings for the immunoprotection of cattle against tick infestations employing the Bm86 antigen are discussed. PMID:10668863

  14. Climatic and Altitudinal Influences on Variation in Macaca Limb Morphology

    PubMed Central

    Weinstein, Karen J.

    2011-01-01

    This study compares limb lengths and joint diameters in the skeletons of six macaque species (Macaca assamensis, M. fascicularis, M. fuscata, M. mulatta, M. nemestrina, and M. thibetana) from a broad range of habitats and climates in order to test whether ambient temperatures, latitude, and altitude influence interspecific variation in limb morphology in this widely dispersed genus. Analysis of variance, principal component analysis, and partial correlation analysis reveal that species from temperate latitudes and high elevations tend to have short limbs and large joint diameters for their sizes while species from tropical latitudes and low elevations tend to have long limbs and small joint diameters. Interspecific variations in intra- and interlimb length proportions also reflect phylogeny and subtle differences in locomotion. The results of this study suggest that climatic conditions are important factors among many ecological variables that influence limb morphology in this geographically widespread genus. PMID:22567298

  15. Molecular evolution and antigenic variation of European brown hare syndrome virus (EBHSV).

    PubMed

    Lopes, Ana M; Capucci, Lorenzo; Gavier-Widén, Dolores; Le Gall-Reculé, Ghislaine; Brocchi, Emiliana; Barbieri, Ilaria; Quéméner, Agnès; Le Pendu, Jacques; Geoghegan, Jemma L; Holmes, Edward C; Esteves, Pedro J; Abrantes, Joana

    2014-11-01

    European brown hare syndrome virus (EBHSV) is the aetiological agent of European brown hare syndrome (EBHS), a disease affecting Lepus europaeus and Lepus timidus first diagnosed in Sweden in 1980. To characterize EBHSV evolution we studied hare samples collected in Sweden between 1982 and 2008. Our molecular clock dating is compatible with EBHSV emergence in the 1970s. Phylogenetic analysis revealed two lineages: Group A persisted until 1989 when it apparently suffered extinction; Group B emerged in the mid-1980s and contains the most recent strains. Antigenic differences exist between groups, with loss of reactivity of some MAbs over time, which are associated with amino acid substitutions in recognized epitopes. A role for immune selection is also supported by the presence of positively selected codons in exposed regions of the capsid. Hence, EBHSV evolution is characterized by replacement of Group A by Group B viruses, suggesting that the latter possess a selective advantage. PMID:25155199

  16. Influence of ionization states of antigen on anti-fluorescein antibodies

    NASA Astrophysics Data System (ADS)

    Fukunishi, Hiroaki

    2012-10-01

    Ratios of anion and di-anion states of fluorescein (FLU(-1) and FLU(-2)) are 21.2% and 78.8%, respectively, in the neutral pH. We investigated the influence of ionization states of antigen on anti-fluorescein antibodies. For this purpose, steered molecular dynamics (SMD) simulations were performed. Potential of mean forces (PMF) based on Jarzynski equality showed that wild-type (4-4-20) more strongly binds to FLU(-1) than FLU(-2), whereas its femtomolar-affinity mutant (4M5.3) more strongly binds to FLU(-2) than FLU(-1). It was speculated that the environment or the process of in vivo antibody production had been different from those of the protein engineering.

  17. S100B and the influence of seasonal variation.

    PubMed

    Henriksson, Anders E

    2016-07-01

    Background A blood test for S100B can be used to rule out intracranial complications after minor head injury and thereby reduce the need for computed tomography (CT) examinations. The aim of this study was to investigate the clinical importance of a possible influence of seasonal variation on S100B. Methods The individual seasonal variation of S100B in 69 healthy volunteers living at latitudes with extremely variable seasonal exposure to sunlight was investigated. Results The mean serum concentration of S100B was 13% higher in August than in February, but however, not statistically significant (p = 0.068). A good agreement between summer and winter S100B values was confirmed by Bland-Altman analysis and a significant correlation (r = 0.317, p = 0.008) was shown between summer and winter S100B values. Conclusion This study did not show any clinical importance of seasonal variation of S100B that may influence the decision of CT scanning patients with head injuries. PMID:26982090

  18. Consumer trait variation influences tritrophic interactions in salt marsh communities.

    PubMed

    Hughes, Anne Randall; Hanley, Torrance C; Orozco, Nohelia P; Zerebecki, Robyn A

    2015-07-01

    The importance of intraspecific variation has emerged as a key question in community ecology, helping to bridge the gap between ecology and evolution. Although much of this work has focused on plant species, recent syntheses have highlighted the prevalence and potential importance of morphological, behavioral, and life history variation within animals for ecological and evolutionary processes. Many small-bodied consumers live on the plant that they consume, often resulting in host plant-associated trait variation within and across consumer species. Given the central position of consumer species within tritrophic food webs, such consumer trait variation may play a particularly important role in mediating trophic dynamics, including trophic cascades. In this study, we used a series of field surveys and laboratory experiments to document intraspecific trait variation in a key consumer species, the marsh periwinkle Littoraria irrorata, based on its host plant species (Spartina alterniflora or Juncus roemerianus) in a mixed species assemblage. We then conducted a 12-week mesocosm experiment to examine the effects of Littoraria trait variation on plant community structure and dynamics in a tritrophic salt marsh food web. Littoraria from different host plant species varied across a suite of morphological and behavioral traits. These consumer trait differences interacted with plant community composition and predator presence to affect overall plant stem height, as well as differentially alter the density and biomass of the two key plant species in this system. Whether due to genetic differences or phenotypic plasticity, trait differences between consumer types had significant ecological consequences for the tritrophic marsh food web over seasonal time scales. By altering the cascading effects of the top predator on plant community structure and dynamics, consumer differences may generate a feedback over longer time scales, which in turn influences the degree of trait

  19. Consumer trait variation influences tritrophic interactions in salt marsh communities

    PubMed Central

    Hughes, Anne Randall; Hanley, Torrance C; Orozco, Nohelia P; Zerebecki, Robyn A

    2015-01-01

    The importance of intraspecific variation has emerged as a key question in community ecology, helping to bridge the gap between ecology and evolution. Although much of this work has focused on plant species, recent syntheses have highlighted the prevalence and potential importance of morphological, behavioral, and life history variation within animals for ecological and evolutionary processes. Many small-bodied consumers live on the plant that they consume, often resulting in host plant-associated trait variation within and across consumer species. Given the central position of consumer species within tritrophic food webs, such consumer trait variation may play a particularly important role in mediating trophic dynamics, including trophic cascades. In this study, we used a series of field surveys and laboratory experiments to document intraspecific trait variation in a key consumer species, the marsh periwinkle Littoraria irrorata, based on its host plant species (Spartina alterniflora or Juncus roemerianus) in a mixed species assemblage. We then conducted a 12-week mesocosm experiment to examine the effects of Littoraria trait variation on plant community structure and dynamics in a tritrophic salt marsh food web. Littoraria from different host plant species varied across a suite of morphological and behavioral traits. These consumer trait differences interacted with plant community composition and predator presence to affect overall plant stem height, as well as differentially alter the density and biomass of the two key plant species in this system. Whether due to genetic differences or phenotypic plasticity, trait differences between consumer types had significant ecological consequences for the tritrophic marsh food web over seasonal time scales. By altering the cascading effects of the top predator on plant community structure and dynamics, consumer differences may generate a feedback over longer time scales, which in turn influences the degree of trait

  20. Genetic factors influence level of proteinuria in cationic antigen-induced immune complex glomerulonephritis in the rat.

    PubMed Central

    Kato, A; Thaiss, F; Oite, T; Günther, E; Batsford, S; Vogt, A

    1985-01-01

    The influence of genetic factors on the susceptibility of the rat to cationic antigen-induced in situ immune complex glomerulonephritis was investigated. The levels of proteinuria developing in 11 inbred strains of rats differing in MHC and in genetic background varied markedly. Susceptibility was not MHC associated but resided in the genetic background. PMID:3159528

  1. Antigen-presenting genes and genomic copy number variations in the Tasmanian devil MHC

    PubMed Central

    2012-01-01

    Background The Tasmanian devil (Sarcophilus harrisii) is currently under threat of extinction due to an unusual fatal contagious cancer called Devil Facial Tumour Disease (DFTD). DFTD is caused by a clonal tumour cell line that is transmitted between unrelated individuals as an allograft without triggering immune rejection due to low levels of Major Histocompatibility Complex (MHC) diversity in Tasmanian devils. Results Here we report the characterization of the genomic regions encompassing MHC Class I and Class II genes in the Tasmanian devil. Four genomic regions approximately 960 kb in length were assembled and annotated using BAC contigs and physically mapped to devil Chromosome 4q. 34 genes and pseudogenes were identified, including five Class I and four Class II loci. Interestingly, when two haplotypes from two individuals were compared, three genomic copy number variants with sizes ranging from 1.6 to 17 kb were observed within the classical Class I gene region. One deletion is particularly important as it turns a Class Ia gene into a pseudogene in one of the haplotypes. This deletion explains the previously observed variation in the Class I allelic number between individuals. The frequency of this deletion is highest in the northwestern devil population and lowest in southeastern areas. Conclusions The third sequenced marsupial MHC provides insights into the evolution of this dynamic genomic region among the diverse marsupial species. The two sequenced devil MHC haplotypes revealed three copy number variations that are likely to significantly affect immune response and suggest that future work should focus on the role of copy number variations in disease susceptibility in this species. PMID:22404855

  2. Circadian variation of tissue plasminogen activator and its inhibitor, von Willebrand factor antigen, and prostacyclin stimulating factor in men with ischaemic heart disease.

    PubMed Central

    Bridges, A B; McLaren, M; Scott, N A; Pringle, T H; McNeill, G P; Belch, J J

    1993-01-01

    OBJECTIVES--To determine whether plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor antigen, and prostacyclin stimulating factor and plasminogen activator inhibitor activity show circadian variation in men with ischaemic heart disease. DESIGN--Blood samples were obtained every four hours for 24 hours from 10 men with ischaemic heart disease. The men were ambulant from 08:10 until 00:00 when they went to bed and they remained in bed until 08:00 the following morning. PATIENTS--Ten men with positive diagnostic exercise tolerance tests with no significant past history, who were not regularly taking any medical treatment except for glyceryl trinitrate. RESULTS--There was significant circadian variation in plasminogen activator inhibitor activity (p = 0.001) (peak value 04:00 and trough value 20:00), but not in plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor, or prostacyclin stimulating factor. CONCLUSION--Men with ischaemic heart disease showed a significant circadian variation in fibrinolysis. The combination of peak values of plasminogen activator inhibitor activity and failure of plasma concentrations of tissue plasminogen activator antigen to increase in the early morning must predispose to thrombosis at this time. The circadian variation in fibrinolysis may contribute to the increased incidence of myocardial infarction in the morning. PMID:8435236

  3. Schistosomiasis Coinfection in Children Influences Acquired Immune Response against Plasmodium falciparum Malaria Antigens

    PubMed Central

    Gaayeb, Lobna; Schacht, Anne-Marie; Charrier, Nicole; De Clerck, Dick; Dompnier, Jean-Pierre; Pillet, Sophie; Garraud, Olivier; N'Diaye, Abdoulaye A.; Riveau, Gilles

    2010-01-01

    Background Malaria and schistosomiasis coinfection frequently occurs in tropical countries. This study evaluates the influence of Schistosoma haematobium infection on specific antibody responses and cytokine production to recombinant merozoite surface protein-1-19 (MSP1-19) and schizont extract of Plasmodium falciparum in malaria-infected children. Methodology Specific IgG1 to MSP1-19, as well as IgG1 and IgG3 to schizont extract were significantly increased in coinfected children compared to P. falciparum mono-infected children. Stimulation with MSP1-19 lead to a specific production of both interleukin-10 (IL-10) and interferon-γ (IFN-γ), whereas the stimulation with schizont extract produced an IL-10 response only in the coinfected group. Conclusions Our study suggests that schistosomiasis coinfection favours anti-malarial protective antibody responses, which could be associated with the regulation of IL-10 and IFN-γ production and seems to be antigen-dependent. This study demonstrates the importance of infectious status of the population in the evaluation of acquired immunity against malaria and highlights the consequences of a multiple infection environment during clinical trials of anti-malaria vaccine candidates. PMID:20856680

  4. TH1 and TH2 responses are influenced by HLA antigens in healthy neonates vaccinated with recombinant hepatitis B vaccine.

    PubMed

    Jafarzadeh, Abdollah; Shokri, Fazel

    2012-12-01

    The immune response to hepatitis B surface antigen (HBsAg) is influenced by several factors, of which HLA antigens and balanced secretion of Th1/Th2 cytokines play important roles. The aim of this study was to evaluate the influence of HLA antigens on cytokine secretion by HBsAg-stimulated peripheral blood mononuclear cells (PBMC) from healthy neonates vaccinated with recombinant HBsAg. PBMCs were isolated from 48 Iranian neonates vaccinated with a recombinant HBV vaccine. The cells were stimulated in vitro with rHBsAg and the concentration of IL-4, IL-10, IL-12 and IFN-γ were quantitated in culture supernatant by sandwich ELISA. HLA typing was performed by microlymphocytotoxicity method. Significant diminished secretion of both Th1 (IFN-γ) and Th2 (IL-4, IL-10) cytokines was observed in HBsAg-stimulated PBMC from vaccinees expressing the HLA-DR7 compared to DR7 negative vaccinees. Similarly, lower production of these cytokines was also observed in vaccinees with DR7-DR53-DQ2, B7-DR7-DR53-DQ2 and A2-DR7-DR53-DQ2 haplotypes (p<0.05, p <0.005). While HBsAg-stimulated PBMC of DR13+ subjects produced lower levels of Th2-type cytokines (IL-4 and IL-10), those of HLA-B8+ or HLA-A9+ subjects produced higher levels of Th2-type cytokines. Cytokine secretion in response to PHA mitogen was not associated with a given HLA antigen or haplotype and was similarly represented in all groups of subjects irrespective of their HLA complex. These results indicate that HLA antigens may differentially influence cytokine secretion by HBsAg-specific T-cells of healthy neonates vaccinated with recombinant HB vaccine. This phenomenon may have an important implication for control of the immune response to HBsAg vaccine. PMID:23264407

  5. The influence of solar spectral variations on global radiative balance

    NASA Astrophysics Data System (ADS)

    Gao, Feng-Ling; Tao, Le-Ren; Cui, Guo-Min; Xu, Jia-Liang; Hua, Tse-Chao

    2015-01-01

    The total solar irradiance (TSI) has been the sole solar input in many climate models for lack of long and reliable time series of solar spectral irradiance (SSI) measurements currently. However, based on the recent SSI measurements by the Solar Radiation and Climate Experiment, which is able to provide full and accurate SSI measurements, the influence of SSI variations on global radiative balance between the descending phase of previous solar cycle in December 2007 and the ascending phase of the current solar cycle in the first half 2010 has been studied in this paper. The results show that the relatively larger TSI in the first half 2010 was mainly due to the ultraviolet and near infrared radiation enhancements, with average increases of 0.11% in 200-400 nm and 0.05% in 760-4000 nm respectively, while the radiation in visible region of 400-760 nm decreased by 0.05%. According to the measurements of ozone from the Aura-Microwave Limb Sounder satellite, the global average stratospheric ozone increased markedly in the layer of 25-40 km at the same time. The visible radiation decrease and stratospheric ozone increase together contributed to the smaller solar radiation at the tropopause for each month of the first half 2010 as compared with that in December 2007, with the maximum decrease of 0.15 W m-2 in March 2010. The study reveals that SSI variations in the ascending solar phase may also cool the Earth-atmosphere system.

  6. Differences in genetic variation in antigen-processing machinery components and association with cervical carcinoma risk in two Indonesian populations.

    PubMed

    Mehta, Akash M; Spaans, Vivian M; Mahendra, Nyoman Bayu; Osse, Elisabeth M; Vet, Jessica N I; Purwoto, Gatot; Surya, I G D; Cornian, Santoso; Peters, Alexander A; Fleuren, Gert J; Jordanova, Ekaterina S

    2015-06-01

    Genetic variation of antigen-processing machinery (APM) components has been shown to be associated with cervical carcinoma risk and outcome in a genetically homogeneous Dutch population. However, the role of APM component single nucleotide polymorphisms (SNPs) in genetically heterogeneous populations with different distributions of human papillomavirus (HPV) subtypes remains unclear. Eleven non-synonymous, coding SNPs in the TAP1, TAP2, LMP2, LMP7 and ERAP1 genes were genotyped in cervical carcinoma patients and healthy controls from two distinct Indonesian populations (Balinese and Javanese). Individual genotype and allele distributions were investigated using single-marker analysis, and combined SNP effects were assessed by haplotype construction and haplotype interaction analysis. Allele distribution patterns in Bali and Java differed in relation to cervical carcinoma risk, with four ERAP1 SNPs and one TAP2 SNP in the Javanese population showing significant association with cervical carcinoma risk, while in the Balinese population, only one TAP2 SNP showed this association. Multimarker analysis demonstrated that in the Javanese patients, one specific haplotype, consisting of the ERAP1-575 locus on chromosome 5 and the TAP2-379 and TAP2-651 loci on chromosome 6, was significantly associated with cervical carcinoma risk (global P = 0.008); no significant haplotype associations were found in the Balinese population. These data indicate not only that genetic variation in APM component genes is associated with cervical carcinoma risk in Indonesia but also that the patterns of association differ depending on background genetic composition and possibly on differences in HPV type distribution. PMID:25796583

  7. Influence of megapolis on the physical field variations

    NASA Astrophysics Data System (ADS)

    Riabova, Svetlana; Loktev, Dmitry; Spivak, Alexander

    2016-04-01

    The research of geophysical fields in the conditions of megapolis attracts particular interest not only in terms of their influence on the operation of precision equipment and technological processes associated with nanotechnology, but also it is perhaps the most important in terms of the formation of a special human and other biological objects' habitat. Indeed, the megapolis causes significant changes in regime of the physical fields both directly and indirectly. Negative factors of megapolis associated with elevated vibrations of soil as a result of traffic, acoustic load in the construction of infrastructure and transport communications, etc. are complemented by another negative factor, which until quite recently wasn't known much. It is a variation of physical fields (primarily electric and magnetic) induced by anthropogenic activities. As a result of the evolution a man has adapted to the natural regime of physical fields. Therefore, any, even the short-term changes of physical fields in the environment, their deviations from the natural rate can have a significant influence on human health including changes in the psycho-emotional state. In the present work we have evaluated the influence of the megapolis (in our case, Moscow) on the nature and regime of microseismic, electric and acoustic field in the surface atmosphere. We have analyzed data obtained as a result of continuous simultaneous registration of physical fields and meteorological parameters at the Center for geophysical monitoring of Moscow of Institute of Geosphere Dynamics of Russian Academy of Sciences. For determination of the characteristics of physical fields in the megapolis obtained data were compared with the results of the registration carried out at the Geophysical Observatory "Mikhnevo" of IDG RAS (located 85 km south from Moscow). The work is shown that the influence of the megapolis appears to increase the amplitude of physical fields, change of their spectral composition

  8. Detailed Analysis of Sequence Changes Occurring during vlsE Antigenic Variation in the Mouse Model of Borrelia burgdorferi Infection

    PubMed Central

    Coutte, Loïc; Botkin, Douglas J.; Gao, Lihui; Norris, Steven J.

    2009-01-01

    Lyme disease Borrelia can infect humans and animals for months to years, despite the presence of an active host immune response. The vls antigenic variation system, which expresses the surface-exposed lipoprotein VlsE, plays a major role in B. burgdorferi immune evasion. Gene conversion between vls silent cassettes and the vlsE expression site occurs at high frequency during mammalian infection, resulting in sequence variation in the VlsE product. In this study, we examined vlsE sequence variation in B. burgdorferi B31 during mouse infection by analyzing 1,399 clones isolated from bladder, heart, joint, ear, and skin tissues of mice infected for 4 to 365 days. The median number of codon changes increased progressively in C3H/HeN mice from 4 to 28 days post infection, and no clones retained the parental vlsE sequence at 28 days. In contrast, the decrease in the number of clones with the parental vlsE sequence and the increase in the number of sequence changes occurred more gradually in severe combined immunodeficiency (SCID) mice. Clones containing a stop codon were isolated, indicating that continuous expression of full-length VlsE is not required for survival in vivo; also, these clones continued to undergo vlsE recombination. Analysis of clones with apparent single recombination events indicated that recombinations into vlsE are nonselective with regard to the silent cassette utilized, as well as the length and location of the recombination event. Sequence changes as small as one base pair were common. Fifteen percent of recovered vlsE variants contained “template-independent” sequence changes, which clustered in the variable regions of vlsE. We hypothesize that the increased frequency and complexity of vlsE sequence changes observed in clones recovered from immunocompetent mice (as compared with SCID mice) is due to rapid clearance of relatively invariant clones by variable region-specific anti-VlsE antibody responses. PMID:19214205

  9. The expression of desmosomal and corneodesmosomal antigens shows specific variations during the terminal differentiation of epidermis and hair follicle epithelia.

    PubMed

    Mils, V; Vincent, C; Croute, F; Serre, G

    1992-09-01

    Using five monoclonal antibodies (MAb), we studied by indirect immunofluorescence the desmosomes and a junctional structure specific to cornified layers, the corneodesmosome, in normal and plantar epidermis and in the various sheaths of the anagen hair follicle. The monoclonal antibodies DP1&2.2-15, PG5.1, and DG3.10, specific for desmoplakins I/II, plakoglobin, and desmoglein I, respectively, were used to study the desmosome antigens, and G36-19 and G20-21 to study the corneodesmosome antigens. The distribution and sequence of expression of the five antigens allowed the nine epithelial differentiation pathways studied to be merged into four distinct families: non-plantar epidermis, characterized by the absence of desmosome and corneodesmosome antigens in the stratum corneum; the outer root sheath of the hair follicle, which behaves like the viable layers of the epidermis with regard to the desmosome antigens but does not express the corneodesmosome antigens; plantar epidermis and the three components of the inner root sheath in which the corneodesmosome antigens are present up to the desquamating layer; and the three components of the hair shaft, which are characterized by the absence of expression of both the desmosome and the corneodesmosome antigens in its mature portion. PMID:1506670

  10. The influence of monogalactosyldiacylglycerols from different marine macrophytes on immunogenicity and conformation of protein antigen of tubular immunostimulating complex.

    PubMed

    Sanina, Nina M; Kostetsky, Eduard Y; Shnyrov, Valery L; Tsybulsky, Alexander V; Novikova, Olga D; Portniagina, Olga Y; Vorobieva, Natalia S; Mazeika, Andrey N; Bogdanov, Mikhail V

    2012-04-01

    The tubular immunostimulating complex (TI-complex) is a novel nanoparticulate antigen delivery system consisting of cholesterol, triterpene glycoside cucumarioside A(2)-2, and glycolipid monogalactosyldiacylglycerol (MGDG) isolated from marine macrophytes. MGDG is crucial for the formation of a lipid matrix for the protein antigen incorporated in TI-complexes. Fatty acid composition and the physical state of this glycolipid depend on the taxonomic position of marine macrophytes. Therefore, the aim of the present work was to study the capacity of MGDGs, isolated from five species of marine macrophytes, to influence conformation and to enhance immunogenicity of porin from Yersinia pseudotuberculosis (YOmpF) as a model antigen of subunit vaccine based on TI-complexes. The trimeric porin was chosen for these experiments, because it was approximately two times more immunogenic than monomeric porin incorporated in TI-complexes. Immunization of mice with YOmpF within TI-complexes, comprised of different MGDGs, revealed a dependence of the immunostimulating effect of TI-complexes on the microvicosity of this glycolipid. TI-complexes comprising MGDGs from Sargassum pallidum and Ulva fenestrata with medium microviscosity induced maximal levels of anti-porin antibodies (four times higher when compared with those induced by pure porin). The adjuvant effect of TI-complexes based on other MGDGs varied by 2.8, 2.3 and 1.3 times for TI-complexes comprised of MGDGs from Zostera marina, Ahnfeltia tobuchiensis, and Laminaria japonica, respectively. MGDGs are also able to influence cytokine mechanisms of immunological regulation. DSC and spectroscopic studies showed that maximal immunostimulating effect of TI-complexes correlated with a moderate stabilizing influence of MGDGs from S. pallidum and U. fenestrata on the conformation of porin. The results obtained suggest lipid "nanofluidics" as a novel strategy for optimizing the immune response to protein antigens within lipid

  11. Prostate-specific Antigen Density Variation Rate as a Potential Guideline Parameter for Second Prostate Cancer Detection Biopsy

    PubMed Central

    Xie, Gan-Sheng; Lyv, Jin-Xing; Li, Gang; Yan, Chun-Yin; Hou, Jian-Quan; Pu, Jin-Xian; Ding, Xiang; Huang, Yu-Hua

    2016-01-01

    Background: The diagnostic value of current prostate-specific antigen (PSA) tests is challenged by the poor detection rate of prostate cancer (PCa) in repeat prostate biopsy. In this study, we proposed a novel PSA-related parameter named PSA density variation rate (PSADVR) and designed a clinical trial to evaluate its potential diagnostic value for detecting PCa on a second prostate biopsy. Methods: Data from 184 males who underwent second ultrasound-guided prostate biopsy 6 months after the first biopsy were included in the study. The subjects were divided into PCa and non-PCa groups according to the second biopsy pathological results. Prostate volume, PSA density (PSAD), free-total PSA ratio, and PSADVR were calculated according to corresponding formulas at the second biopsy. These parameters were compared using t-test or Mann-Whitney U-test between PCa and non-PCa groups, and receiver operating characteristic analysis were used to evaluate their predictability on PCa detection. Results: PCa was detected in 24 patients on the second biopsy. Mean values of PSA, PSAD, and PSADVR were greater in the PCa group than in the non-PCa group (8.39 μg/L vs. 7.16 μg/L, 0.20 vs. 0.16, 14.15% vs. −1.36%, respectively). PSADVR had the largest area under the curve, with 0.667 sensitivity and 0.824 specificity when the cutoff was 10%. The PCa detection rate was significantly greater in subjects with PSADVR >10% than PSADVR ≤10% (28.6% vs. 6.5%, P < 0.001). In addition, PSADVR was the only parameter in this study that showed a significant correlation with mid-to-high-risk PCa (r = 0.63, P = 0.03). Conclusions: Our results demonstrated that PSADVR improved the PCa detection rate on second biopsies, especially for mid-to-high-risk cancers requiring prompt treatment. PMID:27453228

  12. Sequence Variation Analysis of Epstein-Barr Virus Nuclear Antigen 1 Gene in the Virus Associated Lymphomas of Northern China

    PubMed Central

    Sun, Lingling; Zhao, Zhenzhen; Liu, Song; Liu, Xia; Sun, Zhifu; Luo, Bing

    2015-01-01

    Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is the only viral protein expressed in all EBV-positive tumors as it is essential for the maintenance, replication and transcription of the virus genome. According to the polymorphism of residue 487 in EBNA1 gene, EBV isolates can be classified into five subtypes: P-ala, P-thr, V-val, V-leu and V-pro. Whether these EBNA1 subtypes contribute to different tissue tropism of EBV and are consequently associated with certain malignancies remain to be determined. To elucidate the relationship, one hundred and ten EBV-positive lymphoma tissues of different types from Northern China, a non-NPC endemic area, were tested for the five subtypes by nested-PCR and DNA sequencing. In addition, EBV type 1 and type 2 classification was typed by using standard PCR assays across type-specific regions of the EBNA3C genes. Four EBNA1 subtypes were identified: V-val (68.2%, 75/110), P-thrV (15.5%, 17/110), V-leuV (3.6%, 4/110) and P-ala (10.9%, 12/110). The distribution of the EBNA1 subtypes in the four lymphoma groups was not significantly different (p = 0.075), neither was that of the EBV type 1/type 2 (p = 0.089). Compared with the previous data of gastric carcinoma (GC), nasopharyngeal carcinoma (NPC) and throat washing (TW) from healthy donors, the distribution of EBNA1 subtypes in lymphoma differed significantly (p = 0.016), with a little higher frequency of P-ala subtype. The EBV type distribution between lymphoma and the other three groups was significantly different (p = 0.000, p = 0.000, p = 0.001, respectively). The proportion of type 1 and type 2 mixed infections was higher in lymphoma than that in GC, NPC and TW. In lymphomas, the distribution of EBNA1 subtypes in the three EBV types was not significantly different (p = 0.546). These data suggested that the variation patterns of EBNA1 gene may be geographic-associated rather than tumor-specific and the role of EBNA1 gene variations in tumorigenesis needs more extensive and

  13. Influence of Compositional Variations on Floc Size and Strength

    NASA Astrophysics Data System (ADS)

    Yin, H.; Tan, X.; Reed, A. H.; Furukawa, Y.; Zhang, G.

    2010-12-01

    Clay-biopolymer micro aggregates or flocs are abundant in waters, including rivers, lakes, and oceans. Owing to their small size and charged surfaces, fine-grained inorganic sediment particles, mainly clays, interact actively with organic substances, such as organic matter and biogenic polymers, to form aggregates or flocs, typically in the size of 10-1000 μm. The flocs in ocean waters are also termed “marine snow”. These flocs are typically porous, tenuous, and soft in nature. During transport in suspension, they may breakdown and decrease in size if the turbulent shear stress exceeds their strength. They may also collide and form larger ones if the shear stress is relatively small. Since flocs of different size and structure settle at different velocities, understanding their strength is also of essential importance for sediment hydrodynamics, transport, and management. Our study focuses on investigating the influence of compositional variations on floc size and strength so that a better understanding of floc dynamics can be achieved. A laser diffraction-based Cilas® particle size and shape analyzer with controllable fluid circulation velocity was employed to conduct floc size measurements and shape imaging, the latter achieved by a high resolution inverted optical microscope, which is also installed with the size analyzer. Totally two clay minerals, kaolinite and illite, were tested as the model inorganic solid skeleton minerals for floc formation, and two biopolymers, anionic xanthan gum and neutral guar gum, were chosen as analogs of naturally occurring organic matter or biopolymers to simulate clay-biopolymer floc formation. Moreover, the concentration of both organic and inorganic phases was varied. The floc breakage or tensile strength was indirectly estimated by the varied fluid flow velocity in the particle size analyzer’s circulation system. For each individual composition, stable flocs were formed by three different fluid circulating velocities

  14. Human Leukocyte Antigens Influence the Antibody Response to Hepatitis B Vaccine.

    PubMed

    Jafarzadeh, Abdollah; Bagheri-Jamebozorgi, Masoome; Nemati, Maryam; Golsaz-Shirazi, Forough; Shokri, Fazel

    2015-06-01

    Hepatitis B virus (HBV) infection and its sequelae such as cirrhosis and hepatocellular carcinoma has remained a serious public health problem throughout the world. The WHO strategy for effective control of HBV infection and its complications is mass vaccination of neonates and children within the framework of Expanded Programme on Immunization (EPI). Vaccination with hepatitis B surface antigen (HBsAg) induces protective antibody response (anti-HBs ≥ 10 IU/L) in 90-99% of vaccinees. The lack of response to HBsAg has been attributed to a variety of immunological mechanisms, including defect in antigen presentation, defect in HBsAg-specific T and/or B cell repertoires, T-cell suppression, increase in the regulatory T cell count, lack of necessary help of T-cells for production of anti-HBs by B cells, defect in Th1 and/or Th2 cytokine production and selective killing of HBsAg-specific B-cells by human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes. The HLA complex plays an important role in many of these immunological processes. A variety of HLA class I, II, and III alleles and antigens have been reported to be associated with antibody response to HBsAg vaccination in different ethnic populations. Moreover, some HLA haplotypes were also associated with responsiveness to HBsAg. In this review the association of the HLA specificities with antibody response to hepatitis B (HB) vaccine is discussed. PMID:26546891

  15. P. falciparum Infection Durations and Infectiousness Are Shaped by Antigenic Variation and Innate and Adaptive Host Immunity in a Mathematical Model

    PubMed Central

    Eckhoff, Philip

    2012-01-01

    Many questions remain about P. falciparum within-host dynamics, immunity, and transmission–issues that may affect public health campaign planning. These gaps in knowledge concern the distribution of durations of malaria infections, determination of peak parasitemia during acute infection, the relationships among gametocytes and immune responses and infectiousness to mosquitoes, and the effect of antigenic structure on reinfection outcomes. The present model of intra-host dynamics of P. falciparum implements detailed representations of parasite and immune dynamics, with structures based on minimal extrapolations from first-principles biology in its foundations. The model is designed to quickly and readily accommodate gains in mechanistic understanding and to evaluate effects of alternative biological hypothesis through in silico experiments. Simulations follow the parasite from the liver-stage through the detailed asexual cycle to clearance while tracking gametocyte populations. The modeled immune system includes innate inflammatory and specific antibody responses to a repertoire of antigens. The mechanistic focus provides clear explanations for the structure of the distribution of infection durations through the interaction of antigenic variation and innate and adaptive immunity. Infectiousness to mosquitoes appears to be determined not only by the density of gametocytes but also by the level of inflammatory cytokines, which harmonizes an extensive series of study results. Finally, pre-existing immunity can either decrease or increase the duration of infections upon reinfection, depending on the degree of overlap in antigenic repertoires and the strength of the pre-existing immunity. PMID:23028698

  16. RecA mediates MgpB and MgpC phase and antigenic variation in Mycoplasma genitalium, but plays a minor role in DNA repair

    PubMed Central

    Burgos, Raul; Wood, Gwendolyn E.; Young, Lei; Glass, John I.; Totten, Patricia A.

    2012-01-01

    Summary Mycoplasma genitalium, a sexually transmitted human pathogen, encodes MgpB and MgpC adhesins that undergo phase and antigenic variation through recombination with archived “MgPar” donor sequences. The mechanism and molecular factors required for this genetic variation are poorly understood. In this study, we estimate that sequence variation at the mgpB/C locus occurs in vitro at a frequency of >1.25 × 10−4 events/ genome/generation using a quantitative anchored-PCR assay. This rate was dramatically reduced in a recA deletion mutant and increased in a complemented strain overexpressing RecA. Similarly, the frequency of hemadsorption-deficient phase variants was reduced in the recA mutant, but restored by complementation. Unlike Escherichia coli, inactivation of recA in M. genitalium had a minimal effect on survival after exposure to mitomycin C or UV irradiation. In contrast, a deletion mutant for the predicted nucleotide excision repair (NER) uvrC gene, showed growth defects and was exquisitely sensitive to DNA damage. We conclude that M. genitalium RecA has a primary role in mgpB/C-MgPar recombination leading to antigenic and phase variation, yet plays a minor role in DNA repair. Our results also suggest that M. genitalium possess an active NER system, possibly representing the main DNA repair pathway in this minimal bacterium. PMID:22686427

  17. Genetic basis of antigenic variation in foot-and-mouth disease serotype A viruses from the Middle East☆

    PubMed Central

    Upadhyaya, Sasmita; Ayelet, Gelagay; Paul, Guntram; King, Donald P.; Paton, David J.; Mahapatra, Mana

    2014-01-01

    Foot-and-mouth disease viruses (FMDV) from serotype A exhibit high antigenic diversity. Within the Middle East, a strain called A-Iran-05 emerged in 2003, and subsequently replaced the A-Iran-96 and A-Iran-99 strains that were previously circulating in the region. Viruses from this strain did not serologically match with the established A/Iran/96 vaccine, although most early samples matched with the older A22/Iraq vaccine. However, many viruses from this strain collected after 2006 had poor serological match with the A22/Iraq vaccine necessitating the development of a new vaccine strain (A/TUR/2006). More recently, viruses from the region now exhibit lower cross-reactivity with the A/TUR/2006 antisera highlighting the inadequacy of the serotype A vaccines used in the region. In order to understand the genetic basis of these antigenic phenotypes, we have determined the full capsid sequence for 57 Middle Eastern viruses isolated between 1996 and 2011 and analysed these data in context of antigenic relationship (r1) values that were generated using antisera to A22/Iraq and A/TUR/2006. Comparisons of capsid sequences identified substitutions in neutralising antigenic sites (1, 2 and 4), which either individually or together underpin these observed antigenic phenotypes. PMID:24035435

  18. Sequence Variation and Immunologic Cross-Reactivity among Babesia bovis Merozoite Surface Antigen 1 Proteins from Vaccine Strains and Vaccine Breakthrough Isolates

    PubMed Central

    LeRoith, Tanya; Brayton, Kelly A.; Molloy, John B.; Bock, Russell E.; Hines, Stephen A.; Lew, Ala E.; McElwain, Terry F.

    2005-01-01

    The Babesia bovis merozoite surface antigen 1 (MSA-1) is an immunodominant membrane glycoprotein that is the target of invasion-blocking antibodies. While antigenic variation has been demonstrated in MSA-1 among strains from distinct geographical areas, the extent of sequence variation within a region where it is endemic and the effect of variation on immunologic cross-reactivity have not been assessed. In this study, sequencing of MSA-1 from two Australian B. bovis vaccine strains and 14 breakthrough isolates from vaccinated animals demonstrated low sequence identity in the extracellular region of the molecule, ranging from 19.8 to 46.7% between the T vaccine strain and eight T vaccine breakthrough isolates, and from 18.7 to 99% between the K vaccine strain and six K vaccine breakthrough isolates. Although MSA-1 amino acid sequence varied substantially among strains, overall predicted regions of hydrophilicity and hydrophobicity in the extracellular domain were conserved in all strains examined, suggesting a conserved functional role for MSA-1 despite sequence polymorphism. Importantly, the antigenic variation created by sequence differences resulted in a lack of immunologic cross-reactivity among outbreak strains using sera from animals infected with the B. bovis vaccine strains. Additionally, sera from cattle hyperinfected with the Mexico strain of B. bovis and shown to be clinically immune did not cross-react with MSA-1 from any other isolate tested. The results indicate that isolates of B. bovis capable of evading vaccine-induced immunity contain an msa-1 gene that is significantly different from the msa-1 of the vaccine strain, and that the difference can result in a complete lack of cross-reactivity between MSA-1 from vaccine and breakthrough strains in immunized animals. PMID:16113254

  19. Influence of non-inherited maternal HLA-DR antigens on susceptibility to rheumatoid arthritis

    PubMed Central

    van der Horst-Bru..., I E; Hazes, J; Schreuder, G; Radstake, T; Barrera, P; van de Putte, L B A; Mustamu, D; van Schaardenburg, D; Breedveld, F; de Vries, R R P

    1998-01-01

    OBJECTIVE—It has recently been observed that non-inherited maternal DR4 antigens (NIMAs) of DR4 negative rheumatoid arthritis (RA) patients were increased compared with non-inherited paternal DR4 antigens (NIPAs). The aim of this study was to determine the prevalence of non-inherited DR4 antigens and DRB1 alleles in parents of RA patients. 
METHODS—HLA-DR serology and DRB1 typing was performed in 97 RA patients and their parents. NIMA and NIPA frequencies were compared, stratified according to the presence of DR4 and/or the shared epitope (SE).
RESULTS—In DR4 negative patients, NIMA DR4 was increased compared with NIPA DR4 (OR 3.10, 95% CI 0.76, 12.70). When combined with results from a previous study this increase was significant (OR 3.65, 95% CI 1.29, 10.31). The NIMA effect of SE positive DR4 subtypes in this study (OR 4.73, 95% CI 0.94, 23.8) was stronger than the NIMA effect of combined SE positive DRB1 alleles (OR 2.19 95% CI 0.36, 13.22).
CONCLUSIONS—The association between non-inherited maternal HLA-DR4 alleles and the susceptibility to RA was observed in two independent populations.

 Keywords: rheumatoid arthritis; non-inherited maternal DR4 antigens; HLA; genetics PMID:9924209

  20. Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis

    PubMed Central

    Tschochner, Monika; Leary, Shay; Cooper, Don; Strautins, Kaija; Chopra, Abha; Clark, Hayley; Choo, Linda; Dunn, David; James, Ian; Carroll, William M.; Kermode, Allan G.; Nolan, David

    2016-01-01

    Background Epstein-Barr virus (EBV) infection represents a major environmental risk factor for multiple sclerosis (MS), with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1)-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome. Methods Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan) and candidates were evaluated for cross recognition with human brain proteins. Results EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off). In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes (‘AEG’: aa 481–496 and ‘MVF’: aa 562–577), and two putative epitopes between positions 502–543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis. Conclusions This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains

  1. Strain variations in the murine cellular immune response to the phenolic glycolipid I antigen of Mycobacterium leprae.

    PubMed Central

    Koster, F T; Teuscher, C; Matzner, P; Umland, E; Yanagihara, D; Brennan, P J; Tung, K S

    1986-01-01

    The cellular immune response to the Mycobacterium leprae-specific phenolic glycolipid I was examined in inbred mice immunized with M. leprae by in vivo delayed cutaneous hypersensitivity and in vitro lymphocyte proliferation. Whereas all mouse strains responded to M.leprae-induced delayed-type hypersensitivity and lymphocyte proliferation, only BALB.K was responsive in both assays to the glycolipid. Responsiveness was determined in part by non-H-2 genes, while the influence of H-2 genes was not apparent. Among congenic BALB/c mice differing only at Igh-C allotype loci, variations in responsiveness were found in both delayed-type hypersensitivity and lymphocytes proliferation assays, indicating a possible role for Igh-C loci-linked genes. Unresponsiveness in the lymphocyte proliferation assay to the glycolipid was inherited as a dominant trait in one set of responder X nonresponder F1 progeny. We conclude that after immunization with M. leprae organisms, the cell-mediated responses to the glycolipid, endowed with a single carbohydrate epitope, are under polygenic control, predominantly non-H-2-linked genes. PMID:3510979

  2. Neisseria gonorrhoeae MutS Affects Pilin Antigenic Variation through Mismatch Correction and Not by pilE Guanine Quartet Binding

    PubMed Central

    Rotman, Ella

    2015-01-01

    ABSTRACT Many pathogens use homologous recombination to vary surface antigens to avoid immune surveillance. Neisseria gonorrhoeae achieves this in part by changing the properties of its surface pili in a process called pilin antigenic variation (AV). Pilin AV occurs by high-frequency gene conversion reactions that transfer silent pilS sequences into the expressed pilE locus and requires the formation of an upstream guanine quartet (G4) DNA structure to initiate this process. The MutS and MutL proteins of the mismatch correction (MMC) system act to correct mismatches after replication and prevent homeologous (i.e., partially homologous) recombination, but MutS orthologs can also bind to G4 structures. A previous study showed that mutation of MutS resulted in a 3-fold increase in pilin AV, which could be due to the loss of MutS antirecombination properties or loss of G4 binding. We tested two site-directed separation-of-function MutS mutants that are both predicted to bind to G4s but are not able to perform MMC. Pilus phase variation assays and DNA sequence analysis of pilE variants produced in these mutants showed that all three mutS mutants and a mutL mutant had similar increased frequencies of pilin AV. Moreover, the mutS mutants all showed similar increased levels of pilin AV-dependent synthetic lethality. These results show that antirecombination by MMC is the reason for the effect that MutS has on pilin AV and is not due to pilE G4 binding by MutS. IMPORTANCE Neisseria gonorrhoeae continually changes its outer surface proteins to avoid recognition by the immune system. N. gonorrhoeae alters the antigenicity of the pilus by directed recombination between partially homologous pilin copies in a process that requires a guanine quartet (G4) structure. The MutS protein of the mismatch correction (MMC) system prevents recombination between partially homologous sequences and can also bind to G4s. We confirmed that loss of MMC increases the frequency of pilin antigenic

  3. Characterization and allelic variation of the transporters associated with antigen processing (TAP) genes in the domestic dog (Canis lupus familiaris).

    PubMed

    Gojanovich, Gregory S; Ross, Peter; Holmer, Savannah G; Holmes, Jennifer C; Hess, Paul R

    2013-12-01

    The function of the transporters associated with antigen processing (TAP) complex is to shuttle antigenic peptides from the cytosol to the endoplasmic reticulum to load MHC class I molecules for CD8(+) T-cell immunosurveillance. Here we report the promoter and coding regions of the canine TAP1 and TAP2 genes, which encode the homologous subunits forming the TAP heterodimer. By sampling genetically divergent breeds, polymorphisms in both genes were identified, although there were few amino acid differences between alleles. Splice variants were also found. When aligned to TAP genes of other species, functional regions appeared conserved, and upon phylogenetic analysis, canine sequences segregated appropriately with their orthologs. Transfer of the canine TAP2 gene into a murine TAP2-defective cell line rescued surface MHC class I expression, confirming exporter function. This data should prove useful in investigating the association of specific TAP defects or alleles with immunity to intracellular pathogens and cancer in dogs. PMID:23892057

  4. Characterization and allelic variation of the transporters associated with antigen processing (TAP) genes in the domestic dog (Canis lupus familiaris)

    PubMed Central

    Gojanovich, Gregory S.; Ross, Peter; Holmer, Savannah R.; Holmes, Jennifer C.; Hess, Paul R.

    2013-01-01

    The function of the transporters associated with antigen processing (TAP) complex is to shuttle antigenic peptides from the cytosol to the endoplasmic reticulum to load MHC class I molecules for CD8+ T-cell immunosurveillance. Here we report the promoter and coding regions of the canine TAP1 and TAP2 genes, which encode the homologous subunits forming the TAP heterodimer. By sampling genetically divergent breeds, polymorphisms in both genes were identified, although there were few amino acid differences between alleles. Splice variants were also found. When aligned to TAP genes of other species, functional regions appeared conserved, and upon phylogenetic analysis, canine sequences segregated appropriately with their orthologs. Transfer of the canine TAP2 gene into a murine TAP2-defective cell line rescued surface MHC class I expression, confirming exporter function. This data should prove useful in investigating the association of specific TAP defects or alleles with immunity to intracellular pathogens and cancer in dogs. PMID:23892057

  5. The vls antigenic variation systems of Lyme disease Borrelia: eluding host immunity through both random, segmental gene conversion and framework heterogeneity

    PubMed Central

    Norris, Steven J.

    2015-01-01

    Summary Spirochetes that cause Lyme borreliosis (also called Lyme disease) possess the vls locus, encoding an elaborate antigenic variation system. This locus contains the expression site vlsE as well as a contiguous array of vls silent cassettes, which contain variations of the central cassette region of vlsE. The locus is present on one of the many linear plasmids in the organism, e.g. plasmid lp28-1 in the strain B. burgdorferi B31. Changes in the sequence of vlsE occur continuously during mammalian infection and consist of random, segmental, unidirectional recombination events between the silent cassettes and the cassette region of vlsE. These gene conversion events do not occur during in vitro culture or the tick portion of the infection cycle of Borrelia burgdorferi or the other related Borrelia species that cause Lyme disease. The mechanism of recombination is largely unknown, but requires the RuvAB Holliday junction branch migrase. Other features of the vls locus also appear to be required, including cis locations of vlsE and the silent cassettes and high G+C content and GC skew. The vls system is required for long-term survival of Lyme Borrelia in infected mammals and represents an important mechanism of immune evasion. In addition to sequence variation, immune selection also results in significant heterogeneity in the sequence of the surface lipoprotein VlsE. Despite antigenic variation, VlsE generates a robust antibody response, and both full length VlsE and the C6 peptide (corresponding to invariant region 6) are widely used in immunodiagnostic tests for Lyme disease. PMID:26104445

  6. The Influence of Daily Variation in Teacher Performance on the Reliability and Validity of Assessment Data.

    ERIC Educational Resources Information Center

    Cronin, Linda; Capie, William

    The influence of day-to-day variation in teacher performance on the reliability and validity of teacher assessment was examined. An attempt was made to identify and quantify sources of score variation attributable to differences in teacher performance, day of observation, observers, and test subscales; and to determine their effects on reliability…

  7. Possibility to explain global climate variations by earthquakes influence

    NASA Astrophysics Data System (ADS)

    Molchanov, O.

    2009-12-01

    An additional natural source of the global warming could be heat flux from seismicity. Estimated earthquakes energy release in the near-equatorial Pacific area during a year ≈ 1020 J that is equivalent to the energy released in the detonation about one million atomic bombs of Hiroshima class and produce average power flux due to seismicity ≈ 0.3-1 W/m2 . We have analyzed together the slow climate temperature variations in the near-equatorial Pacific Ocean area (SSTOI indices) and crustal seismic activity in the same region during 1973-2008 time period using correlation analysis and found similarity in seismic and ENSO periodicities (the latter with time lag about 1.5 years). Trends of the processes are also similar showing about 2 times increase in average seismic energy release during the whole period of analysis and conventional 0.10C/(10 years) increase in SSTOI index anomalies. Our main conclusion is on real possibility of climate-seismicity coupling. It is rather probable that at least partially climate ENSO oscillations and temperature anomaly trends are induced by similar variation in seismicity. A mechanism of several years periodicity in the seismic activity is unclear at present. Probably it is initiated in the upper mantle of the Earth (depth 600-700 km) and then penetrates in the crust as so-called deformation (or stress) wave with time delay from 3 to 10 years [1] [1] O.A. Molchanov and S. Uyeda, Upward migration of earthquake hypocenters in Japan,Kurile- Kamchatka and Sunda subduction zones, Physics and Chemistry of the Earth, 34, 423-430, 2009; doi:10.1016/j.pce.2008.09.011.

  8. [Seasonal variation and related influencing factors for tuberculosis].

    PubMed

    Zhang, Z B; Lu, Z Q; Xie, H; Duan, Q H

    2016-08-10

    Tuberculosis is recognized as a chronic respiratory infectious disease and still one of the important public health issues in the world. Douglas reported an unique seasonal pattern (summer peak) of tuberculosis, when compared with most other respiratory diseases in 1996. Since then, there had been many other researchers notified various patterns of seasonality on TB. This paper reviewed all the studies published in the last five years and analyzed the current findings on seasonal variability and influencing factors, in order to explore the risk factors to provide evidence for prevention and control strategies on tuberculosis. PMID:27539356

  9. Diversity of O-Antigen Repeat Unit Structures Can Account for the Substantial Sequence Variation of Wzx Translocases

    PubMed Central

    Hong, Yaoqin

    2014-01-01

    The most common system for synthesis of cell surface polysaccharides is the Wzx/Wzy-dependent pathway, which involves synthesis, on the cytoplasmic face of the cell membrane, of repeat units, which are then translocated to the periplasmic face by a Wzx translocase and then polymerized by Wzy to generate the polysaccharide. One such polysaccharide is O antigen, which is incorporated into lipopolysaccharide (LPS). The O antigen is extremely variable, with over 186 forms in Escherichia coli. Wzx proteins are also very diverse, but they have been thought to be specific only for the first sugar of the repeat units. However, recent studies demonstrated examples in which Wzx translocases have considerable preference for their native repeat unit, showing that specificity can extend well beyond the first sugar. These results appear to be in conflict with the early conclusions, but they involved specificity for side branch residues and could be a special case. Here we take six Wzx translocases that were critical in the earlier studies on the importance of the first sugar and assess their ability to translocate the Escherichia coli O16 and O111 repeat units. We use gene replacements to optimize maintenance of expression level and show that under these conditions the native translocases are the most effective for their native repeat unit, being, respectively, 64-fold and 4-fold more effective than the next best. We conclude that Wzx translocases are commonly adapted to their native repeat unit, which provides an explanation for the great diversity of wzx genes. PMID:24532778

  10. Planetary Wave Influence on Wintertime OH Meinel Longitudinal Variation?

    NASA Astrophysics Data System (ADS)

    Winick, J. R.; Picard, R. H.; Wintersteiner, P. P.; Mlynczak, M. G.; Russell, J. M.; Gordley, L.

    2009-05-01

    We report on very unusual conditions in the upper mesosphere during the boreal winters of 2004 and 2006. Unusually bright OH volume emissions, as measured by TIMED/SABER, occurred in the region north of 60N. These emissions also occurred at unusually low altitudes, while at the same time very high temperatures characterized the upper mesosphere. These large perturbations allowed us to see more clearly longitudinal spatial and temporal variations that were present in the emissions. The affected areas varied in size and location on time scales of a few days and had a distinct planetary-wave wave-1 structure. We present data demonstrating the variability in the emissions and temperatures throughout the polar region and the correlations among them, and we contrast their behavior with that in normal years. The underlying cause of the correlations and longitudinal structure appears to be greatly enhanced downwelling in the upper mesosphere, which in turn was produced by unusual dynamical conditions in the lower atmosphere, consisting of stratospheric warmings and perturbations of wave structures within the polar vortex.

  11. Influence of Atmospheric CO2 Variation on Strom Track Behavior

    NASA Astrophysics Data System (ADS)

    Martynova, Yuliya; Krupchatnikov, Vladimir

    2015-04-01

    The storm tracks are the regions of strong baroclinicity where surface cyclones occur. The effect of increase with following decrease of anthropogenic load on storm tracks activity in the Northern Hemisphere was studied. The global climate system model of intermediate complexity ('Planet Simulator', Fraedrich K. et al., 2005) was used in this study. Anthropogenic forcing was set according to climatic scenario RCP8.5 continued till 4000 AD with fixed CO2 concentration till 3000 AD and linear decrease of anthropogenic load to preindustrial value at two different rates: for 100 and 1000 years. Modeling data analysis showed meridional shift of storm tracks due to atmospheric CO2 concentration variation. When CO2 concentration increases storm tracks demonstrate poleward shifting. When CO2 concentration decreases to preindustrial value storm tracks demonstrate a tendency to equator-ward shifting. Storm tracks, however, don't recover their original activity and location to the full. This manifests itself particularly for 'fast' CO2 concentration decrease. Heat and moisture fluxes demonstrate the same behavior. In addition, analysis of eddy length scale (Kidston J. Et al., 2011) showed their increase at mid-latitudes and decrease at tropic latitudes due to intensive CO2 concentration increase. This might cause poleward shift of mid-latitude jets. Acknowledgements. This work is partially supported by SB RAS project VIII.80.2.1, RFBR grant 13-05-12034, 13-05-00480, 14-05-00502 and grant of the President of the Russian Federation. Fraedrich K., Jansen H., Kirk E., Luksch U., and Lunkeit F. The Planet Simulator: Towards a user friendly model // Meteorol. Zeitschrift. 2005, 14, 299-304. Kidston J., Vallis G.K., Dean S.M., Renwick J.A. Can the increase in the eddy length scale ander global warming cause the poleward shift of the jet streams? // J. Climate. 2011, V.24. P. 3764-3780.

  12. The influence of statistical variations on image quality

    NASA Astrophysics Data System (ADS)

    Hultgren, Bror; Hertel, Dirk; Bullitt, Julian

    2006-01-01

    For more than thirty years imaging scientists have constructed metrics to predict psychovisually perceived image quality. Such metrics are based on a set of objectively measurable basis functions such as Noise Power Spectrum (NPS), Modulation Transfer Function (MTF), and characteristic curves of tone and color reproduction. Although these basis functions constitute a set of primitives that fully describe an imaging system from the standpoint of information theory, we found that in practical imaging systems the basis functions themselves are determined by system-specific primitives, i.e. technology parameters. In the example of a printer, MTF and NPS are largely determined by dot structure. In addition MTF is determined by color registration, and NPS by streaking and banding. Since any given imaging system is only a single representation of a class of more or less identical systems, the family of imaging systems and the single system are not described by a unique set of image primitives. For an image produced by a given imaging system, the set of image primitives describing that particular image will be a singular instantiation of the underlying statistical distribution of that primitive. If we know precisely the set of imaging primitives that describe the given image we should be able to predict its image quality. Since only the distributions are known, we can only predict the distribution in image quality for a given image as produced by the larger class of 'identical systems'. We will demonstrate the combinatorial effect of the underlying statistical variations in the image primitives on the objectively measured image quality of a population of printers as well as on the perceived image quality of a set of test images. We also will discuss the choice of test image sets and impact of scene content on the distribution of perceived image quality.

  13. Notch Ankyrin Repeat Domain Variation Influences Leukemogenesis and Myc Transactivation

    PubMed Central

    Aster, Jon C.; Bodnar, Nick; Xu, Lanwei; Karnell, Fredrick; Milholland, John M.; Maillard, Ivan; Histen, Gavin; Nam, Yunsun; Blacklow, Stephen C.; Pear, Warren S.

    2011-01-01

    Background The functional interchangeability of mammalian Notch receptors (Notch1-4) in normal and pathophysiologic contexts such as cancer is unsettled. We used complementary in vivo, cell-based and structural analyses to compare the abilities of activated Notch1-4 to support T cell development, induce T cell acute lymphoblastic leukemia/lymphoma (T-ALL), and maintain T-ALL cell growth and survival. Principal Findings We find that the activated intracellular domains of Notch1-4 (ICN1-4) all support T cell development in mice and thymic organ culture. However, unlike ICN1-3, ICN4 fails to induce T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) and is unable to rescue the growth of Notch1-dependent T-ALL cell lines. The ICN4 phenotype is mimicked by weak gain-of-function forms of Notch1, suggesting that it stems from a failure to transactivate one or more critical target genes above a necessary threshold. Experiments with chimeric receptors demonstrate that the Notch ankyrin repeat domains differ in their leukemogenic potential, and that this difference correlates with activation of Myc, a direct Notch target that has an important role in Notch-associated T-ALL. Conclusions/Significance We conclude that the leukemogenic potentials of Notch receptors vary, and that this functional difference stems in part from divergence among the highly conserved ankyrin repeats, which influence the transactivation of specific target genes involved in leukemogenesis. PMID:22022427

  14. Intraspecific variation influences natural settlement of eastern oysters.

    PubMed

    Smee, Delbert L; Overath, R Deborah; Johnson, Keith D; Sanchez, James A

    2013-11-01

    As populations decline, their intraspecific diversity also diminishes. Population decline may be exacerbated if a decrease in intraspecific diversity also reduces important ecological functions that maintain population numbers. Oyster reefs are severely overharvested, declining by ~85 % worldwide. We tested how increasing within-species diversity of eastern oysters (Crassostrea virginica) using transplants would affect recruitment of oyster larvae, a key function necessary to maintain future populations. If harvesting reduces population numbers, within-species diversity, and connectivity, then oysters may lose the ability to adapt to changing environmental conditions as well as incur lower levels of recruitment that may hasten their decline. Results from laboratory and field studies indicated that oyster larvae use chemical cues from adult oysters and not from associated fouling communities to select settlement sites. To test how increasing within-species diversity of oysters affected recruitment, we collected oysters from three distinct bay systems in Texas, USA, and compared natural settlement in treatments where all oysters were from a single bay to a mixture of all three bays. Significantly greater recruitment occurred in mixed treatments in 2010, 2011, and 2012 even though oyster recruitment varied by order of magnitude during this time. The net biodiversity effect was positive in all 3 years, indicating that increased recruitment in mixed treatments can be greater than the additive effect of the single bay treatments. Losing intraspecific diversity may reduce recruitment and lead to further declines in oyster populations, illustrating the need for understanding how intraspecific diversity influences ecological functions. PMID:23543216

  15. How Rainfall Variation Influences Reproductive Patterns of African Savanna Ungulates in an Equatorial Region Where Photoperiod Variation Is Absent.

    PubMed

    Ogutu, Joseph O; Owen-Smith, Norman; Piepho, Hans-Peter; Dublin, Holly T

    2015-01-01

    In high temperate latitudes, ungulates generally give birth within a narrow time window when conditions are optimal for offspring survival in spring or early summer, and use changing photoperiod to time conceptions so as to anticipate these conditions. However, in low tropical latitudes day length variation is minimal, and rainfall variation makes the seasonal cycle less predictable. Nevertheless, several ungulate species retain narrow birth peaks under such conditions, while others show births spread quite widely through the year. We investigated how within-year and between-year variation in rainfall influenced the reproductive timing of four ungulate species showing these contrasting patterns in the Masai Mara region of Kenya. All four species exhibited birth peaks during the putative optimal period in the early wet season. For hartebeest and impala, the birth peak was diffuse and offspring were born throughout the year. In contrast, topi and warthog showed a narrow seasonal concentration of births, with conceptions suppressed once monthly rainfall fell below a threshold level. High rainfall in the previous season and high early rains in the current year enhanced survival into the juvenile stage for all the species except impala. Our findings reveal how rainfall variation affecting grass growth and hence herbivore nutrition can govern the reproductive phenology of ungulates in tropical latitudes where day length variation is minimal. The underlying mechanism seems to be the suppression of conceptions once nutritional gains become insufficient. Through responding proximally to within-year variation in rainfall, tropical savanna ungulates are less likely to be affected adversely by the consequences of global warming for vegetation phenology than northern ungulates showing more rigid photoperiodic control over reproductive timing. PMID:26295154

  16. How Rainfall Variation Influences Reproductive Patterns of African Savanna Ungulates in an Equatorial Region Where Photoperiod Variation Is Absent

    PubMed Central

    Ogutu, Joseph O.; Owen-Smith, Norman; Piepho, Hans-Peter; Dublin, Holly T.

    2015-01-01

    In high temperate latitudes, ungulates generally give birth within a narrow time window when conditions are optimal for offspring survival in spring or early summer, and use changing photoperiod to time conceptions so as to anticipate these conditions. However, in low tropical latitudes day length variation is minimal, and rainfall variation makes the seasonal cycle less predictable. Nevertheless, several ungulate species retain narrow birth peaks under such conditions, while others show births spread quite widely through the year. We investigated how within-year and between-year variation in rainfall influenced the reproductive timing of four ungulate species showing these contrasting patterns in the Masai Mara region of Kenya. All four species exhibited birth peaks during the putative optimal period in the early wet season. For hartebeest and impala, the birth peak was diffuse and offspring were born throughout the year. In contrast, topi and warthog showed a narrow seasonal concentration of births, with conceptions suppressed once monthly rainfall fell below a threshold level. High rainfall in the previous season and high early rains in the current year enhanced survival into the juvenile stage for all the species except impala. Our findings reveal how rainfall variation affecting grass growth and hence herbivore nutrition can govern the reproductive phenology of ungulates in tropical latitudes where day length variation is minimal. The underlying mechanism seems to be the suppression of conceptions once nutritional gains become insufficient. Through responding proximally to within-year variation in rainfall, tropical savanna ungulates are less likely to be affected adversely by the consequences of global warming for vegetation phenology than northern ungulates showing more rigid photoperiodic control over reproductive timing. PMID:26295154

  17. Individual variation in life history characteristics can influence extinction risk (vol 144, pg 61, 2001) Correction

    SciTech Connect

    Jager, Yetta

    2009-01-01

    The white sturgeon (Acipenser transmontanus) shows great individual variation in the age at maturation. This study examines the consequences of model assumptions about individual variation in the age at maturation on predicted population viability. I considered: (1) the effects of variation in age at maturation alone; (2) the effects of heritability; and (3) the influence of a stable and an altered selective regime. Two selective regimes represented conditions before and after the impoundment of a river, blocking access of anadromous white sturgeon populations to the ocean. In contrast to previous simulation studies, I found that increased individual variation in the age at maturity did not necessarily lead to a higher likelihood of persistence. Individual variation increased the simulated likelihood of persistence when the variation was heritable and the selective regime had changed such that the mean age at maturity was no longer optimal.

  18. Operator Influence on Blinded Diagnostic Accuracy of Point-of-Care Antigen Testing for Group A Streptococcal Pharyngitis.

    PubMed

    Penney, Carla; Porter, Robert; O'Brien, Mary; Daley, Peter

    2016-01-01

    Background. Acute pharyngitis caused by Group A Streptococcus (GAS) is a common presentation to pediatric emergency departments (ED). Diagnosis with conventional throat culture requires 18-24 hours, which prevents point-of-care treatment decisions. Rapid antigen detection tests (RADT) are faster, but previous reports demonstrate significant operator influence on performance. Objective. To measure operator influence on the diagnostic accuracy of a RADT when performed by pediatric ED nurses and clinical microbiology laboratory technologists, using conventional culture as the reference standard. Methods. Children presenting to a pediatric ED with suspected acute pharyngitis were recruited. Three pharyngeal swabs were collected at once. One swab was used to perform the RADT in the ED, and two were sent to the clinical microbiology laboratory for RADT and conventional culture testing. Results. The RADT when performed by technologists compared to nurses had a 5.1% increased sensitivity (81.4% versus 76.3%) (p = 0.791) (95% CI for difference between technologists and nurses = -11% to +21%) but similar specificity (97.7% versus 96.6%). Conclusion. The performance of the RADT was similar between technologists and ED nurses, although adequate power was not achieved. RADT may be employed in the ED without clinically significant loss of sensitivity. PMID:27579047

  19. Operator Influence on Blinded Diagnostic Accuracy of Point-of-Care Antigen Testing for Group A Streptococcal Pharyngitis

    PubMed Central

    O'Brien, Mary

    2016-01-01

    Background. Acute pharyngitis caused by Group A Streptococcus (GAS) is a common presentation to pediatric emergency departments (ED). Diagnosis with conventional throat culture requires 18–24 hours, which prevents point-of-care treatment decisions. Rapid antigen detection tests (RADT) are faster, but previous reports demonstrate significant operator influence on performance. Objective. To measure operator influence on the diagnostic accuracy of a RADT when performed by pediatric ED nurses and clinical microbiology laboratory technologists, using conventional culture as the reference standard. Methods. Children presenting to a pediatric ED with suspected acute pharyngitis were recruited. Three pharyngeal swabs were collected at once. One swab was used to perform the RADT in the ED, and two were sent to the clinical microbiology laboratory for RADT and conventional culture testing. Results. The RADT when performed by technologists compared to nurses had a 5.1% increased sensitivity (81.4% versus 76.3%) (p = 0.791) (95% CI for difference between technologists and nurses = −11% to +21%) but similar specificity (97.7% versus 96.6%). Conclusion. The performance of the RADT was similar between technologists and ED nurses, although adequate power was not achieved. RADT may be employed in the ED without clinically significant loss of sensitivity. PMID:27579047

  20. In silico analyses of antigenicity and surface structure variation of an emerging porcine circovirus genotype 2b mutant, prevalent in southern China from 2013 to 2015.

    PubMed

    Zhan, Yang; Wang, Naidong; Zhu, Zhe; Wang, Zhanfeng; Wang, Aibing; Deng, Zhibang; Yang, Yi

    2016-04-01

    Porcine circovirus type 2 (PCV2) is the pivotal pathogen causing porcine circovirus-associated diseases. In this study, 62 PCV2 isolates were identified from seven farms in southern China from 2013 to 2015 and phylogenetic trees were reconstructed based on whole-genome sequences or the cap gene. In this investigation, PCV2b was the main genotype in circulation throughout these farms. Furthermore, an emerging mutant (PCV2b-1C), isolated from PCV2-vaccinated farms, was the predominant strain prevalent on these farms. In addition, we isolated a new cluster that may represent evolution of the virus through recombination of PCV2b-1A/1B and PCV2b-1C. Finally, we discuss evidence that antigenicity and surface structure variation of the capsid resulted from mutation of the C-terminal loop (Loop CT) of the PCV2b-1C Cap in silico. PMID:26758466

  1. Inactivation of Genes for Antigenic Variation in the Relapsing Fever Spirochete Borrelia hermsii Reduces Infectivity in Mice and Transmission by Ticks

    PubMed Central

    Raffel, Sandra J.; Battisti, James M.; Fischer, Robert J.; Schwan, Tom G.

    2014-01-01

    Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host’s acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete’s alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector. PMID:24699793

  2. Inactivation of genes for antigenic variation in the relapsing fever spirochete Borrelia hermsii reduces infectivity in mice and transmission by ticks.

    PubMed

    Raffel, Sandra J; Battisti, James M; Fischer, Robert J; Schwan, Tom G

    2014-04-01

    Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host's acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream Vmp and produce a different outer surface protein, the variable tick protein (Vtp), during persistent infection in the tick salivary glands. Thus the production of Vmps in mammalian blood versus Vtp in ticks is a dominant feature of the spirochete's alternating life cycle. We constructed two mutants, one which was unable to produce a Vmp and the other was unable to produce Vtp. The mutant lacking a Vmp constitutively produced Vtp, was attenuated in mice, produced lower cell densities in blood, and was unable to relapse in animals after its initial spirochetemia. This mutant also colonized ticks and was infectious by tick-bite, but remained attenuated compared to wild-type and reconstituted spirochetes. The mutant lacking Vtp also colonized ticks but produced neither Vtp nor a Vmp in tick salivary glands, which rendered the spirochete noninfectious by tick bite. Thus the ability of B. hermsii to produce Vmps prolonged its survival in blood, while the synthesis of Vtp was essential for mammalian infection by the bite of its tick vector. PMID:24699793

  3. Separating Pumping and Other Influences on Groundwater Head Variation

    NASA Astrophysics Data System (ADS)

    Shapoori, V.; Western, A. W.; Peterson, T. J.; Costelloe, J.

    2012-12-01

    The dynamics of unconfined groundwater levels are usually the result of numerous and interacting factors, such as land cover change, climate variability and groundwater pumping. Estimating the impact from pumping is highly significant for resource management but also very challenging. A variety of methods are used to model water-table dynamics influenced by pumping, ranging from spatially explicit, numerical models to stochastic approaches. Transfer function noise (TFN) modelling can be used to model the dynamic behaviour of a wide range of hydrologic variables, including time series of groundwater head. Recently, TFN models have been developed to better link water table dynamics with different types of individual stresses, including pumping (Von Asmuth et al. 2002). Peterson & Western (2011) advanced the transfer function noise model of Von Asmuth et al. (2002) to account for non-linear hydrological processes by inclusion of a parsimonious vertically lumped soil moisture storage(SMS). Shapoori et al. (2011) proposed an improved time series formulation for estimation of the impacts of pumping. That study undertook a synthetic assessment of the ability of a range of time series models to represent the impacts of pumping by applying them to groundwater head time series from a synthetic aquifer. This paper further expands the Shapoori at al. (2011) time series method for quantifying the impact of groundwater pumping within unconfined sedimentary aquifers by applying it to real data and by taking account of a surface water body. The study area is the Clydebank groundwater subregion located in Victoria Australia. Nine salinity control pumping bores are used in some of the worst salinity areas to lower the groundwater table and consequently reduce soil salinity. The method has been applied to 43 observation bores and the results show that the model has good predictive performance with mean and minimum coefficient efficiency values of 0.7 and 0.5 respectively. In addition

  4. Estimating the extent of stress influence by using earthquake triggering groundwater level variations in Taiwan

    NASA Astrophysics Data System (ADS)

    Wang, Shih-Jung; Hsu, Kuo-Chin; Lai, Wen-Chi; Wang, Chein-Lee

    2015-11-01

    Groundwater level variations associated with earthquake events may reveal useful information. This study estimates the extent of stress influence, defined as the distance over which an earthquake can induce a step change of the groundwater level, using earthquake-triggering groundwater level variations in Taiwan. Groundwater variations were first characterized based on the dynamics of groundwater level changes dominantly triggered by earthquakes. The step-change data in co-seismic groundwater level variations were used to analyze the extent of stress influence for earthquakes. From the data analysis, the maximum extent of stress influence is 250 km around Taiwan. A two-dimensional approach was adopted to develop two models for estimating the maximum extent of stress influence for earthquakes. From the developed models, the extent of stress influence is proportional to the earthquake magnitude and inversely proportional to the groundwater level change. The model equations can be used to calculate the influence radius of stress from an earthquake by using the observed change of groundwater level and the earthquake magnitude. The models were applied to estimate the area of anomalous stress, defined as the possible areas where the strain energy is accumulated, using the cross areas method. The results show that the estimated area of anomalous stress is close to the epicenter. Complex geological structures and material heterogeneity and anisotropy may explain this disagreement. More data collection and model refinements can improve the proposed model. This study shows the potential of using groundwater level variations for capturing seismic information. The proposed concept of extent of stress influence can be used to estimate the earthquake effect in hydraulic engineering, mining engineering, and carbon dioxide sequestration, etc. This study provides a concept for estimating the possible areas of anomalous stress for a forthcoming earthquake.

  5. Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli

    PubMed Central

    Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

    2015-01-01

    Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue. PMID:26517723

  6. Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli.

    PubMed

    Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

    2015-01-01

    Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue. PMID:26517723

  7. Influence of Fas on the regulation of the response of an anti-nuclear antigen B cell clonotype to foreign antigen.

    PubMed

    Alabyev, Boris; Vuyyuru, Raja; Manser, Tim

    2008-10-01

    A peripheral B cell tolerance checkpoint appears to be operative during the germinal center (GC) reaction. We previously showed that a transgenic BCR clonotype that is 'dual reactive' for the hapten arsonate (Ars) and nuclear auto-antigens is stimulated to enter the GC response via Ars immunization. However, the participation of this clonotype in this response wanes with time and it gives rise to few memory B cells capable of mounting a secondary anti-Ars IgG response. Enforced expression of Bcl-2 partially rescues the GC and memory B cell responses of this clonotype, suggesting that apoptotic pathways are involved in the action of the GC tolerance checkpoint. Since GC B cells substantially up-regulate levels of expression of the Fas apoptotic death receptor, we determined whether an intrinsic Fas deficient could rescue the participation of this clonotype in the GC response. It could not, strongly indicating that Fas expression by autoreactive GC B cells is not necessary for their elimination. In addition, experiments in which Fas-sufficient dual reactive clonotype B cells were transferred to Fas-deficient hosts revealed an absence of participation of these B cells in the GC and IgG anti-Ars responses. We present data consistent with the idea that T cells in Fas-deficient hosts are primed to express elevated levels of FasL and eliminate antigen-activated B cells that up-regulate Fas. PMID:18689725

  8. Influence of the primary emulsification procedure on the characteristics of small protein-loaded PLGA microparticles for antigen delivery.

    PubMed

    Wischke, C; Borchert, H-H

    2006-06-01

    Microparticles prepared from poly(lactic-co-glycolic acid) (PLGA) using a W1/O/W2 double emulsion solvent evaporation method are suitable vehicles for the delivery of proteins to antigen presenting cells, e.g. dendritic cells. In this study, the influence of different techniques for the preparation of the primary W1/O emulsion was investigated with respect to the protein localization within the microparticles, morphological characteristics of these particles, protein burst release and the native state of the released protein. Bovine serum albumin bearing fluorescein isothiocyanate (FITC-BSA) was used as model protein. A static micromixer was applied for the preparation of the W1/O/W2 double emulsion. Employing a rotor-stator homogenizer (Ultra-Turrax) for primary emulsification, microcapsules with a high burst release were produced, because nearly all FITC-BSA was attached to the outside of the particle wall. Using a high pressure homogenizer or an ultrasonic procedure resulted in the formation of microspheres with homogeneous protein distribution and a reduced burst release. PMID:16854818

  9. Do human leukocyte antigen E polymorphisms influence graft-versus-leukemia after allogeneic hematopoietic stem cell transplantation?

    PubMed

    Hosseini, Ehteramolsadat; Schwarer, Anthony P; Ghasemzadeh, Mehran

    2015-03-01

    Hematopoietic-stem-cell transplantation (HSCT) is complicated by histocompatibility-dependent immune responses such as graft-versus-host disease, relapse, and graft rejection. The severity of these common adverse effects is directly related to the degree of human leukocyte antigen (HLA) incompatibility. In addition to the key role of classic HLA matching in influencing HSCT outcome, several lines of evidence suggest an important role for nonclassic major histocompatibility complex class I molecule, HLA-E. The interaction of HLA-E with NKG2A, its main receptor on natural killer cells, modulates cell-mediated cytotoxicity and cytokine production, an important role in innate immune responses. In addition, the HLA-E molecule can present peptides to different subtypes of T cells that may either support graft-versus-leukemia effects or be involved in bridging innate and acquired immunity. To date, the role of HLA-E and its polymorphisms in HSCT outcomes such as graft-versus-host disease, transplant-related mortality, and improved survival has been published by a number of groups. In addition, these data suggest an association between HLA-E polymorphisms and relapse. Whether the engagement of the HLA-E molecule in the modulation of donor T cells is involved in the graft-versus-leukemia effect, or whether a different mechanism of HLA-E dependent reduction of relapse is involved, requires further investigation. PMID:25434712

  10. Antigenic Variation of East/Central/South African and Asian Chikungunya Virus Genotypes in Neutralization by Immune Sera

    PubMed Central

    Chua, Chong-Long; Sam, I-Ching; Merits, Andres; Chan, Yoke-Fun

    2016-01-01

    Background Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus which causes epidemics of fever, severe joint pain and rash. Between 2005 and 2010, the East/Central/South African (ECSA) genotype was responsible for global explosive outbreaks across India, the Indian Ocean and Southeast Asia. From late 2013, Asian genotype CHIKV has caused outbreaks in the Americas. The characteristics of cross-antibody efficacy and epitopes are poorly understood. Methodology/Principal Findings We characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008–2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes. Conclusion/Significance Immune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued

  11. Influence of growth temperature of Escherichia coli on K1 capsular antigen production and resistance to opsonization.

    PubMed Central

    Bortolussi, R; Ferrieri, P; Quie, P G

    1983-01-01

    When Escherichia coli strains that produce K1 capsular polysaccharide antigen at 37 degrees C were grown at 22 degrees C, K1 antigen was not detected in the supernatant or washed-cell fraction of broth cultures. Significant amounts of K1 polysaccharide were detected only when the organism was grown at temperatures of 30 degrees C or higher. Rabbits immunized with an E. coli K1 strain (serotype O18ac:K1:H7) grown at 37 degrees C produced agglutinating antibody to somatic antigen and precipitating and agglutinating antibody to capsular K1 antigen; those immunized with this strain grown at 22 degrees C produced antibody to somatic antigen, but not to K1 antigen. Antibody to somatic antigen was markedly reduced by adsorption with the organism grown at 22 degrees C, while antibody to capsular antigen was not. E. coli K1 strains grown at 37 degrees C (K1 present) resisted phagocytosis and killing if they were opsonized solely by the alternative complement pathway (ACP) using magnesium ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid-chelated serum. When these strains were grown at 22 degrees C (K1 absent), they were opsonized efficiently by the ACP (28 versus 94% killing, respectively; P less than 0.001). In addition, a non-K1 mutant of an E. coli K1 strain was opsonized efficiently by the ACP although its encapsulated K1 parent was not. Sensitivity of E. coli strains to the bactericidal activity of serum was observed in strains with and without K1 capsular antigen. These studies demonstrated that production of K1 polysaccharide antigen was regulated by environmental temperature and that K1 capsule plays an essential role in rendering the organism resistant to opsonization by the ACP. PMID:6341228

  12. Individual Variation in Agrammatism: A Single Case Study of the Influence of Interaction

    ERIC Educational Resources Information Center

    Beeke, Suzanne; Wilkinson, Ray; Maxim, Jane

    2007-01-01

    Background: Agrammatic speech can manifest in different ways in the same speaker if task demands change. Individual variation is considered to reflect adaptation, driven by psycholinguistic factors such as underlying deficit. Recently, qualitative investigations have begun to show ways in which conversational interaction can influence the form of…

  13. Influence of magnetization variations in the free layer on a non-volatile magnetic flip flop

    NASA Astrophysics Data System (ADS)

    Windbacher, Thomas; Makarov, Alexander; Sverdlov, Viktor; Selberherr, Siegfried

    2015-06-01

    Recently, we proposed an alternative non-volatile magnetic flip flop which allows high integration density. This work extends the up to now gained results to the devices' functionality under statistically distributed magnetization variations of its free layer. Assuming position uncorrelated random fluctuations in the free layer, that the variations are fixed with respect to time, and that small deviations from its mean are more likely than big ones, a Gaussian distribution was chosen to model the random fluctuations. The random variations were added to the simulations as a position dependent Zeeman term and their influence was varied by changing the variance of the distribution scaled in percent of the free layers saturation magnetization. The results with and without thermal excitation show that the flip flop is capable of operating under high free layer field variations.

  14. Regional variation of climatic influences on West Nile virus outbreaks in the United States.

    PubMed

    Wimberly, Michael C; Lamsal, Aashis; Giacomo, Paolla; Chuang, Ting-Wu

    2014-10-01

    The national resurgence of human West Nile virus (WNV) disease in 2012 raised questions about the factors responsible for WNV outbreaks. Interannual climatic variations may influence WNV amplification and transmission to humans through multiple pathways, including mosquito breeding habitats, gonotrophic cycles, extrinsic incubation, avian communities, and human behavior. We examined the influences of temperature and precipitation anomalies on interannual variation in human WNV cases in three regions of the United States. There were consistent positive influences of winter temperatures, weaker and more variable positive effects of spring and summer temperatures, and highly variable precipitation effects that ranged from positive to negative. The overwintering period may be a particularly important climatic constraint on the dynamics of WNV in cold-temperate regions of North America. Geographic differences in the seasonal timing and relative importance of climatic drivers of WNV risk likely reflect underlying variability in key ecological and social characteristics. PMID:25092814

  15. Daily variations in pathogenic bacterial populations in a monsoon influenced tropical environment.

    PubMed

    Khandeparker, Lidita; Anil, Arga Chandrashekar; Naik, Sneha D; Gaonkar, Chetan C

    2015-07-15

    Changing climatic conditions have influenced the monsoon pattern in recent years. Variations in bacterial population in one such tropical environment were observed everyday over two years and point out intra and inter annual changes driven by the intensity of rainfall. Vibrio spp. were abundant during the monsoon and so were faecal coliforms. Vibrio alginolyticus were negatively influenced by nitrate, whereas, silicate and rainfall positively influenced Vibrio parahaemolyticus numbers. It is also known that pathogenic bacteria are associated with the plankton. Changes in the abundance of plankton, which are governed mainly by environmental changes, could be responsible for variation in pathogenic bacterial abundance during monsoon, other than the land runoff due to precipitation and influx of fresh water. PMID:25956443

  16. The influence of floral symmetry, dependence on pollinators and pollination generalization on flower size variation

    PubMed Central

    Lázaro, A.; Totland, Ø.

    2014-01-01

    Background and Aims The pollinator-mediated stabilizing selection hypothesis suggests that the specialized pollination system of zygomorphic flowers might cause stabilizing selection, reducing their flower size variation compared with actinomorphic flowers. However, the degree of ecological generalization and of dependence on pollinators varies greatly among species of both flower symmetry types and this may also affect flower size variation. Methods Data on 43 species from two contrasting communities (one alpine and one lowland community) were used to test the relationships and interactions between flower size phenotypic variation, floral symmetry, ecological pollination generalization and species' dependence on pollinators. Key Results Contrary to what was expected, higher flower size variation was found in zygomorphic than in actinomorphic species in the lowland community, and no difference in flower size variation was found between symmetry types in the alpine community. The relationship between floral symmetry and flower size variation depended on ecological generalization and species' dependence on pollinators, although the influence of ecological generalization was only detected in the alpine community. Zygomorphic species that were highly dependent on pollinators and that were ecologically specialized were less variable in flower size than ecologically generalist and selfing zygomorphic species, supporting the pollinator-mediated stabilizing selection hypothesis. However, these relationships were not found in actinomorphic species, probably because they are not dependent on any particular pollinator for efficient pollination and therefore their flower size always shows moderate levels of variation. Conclusions The study suggests that the relationship between flower size variation and floral symmetry may be influenced by population-dependent factors, such as ecological generalization and species' dependence on pollinators. PMID:24838838

  17. Leucine-responsive regulatory protein Lrp and PapI homologues influence phase variation of CS31A fimbriae.

    PubMed

    Graveline, Richard; Garneau, Philippe; Martin, Christine; Mourez, Michaël; Hancock, Mark A; Lavoie, Rémi; Harel, Josée

    2014-08-15

    CS31A, a K88-related surface antigen specified by the clp operon, is a member of the type P family of adhesive factors and plays a key role in the establishment of disease caused by septicemic and enterotoxigenic Escherichia coli strains. Its expression is under the control of methylation-dependent transcriptional regulation, for which the leucine-responsive regulatory protein (Lrp) is essential. CS31A is preferentially in the OFF state and exhibits distinct regulatory features compared to the regulation of other P family members. In the present study, surface plasmon resonance and DNase I protection assays showed that Lrp binds to the distal moiety of the clp regulatory region with low micromolar affinity compared to its binding to the proximal moiety, which exhibits stronger, nanomolar affinity. The complex formation was also influenced by the addition of PapI or FooI, which increased the affinity of Lrp for the clp distal and proximal regions and was required to induce phase variation. The influence of PapI or FooI, however, was predominantly associated with a more complete shutdown of clp expression, in contrast to what has previously been observed with AfaF (a PapI ortholog). Taken together, these results suggest that the preferential OFF state observed in CS31A cells is mainly due to the weak interaction of the leucine-responsive regulatory protein with the clp distal region and that the PapI homolog favors the OFF phase. Within the large repertoire of fimbrial variants in the P family, our study illustrates that having a fimbrial operon that lacks its own PapI ortholog allows it to be more flexibly regulated by other orthologs in the cell. PMID:24914179

  18. Influence of clinical and laboratory variables on faecal antigen ELISA results in dogs with canine parvovirus infection.

    PubMed

    Proksch, A L; Unterer, S; Speck, S; Truyen, U; Hartmann, K

    2015-06-01

    False negative faecal canine parvovirus (CPV) antigen ELISA results in dogs with CPV infection are common, but the factors that lead to these false negative results are still unknown. The aim of this study was to investigate whether dogs with a false negative faecal CPV antigen ELISA result have milder clinical signs and laboratory changes, a lower faecal virus load, higher faecal and serum CPV antibody titres and a faster recovery than dogs with a positive result. Eighty dogs with CPV infection, confirmed by the presence of clinical signs and a positive faecal CPV polymerase chain reaction (PCR), were assigned to two groups according to their faecal antigen ELISA result. Time until presentation, severity of symptoms, laboratory parameters, faecal virus load, faecal and serum antibody titres, and CPV sequencing data were compared between both groups. In 38/80 dogs that were hospitalised until recovery, the time to recovery, mortality, and the course of the disease were compared between dogs with positive and negative faecal antigen ELISA results. Of the 80 dogs included, 41 (51.3%) had a false negative faecal antigen ELISA result. ELISA-negative dogs had a significantly shorter time until presentation, lower frequency of defaecation, lower faecal virus load, and higher serum antibody concentrations than ELISA-positive dogs. Laboratory changes, CPV shedding, and outcomes were not associated with faecal antigen ELISA results. In conclusion, low faecal CPV load and antibodies binding to CPV antigen in faeces are likely to be important reasons for false negative faecal antigen ELISA results. Dogs with clinical signs of CPV infection should be retested by faecal PCR. PMID:25920770

  19. Influence of Hydration Status on Changes in Plasma Cortisol, Leukocytes, and Antigen-Stimulated Cytokine Production by Whole Blood Culture following Prolonged Exercise.

    PubMed

    Svendsen, Ida S; Killer, Sophie C; Gleeson, Michael

    2014-01-01

    Elevated antigen-stimulated anti-inflammatory cytokine production appears to be a risk factor for upper respiratory tract illness in athletes. The purpose of this study was to determine the effects of prolonged exercise and hydration on antigen-stimulated cytokine production. Twelve healthy males cycled for 120 min at 60% [Formula: see text] on two occasions, either euhydrated or moderately hypohydrated (induced by fluid restriction for 24 h). Blood samples were collected before and after exercise and following 2 h recovery for determination of cell counts, plasma cortisol, and in vitro antigen-stimulated cytokine production by whole blood culture. Fluid restriction resulted in mean body mass loss of 1.3% and 3.9% before and after exercise, respectively. Exercise elicited a significant leukocytosis and elevated plasma cortisol, with no differences between trials. IL-6 production was significantly reduced 2 h postexercise (P < 0.05), while IL-10 production was elevated postexercise (P < 0.05). IFN- γ and IL-2 production tended to decrease postexercise. No significant effect of hydration status was observed for the measured variables. Prolonged exercise appears to result in augmented anti-inflammatory cytokine release in response to antigen challenge, possibly coupled with acute suppression of proinflammatory cytokine production, corresponding with studies using mitogen or endotoxin as stimulant. Moderate hypohydration does not appear to influence these changes. PMID:24967270

  20. Variations and Defects: Influence on Performance and Safety of Aerospace Missions

    NASA Technical Reports Server (NTRS)

    Turner, Irem Y.; Koga, Dennis (Technical Monitor)

    2001-01-01

    The overall goal of this project is to determine sources of normal and abnormal statistical variation for helicopter transmission vibrations. One current application is HUMS technology for helicopters. The design and manufacturing research hypothesis is that statistical variation due to design and manufacturing is a significant source of unreliability and eventual failures of systems. The Systems Health and Safety group research objectives include the following: (1) to develop empirical database for modeling and evaluation; (2) to identify and model factors that influence vibrations; (3) to develop algorithms for damage detection; (4) to determine 'hit' and 'false alarm' rates; and (5) to understand the fundamentals of transmission vibrations.

  1. Human leukocyte antigen-G polymorphism influences the age of onset and autoantibody status in rheumatoid arthritis.

    PubMed

    Mariaselvam, C M; Chaaben, A B; Salah, S; Charron, D; Krishnamoorthy, R; Tamouza, R; Negi, V S

    2015-03-01

    The study was conducted to investigate the frequency of three gene polymorphisms in the 3'-untranslated region (3'-UTR) of human leucocyte antigen-G (HLA-G) gene in south Indian patients with rheumatoid arthritis (RA) and analyze their influence on disease susceptibility, phenotype and treatment response. HLA-G 14 bp insertion (Ins)/deletion (del) (rs66554220), HLA-G +3142G>C (rs1063320) and +3187A>G (rs9380142) polymorphism was analyzed in 221 RA patients and 200 healthy controls. Frequency of HLA-G genotypes or alleles did not differ between patients and controls. Analysis based on rheumatoid factor (RF) status revealed that the frequency of allele 'A' (rs9380142) was significantly higher in RF-positive than in RF-negative patients [84% vs 74%, Yates-corrected P value (Pc) = 0.04, odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.0-3.2]. A similar difference was maintained in RF-positive female patients than their RF-negative counterparts (83% vs 71%, Pc = 0.02, OR = 1.9, 95% CI = 1.0 to 3.4) and between RF-positive and RF-negative young onset RA (YORA) patients (84% vs 73%, Pc = 0.03, OR = 1.9, 95% CI = 1.0-3.2), suggesting that rs9380142 polymorphism influenced RF status. The 14 bp Ins allele of rs66554220 was significantly more prevalent in RF-positive YORA than in RF-positive late onset RA (LORA) patients (51% vs 25%, P = 0.03, OR = 3.1, 95% CI = 1.1-9.8). Frequency of the four major haplotypes [InsGA (48%), DelGA (22%), DelCG (18%), DelCA (9.7%)] observed did not differ between cases and controls. HLA-G does not appear to be a risk factor for development of RA in south Indian Tamils but may act as a genetic modifier of clinical phenotype in terms of autoantibody production, gender preference and age at disease onset. PMID:25656292

  2. Evolution of the capsid protein genes of foot-and-mouth disease virus: antigenic variation without accumulation of amino acid substitutions over six decades.

    PubMed Central

    Martínez, M A; Dopazo, J; Hernández, J; Mateu, M G; Sobrino, F; Domingo, E; Knowles, N J

    1992-01-01

    The genetic diversification of foot-and-mouth disease virus (FMDV) of serotype C over a 6-decade period was studied by comparing nucleotide sequences of the capsid protein-coding regions of viruses isolated in Europe, South America, and The Philippines. Phylogenetic trees were derived for VP1 and P1 (VP1, VP2, VP3, and VP4) RNAs by using the least-squares method. Confidence intervals of the derived phylogeny (significance levels of nodes and standard deviations of branch lengths) were placed by application of the bootstrap resampling method. These procedures defined six highly significant major evolutionary lineages and a complex network of sublines for the isolates from South America. In contrast, European isolates are considerably more homogeneous, probably because of the vaccine origin of several of them. The phylogenetic analysis suggests that FMDV CGC Ger/26 (one of the earliest FMDV isolates available) belonged to an evolutionary line which is now apparently extinct. Attempts to date the origin (ancestor) of the FMDVs analyzed met with considerable uncertainty, mainly owing to the stasis noted in European viruses. Remarkably, the evolution of the capsid genes of FMDV was essentially associated with linear accumulation of silent mutations but continuous accumulation of amino acid substitutions was not observed. Thus, the antigenic variation attained by FMDV type C over 6 decades was due to fluctuations among limited combinations of amino acid residues without net accumulation of amino acid replacements over time. PMID:1316467

  3. Contribution of genetic variation rs266882 to prostate-specific antigen levels in healthy controls with serum PSA below 2.0 ng/ml.

    PubMed

    Song, Jaeman; Park, Heeyoon; Lee, Gilho

    2013-04-01

    We evaluated the impact of genetic variation in the prostate-specific antigen (PSA) gene (rs266882) on serum PSA levels in healthy men as well as risk factors for benign prostate hypertrophy (BPH) and prostate cancer. The study population comprised 91 men with PSA levels below 2.0 ng/ml as healthy controls, 78 men with PSA 2-10 ng/ml as a BPH group, and 128 prostate cancer patients, all in Korea. DNA was amplified by polymerase chain reaction and the product was sequenced. We found that PSA levels were associated with a G/A polymorphism only in healthy controls. The transition, however, was not associated with PSA levels of BPH and cancer patients, nor was it a risk factor. In conclusion, this genetic factor is important for determining serum PSA levels in the naive group, whereas the disruption of prostatic architecture in BPH or prostate cancer may be a major determining factor for PSA levels. PMID:23315126

  4. Intrapersonal variation in consumer susceptibility to normative influence: toward a better understanding of brand choice decisions.

    PubMed

    Orth, Ulrich R; Kahle, Lynn R

    2008-08-01

    The authors examined intrapersonal variation in consumer susceptibility to normative influence as a key mediator of wine brand choice. On the basis of a consumer sample, the authors found that individual values and social identity complexity affect consumer susceptibility to normative influence with downstream effects on (a) which brand benefits consumers desire in wine and (b) choice. Individuals higher on internal values and with more complex social identities were less susceptible to normative influence and placed less emphasis on social brand benefits. Separate examinations of consumption scenarios with and without salient reference groups showed that reference group salience interacts with personal values and social identity complexity in affecting consumer susceptibility to normative influence, which in turn affects which brand benefits consumers desire and consequently choice. PMID:18807420

  5. Spacebased Observations of Oceanic Influence on the Annual Variation of South American Water Balance

    NASA Technical Reports Server (NTRS)

    Liu, W. Timothy; Xie, Xiaosu; Tang, Wenqing; Zlotnicki, Victor

    2006-01-01

    The mass change of South America (SA) continent measured by the Gravity Recovery and Climate Experiment (GRACE) imposes a constraint on the uncertainties in estimating the annual variation of rainfall measured by Tropical Rain Measuring Mission (TRMM) and ocean moisture influx derived from QuikSCAT data. The approximate balance of the mass change rate with the moisture influx less climatological river discharge, in agreement with the conservation principle, bolsters not only the credibility of the spacebased measurements, but supports the characterization of ocean's influence on the annual variation of continental water balance. The annual variation of rainfall is found to be in phase with the mass change rate in the Amazon and the La Plata basins, and the moisture advection across relevant segments of the Pacific and Atlantic coasts agrees with the annual cycle of rainfall in the two basins and the Andes mountains.

  6. The Influence of Spatial Variations of Diffusion Length on Charge Collected by Diffusion from Ion Tracks

    NASA Technical Reports Server (NTRS)

    Edmonds, L. D.

    1996-01-01

    Charge collected by diffusion from ion tracks in a semiconductor substrate may be influenced by the substrate diffusion length, which is related to recombination losses. A theoretical analysis shows that, excluding some extreme cases, charge collection is insensitive to spatial variations in the diffusion length funciton, so it is possible to define an effective diffusion length having the property that collected charge can be approximated by assuming a uniform diffusion length equal to this effective value.

  7. Evidence of antigen receptor-influenced oligoclonal B lymphocyte expansion in the synovium of a patient with longstanding rheumatoid arthritis.

    PubMed Central

    Lee, S K; Bridges, S L; Kirkham, P M; Koopman, W J; Schroeder, H W

    1994-01-01

    Plasma cell infiltration of synovium is common in longstanding rheumatoid arthritis (RA). The mechanism(s) underlying synovial B cell proliferation remains unclear. One theory invokes nonspecific polyclonal stimuli; another implicates antigen as the driving force. Antigen-driven repertoires are characteristically enriched for related sets of V gene segments containing similar sequence in the antigen binding site (complementarity-determining regions; CDRs). To study the forces shaping B cell proliferation, we analyzed V kappa transcripts expressed in the synovium of an RA patient. We found Humkv325, a developmentally regulated V kappa III gene segment associated with autoantibody reactivity, in > 10% of randomly-chosen synovial C kappa cDNAs. Two sets of sequences contained identical charged amino acid residues at the V kappa-J kappa join, apparently due to N region addition. We generated "signature" oligonucleotides from these CDR3s and probed PCR amplified V kappa products from the synovium and PBLs of the same patient, and from PBLs and spleen of individuals without rheumatic disease. Significant expression of transcripts containing these unique CDR3 sequences occurred only in the patient's synovium. Thus, in this synovium there is expansion of a limited set of B cell clones expressing antigen receptors that bear evidence of antigen selection. Images PMID:8282807

  8. Factors influencing the variations of PM10 aerosol dust in Klang Valley, Malaysia during the summer

    NASA Astrophysics Data System (ADS)

    Juneng, Liew; Latif, Mohd Talib; Tangang, Fredolin

    2011-08-01

    The associations between the variations of PM10 concentration during summer monsoon dry seasons over the Klang Valley, Malaysia and the local meteorological factors, synoptic weather conditions as well as the regional hotspots number were examined based on simple multiple linear regression analysis. The regressive relationships established, suggest that the variation of PM10 in Klang Valley was governed significantly by all of the examined factors. Local meteorological conditions are among those factors which governed the largest day-to-day variations of PM10 concentration in the Klang Valley areas during the dry season. When augmented by synoptic meteorological variables and foreign emission sources, a remarkable increase in the explained variance was apparent. On the other hand, domestic burning sources only had a minimal impact on PM10 fluctuations. Important synoptic weather patterns which influence the air pollution variations were also identified. These synoptic conditions include the strengthening of the summer monsoon southwesterly winds over the equatorial area. In addition, the formation of cyclonic circulation, associated with typhoon formation over the north-west Pacific and the South China Sea as well as over the Bay of Bengal, are found to have had a profound impact on PM10 variations over the Malaysian region through the modulation of regional moisture distributions.

  9. Influence of some sow characteristics on within-litter variation of piglet birth weight.

    PubMed

    Quesnel, H; Brossard, L; Valancogne, A; Quiniou, N

    2008-12-01

    Within-litter variation of piglet birth weight (BW0) is associated with an increased piglet mortality and a high variability in pig weight at weaning and weight or age at slaughter. Data collected in two experimental herds were used to quantify within-litter variability in BW0 and to assess the influence of factors mainly related to the sow. Within 24 h after birth, piglets born alive were individually weighed and stillborn piglets were collectively (first data set) or individually (second data set) weighed. The first data set was restricted to litters with no or only one stillborn piglet (3338 litters). It was used to assess the influence of genetic selection on BW0 variation by comparing litter characteristics before (1994 to 1996) and after (2001 to 2004) the development of hyperprolific sows in this herd. The second data set included all litters (n = 1596) from sows born between 2000 and 2004. For each litter, mean BW0 (mBW0) and its coefficient of variation (CVBW0) were calculated. Then, variance analyses were performed to test the influence of litter size, parity, year of sow birth and season at conception. Prolificacy improvement was associated with an increased CVBW0 in litters from pure Large White (LW) and Landrace × Large White (LR × LW) crossbred sows. The CVBW0 averaged 21% and was significantly influenced by litter size and parity. It increased from 15% to 24% when litter size varied from less than 10 piglets to more than 15 piglets. The proportion of small piglets (i.e. weighing less than 1 kg) increased concomitantly. The CVBW0 was not repeatable from a parity to the following. It was lowest for first and second parities (20%) and thereafter increased progressively. The CVBW0 was positively related to sow's backfat thickness gain during gestation. Taking into account litter size, parity, year of sow birth and season at conception explained 20% of BW0 variation. Thus, major part of heterogeneity is due to other factors, presumably including embryo

  10. Genetic Variation in Functional Traits Influences Arthropod Community Composition in Aspen (Populus tremula L.)

    PubMed Central

    Robinson, Kathryn M.; Ingvarsson, Pär K.; Jansson, Stefan; Albrectsen, Benedicte R.

    2012-01-01

    We conducted a study of natural variation in functional leaf traits and herbivory in 116 clones of European aspen, Populus tremula L., the Swedish Aspen (SwAsp) collection, originating from ten degrees of latitude across Sweden and grown in a common garden. In surveys of phytophagous arthropods over two years, we found the aspen canopy supports nearly 100 morphospecies. We identified significant broad-sense heritability of plant functional traits, basic plant defence chemistry, and arthropod community traits. The majority of arthropods were specialists, those coevolved with P. tremula to tolerate and even utilize leaf defence compounds. Arthropod abundance and richness were more closely related to plant growth rates than general chemical defences and relationships were identified between the arthropod community and stem growth, leaf and petiole morphology, anthocyanins, and condensed tannins. Heritable genetic variation in plant traits in young aspen was found to structure arthropod community; however no single trait drives the preferences of arthropod folivores among young aspen genotypes. The influence of natural variation in plant traits on the arthropod community indicates the importance of maintaining genetic variation in wild trees as keystone species for biodiversity. It further suggests that aspen can be a resource for the study of mechanisms of natural resistance to herbivores. PMID:22662190

  11. Provincial variation of carbon emissions from bituminous coal: Influence of inertinite and other factors

    USGS Publications Warehouse

    Quick, J.C.; Brill, T.

    2002-01-01

    We observe a 1.3 kg C/net GJ variation of carbon emissions due to inertinite abundance in some commercially available bituminous coal. An additional 0.9 kg C/net GJ variation of carbon emissions is expected due to the extent of coalification through the bituminous rank stages. Each percentage of sulfur in bituminous coal reduces carbon emissions by about 0.08 kg C/net GJ. Other factors, such as mineral content, liptinite abundance and individual macerals, also influence carbon emissions, but their quantitative effect is less certain. The large range of carbon emissions within the bituminous rank class suggests that rank- specific carbon emission factors are provincial rather than global. Although carbon emission factors that better account for this provincial variation might be calculated, we show that the data used for this calculation may vary according to the methods used to sample and analyze coal. Provincial variation of carbon emissions and the use of different coal sampling and analytical methods complicate the verification of national greenhouse gas inventories. Published by Elsevier Science B.V.

  12. Oral antigen exposure in extreme early life in lambs influences the magnitude of the immune response which can be generated in later life

    PubMed Central

    2013-01-01

    Background Previous investigations in newborn lambs determined that adenovirus-mediated expression of antigen to a localized region of the gut induced antigen-specific mucosal and systemic immunity. These experiments were limited in that the localized region of the gut to which antigen was introduced was sterile and the influence of colostrum on the antigen was not assessed but they do suggest that mucosal vaccines may be an effective vaccination strategy to protect neonatal lambs. We propose that persistent oral antigen exposure introduced in extreme early life can induce immunity in lambs, despite the presence of commensal bacteria and colostrum. Results To test this hypothesis, conventionally raised newborn lambs (n = 4 per group) were gavaged with ovalbumin (OVA) starting the day after birth for either a single day (2.27 g), every day for 3 days (0.23 g/day), or every day for 3 days then every second day until nine days of age (0.023 g/day). Lambs gavaged with OVA for 3 to 9 days developed significant serum anti-OVA IgG titres (p < 0.05), but not IgA titres, relative to control lambs (n = 4) after 3 and 4 weeks. At 4 weeks of age, lambs were immunized with OVA in Incomplete Freund’s Adjuvant via intraperitoneal (i.p.) injection then lambs were euthanized at 7 weeks. Serum anti-OVA IgG titres were further augmented after i.p. immunization indicating immunity persisted and tolerance was not induced. Serum IgA titres remained low regardless of treatment. It is known that i.p. priming of sheep with antigen in Freund’s complete adjuvant leads to an enhanced number of IgA and IgG antibody containing cells in the respiratory mucosa (Immunology 53(2):375–384, 1984). Lambs gavaged with a single bolus of 2.27 g OVA prior to i.p. immunization showed very low titres of anti-OVA IgA in the lung lavage. These data suggest that a single, high dose exposure to OVA can promote tolerance which impacts response to systemic vaccination in later life

  13. Experimental study of the influence of flow passage subtle variation on mixed-flow pump performance

    NASA Astrophysics Data System (ADS)

    Bing, Hao; Cao, Shuliang

    2014-05-01

    In the mixed-flow pump design, the shape of the flow passage can directly affect the flow capacity and the internal flow, thus influencing hydraulic performance, cavitation performance and operation stability of the mixed-flow pump. However, there is currently a lack of experimental research on the influence mechanism. Therefore, in order to analyze the effects of subtle variations of the flow passage on the mixed-flow pump performance, the frustum cone surface of the end part of inlet contraction flow passage of the mixed-flow pump is processed into a cylindrical surface and a test rig is built to carry out the hydraulic performance experiment. In this experiment, parameters, such as the head, the efficiency, and the shaft power, are measured, and the pressure fluctuation and the noise signal are also collected. The research results suggest that after processing the inlet flow passage, the head of the mixed-flow pump significantly goes down; the best efficiency of the mixed-flow pump drops by approximately 1.5%, the efficiency decreases more significantly under the large flow rate; the shaft power slightly increases under the large flow rate, slightly decreases under the small flow rate. In addition, the pressure fluctuation amplitudes on both the impeller inlet and the diffuser outlet increase significantly with more drastic pressure fluctuations and significantly lower stability of the internal flow of the mixed-flow pump. At the same time, the noise dramatically increases. Overall speaking, the subtle variation of the inlet flow passage leads to a significant change of the mixed-flow pump performance, thus suggesting a special attention to the optimization of flow passage. This paper investigates the influence of the flow passage variation on the mixed-flow pump performance by experiment, which will benefit the optimal design of the flow passage of the mixed-flow pump.

  14. The influence of variations of vegetation and soil moisture on surface weather and atmospheric circulation

    SciTech Connect

    Yang, R.

    1992-01-01

    The influence of variations of vegetation and soil moisture on surface weather and atmospheric circulation is studied through the use of the Simple Biosphere Model (SiB) and the Center for Ocean-Land-Atmosphere interactions (COLA) GCM. Tests for the SiB sensitivity to the conversion of the forest to other short vegetation or bare soil were performed at Amazonian and Great Plains sites, and a North Wales spruce forest site respectively. The results show that deforestation has a significant influence on the local surface energy budget and surface weather. The influence is especially prominent at the Amazon and Great Plains sites, and larger in summer than in other seasons. The influence on the partitioning of surface incoming radiative energy is generally constrained by the local atmospheric boundary condition. The sensitivity of the COLA GCM to changes in initial soil wetness (ISW) is determined by repeating three 10-day model integrations with the same initial and boundary conditions as the control runs except the values of ISW, which are revised at 69 model grid points covering much of the continental U.S. It is found that the relations between the changes in the 5-day mean forecast surface air temperature/surface specific humidity and the changes in ISW depend upon vegetation type and the values of ISW, and can be approximated by regression equations. These relations are also confirmed with independent data. With the ISW revised based on these regression equations the surface forecasts of the revised runs are consistently improved. The spatial scale of the ISW anomaly determines the degree and range of the influence. The influence of a small regional ISW change is mainly confined to the local region and to low atmospheric levels. The influence on surface fluxes is strong and persists for more than one month, but the effects on precipitation are relatively weak, changeable, and complex, particularly when an interactive cloud scheme is used.

  15. Variation in effects of non-Hodgkin lymphoma risk factors according to the human leukocyte antigen (HLA)-DRB1*01:01 allele and ancestral haplotype 8.1.

    PubMed

    Wang, Sophia S; Lu, Yani; Rothman, Nathaniel; Abdou, Amr M; Cerhan, James R; De Roos, Anneclaire; Davis, Scott; Severson, Richard K; Cozen, Wendy; Chanock, Stephen J; Bernstein, Leslie; Morton, Lindsay M; Hartge, Patricia

    2011-01-01

    Genetic variations in human leukocyte antigens (HLA) are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL) and the HLA-DRB1*01:01 allele and extended ancestral haplotype (AH) 8.1 (HLA-A*01-B*08-DR*03-TNF-308A). To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors among 685 NHL cases and 646 controls from a United States population-based case-control study. We calculated odds ratios and 95% confidence intervals by HLA allele or haplotype status, adjusted for sex, age, race and study center for NHL and two major subtypes using polychotomous unconditional logistic regression models. The previously reported elevation in NHL risk associated with exposures to termite treatment and polychlorinated biphenyls were restricted to individuals who did not possess HLA-DRB1*01:01. Previous associations for NHL and DLBCL with decreased sun exposure, higher BMI, and autoimmune conditions were statistically significant only among those with AH 8.1, and null among those without AH 8.1. Our results suggest that NHL risk factors vary in their association based on HLA-DRB1*01:01 and AH 8.1 status. Our results further suggest that certain NHL risk factors may act through a common mechanism to alter NHL risk. Finally, control participants with either HLA-DRB1*01:01 or AH 8.1 reported having a family history of NHL twice as likely as those who did not have either allele or haplotype, providing the first empirical evidence that HLA associations may explain some of the well-established relationship between family history and NHL risk. PMID:22096508

  16. Variation in Effects of Non-Hodgkin Lymphoma Risk Factors According to the Human Leukocyte Antigen (HLA)-DRB1*01:01 Allele and Ancestral Haplotype 8.1

    PubMed Central

    Wang, Sophia S.; Lu, Yani; Rothman, Nathaniel; Abdou, Amr M.; Cerhan, James R.; De Roos, Anneclaire; Davis, Scott; Severson, Richard K.; Cozen, Wendy; Chanock, Stephen J.; Bernstein, Leslie; Morton, Lindsay M.; Hartge, Patricia

    2011-01-01

    Genetic variations in human leukocyte antigens (HLA) are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL) and the HLA-DRB1*01:01 allele and extended ancestral haplotype (AH) 8.1 (HLA-A*01-B*08-DR*03-TNF-308A). To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors among 685 NHL cases and 646 controls from a United States population-based case-control study. We calculated odds ratios and 95% confidence intervals by HLA allele or haplotype status, adjusted for sex, age, race and study center for NHL and two major subtypes using polychotomous unconditional logistic regression models. The previously reported elevation in NHL risk associated with exposures to termite treatment and polychlorinated biphenyls were restricted to individuals who did not possess HLA-DRB1*01:01. Previous associations for NHL and DLBCL with decreased sun exposure, higher BMI, and autoimmune conditions were statistically significant only among those with AH 8.1, and null among those without AH 8.1. Our results suggest that NHL risk factors vary in their association based on HLA-DRB1*01:01 and AH 8.1 status. Our results further suggest that certain NHL risk factors may act through a common mechanism to alter NHL risk. Finally, control participants with either HLA-DRB1*01:01 or AH 8.1 reported having a family history of NHL twice as likely as those who did not have either allele or haplotype, providing the first empirical evidence that HLA associations may explain some of the well-established relationship between family history and NHL risk. PMID:22096508

  17. Influence of smoking and gender on diurnal variations of heart rate reactivity in humans.

    PubMed

    Adan, A; Sánchez-Turet, M

    2001-01-12

    We evaluated the influence of smoking and gender on diurnal variations of heart rate reactivity during performance of two vigilance tasks (auditory and visual) and a working memory task. Heart rate was measured hourly (08:00-21:00 h) at rest and during performance tasks in 20 smokers (ten men, ten women) and 20 non-smokers (ten men, ten women). Smoking and gender influenced reactivity only at certain times, especially at the earliest and latest hours and during the post-lunch period. Smokers displayed major post-lunch interference and a pattern of lowered stress in the second half of the day. Women showed greater reactivity at the first daily recording, although their levels later became similar to the men's and were even lower. The statement that women are myocardial hyperreactors must be further investigated, as it seems women may take longer than men to adapt to a task. PMID:11121882

  18. Marine and terrestrial influences on interannual CO{sub 2} variations at Mauna Loa and the South Pole

    SciTech Connect

    Dettinger, M.D.; Ghil, M.

    1997-11-01

    Data are presented and very briefly discussed regarding interannual variations of atmospheric carbon dioxide (CO{sub 2}) concentrations. Interannual variations are isolated from monthly concentrations by using singular-spectrum analysis of CO{sub 2} and atmospheric carbon isotopic ratios at Mauna Loa, Hawaii, United States and at the South Pole. Interannual variations are shared at the two sites, and can be used to differentiate between marine and land-surface responses to different interannual climate variations on global scales. Two time-scales are compared: (1) quasi-quadrennial (QQ) and (2) 3-year. Phase relations indicate that QQ variations are dominated by terrestrial influences, whereas the 3-year variations reflect marine (upwelling) influences in the eastern Pacific. The contrasting CO{sub 2} responses on these two time scales thus provide a useful measure of differences in global climate responses, and especially in terrestrial-ecosystem responses to different tropical forcings. 1 fig.

  19. Proton cellular influx as a probable mechanism of variation potential influence on photosynthesis in pea.

    PubMed

    Sukhov, Vladimir; Sherstneva, Oksana; Surova, Lyubov; Katicheva, Lyubov; Vodeneev, Vladimir

    2014-11-01

    Electrical signals (action potential and variation potential, VP) caused by environmental stimuli are known to induce various physiological responses in plants, including changes in photosynthesis; however, their functional mechanisms remain unclear. In this study, the influence of VP on photosynthesis in pea (Pisum sativum L.) was investigated and the proton participation in this process analysed. VP, induced by local heating, inactivated photosynthesis and activated respiration, with the initiation of the photosynthetic response connected with inactivation of the photosynthetic dark stage; however, direct VP influence on the light stage was also probable. VP generation was accompanied with pH increases in apoplasts (0.17-0.30 pH unit) and decreases in cytoplasm (0.18-0.60 pH unit), which probably reflected H(+) -ATPase inactivation and H(+) influx during this electrical event. Imitation of H(+) influx using the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) induced a photosynthetic response that was similar with a VP-induced response. Experiments on chloroplast suspensions showed that decreased external pH also induced an analogous response and that its magnitude depended on the magnitude of pH change. Thus, the present results showed that proton cellular influx was the probable mechanism of VP's influence on photosynthesis in pea. Potential means of action for this influence are discussed. PMID:24635649

  20. [Influence of different products of platelet membrane glycoprotein monoclonal antibodies used internationally on tests for monoclonal antibody-specific immobilization of platelet antigens].

    PubMed

    Tang, Qiu-Min; Shen, Wei-Dong; Zhong, Zhou-Lin; Zhou, Yan; Wu, Guo-Guang

    2009-08-01

    This study was aimed to investigate the influence of different platelet membrane glycoprotein monoclonal antibodies (McAb) which are common used in laboratories on the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) technique according to the request of 14th International Society of Blood Transfusion Platelet Immunology Workshop. 30 participant laboratories were provided with 10 known human platelet antigen (HPA) antibodies, 1 normal serum, 9 different McAbs (against GPIIb/IIIa, GPIa/IIa, GPIb/IX and GPIV respectively), and the same protocol. Each participant laboratory carried out the test as the protocol to compare the results of different McAbs against the same glycoprotein and submitted the data to organizer. The results indicated that in McAbs against GPIIb/IIIa, AP2, Gi-5 and PL2-73 showed higher mean S/CO than that of others; in GPIa/IIa, MBC202.2 and 143.1 showed higher mean S/CO than that of others; in GPIb/IX, 142.11 and CLB-MB45 (CD42b) showed higher mean S/CO than that of others; as to GPIV, 131.4 showed higher mean S/CO. In conclusion, capture effects of various McAbs are different, so that different products of McAbs exert influences on the sensitivity of MAIPA. To use a panel of McAbs against the same glycoprotein may avoid the false negative results. PMID:19698264

  1. Genetic variation in offspring indirectly influences the quality of maternal behaviour in mice

    PubMed Central

    Ashbrook, David George; Gini, Beatrice; Hager, Reinmar

    2015-01-01

    Conflict over parental investment between parent and offspring is predicted to lead to selection on genes expressed in offspring for traits influencing maternal investment, and on parentally expressed genes affecting offspring behaviour. However, the specific genetic variants that indirectly modify maternal or offspring behaviour remain largely unknown. Using a cross-fostered population of mice, we map maternal behaviour in genetically uniform mothers as a function of genetic variation in offspring and identify loci on offspring chromosomes 5 and 7 that modify maternal behaviour. Conversely, we found that genetic variation among mothers influences offspring development, independent of offspring genotype. Offspring solicitation and maternal behaviour show signs of coadaptation as they are negatively correlated between mothers and their biological offspring, which may be linked to costs of increased solicitation on growth found in our study. Overall, our results show levels of parental provisioning and offspring solicitation are unique to specific genotypes. DOI: http://dx.doi.org/10.7554/eLife.11814.001 PMID:26701914

  2. Heritable influences on amygdala and orbitofrontal cortex contribute to genetic variation in core dimensions of personality

    PubMed Central

    Lewis, G.J.; Panizzon, M.S.; Eyler, L.; Fennema-Notestine, C.; Chen, C.-H.; Neale, M.C.; Jernigan, T.L.; Lyons, M.J.; Dale, A.M.; Kremen, W.S.; Franz, C.E.

    2015-01-01

    While many studies have reported that individual differences in personality traits are genetically influenced, the neurobiological bases mediating these influences have not yet been well characterized. To advance understanding concerning the pathway from genetic variation to personality, here we examined whether measures of heritable variation in neuroanatomical size in candidate regions (amygdala and medial orbitofrontal cortex) were associated with heritable effects on personality. A sample of 486 middle-aged (mean = 55 years) male twins (complete MZ pairs = 120; complete DZ pairs = 84) underwent structural brain scans and also completed measures of two core domains of personality: positive and negative emotionality. After adjusting for estimated intracranial volume, significant phenotypic (rp) and genetic (rg) correlations were observed between left amygdala volume and positive emotionality (rp = .16, p < .01; rg = .23, p < .05, respectively). In addition, after adjusting for mean cortical thickness, genetic and nonshared-environmental correlations (re) between left medial orbitofrontal cortex thickness and negative emotionality were also observed (rg = .34, p < .01; re = −.19, p < .05, respectively). These findings support a model positing that heritable bases of personality are, at least in part, mediated through individual differences in the size of brain structures, although further work is still required to confirm this causal interpretation. PMID:25263286

  3. Natural Genetic Variation Influences Protein Abundances in C. elegans Developmental Signalling Pathways

    PubMed Central

    Singh, Kapil Dev; Roschitzki, Bernd; Snoek, L. Basten; Grossmann, Jonas; Zheng, Xue; Elvin, Mark; Kamkina, Polina; Schrimpf, Sabine P.; Poulin, Gino B.; Kammenga, Jan E.; Hengartner, Michael O.

    2016-01-01

    Complex traits, including common disease-related traits, are affected by many different genes that function in multiple pathways and networks. The apoptosis, MAPK, Notch, and Wnt signalling pathways play important roles in development and disease progression. At the moment we have a poor understanding of how allelic variation affects gene expression in these pathways at the level of translation. Here we report the effect of natural genetic variation on transcript and protein abundance involved in developmental signalling pathways in Caenorhabditis elegans. We used selected reaction monitoring to analyse proteins from the abovementioned four pathways in a set of recombinant inbred lines (RILs) generated from the wild-type strains N2 (Bristol) and CB4856 (Hawaii) to enable quantitative trait locus (QTL) mapping. About half of the cases from the 44 genes tested showed a statistically significant change in protein abundance between various strains, most of these were however very weak (below 1.3-fold change). We detected a distant QTL on the left arm of chromosome II that affected protein abundance of the phosphatidylserine receptor protein PSR-1, and two separate QTLs that influenced embryonic and ionizing radiation-induced apoptosis on chromosome IV. Our results demonstrate that natural variation in C. elegans is sufficient to cause significant changes in signalling pathways both at the gene expression (transcript and protein abundance) and phenotypic levels. PMID:26985669

  4. Differential presentation of endogenous and exogenous hepatitis B surface antigens influences priming of CD8(+) T cells in an epitope-specific manner.

    PubMed

    Riedl, Petra; Reiser, Michael; Stifter, Katja; Krieger, Jana; Schirmbeck, Reinhold

    2014-07-01

    Little is known about whether presentation of endogenous and exogenous hepatitis B virus (HBV) surface antigens on APCs targeted by vaccination and/or virus-harboring hepatocytes influences de novo priming of CD8(+) T cells. We showed that surface antigen-expressing transfectants exclusively display a K(b) /S190 epitope, whereas cells pulsed with recombinant surface particles (rSPs) exclusively present a K(b) /S208 epitope to CD8(+) T cells. The differential presentation of these epitopes largely reflects the selective, but not exclusive, priming of K(b) /S190- and K(b) /S208-specific T cells in C57BL/6 mice by endogenous/DNA- or exogenous/protein-based vaccines, respectively. Silencing the K(b) /S190 epitope (K(b) /S190V194F ) in antigen-expressing vectors rescued the presentation of the K(b) /S208 epitope in stable transfectants and significantly enhanced priming of K(b) /S208-specific T cells in C57BL/6 mice. A K(b) /S190-mediated immunodominance operating in surface antigen-expressing cells, but not in rSP-pulsed cells, led to an efficient suppression in the presentation of the K(b) /S208 epitope and a consequent decrease in the priming of K(b) /S208-specific T cells. This K(b) /S190-mediated immunodominance also operated in 1.4HBV-S(mut) transgenic (tg) hepatocytes selectively expressing endogenous surface antigens and allowed priming of K(b) /S208- but not K(b) /S190-specific T cells in 1.4HBV-S(mut) tg mice. However, IFN-γ(+) K(b) /S208-specific T cells could not inhibit HBV replication in the liver of 1.4HBV-S(mut) tg mice. These results have practical implications for the design of T-cell-stimulating therapeutic vaccines. PMID:24723392

  5. Influence of Different Parameters on a Dual-Fractal Analysis for Antigen-Antibody Binding Kinetics for Biosensor Applications

    PubMed

    Milum; Sadana

    1997-03-01

    The diffusion-limited binding kinetics of antigen (or antibody) in solution to antibody (or antigen) immobilized on a biosensor surface is analyzed within a fractal framework. The fit obtained by a dual-fractal analysis is compared with that obtained from a single-fractal analysis. In some cases, the dual-fractal analysis provides an improved fit when compared with a single-fractal analysis. This was indicated by the regression analysis provided by Sigmaplot (46). It is of interest to note that the state of disorder (or the fractal dimension) and the binding rate coefficient both increase as the reaction progresses on the biosensor surface. For example, for the binding of HIV-1 p24 in solution to monoclonal antibody (MAb) 18 covalently attached to a biosensor surface (49), an increase in the fractal dimension by 59% from a value of Df1 equal to 1.91 to Df2 equal to 2.95 leads to an increase in the binding rate coefficient by a factor of 15 from k1 equal to 21.1 to k2 equal to 339. Also, the binding of MAb 6301 and 6303 in solution to insulin growth factor binding protein-1 (IGFBP-1) covalently attached to the sensor surface is adequately described by a single-fractal analysis (48). The binding of MAb 6302 to IGFBP-1, however, requires dual fractals. This indicates a difference in the binding mechanisms of these MAbs. The different examples analyzed and presented together provide a means by which the antigen-antibody reactions may be better controlled by noting the magnitude of the changes in the fractal dimension and in the binding rate coefficient as the reaction progresses on the biosensor surface. Also, the magnitude of the changes in the binding rate coefficients (k1 and k2) and in the fractal dimensions (Df1 and Df2) as different parameters are changed for the different biosensor applications are of particular value. PMID:9245322

  6. Influence of interannual variations in transport on summertime abundances of ozone over the Middle East

    NASA Astrophysics Data System (ADS)

    Liu, Jane J.; Jones, Dylan B. A.; Zhang, Shunli; Kar, Jay

    2011-10-01

    We used the GEOS-Chem model to investigate the impact of interannual variations in transport on summertime ozone abundances (between 1987 and 2006) in the middle troposphere over the Middle East. We found that ozone abundances fluctuated interannually by about ±7% (or ±6 ppbv from the 20-year mean of ˜80 ppbv). In the 20-year mean, ozone transported from Asia and ozone produced locally were the dominant sources of ozone, accounting for 31% and 23%, respectively, of ozone abundances over the Middle East, with an interannual variability of ±30% and ±15%, respectively. We found that the interannual variations in the Asian and local sources were related to the strengths of the South Asian High and the Arabian anticyclone, respectively. In years when the Asian influence was weaker in the region, transport from other areas, such as North America, was enhanced. Consequently, variations in ozone transported from Asia were strongly anti-correlated with variations in ozone transported from North America, for example, with a correlation coefficient of r = -0.75. This trade-off between transport from Asia and other regions was found to be linked to the position and strength of the subtropical westerly jet over central Asia. When the westerly jet is displaced poleward, transport of ozone from Asia is enhanced and transport from North America and other regions in the Northern Hemisphere is diminished. In contrast, when the jet is displaced equatorward, transport of ozone from Asia is diminished and transport from North America and other regions in the Northern Hemisphere is enhanced. These results suggest that climate-related changes in the position of the westerly jet will have implications for the transport of pollution into the Middle East.

  7. Isotopic variation in five species of stream fishes under the influence of different land uses.

    PubMed

    Carvalho, D R; Castro, D; Callisto, M; Moreira, M Z; Pompeu, P S

    2015-09-01

    The aim of this study was to test if changes in land use alter the isotopic signature of fish species, promoting changes in the trophic position and food resource partitioning between these consumers. Three different systems were investigated: pasture streams (n = 3), streams in sugar cane plantations (n = 3) and reference streams (n = 3). Fish species Aspidoras fuscoguttatus, Astyanax altiparanae, Characidium zebra, Hisonotus piracanjuba and Knodus moenkhausii were selected, and their nitrogen and carbon isotopic compositions were estimated to assess changes in the trophic level and partitioning of food items consumed. The composition of δ(13) C (‰) only differed among the land use categories for A. altiparanae, H. piracanjuba and K. moenkhausii. Resource partitioning was different for all species, with changes in the sources or proportions they consumed in each land use category, but only A. altiparanae introduced new food sources in large quantity in altered land uses. It is important to note, however, that the results from the resource partitioning analysis are limited due to large overlapping of isotopic signatures between the analysed food resources. All fish species exhibited variation in δ(15) N (‰), with the highest values found in streams under sugar cane or pasture influence. Despite the variation in nitrogen isotopic values, only C. zebra and H. piracanjuba displayed changes in trophic level. Therefore, it is believed that the increase in the δ(15) N (‰) value of the individuals collected in streams under the influence of sugar cane or pasture was due to the greater influence of livestock dung and chemical and organic fertilizers. The results also highlight the importance of studying consumer species along with all forms of resources available at each location separately, because the signatures of these resources also vary within different land uses. PMID:26201419

  8. Investigation of the Sedimentation Behavior of Aluminum Phosphate: Influence of pH, Ionic Strength, and Model Antigens.

    PubMed

    Muthurania, Kevin; Ignatius, Arun Alphonse; Jin, Zhaowei; Williams, Jennifer; Ohtake, Satoshi

    2015-11-01

    Evaluation of the physical characteristics of vaccines formulated in the presence of adjuvants, such as aluminum salts (Alum), is an important step in the development of vaccines. Depending on the formulation conditions and the associated electrostatic interactions of the adjuvant particles, the vaccine suspension may transition between flocculated and deflocculated states. The impact of practical formulation parameters, including pH, ionic strength, and the presence of model antigens, has been correlated to the sedimentation behavior of aluminum phosphate suspensions. A novel approach for the characterization of suspension properties of Alum has been developed to predict the flocculated state of the system using a sedimentation analysis-based tool (Turbiscan®). Two sedimentation parameters, the settling onset time (Sonset) and the sedimentation volume ratio (SVR) can be determined simultaneously in a single measurement. The results demonstrate the suspension characteristics to be significantly altered by solution conditions (pH and ionic strength) and the charge state of bound antigens. Formulation conditions that promote the flocculated state of the suspension are characterized by faster Sonset and higher SVR, and are generally easy to resuspend. The Turbiscan® method described herein is a useful tool for the characterization of aluminum-containing suspensions and may be adapted for screening and optimization of suspension-based vaccine formulations in general. PMID:26205044

  9. Pathways of Antigen Processing

    PubMed Central

    Blum, Janice S.; Wearsch, Pamela A.; Cresswell, Peter

    2014-01-01

    T cell recognition of antigen presenting cells depends on their expression of a spectrum of peptides bound to Major Histocompatibility Complex class I (MHC-I) and class II (MHC-II) molecules. Conversion of antigens from pathogens or transformed cells into MHC-I and MHC-II-bound peptides is critical for mounting protective T cell responses, and similar processing of self proteins is necessary to establish and maintain tolerance. Cells use a variety of mechanisms to acquire protein antigens, from translation in the cytosol to variations on the theme of endocytosis, and to degrade them once acquired. In this review we highlight the aspects of MHC-I and MHC-II biosynthesis and assembly that have evolved to intersect these pathways and sample the peptides that are produced. PMID:23298205

  10. Isotypic variation in antibody responses in a community in Papua New Guinea to larval and adult antigens during infection, and following reinfection, with the hookworm Necator americanus.

    PubMed

    Pritchard, D I; Walsh, E A; Quinell, R J; Raiko, A; Edmonds, P; Keymer, A E

    1992-11-01

    The natural infection of a community with the hookworm Necator americanus induces a vigorous humoral response to both larval and adult parasite antigens. This response occurs in all five human antibody isotypes, and data are presented to show that, at the population level, isotypes respond differently, following chemotherapy and during reinfection, to changes in antigen stimulation. The differential response probably reflects the fact that the parasite, during the course of its life cycle, presents different amounts of antigens at different anatomical locations. It is suggested that IgG and IgM responses against adult excretory-secretory (ES) products most accurately reflect the efficacy of chemotherapy, and the load of resident adult infection, while IgG responses against larval somatic antigens reflect continuous exposure to infection. These hypotheses should now be tested, at the level of the individual, in a longitudinal manner using more closely spaced sampling intervals. This repetitive sampling, and the inclusion of a measure of the exposure of the population to infective stages, will allow more definitive conclusions to be made about the role of the immune response in controlling worm burdens. PMID:1470481

  11. Spatial variation in fish assemblages across a beaver-influenced successional landscape

    USGS Publications Warehouse

    Schlosser, I.J.; Kallemeyn, L.W.

    2000-01-01

    Beavers are increasingly viewed as 'ecological engineers,' having broad effects on physical, chemical, and biological attributes of north-temperate landscapes. We examine the influence of both local successional processes associated with beaver activity and regional geomorphic boundaries on spatial variation in fish assemblages along the Kabetogama Peninsula in Voyageurs National Park, northern Minnesota, USA. Fish abundance and species richness exhibited considerable variation among drainages along the peninsula. Geological barriers to fish dispersal at outlets of some drainages has reduced fish abundance and species richness. Fish abundance and species richness also varied within drainages among local environments associated with beaver pond succession. Fish abundance was higher in upland ponds than in lowland ponds, collapsed ponds, or streams, whereas species richness was highest in collapsed ponds and streams. Cluster analyses based on fish abundance at sites classified according to successional environment indicated that four species (northern redbelly dace, Phoxinus eos; brook stickleback, Culaea inconstans; finescale dace, P. neogaeus; and fathead minnow, Pimephales promelas), were predominant in all successional environments. Several less abundant species were added in collapsed ponds and streams, with smaller size classes of large lake species (e.g., black crappie, Pomoxis nigromaculatus; smallmouth bass, Micropertus dolomieui; yellow perch, Perca flavescens; and burbot, Lota lota) being a component of these less abundant species. The addition of smaller size classes of large lake species indicates that dispersal of early life-history stages from Kabetogama Lake played a role in determining the species richness and composition of less abundant species in successional environments on the peninsula. Furthermore, collapsed-pond and stream environments closer to Kabetogama Lake had higher species richness than similar successional sites located farther from

  12. Pubertal Onset in Girls is Strongly Influenced by Genetic Variation Affecting FSH Action

    PubMed Central

    Hagen, Casper P.; Sørensen, Kaspar; Aksglaede, Lise; Mouritsen, Annette; Mieritz, Mikkel G.; Tinggaard, Jeanette; Wohlfart-Veje, Christine; Petersen, Jørgen Holm; Main, Katharina M.; Meyts, Ewa Rajpert-De; Almstrup, Kristian; Juul, Anders

    2014-01-01

    Age at pubertal onset varies substantially in healthy girls. Although genetic factors are responsible for more than half of the phenotypic variation, only a small part has been attributed to specific genetic polymorphisms identified so far. Follicle-stimulating hormone (FSH) stimulates ovarian follicle maturation and estradiol synthesis which is responsible for breast development. We assessed the effect of three polymorphisms influencing FSH action on age at breast deveopment in a population-based cohort of 964 healthy girls. Girls homozygous for FSHR -29AA (reduced FSH receptor expression) entered puberty 7.4 (2.5–12.4) months later than carriers of the common variants FSHR -29GG+GA, p = 0.003. To our knowledge, this is the strongest genetic effect on age at pubertal onset in girls published to date. PMID:25231187

  13. Factors Influencing Measurement of Serum Iron Concentration in Dogs: Diurnal Variation and Hyperferritinemia

    PubMed Central

    CHIKAZAWA, Seishiro; HORI, Yasutomo; KANAI, Kazutaka; ITO, Naoyuki; HOSHI, Fumio; ORINO, Koichi; WATANABE, Kiyotaka; HIGUCHI, Seiichi

    2013-01-01

    ABSTRACT We evaluated diurnal variation and hyperferritinemia as factors that influence the values of serum iron concentration in dogs, using the International Committee for Standardization in Hematology (ICSH) colorimetric method. Serum iron levels were significantly higher in the morning than in the evening in 6 clinically healthy beagle dogs, and the maximum decrease in serum iron concentration was 47.3%. Moreover, the change in serum iron concentrations in 22 clinical canine cases with various serum ferritin levels was evaluated by immunoprecipitation of ferritin. The rate of decline in the serum iron concentrations positively correlated with serum ferritin levels (r=0.48, P=0.024). These results show that it is necessary to consider the sampling time and serum ferritin level for accurate interpretation of serum iron concentrations in dogs. PMID:23877842

  14. Design considerations for liposomal vaccines: Influence of formulation parameters on antibody and cell-mediated immune responses to liposome associated antigens

    PubMed Central

    Watson, Douglas S.; Endsley, Aaron N.; Huang, Leaf

    2012-01-01

    Liposomes (phospholipid bilayer vesicles) are versatile and robust delivery systems for induction of antibody and T lymphocyte responses to associated subunit antigens. In the last 15 years, liposome vaccine technology has matured and now several vaccines containing liposome-based adjuvants have been approved for human use or have reached late stages of clinical evaluation. Given the intensifying interest in liposome-based vaccines, it is important to understand precisely how liposomes interact with the immune system and stimulate immunity. It has become clear that the physicochemical properties of liposomal vaccines – method of antigen attachment, lipid composition, bilayer fluidity, particle charge, and other properties – exert dramatic effects on the resulting immune response. Here, we present a comprehensive review of the physicochemical properties of liposomal vaccines and how they influence immune responses. A discussion of novel and emerging immunomodulators that are suitable for inclusion in liposomal vaccines is also presented. Through a comprehensive analysis of the body of liposomal vaccine literature, we enumerate a series of principles that can guide the rational design of liposomal vaccines to elicit immune responses of a desired magnitude and quality. We also identify major unanswered questions in the field, pointing the direction for future study. PMID:22306376

  15. Common variations in the pretest environment influence genotypic comparisons in models of anxiety.

    PubMed

    Izídio, G S; Lopes, D M; Spricigo, L; Ramos, A

    2005-10-01

    The behavioral characterization of rodent strains in different studies and laboratories can provide unreplicable results even when genotypes are kept constant and environmental control is maximized. In the present study, the influence of common laboratory environmental variables and their interaction with genotype on the results of behavioral tests of anxiety/emotionality were investigated. To this end, the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which are known to differ for numerous emotionality-related behaviors, were tested in the open field (OF), elevated plus maze (EPM) and black/white box (BWB), while three environmental factors were systematically controlled and analyzed: (1) the experimenter handling the animal (familiar or unfamiliar); (2) the position of the home cage (top or bottom shelf of the rack) and (3) the behavioral state of the animal immediately before the test (arousal or rest). Experimenter familiarity did not alter the behavior of rats in the OF. Cage position, on the other hand, influenced the behavior in the OF and BWB, with rats housed in top cages appearing less anxious than those housed in the bottom. In the BWB (but not in the OF), these effects were genotype dependent. Finally, the behavioral state of the animals prior to testing altered the results of the EPM in a strain-dependent manner, with some anxiety-related genotypic differences being found only among rats that were aroused in their home cages. This study showed that common variations in the laboratory environment interact with genotype in behavioral tests of anxiety/emotionality. Recognizing and understanding such variations can help in the design of more effective experiments. PMID:16176387

  16. Influences of vowel and tone variation on emergent word knowledge: a cross-linguistic investigation.

    PubMed

    Singh, Leher; Hui, Tam Jun; Chan, Calista; Golinkoff, Roberta Michnick

    2014-01-01

    To learn words, infants must be sensitive to native phonological contrast. While lexical tone predominates as a source of phonemic contrast in human languages, there has been little investigation of the influences of lexical tone on word learning. The present study investigates infants' sensitivity to tone mispronunciations in two groups of infants. For one group (Chinese learners), tone is phonemic in their native language, and for the second group (English learners), tone is non-phonemic and constituted suprasegmental variation. In Experiment 1, English learners were trained on novel word-object pairings and tested on their recognition of correct pronunciations, tone and vowel mispronunciations of these words at 18 and 24 months. In Experiment 2a, bilingual English-Chinese learners were tested on a similar task translated into Chinese at the same age intervals. Results demonstrate that non-tonal learners treated tonal and vowel substitutions alike as mispronunciations at 18 months but only treated vowel substitutions as mispronunciations at 24 months. Tonal learners treated both tonal and vowel substitutions as mispronunciations at both ages. In Experiment 2b, bilingual non-tone language learners were tested on the same set of tasks replicating a similar set of results as monolingual non-tone language learners (Experiment 1). Findings point to an early predisposition to treat tone as a defining characteristic of words regardless of its lexical relevance at 18 months. Between 18 and 24 months, learners appear to ascribe lexical relevance to tone in a language-specific manner. The current study identifies the influences of tone variation on memories for newly learned words and the time period during which lexical tone - a highly frequent constituent of human languages - actually becomes lexical for early learners. Findings are contextualized with prevailing models of the developing lexicon. PMID:24118787

  17. Defining the Influence of Germline Variation on Metastasis Using Systems Genetics Approaches.

    PubMed

    Lee, M; Crawford, N P S

    2016-01-01

    Cancer is estimated to be responsible for 8 million deaths worldwide and over half a million deaths every year in the United States. The majority of cancer-related deaths in solid tumors is directly associated with the effects of metastasis. While the influence of germline factors on cancer risk and development has long been recognized, the contribution of hereditary variation to tumor progression and metastasis has only gained acceptance more recently. A variety of approaches have been used to define how hereditary variation influences tumor progression and metastasis. One approach that garnered much early attention was epidemiological studies of cohorts of cancer patients, which demonstrated that specific loci within the human genome are associated with a differential propensity for aggressive tumor development. However, a powerful, and somewhat underutilized approach has been the use of systems genetics approaches in transgenic mouse models of human cancer. Such approaches are typically multifaceted, and involve integration of multiple lines of evidence derived, for example, from genetic and transcriptomic screens of genetically diverse mouse models of cancer, coupled with bioinformatics analysis of human cancer datasets, and functional analysis of candidate genes. These methodologies have allowed for the identification of multiple hereditary metastasis susceptibility genes, with wide-ranging cellular functions including regulation of gene transcription, cell proliferation, and cell-cell adhesion. In this chapter, we review how each of these approaches have facilitated the identification of these hereditary metastasis modifiers, the molecular functions of these metastasis-associated genes, and the implications of these findings upon patient survival. PMID:27613130

  18. Quantifying the influence of melt on velocity variations at a large Greenland outlet glacier

    NASA Astrophysics Data System (ADS)

    Andersen, M. L.; Nettles, M.; Elosegui, P.; Larsen, T.; Hamilton, G. S.; Stearns, L. A.

    2010-12-01

    The flow speed of Greenland outlet glaciers is governed by many factors, some of which are poorly understood. One such factor is surface-generated melt water, which has been shown to have a significant effect by enhancing basal lubrication. Previously, we have demonstrated a correlation between variations in glacier flow speed and meltwater input at Helheim Glacier, East Greenland. Here, we analyze local and across-glacier melt water estimates along with daily GPS-derived mean surface velocities from the same area to investigate spatial and temporal variations in glacier response to melt-water input. We perform linear least-squares fits of velocity to melt and thereby invert for a sensitivity value with which to produce predicted velocity records. We also investigate the seasonal variability of melt influence in 2008. We track the residual misfits for a sliding time window using steps of one day while performing the inversion for each step. We detect decreasing values of sensitivity with distance along the flowline from the calving front. Moreover, we observe that misfits drop gradually as the season progresses, accompanied by a steep increase in modeled sensitivity. Toward the end of the season, a very strong correlation between melt and surface displacement occurs and is sustained for ~6 days. We interpret this change as reflecting a gradual change in subglacial hydraulic routing from a tunnel-dominated to a linked-cavity dominated system and back. Investigations of melt-water influence on fast outlet glacier flow may be key in understanding solid mass loss from the Greenland Ice Sheet, which has been shown to comprise half of the current negative mass budget.

  19. Axillary dissection in primary breast cancer: variations of the surgical technique and influence on morbidity

    PubMed Central

    Wojcinski, Sebastian; Nuengsri, Sirin; Hillemanns, Peter; Schmidt, Werner; Deryal, Mustafa; Ertan, Kubilay; Degenhardt, Friedrich

    2012-01-01

    Lymphedema of the arm is the most common and impairing complication after breast cancer surgery with axillary lymph node dissection (ALND). Our prospective study evaluated the effect of two different surgical techniques for ALND on postoperative morbidity. Patients were scheduled to undergo ALND. Patients in group 1 (n = 17) underwent the most common and standard technique of ALND, which uses sharp dissection of the tissue and subsequent electro-coagulation of bleedings. Patients in group 2 (n = 17) underwent a modified standard technique of ALND with clamping and ligatures of all resection margins. Postoperative wound secretion was quantified and patients were followed up for 6 months to assess long-term morbidity. The variations in surgical technique had no significant influence on the outcome variables. However, patients in group 2 showed a tendency to less wound secretion (713 versus 802 mL; P = nonsignificant), a decreased rate of immediate postoperative seromas (11.8 versus 23.5%; P = nonsignificant) and less lymphedema after 3 months (29.4 versus 41.2%; P = nonsignificant). Moreover, the number of resected lymph nodes correlated with the total amount of drained fluid (P = 0.006), the duration of the drain (P = 0.015), and the risk for the development of lymphedema after 3 months (P = 0.016). The described variations in surgical technique had no influence on the outcomes of the patients. The number of resected axillary lymph nodes remains the most important risk factor for treatment-related morbidity. Therefore, a well-balanced choice of the extent of the axillary dissection should be the surgeon’s main concern. PMID:22570566

  20. Axillary dissection in primary breast cancer: variations of the surgical technique and influence on morbidity.

    PubMed

    Wojcinski, Sebastian; Nuengsri, Sirin; Hillemanns, Peter; Schmidt, Werner; Deryal, Mustafa; Ertan, Kubilay; Degenhardt, Friedrich

    2012-01-01

    Lymphedema of the arm is the most common and impairing complication after breast cancer surgery with axillary lymph node dissection (ALND). Our prospective study evaluated the effect of two different surgical techniques for ALND on postoperative morbidity. Patients were scheduled to undergo ALND. Patients in group 1 (n = 17) underwent the most common and standard technique of ALND, which uses sharp dissection of the tissue and subsequent electro-coagulation of bleedings. Patients in group 2 (n = 17) underwent a modified standard technique of ALND with clamping and ligatures of all resection margins. Postoperative wound secretion was quantified and patients were followed up for 6 months to assess long-term morbidity. The variations in surgical technique had no significant influence on the outcome variables. However, patients in group 2 showed a tendency to less wound secretion (713 versus 802 mL; P = nonsignificant), a decreased rate of immediate postoperative seromas (11.8 versus 23.5%; P = nonsignificant) and less lymphedema after 3 months (29.4 versus 41.2%; P = nonsignificant). Moreover, the number of resected lymph nodes correlated with the total amount of drained fluid (P = 0.006), the duration of the drain (P = 0.015), and the risk for the development of lymphedema after 3 months (P = 0.016). The described variations in surgical technique had no influence on the outcomes of the patients. The number of resected axillary lymph nodes remains the most important risk factor for treatment-related morbidity. Therefore, a well-balanced choice of the extent of the axillary dissection should be the surgeon's main concern. PMID:22570566

  1. The environmental magnetic record of palaeoenvironmental variations during the past 3100 years: A possible solar influence?

    NASA Astrophysics Data System (ADS)

    Sandeep, K.; Shankar, R.; Warrier, Anish K.; Weijian, Z.; Xuefeng, Lu

    2015-07-01

    Sediments from Pookot Lake (PK) in southern India have provided a record of local environmental changes and catchment processes during the past 3100 cal. years B.P. Variations in the rock magnetic parameters (χlf, χfd, χARM and IRM's at different field strengths) of sediments from two AMS 14C-dated cores reflect climate-induced changes in the catchment of Pookot Lake. Assuming that rainfall is most likely the dominant driving mechanism behind the rock magnetic variations of PK sediments, the environmental history of the site has been reconstructed. Rock magnetic parameters exhibit significant variations during the past 3100 years. The palaeoenvironmental history of the Pookot Lake region may be divided into three phases. During the first phase (~ 3100 to 2500 cal. years B.P.), catchment erosion and detrital influx were high, indicating a strong monsoon. The second phase, which lasted from 2500 to 1000 cal. years B.P., was characterised by low and steady rainfall, resulting in a low and uniform catchment erosion and detrital influx. Phase 2 was interspersed with brief intervals of strong monsoon and characterised by frequent drying up of the lake. During Phase 3 (~ 1000 cal. years B.P. to the present), catchment erosion was high, indicating a shift to strong monsoonal conditions. It appears that monsoonal rainfall in the region is influenced by solar activity, with periods of high total solar irradiance being characterised by high rainfall and vice versa; it was relatively low during the Little Ice Age and high during the Medieval Warm Period. The magnetic susceptibility (χlf) data exhibit a number of periodicities which might have a solar origin. The χlf record exhibits similarities with other continental and marine palaeoclimatic records from the region, indicating that regional trends in the monsoon during the Late Holocene are broadly similar.

  2. Influence of climate on malaria transmission depends on daily temperature variation.

    PubMed

    Paaijmans, Krijn P; Blanford, Simon; Bell, Andrew S; Blanford, Justine I; Read, Andrew F; Thomas, Matthew B

    2010-08-24

    Malaria transmission is strongly influenced by environmental temperature, but the biological drivers remain poorly quantified. Most studies analyzing malaria-temperature relations, including those investigating malaria risk and the possible impacts of climate change, are based solely on mean temperatures and extrapolate from functions determined under unrealistic laboratory conditions. Here, we present empirical evidence to show that, in addition to mean temperatures, daily fluctuations in temperature affect parasite infection, the rate of parasite development, and the essential elements of mosquito biology that combine to determine malaria transmission intensity. In general, we find that, compared with rates at equivalent constant mean temperatures, temperature fluctuation around low mean temperatures acts to speed up rate processes, whereas fluctuation around high mean temperatures acts to slow processes down. At the extremes (conditions representative of the fringes of malaria transmission, where range expansions or contractions will occur), fluctuation makes transmission possible at lower mean temperatures than currently predicted and can potentially block transmission at higher mean temperatures. If we are to optimize control efforts and develop appropriate adaptation or mitigation strategies for future climates, we need to incorporate into predictive models the effects of daily temperature variation and how that variation is altered by climate change. PMID:20696913

  3. Influence of seasonal variation on the phenology and liriodenine content of Annona lutescens (Annonaceae).

    PubMed

    Castro-Moreno, Marisol; Tinoco-Ojangurén, Clara Leonor; Cruz-Ortega, Ma Del Rocío; González-Esquinca, Alma Rosa

    2013-07-01

    Annona lutescens Saff. (Annonaceae) grows as a native tree in Chiapas, Mexico in Tropical Dry Forest habitat. Like most Annonaceae, it biosynthesizes benzylisoquinoline alkaloids, mostly liriodenine. To determine the influence of seasonal changes in the accumulation of liriodenine, the monthly variation of liriodenine content in roots, stems and leaves of mature and young trees was observed. These parts of young and mature A. lutescens trees were collected monthly over a 1 year period and the alkaloids were extracted; the liriodenine was quantified by high-resolution liquid chromatography. The phenological stages of the species were also assessed (leaf development, flowering and fruiting) using the Biologische Bundesanstalt, Bundessortenamt und Chemische Industrie (BBCH) scale. The analysis of both young and mature trees showed a significant increase in the liriodenine concentration occurs within roots during the dry season, which coincides with leaf fall. A significant decrease also occurred at the beginning of the rainy season (the period of leaf growth); the liriodenine content for the next rainy season did not reach the levels of the previous dry season. The climatic variation induced phenological and physiological changes in this species. PMID:23389399

  4. Do differences in Toxoplasma prevalence influence global variation in secondary sex ratio? Preliminary ecological regression study.

    PubMed

    Dama, Madhukar S; Martinec Nováková, Lenka; Flegr, Jaroslav

    2016-08-01

    Sex of the fetus is genetically determined such that an equal number of sons and daughters are born in large populations. However, the ratio of female to male births across human populations varies significantly. Many factors have been implicated in this. The theory that natural selection should favour female offspring under suboptimal environmental conditions implies that pathogens may affect secondary sex ratio (ratio of male to female births). Using regression models containing 13 potential confounding factors, we have found that variation of the secondary sex ratio can be predicted by seroprevalence of Toxoplasma across 94 populations distributed across African, American, Asian and European continents. Toxoplasma seroprevalence was the third strongest predictor of secondary sex ratio, β = -0·097, P < 0·01, after son preference, β = 0·261, P < 0·05, and fertility, β = -0·145, P < 0·001. Our preliminary results suggest that Toxoplasma gondii infection could be one of the most important environmental factors influencing the global variation of offspring sex ratio in humans. The effect of latent toxoplasmosis on public health could be much more serious than it is usually supposed to be. PMID:27350331

  5. CFD investigation of the influence of volute geometrical variations on hydrodynamic characteristics of circulator pump

    NASA Astrophysics Data System (ADS)

    Wu, Denghao; Yuan, Shouqi; Ren, Yun; Mu, Jiegang; Yang, Youdong; Liu, Jian

    2016-03-01

    Improper design of volute geometry can be the main cause that leads to unsteady pressure pulsation and radial force in pumps. Therefore, it is important to understand the influence of volute geometrical parameters on hydrodynamic characteristics of pump and the mechanism. However, the existing studies are limited to investigate the influence of only one or two volute geometrical parameters each time, and a systematic study of the influence of the combinations of different volute geometrical parameters on the pump's hydrodynamic characteristics is missing. In this paper, a study on the understanding of the influence of volute geometrical variations on hydrodynamic characteristics of a high speed circulator pump by using computational fluid dynamics(CFD) technology is presented. Five main volute geometrical parameters D 3, A 8, α 0, φ 0 and R t are selected and 25 different volute configurations are generated by using design of experiments(DOE) method. The 3D unsteady flow numerical simulations, which are based on the SST k- w turbulence model and sliding mesh technique provided by CFX, are executed on the 25 different volute configurations. The hydraulic performance, pressure pulsation and unsteady radial force inside the pump at design condition are obtained and analyzed. It has been found that volute geometrical parameters D 3 and A 8 are major influence factors on hydrodynamic characteristics of the pump, while α 0, φ 0 and R t are minor influence factors. The minimum contribution from both D 3 and A 8 is 58% on head, and maximum contribution from both D 3 and A 8 is 90% on pressure pulsation. Regarding the pressure pulsation intensity, two peaks can be found. One is in the tongue area and the other is in the diffusor area. The contributions are around 60% from tongue and 25% from diffusor, respectively. The amplitude of pressure pulsation has a quadratic polynomial functional relationship with respect to D 3/ D 2 and A 8/ A 10, and fluctuating level of

  6. Minor interspecies variations in the sequence of the gp53 TSL-1 antigen of Trichinella define species-specific immunodominant epitopes.

    PubMed

    Perteguer, M J; Rodríguez, E; Romarís, F; Escalante, M; Bonay, P; Ubeira, F M; Gárate, M T

    2004-06-01

    Among the Trichinella TSL-1 antigens, whose antigenicity is generally due mainly to tyvelose-containing epitopes, gp53 is unusual in that its antigenicity is due mainly to protein epitopes. In the present study we mapped two of these epitopes, recognized by monoclonal antibodies (mAbs) that specifically recognize gp53 from all encysting Trichinella species (mAb US9), or gp53 from Trichinella spiralis alone (mAb US5). Based on previously published sequences of this glycoprotein [Mol. Biochem. Parasitol. 72 (1995) 253], in this study, we cloned the full gp53 cDNA from a new strain, Trichinella britovi (ISS 11; AN: ), and from another T. spiralis isolate (ISS 115; AN: ). The gp53 sequence comprised an ORF of 1239bp, coding for 412 amino acids, with 61 nucleotide differences (resulting in 38 residue changes) between the two species. Mapping of US5- and US9-recognized epitopes was undertaken through the construction and expression in the pGEX4T vector of truncated gp53 peptides, and by the construction of peptides derived from the antigenic regions. The epitope recognized by mAb US9 was a linear peptide of 8 residues, 33Met- 40Ser, located in the amino-terminal region, while the corresponding epitope recognized by mAb US5 was a 47-amino acid sequence containing two alpha-helix regions flanked by random coils, 290Thr- 336Lys. Molecular modeling of these peptides seems to indicate that recognition of the US9 epitope depends on the presence of two available hydroxyl groups provided by one methionine and one serine on T. spiralis gp53 (not present on Trichinella pseudospiralis gp53). Additionally, the stability of the US5 epitope seems to depend on correct folding of the 47-amino acid sequence (only present in T. spiralis). The relevance of these findings for understanding the antigenic recognition of Trichinella TSL-1 antigens, and for further studies to investigate possible function(s) of gp53 in Trichinella, is discussed. PMID:15163539

  7. Patient-specific factors influence somatic variation patterns in von Hippel–Lindau disease renal tumours

    PubMed Central

    Fei, Suzanne S.; Mitchell, Asia D.; Heskett, Michael B.; Vocke, Cathy D.; Ricketts, Christopher J.; Peto, Myron; Wang, Nicholas J.; Sönmez, Kemal; Linehan, W. Marston; Spellman, Paul T.

    2016-01-01

    Cancer development is presumed to be an evolutionary process that is influenced by genetic background and environment. In laboratory animals, genetics and environment are variables that can largely be held constant. In humans, it is possible to compare independent tumours that have developed in the same patient, effectively constraining genetic and environmental variation and leaving only stochastic processes. Patients affected with von Hippel–Lindau disease are at risk of developing multiple independent clear cell renal carcinomas. Here we perform whole-genome sequencing on 40 tumours from six von Hippel-Lindau patients. We confirm that the tumours are clonally independent, having distinct somatic single-nucleotide variants. Although tumours from the same patient show many differences, within-patient patterns are discernible. Single-nucleotide substitution type rates are significantly different between patients and show biases in trinucleotide mutation context. We also observe biases in chromosome copy number aberrations. These results show that genetic background and/or environment can influence the types of mutations that occur. PMID:27174753

  8. Influence of Arabidopsis thaliana accessions on rhizobacterial communities and natural variation in root exudates

    PubMed Central

    Micallef, Shirley A.; Shiaris, Michael P.; Colón-Carmona, Adán

    2009-01-01

    Plant species is considered to be one of the most important factors in shaping rhizobacterial communities, but specific plant–microbe interactions in the rhizosphere are still not fully understood. Arabidopsis thaliana, for which a large number of naturally occurring ecotype accessions exist, lacks mycorrhizal associations and is hence an ideal model for rhizobacterial studies. Eight Arabidopsis accessions were found to exert a marked selective influence on bacteria associated with their roots, as determined by terminal-restriction fragment length polymorphism (T-RFLP) and ribosomal intergenic spacer analysis (RISA). Community differences in species composition and relative abundance were both significant (P <0.001). The eight distinct and reproducible accession-dependent community profiles also differed from control bulk soil. Root exudates of these variants were analysed by high performance liquid chromatography (HPLC) to try to establish whether the unique rhizobacterial assemblages among accessions could be attributed to plant-regulated chemical changes in the rhizosphere. Natural variation in root exudation patterns was clearly exhibited, suggesting that differences in exudation patterns among accessions could be influencing bacterial assemblages. Other factors such as root system architecture are also probably involved. Finally, to investigate the Arabidopsis rhizosphere further, the phylogenetic diversity of rhizobacteria from accession Cvi-0 is described. PMID:19342429

  9. Variation in normal mood state influences sensitivity to dynamic changes in emotional expression.

    PubMed

    Jackson, Margaret C; Arlegui-Prieto, Maritxu

    2016-03-01

    Normal social functioning depends on the ability to efficiently and accurately detect when someone's facial expression changes to convey positive or negative emotion. While observer mood state has been shown to influence emotion recognition, how variations in normal mood might influence sensitivity to the dynamic emergence of expressions has not yet been addressed. To investigate this, we modified an existing face-morphing paradigm in which a central face gradually changes from neutral to expressive (angry, sad, happy, surprised). Our sample comprised healthy young adults, and current mood state was measured using the PANAS-X. Participants pressed a key as soon as they (1) noticed a physical change in expression (perceptual sensitivity-novel task element), and (2) could clearly conceptualize which expression was emerging (conceptual sensitivity). A final unspeeded response required participants to explicitly label the expression as a measure of recognition accuracy. We measured the percentage morph (expression intensity) at which a perceptual and conceptual change was detected, where greater intensity equates to poorer sensitivity. Increased positive mood reduced perceptual and conceptual sensitivity to angry and sad expressions only (a mood incongruency effect). Of particular interest, increased negative mood decreased conceptual sensitivity for all expressions, but had limited impact on perceptual sensitivity. Thus, heightened negative mood is particularly detrimental for effectively decoding someone else's mood change. This may reflect greater introspection and consumption of attentional resources directed toward the negative self, leaving fewer resources to process emotional signals conveyed by others. This could have important consequences for human social interaction. PMID:26479773

  10. Influence of Reservoir Operation on River Eco-hydrological Regime Variation

    NASA Astrophysics Data System (ADS)

    Chang, J.; Wang, Y.; Li, Y.

    2013-12-01

    With the development of reservoir, river hydrological situation has undergone great changes. Liujiaxia and Longyangxia reservoir which all have great regulation ability were constructed in the upper reaches above Lanzhou station of the Yellow River. In view of the Indicator of Hydrologic Alteration (IHA), the Range of Variability Approach ( RVA ) is used to calculate the eco- hydrological characteristic values and analyze the influence of different reservoir operating modes on the variation of eco-hydrological characteristics of the Yellow River upstream. On the whole, the hydrologic regime at each station downstream of the Liujiaxia reservoir has changed obviously, especially that at Lanzhou station. The overall degree of hydrologic alteration with single reservoir (Liujiaxia) was 72. 64%, and the hydrologic alteration degree with two reservoirs joint operation was 78. 90%. Both of them were belong to high change. Also, after joint operation of Liujiaxia and Longyangxia reservoir, the flow in flood season significantly reduce and the number of high and low flow reversals increase, which would influence the living condition of aquatic organism in the Yellow River, and greatly endanger the aquatic species' reproduction.

  11. Patient-specific factors influence somatic variation patterns in von Hippel-Lindau disease renal tumours.

    PubMed

    Fei, Suzanne S; Mitchell, Asia D; Heskett, Michael B; Vocke, Cathy D; Ricketts, Christopher J; Peto, Myron; Wang, Nicholas J; Sönmez, Kemal; Linehan, W Marston; Spellman, Paul T

    2016-01-01

    Cancer development is presumed to be an evolutionary process that is influenced by genetic background and environment. In laboratory animals, genetics and environment are variables that can largely be held constant. In humans, it is possible to compare independent tumours that have developed in the same patient, effectively constraining genetic and environmental variation and leaving only stochastic processes. Patients affected with von Hippel-Lindau disease are at risk of developing multiple independent clear cell renal carcinomas. Here we perform whole-genome sequencing on 40 tumours from six von Hippel-Lindau patients. We confirm that the tumours are clonally independent, having distinct somatic single-nucleotide variants. Although tumours from the same patient show many differences, within-patient patterns are discernible. Single-nucleotide substitution type rates are significantly different between patients and show biases in trinucleotide mutation context. We also observe biases in chromosome copy number aberrations. These results show that genetic background and/or environment can influence the types of mutations that occur. PMID:27174753

  12. Evidence for horizontal gene transfer of two antigenically distinct O antigens in Bordetella bronchiseptica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antigenic variation is one mechanism pathogens use to avoid immune-mediated competition between closely related strains. Here, we show that two Bordetella bronchiseptica strains, RB50 and 1289, express two antigenically distinct O-antigen serotypes (O1 and O2 respectively). When 18 additional B. b...

  13. A novel laboratory technique demonstrating the influences of RHD zygosity and the RhCcEe phenotype on erythrocyte D antigen expression

    PubMed Central

    McGann, Patrick T.; Despotovic, Jenny M.; Howard, Thad A.; Ware, Russell E.

    2015-01-01

    D antigen is the most immunogenic and clinically relevant antigen within the complex Rh blood group system. Variability of D antigen expression was first described decades ago but has rarely been investigated quantitatively, particularly in the context of RHD zygosity along with RhCcEe serological phenotype. With IRB approval, 107 deidentified blood samples were analyzed. Rh phenotypes were determined serologically by saline technique using monoclonal antibodies against D, C, c, E, and e antigens. RHD zygosity was determined using both PCR-restriction fragment length polymorphisms and quantitative real-time PCR techniques. A novel and robust method was developed for quantitation of erythrocyte D antigen sites using calibrated microspheres and flow cytometry, allowing correlation of D antigen density with RHD zygosity and expression of Rh CcEe antigens. Subjects homozygous for RHD expressed nearly twice the number of D antigen sites compared with RHD hemizygotes (33,560 ± 8,222 for DD versus 17,720 ± 4,471 for Dd, P < 0.0001). Expression of c or E antigens was associated with significantly increased erythrocyte D antigen expression, whereas presence of C or e antigens reduced expression. These data and this novel quantitation method will be important for future studies investigating the clinical relevance of D antigen variability. PMID:22121029

  14. Dynamical influences on the moment of inertia tensor from lateral viscosity variations inferred from seismic tomographic models

    NASA Technical Reports Server (NTRS)

    Zhang, Shuxia; Yuen, David A.

    1994-01-01

    We have investigated the influences of lateral variations of viscosity on the moment of inertia tensor from viscous flows due to the density anomalies in the mantle inferred from seismic tomographic models. The scaling relations between the density and the seismic anomalies is taken as either a constant or a function increasing with depth in accord with the recent high-pressure experimental studies. The viscosity is taken as an exponential function of the 3D density anomaly. In models with an isoviscous background, the effects on the perturbed moment of inertia tensor from the lateral viscosity variations are smaller than those due to variations in the radial viscosity profiles. In mantle models with a background viscosity increasing with depth, the influences of the lateral viscosity variations are significant. The most striking feature in the latter case is that the two off-diagonal elements delta I(sub xz) and delta I(sub yz) in the inertia tensor exhibit greatest sensitivity to lateral variations of the viscosity. While the other elements of the inertia change by only about a few tens of percent in the range of lateral viscosity contrast considered (less than 300), delta I(sub xz) and delta I(sub yz) can vary up to 40 times even with a change in sign, depending on the radial viscosity stratification and the location of the strongest lateral variations. The increase in the velocity-density scaling relation with depth can reduce the influences of the lateral viscosity variations, but it does not change the overall sensitive nature of delta I(sub xz) and delta I(sub yz). This study demonstrates clearly that the lateral viscosity variations, especially in the upper mantle, must be considered in the determination of long-term polar wander, since the variations in the delta I(sub xz) and delta I(sub yz) terms are directly responsible for exciting rotational movements.

  15. Influence of dioxin exposure upon levels of prostate-specific antigen and steroid hormones in Vietnamese men.

    PubMed

    Sun, Xian Liang; Kido, Teruhiko; Honma, Seijiro; Okamoto, Rie; Manh, Ho Dung; Maruzeni, Shoko; Nishijo, Muneko; Nakagawa, Hideaki; Nakano, Takeshi; Koh, Eitetsu; Takasuga, Takumi; Nhu, Dang Duc; Hung, Nguyen Ngoc; Son, Le Ke

    2016-04-01

    Most studies on the relationship between Agent Orange and prostate cancer have focused on US veterans of the Vietnam War. There have been few studies focusing on the relationship between levels of prostate-specific antigen (PSA) and dioxins or steroid hormones in Vietnamese men. In 2009-2011, we collected blood samples from 97 men who had resided in a "dioxin hotspot" and 85 men from a non-sprayed region in Vietnam. Then levels of PSA, dioxins, and steroid hormones were analyzed. Levels of most dioxins, furans, and non-ortho polychlorinated biphenyls were higher in the hotspot than those in the non-sprayed region. Levels of testosterone, dehydroepiandrosterone, and estradiol differed significantly between the hotspot and the non-sprayed region, but there were no correlations between levels of PSA and steroid hormones and dioxins in either of the two regions. Our findings suggest that PSA levels in Vietnamese men are not associated with levels of dioxin or steroid hormones in these two regions. PMID:26758301

  16. Influence of adjuvant and antigen dose on protection induced by an inactivated whole vaccine against Neospora caninum infection in mice.

    PubMed

    Rojo-Montejo, Silvia; Collantes-Fernández, Esther; Regidor-Cerrillo, Javier; Rodríguez-Bertos, Antonio; Prenafeta, Antoni; Gomez-Bautista, Mercedes; Ortega-Mora, Luis M

    2011-02-10

    In this study, the protection afforded by a Neospora caninum inactivated vaccine formulated with three different adjuvants (water-in-oil emulsion, aluminum hydroxide with CpG oligodeoxynucleotides and aluminum hydroxide with ginseng extract) and three different parasite doses (10(5), 5 × 10(5) or 10(6) inactivated whole tachyzoites) was evaluated using a mouse model. Mice were immunized subcutaneously twice at three-week intervals with inactivated Nc-Spain 1H tachyzoites and challenged by intraperitoneal inoculation with 10(6) live Nc-1 tachyzoites. The efficacy of the immunization was evaluated in non-pregnant BALB/c mice on days 1 and 5 (acute infection phase) and days 14 and 30 (chronic infection phase) post-challenge. The results showed the ability of water-in-oil emulsion combined with inactivated 5 × 10(5) tachyzoites to induce protection against neosporosis during the chronic stage, limiting parasite multiplication in the brain. Aluminum hydroxide-ginseng extract and inactivated tachyzoites reduced the number of parasites circulating in the blood during acute phase but failed to limit the establishment of chronic infection. On the other hand, a dose-effect was observed in groups vaccinated with aluminum hydroxide-ginseng extract in which the lesion severity increased as the inactivated tachyzoite dose. This study demonstrates that efficacy can significantly vary depending on the adjuvant, the dose of antigen and the phase of N. caninum infection in which the vaccine is tested. PMID:21067865

  17. The influence from synoptic weather on the variation of air pollution and pollen exposure

    NASA Astrophysics Data System (ADS)

    Grundström, Maria; Dahl, Åslög; Chen, Deliang; Pleijel, Håkan

    2014-05-01

    Exposure to elevated air pollution levels can make people more susceptible to allergies or result in more severe allergic reactions for people with an already pronounced sensitivity to pollen. The aim of this study was to investigate the relationships between urban air pollution (nitrogen oxides, ozone and particles) and airborne Betula pollen in Gothenburg, Sweden, during the pollen seasons for the years 2001-2012. Further, the influence from atmospheric weather pattern on pollen/pollution related risk, using Lamb Weather Types (LWT), was also considered. Daily LWTs were obtained by comparing the variation in atmospheric pressure from a 16 point grid over a given region on earth (scale ~1000km) and essentially describe the air mass movement for the region. They include two non-directional types, cyclonic (C) and anticyclonic (A) and eight directional types depending on the wind direction (N, NE, E... etc.). LWTs with dry and calm meteorological character e.g. limited precipitation and low to moderate wind speeds (A, NE, E, SE) were associated with strongly elevated air pollution and pollen levels where Betula was exceptionally high in LWTs NE and E. The co-variation between Betula pollen and ozone was strong and significant during situations with LWTs A, NE, E and SE. The most important conclusion from this study was that LWTs A, NE, E and SE were associated with high pollen and air pollution levels and can therefore be classified as high risk weather situations for combined air pollution and pollen exposure. Our study shows that LWTs have the potential to be developed into an objective tool for integrated air quality forecasting and a warning system for risk of high exposure situations.

  18. Genetic variation in the serotonin transporter gene influences ERP old/new effects during recognition memory.

    PubMed

    Ross, Robert S; Medrano, Paolo; Boyle, Kaitlin; Smolen, Andrew; Curran, Tim; Nyhus, Erika

    2015-11-01

    Recognition memory is defined as the ability to recognize a previously encountered stimulus and has been associated with spatially and temporally distinct event-related potentials (ERPs). Allelic variations of the serotonin transporter gene (SLC6A4) have recently been shown to impact memory performance. Common variants of the serotonin transporter-linked polymorphic region (5HTTLPR) of the SLC6A4 gene result in long (l) and short (s) allelic variants with carriers of the s allele having lowered transcriptional efficiency. Thus, the current study examines the effects polymorphisms of the SLC6A4 gene have on performance and ERP amplitudes commonly associated with recognition memory. Electroencephalogram (EEG), genetic, and behavioral data were collected from sixty participants as they performed an item and source memory recognition task. In both tasks, participants studied and encoded 200 words, which were then mixed with 200 new words during retrieval. Participants were monitored with EEG during the retrieval portion of each memory task. EEG electrodes were grouped into four ROIs, left anterior superior, right anterior superior, left posterior superior, and right posterior superior. ERP mean amplitudes during hits in the item and source memory task were compared to correctly recognizing new items (correct rejections). Results show that s-carriers have decreased mean hit amplitudes in both the right anterior superior ROI 1000-1500ms post stimulus during the source memory task and the left anterior superior ROI 300-500ms post stimulus during the item memory task. These results suggest that individual differences due to genetic variation of the serotonin transporter gene influences recognition memory. PMID:26423665

  19. Synergistic influences of phase, density, and climatic variation on the dynamics of fluctuating populations.

    PubMed

    Goswami, Varun R; Getz, Lowell L; Hostetler, Jeffrey A; Ozgul, Arpat; Oli, Madan K

    2011-08-01

    Although ecologists have long recognized that certain mammalian species exhibit high-amplitude, often multiannual, fluctuations in abundance, their causes have remained poorly understood and the subject of intense debate. A key contention has been the relative role of density-dependent and density-independent processes in governing population dynamics. We applied capture-mark-recapture analysis to 25 years of monthly trapping data from a fluctuating prairie vole Microtus ochrogaster population in Illinois, USA, to estimate realized population growth rates and associated vital rates (survival and recruitment) and modeled them as a function of vole density and density-independent climatic variation. We also tested for phase dependence and seasonality in the effects of the above processes. Variation in the realized population growth rate was best explained by phase-specific changes in vole density lagged by one month and mean monthly temperatures with no time lags. The underlying vital rates, survival and recruitment, were influenced by the additive and interactive effects of phase, vole density, and mean monthly temperatures. Our results are consistent with the observation that large-scale population fluctuations are characterized by phase-specific changes in demographic and physiological characteristics. Our findings also support the growing realization that the interaction between climatic variables and density-dependent factors may be a widespread phenomenon, and they suggest that the direction and magnitude of such interactive effects may be phase specific. We conclude that density-dependent and density-independent climatic variables work in tandem during each phase of density fluctuations to drive the dynamics of fluctuating populations. PMID:21905434

  20. [Variation characteristic in soil respiration of apple orchard and its biotic and abiotic influencing factors].

    PubMed

    Wang, Rui; Guo, Sheng-Li; Liu, Qing-Fang; Zhang, Yan-Jun; Jiang, Ji-Shao; Guo, Hui-Min; Li, Ru-Jian

    2014-05-01

    To evaluate the orchard variability of soil respiration and the response of soil respiration to its influencing factors is helpful for a deep understanding about the effects of converting cropland to apple orchard. A field experiment was conducted in the Changwu State Key Agro-Ecological Station. Soil respiration, soil temperature, soil moisture and roots biomasses were periodically measured in a mature apple orchard during 2011 and 2012. Soil respiration decreased as the distance from the trunk increased. The cumulative soil respiration in the 0.5 m-distance from the trunk was 20% and 31% higher than that in the 2 m-distance from the trunk, respectively in 2011 and 2012. The temperature sensitivity of soil respiration (Q10) was relatively lower in the 2 m-distance than that in the 0. 5 m-distance in both years. Soil temperature and soil moisture were slightly higher in the 2 m-distance, but there was no significant difference between the 2 m-distance and the 0. 5 m-distance. Soil respiration and soil temperature showed a significant exponential relationship, but there was no positive correlation between soil moisture and soil respiration. Soil temperature changes can explain seasonal variation of soil respiration well, but it could not explain its spatial variability. Root density was an important factor for the spatial variability of soil respiration and Q15. Variation of soil respiration coefficient was 23% -31%. Therefore, the distance from the trunk should be considered when estimating orchards soil respiration. PMID:25055686

  1. Annual variations of carbonaceous PM2.5 in Malaysia: influence by Indonesian peatland fires

    NASA Astrophysics Data System (ADS)

    Fujii, Y.; Tohno, S.; Amil, N.; Latif, M. T.; Oda, M.; Matsumoto, J.; Mizohata, A.

    2015-12-01

    In this study, we quantified carbonaceous PM2.5 in Malaysia through annual observations of PM2.5, focusing on organic compounds derived from biomass burning. We determined organic carbon (OC), elemental carbon and concentrations of solvent-extractable organic compounds (biomarkers derived from biomass burning sources and n-alkanes). We observed seasonal variations in the concentrations of pyrolyzed OC (OP), levoglucosan (LG), mannosan (MN), galactosan, syringaldehyde, vanillic acid (VA) and cholesterol. The average concentrations of OP, LG, MN, galactosan, VA and cholesterol were higher during the southwestern monsoon season (June-September) than during the northeastern monsoon season (December-March), and these differences were statistically significant. Conversely, the syringaldehyde concentration during the southwestern monsoon season was lower. The PM2.5 OP / OC4 mass ratio allowed distinguishing the seven samples, which have been affected by the Indonesian peatland fires (IPFs). In addition, we observed significant differences in the concentrations between the Indonesian peatland fire (IPF) and other samples of many chemical species. Thus, the chemical characteristics of PM2.5 in Malaysia appeared to be significantly influenced by IPFs during the southwestern monsoon season. Furthermore, we evaluated two indicators, the vanillic acid / syringic acid (VA / SA) and LG / MN mass ratios, which have been suggested as indicators of IPFs. The LG / MN mass ratio ranged from 14 to 22 in the IPF samples and from 11 to 31 in the other samples. Thus, the respective variation ranges partially overlapped. Consequently, this ratio did not satisfactorily reflect the effects of IPFs in Malaysia. In contrast, the VA / SA mass ratio may serve as a good indicator, since it significantly differed between the IPF and other samples. However, the OP / OC4 mass ratio provided more remarkable differences than the VA / SA mass ratio, offering an even better indicator. Finally, we

  2. Latitudinal range influences the seasonal variation in the foraging behavior of marine top predators.

    PubMed

    Villegas-Amtmann, Stella; Simmons, Samantha E; Kuhn, Carey E; Huckstadt, Luis A; Costa, Daniel P

    2011-01-01

    Non-migratory resident species should be capable of modifying their foraging behavior to accommodate changes in prey abundance and availability associated with a changing environment. Populations that are better adapted to change will have higher foraging success and greater potential for survival in the face of climate change. We studied two species of resident central place foragers from temperate and equatorial regions with differing population trends and prey availability associated to season, the California sea lion (Zalophus californianus) (CSL) whose population is increasing and the endangered Galapagos sea lion (Zalophus wollebaeki) (GSL) whose population is declining. To determine their response to environmental change, we studied and compared their diving behavior using time-depth recorders and satellite location tags and their diet by measuring C and N isotope ratios during a warm and a cold season. Based on latitudinal differences in oceanographic productivity, we hypothesized that the seasonal variation in foraging behavior would differ for these two species. CSL exhibited greater seasonal variability in their foraging behavior as seen in changes to their diving behavior, foraging areas and diet between seasons. Conversely, GSL did not change their diving behavior between seasons, presenting three foraging strategies (shallow, deep and bottom divers) during both. GSL exhibited greater dive and foraging effort than CSL. We suggest that during the warm and less productive season a greater range of foraging behaviors in CSL was associated with greater competition for prey, which relaxed during the cold season when resource availability was greater. GSL foraging specialization suggests that resources are limited throughout the year due to lower primary production and lower seasonal variation in productivity compared to CSL. These latitudinal differences influence their foraging success, pup survival and population growth reflected in contrasting population

  3. Monitoring water storage variations in the vadose zone with gravimeters - quantifying the influence of observatory buildings

    NASA Astrophysics Data System (ADS)

    Reich, Marvin; Güntner, Andreas; Mikolaj, Michal; Blume, Theresa

    2016-04-01

    Time-lapse ground-based measurements of gravity have been shown to be sensitive to water storage variations in the surroundings of the gravimeter. They thus have the potential to serve as an integrative observation of storage changes in the vadose zone. However, in almost all cases of continuous gravity measurements, the gravimeter is located within a building which seals the soil beneath it from natural hydrological processes like infiltration and evapotranspiration. As water storage changes in close vicinity of the gravimeter have the strongest influence on the measured signal, it is important to understand the hydrology in the unsaturated soil zone just beneath the impervious building. For this reason, TDR soil moisture sensors were installed in several vertical profiles up to a depth of 2 m underneath the planned new gravimeter building at the Geodetic Observatory Wettzell (southeast Germany). In this study, we assess the influence of the observatory building on infiltration and subsurface flow patterns and thus the damping effect on gravimeter data in a two-way approach. Firstly, soil moisture time series of sensors outside of the building area are correlated with corresponding sensors of the same depth beneath the building. The resulting correlation coefficients, time lags and signal to noise relationships are used to find out how and where infiltrating water moves laterally beneath the building and towards its centre. Secondly, a physically based hydrological model (HYDRUS) with high discretization in space and time is set up for the 20 by 20 m area around and beneath the gravimeter building. The simulated spatial distribution of soil moisture in combination with the observed point data help to identify where and to what extent water storage changes and thus mass transport occurs beneath the building and how much this differs to the dynamics of the surroundings. This allows to define the umbrella space, i.e., the volume of the vadose zone where no mass

  4. Pollinator visitation patterns strongly influence among-flower variation in selfing rate

    PubMed Central

    Karron, Jeffrey D.; Holmquist, Karsten G.; Flanagan, Rebecca J.; Mitchell, Randall J.

    2009-01-01

    Background and Aims Adjacent flowers on Mimulus ringens floral displays often vary markedly in selfing rate. We hypothesized that this fine-scale variation in mating system reflects the tendency of bumble-bee pollinators to probe several flowers consecutively on multiflower displays. When a pollinator approaches a display, the first flower probed is likely to receive substantial outcross pollen. However, since pollen carryover in this species is limited, receipt of self pollen should increase rapidly for later flowers. Here the first direct experimental test of this hypothesis is described. Methods In order to link floral visitation sequences with selfing rates of individual flowers, replicate linear arrays were established, each composed of plants with unique genetic markers. This facilitated unambiguous assignment of paternity to all sampled progeny. A single wild bumble-bee was permitted to forage on each linear array, recording the order of floral visits on each display. Once fruits had matured, 120 fruits were harvested (four flowers from each of five floral displays in each of six arrays). Twenty-five seedlings from each fruit were genotyped and paternity was unambiguously assigned to all 3000 genotyped progeny. Key Results The order of pollinator probes on Mimulus floral displays strongly and significantly influenced selfing rates of individual fruits. Mean selfing rates increased from 21 % for initial probes to 78 % for the fourth flower probed on each display. Conclusions Striking among-flower differences in selfing rate result from increased deposition of geitonogamous (among-flower, within-display) self pollen as bumble-bees probe consecutive flowers on each floral display. The resulting heterogeneity in the genetic composition of sibships may influence seedling competition and the expression of inbreeding depression. PMID:19218584

  5. Influence of hemodynamic variations on the pharmacokinetics of landiolol in patients undergoing cardiovascular surgery.

    PubMed

    Matsumoto, Naoki; Aomori, Tohru; Kanamoto, Masafumi; Usui, Tadashi; Shiga, Tatsuya; Yamamoto, Koujirou; Saito, Shigeru

    2012-01-01

    Although landiolol is useful in the emergency management of atrial fibrillation, atrial flutter, and tachycardia, as well as in perioperative arrhythmia control, the influence of hemodynamic changes on the pharmacokinetics of landiolol is unknown. We investigated the influence of hemodynamic variation and the following hepatocirculatory changes after systemic heparinization on the pharmacokinetics of landiolol in patients undergoing cardiovascular surgery under cardiopulmonary bypass. Cardiac output and cardiac index (CI) were continuously monitored in 19 patients using an arterial pressure-based cardiac output monitor. The middle and right hepatic venous blood flow indexes (mHVBFI and rHVBFI) were measured by transesophageal echocardiography, and hemodynamic data were collected at points (T1-T3) as follows: T1, before administration of heparin and after sternotomy; T2, just before systemic heparinization (300 U/kg); T3, 10 min after T2. The plasma concentration of landiolol was measured by HPLC at the same point. After administration of heparin, mean arterial blood pressure, CI, mHVBFI, and rHVBFI were significantly decreased (<0.05). Heart rate was not significantly changed. After systemic heparinization, the landiolol concentration was significantly decreased from 0.407±0.251 µg·mL(-1) to 0.232±0.207 µg·mL(-1) (<0.01). There was no significant difference between T1 and T2 (=0.88). In conclusion, the plasma concentration of landiolol was decreased by diminished CI due to systemic heparinization, but not affected by the change of hepatic blood flow. PMID:22864018

  6. Influence of barriers to movement on within-watershed genetic variation of coastal cutthroat trout

    USGS Publications Warehouse

    Wofford, John E.B.; Gresswell, Robert E.; Banks, M.A.

    2005-01-01

    Because human land use activities often result in increased fragmentation of aquatic and terrestrial habitats, a better understanding of the effects of fragmentation on the genetic heterogeneity of animal populations may be useful for effective management. We used eight microsatellites to examine the genetic structure of coastal cutthroat trout (Oncorhynchus clarki clarki) in Camp Creek, an isolated headwater stream in western Oregon. Our objectives were to determine if coastal cutthroat trout were genetically structured within streams and to assess the effects of natural and anthropogenic barriers on coastal cutthroat trout genetic variation. Fish sampling occurred at 10 locations, and allele frequencies differed significantly among all sampling sections. Dispersal barriers strongly influenced coastal cutthroat trout genetic structure and were associated with reduced genetic diversity and increased genetic differentiation. Results indicate that Camp Creek coastal cutthroat trout exist as many small, partially independent populations that are strongly affected by genetic drift. In headwater streams, barriers to movement can result in genetic and demographic isolation leading to reduced coastal cutthroat trout genetic diversity, and potentially compromising long-term population persistence. When habitat fragmentation eliminates gene flow among small populations, similar results may occur in other species.

  7. Individual variation in the propensity to attribute incentive salience to a food cue: influence of sex

    PubMed Central

    Pitchers, Kyle K.; Flagel, Shelly B.; O’Donnell, Elizabeth G.; Solberg Woods, Leah C.; Sarter, M.; Robinson, Terry E.

    2014-01-01

    There is considerable individual variation in the propensity of animals to attribute incentive salience to discrete reward cues, but to date most of this research has been conducted in male rats. The purpose of this study was to determine whether sex influences the propensity to attribute incentive salience to a food cue, using rats from two different outbred strains (Sprague-Dawley [SD] and Heterogeneous Stock [HS]). The motivational value of a food cue was assessed in two ways: (i) by the ability of the cue to elicit approach towards it and (ii) by its ability to act as a conditioned reinforcer. We found that female SD rats acquired Pavlovian conditioned approach behavior slightly faster than males, but no sex difference was detected in HS rats, and neither strain showed a sex difference in asymptotic performance of approach behavior. Moreover, female approach behavior did not differ across estrous cycle. Compared to males, females made more active responses during the test for conditioned reinforcement, although they made more inactive responses as well. We conclude that although there are small sex differences in performance on these tasks, these are probably not due to a notable sex difference in the propensity to attribute incentive salience to a food cue. PMID:25446811

  8. Lead in Chinese villager house dust: Geographical variation and influencing factors.

    PubMed

    Bi, Xiangyang; Liu, Jinling; Han, Zhixuan; Yang, Wenlin

    2015-12-01

    House dust has been recognized as an important contributor to Pb exposure of children. Here we conducted a comprehensive study to investigate geographical variation of Pb in Chinese villager house dust. The influences of outdoor soil Pb concentrations, dates of construction, house decoration materials, heating types, and site specific pollution on Pb concentrations in house dust were evaluated. The concentrations of Pb in 477 house dust samples collected from twenty eight areas throughout China varied from 12 to 2510 mg/kg, with a median concentration of 42 mg/kg. The median Pb concentrations in different geographical areas ranged from 16 (Zhangjiakou, Hebei) to 195 mg/kg (Loudi, Hunan). No correlations were found between the house dust Pb concentrations and the age of houses, as well as house decoration materials. Whereas outdoor soil, coal combustion, and site specific pollution may be potential Pb sources. Principal component analysis (PCA) confirmed that elemental compositions of the house dust were controlled by both anthropogenic and geogenic sources. Using scanning electron microscopy (SEM), the Pb bearing particles in the house dust were also studied. PMID:26381088

  9. Predation risk and longevity influence variation in fitness of female roe deer (Capreolus capreolus L.).

    PubMed Central

    Kjellander, Petter; Gaillard, Jean-Michel; Hewison, Mark; Liberg, Olof

    2004-01-01

    We studied the effects of population density, red fox predation risk, individual body mass and longevity on female fitness in a free-ranging roe deer population. During the study, population density varied from 9.3 to 36.1 deer km(-2), and red fox abundance varied strongly over years owing to a sarcoptic mange outbreak. In support of our predictions, long-lived females had higher fitness than short-lived ones. Further, fortunate female roe deer that gave birth in years of low red fox abundance attained much higher fitness than those that gave birth in years of high red fox abundance. Longevity and predation risk explained more than half the variation in fitness observed among roe deer females. As a possible effect of small sample size, we found no effect of female body mass or population density at birth. Our study demonstrates that predation risk, a component of environmental stochasticity, may prevent directional selection even when phenotypic quality influences individual fitness. PMID:15504011

  10. Individual variation in the propensity to attribute incentive salience to a food cue: influence of sex.

    PubMed

    Pitchers, Kyle K; Flagel, Shelly B; O'Donnell, Elizabeth G; Woods, Leah C Solberg; Sarter, Martin; Robinson, Terry E

    2015-02-01

    There is considerable individual variation in the propensity of animals to attribute incentive salience to discrete reward cues, but to date most of this research has been conducted in male rats. The purpose of this study was to determine whether sex influences the propensity to attribute incentive salience to a food cue, using rats from two different outbred strains (Sprague-Dawley [SD] and Heterogeneous Stock [HS]). The motivational value of a food cue was assessed in two ways: (i) by the ability of the cue to elicit approach toward it and (ii) by its ability to act as a conditioned reinforcer. We found that female SD rats acquired Pavlovian conditioned approach behavior slightly faster than males, but no sex difference was detected in HS rats, and neither strain showed a sex difference in asymptotic performance of approach behavior. Moreover, female approach behavior did not differ across estrous cycle. Compared to males, females made more active responses during the test for conditioned reinforcement, although they made more inactive responses as well. We conclude that although there are small sex differences in performance on these tasks, these are probably not due to a notable sex difference in the propensity to attribute incentive salience to a food cue. PMID:25446811

  11. Seasonal variation and factors influencing perchlorate in water, snow, soil and corns in Northeastern China.

    PubMed

    Ye, Long; You, Hong; Yao, Jie; Kang, Xi; Tang, Lu

    2013-03-01

    Seasonal variation and influencing factors of perchlorate in snow, surface soil, rain, surface water, groundwater and corn were studied. Seven hundreds and seventy samples were collected in different periods in Harbin and its vicinity, China. Perchlorate concentrations were analyzed by ion chromatography-electrospray mass spectrometry. Results indicate that fireworks and firecrackers display from the Spring Festival to the Lantern Festival (February 2, 2011-February 17, 2011) can result in the occurrence of perchlorate in surface soil and snow. Perchlorate distribution is affected by wind direction in winter. Melting snow which contained perchlorate can dissolve perchlorate in surface soil, and then perchlorate can percolate into groundwater so that perchlorate concentrations in groundwater increased in spring. Perchlorate concentrations in groundwater and surface water decrease after rainy season in summer. Groundwater samples collected in the floodplain areas of the Songhua River and the Ashi River contained higher perchlorate concentrations than that far away with the rivers. The corns have the ability to accumulate perchlorate. PMID:23287025

  12. Using PCDS to study the influence of UV flux variation on the middle atmosphere

    NASA Technical Reports Server (NTRS)

    Heilman, W.

    1986-01-01

    The value of the Pilot Climate Data System (PCDS) in examining the influences of short-period solar flux variations on the middle atmosphere was demonstrated. Several Nimbus satellite data sets proposed for the study exist in the PCDS. Planned for retrieval through the PCDS are ozone mixing ratios and cumulative ozone profiles available from the Backscatter Ultraviolet Spectrophotometer on Nimbus-4. Also to be accessed are Nimbus-7 data sets that will provide ozone and nitrogen dioxide mixing ratios, temperature profiles from the Limb Infrared Monitor of the Stratosphere, and ozone mixing ratio profiles from the Solar Backscatter Ultraviolet Spectrophotometer. Bypassing the time-consuming process of reading raw data tapes, the researchers plan to transfer the PCDS processed data to an IBM PC at Iowa State University. The IBM PC will serve as an intermediate vehicle for transferring the data to the NOAA CYBER 840 at Boulder, Colorado, where research will continue on both an eight-layer radiative-photochemical numerical model and on a nonlinear dynamical model. in this research are the FGGE and ERB data sets. These relevant data sets also reside in the PCDS. Problems associated with remote access to the PCDS were discussed in regard to all the PCDS data sets.

  13. Ozone reaction with interior building materials: Influence of diurnal ozone variation, temperature and humidity

    NASA Astrophysics Data System (ADS)

    Rim, Donghyun; Gall, Elliott T.; Maddalena, Randy L.; Nazaroff, William W.

    2016-01-01

    Elevated tropospheric ozone concentrations are associated with increased morbidity and mortality. Indoor ozone chemistry affects human exposure to ozone and reaction products that also may adversely affect health and comfort. Reactive uptake of ozone has been characterized for many building materials; however, scant information is available on how diurnal variation of ambient ozone influences ozone reaction with indoor surfaces. The primary objective of this study is to investigate ozone-surface reactions in response to a diurnally varying ozone exposure for three common building materials: ceiling tile, painted drywall, and carpet tile. A secondary objective is to examine the effects of air temperature and humidity. A third goal is to explore how conditioning of materials in an occupied office building might influence subsequent ozone-surface reactions. Experiments were performed at bench-scale with inlet ozone concentrations varied to simulate daytime (ozone elevated) and nighttime (ozone-free in these experiments) periods. To simulate office conditions, experiments were conducted at two temperatures (22 °C and 28 °C) and three relative humidity values (25%, 50%, 75%). Effects of indoor surface exposures were examined by placing material samples in an occupied office and repeating bench-scale characterization after exposure periods of 1 and 2 months. Deposition velocities were observed to be highest during the initial hour of ozone exposure with slow decrease in the subsequent hours of simulated daytime conditions. Daily-average ozone reaction probabilities for fresh materials are in the respective ranges of (1.7-2.7) × 10-5, (2.8-4.7) × 10-5, and (3.0-4.5) × 10-5 for ceiling tile, painted drywall, and carpet tile. The reaction probability decreases by 7%-47% across the three test materials after two 8-h periods of ozone exposure. Measurements with the samples from an occupied office reveal that deposition velocity can decrease or increase with time

  14. Differences in Muscle Activity During Cable Resistance Training Are Influenced by Variations in Handle Types.

    PubMed

    Rendos, Nicole K; Heredia Vargas, Héctor M; Alipio, Taislaine C; Regis, Rebeca C; Romero, Matthew A; Signorile, Joseph F

    2016-07-01

    Rendos, NK, Heredia Vargas, HM, Alipio, TC, Regis, RC, Romero, MA, and Signorile, JF. Differences in muscle activity during cable resistance training are influenced by variations in handle types. J Strength Cond Res 30(7): 2001-2009, 2016-There has been a recent resurgence in the use of cable machines for resistance training allowing movements that more effectively simulate daily activities and sports-specific movements. By necessity, these devices require a machine/human interface through some type of handle. Considerable data from material handling, industrial engineering, and exercise training studies indicate that handle qualities, especially size and shape, can significantly influence force production and muscular activity, particularly of the forearm muscles, which affect the critical link in activities that require object manipulation. The purpose for this study was to examine the influence of three different handle conditions: standard handle (StandH), ball handle with the cable between the index and middle fingers (BallIM), and ball handle with the cable between the middle and ring fingers (BallMR), on activity levels (rmsEMG) of the triceps brachii lateral and long heads (TriHLat, TriHLong), brachioradialis (BR), flexor carpi radialis (FCR), extensor carpi ulnaris, and extensor digitorum (ED) during eight repetitions of standing triceps pushdown performed from 90° to 0° elbow flexion at 1.5 s per contractile stage. Handle order was randomized. No significant differences were seen for triceps or BR rmsEMG across handle conditions; however, relative patterns of activation did vary for the forearm muscles by handle condition, with more coordinated activation levels for the FCR and ED during the ball handle conditions. In addition, the rmsEMG for the ED was significantly higher during the BallIM than any other condition and during the BallMR than the StandH. These results indicate that the use of ball handles with the cable passing between different fingers

  15. The influence of task variation on manifestation of fatigue is ambiguous - a literature review.

    PubMed

    Luger, Tessy; Bosch, Tim; Veeger, Dirkjan; de Looze, Michiel

    2014-01-01

    Task variation has been proposed to reduce shoulder fatigue resulting from repetitive hand-arm tasks. This review analyses the effect of task variation, both 'temporal (i.e. change of work-rest ratio)' and 'activity (i.e. job rotation)' variation, on physiological responses, endurance time (ET) and subjective feelings. Pubmed was searched and complemented with references from selected articles, resulting in 17 articles. Temporal variation had some positive effects on the objective parameters, as blood pressure decreased and ET increased, and on the subjective feelings, as perceived discomfort decreased. The observed findings of activity variation showed both positive and negative effects of increased activity variation, while hardly any effects were found on electromyography manifestations of fatigue. In conclusion, the evidence for positive effects of increasing the level of variation is scarce. The number of studies on variation is limited, while in most studies the findings were not controlled for the amount or intensity of work. PMID:24552472

  16. Variations in leopard cat (Prionailurus bengalensis) skull morphology and body size: sexual and geographic influences

    PubMed Central

    Oliveira, Luiz Flamarion B.

    2015-01-01

    The leopard cat, Prionailurus bengalensis (Kerr, 1792), is one of the most widespread Asian cats, occurring in continental eastern and southeastern Asia. Since 1929, several studies have focused on the morphology, ecology, and taxonomy of leopard cats. Nevertheless, hitherto there has been no agreement on basic aspects of leopard cat biology, such as the presence or absence of sexual dimorphism, morphological skull and body differences between the eleven recognized subspecies, and the biogeography of the different morphotypes. Twenty measurements on 25 adult leopard cat skulls from different Asian localities were analyzed through univariate and multivariate statistical approaches. Skull and external body measurements from studies over the last 77 years were assembled and organized in two categories: full data and summary data. Most of this database comprises small samples, which have never been statistically tested and compared with each other. Full data sets were tested with univariate and multivariate statistical analyses; summary data sets (i.e., means, SDs, and ranges) were analyzed through suitable univariate approaches. The independent analyses of the data from these works confirmed our original results and improved the overview of sexual dimorphism and geographical morphological variation among subspecies. Continental leopard cats have larger skulls and body dimensions. Skulls of Indochinese morphotypes have broader and higher features than those of continental morphotypes, while individuals from the Sunda Islands have skulls with comparatively narrow and low profiles. Cranial sexual dimorphism is present in different degrees among subspecies. Most display subtle sex-related variations in a few skull features. However, in some cases, sexual dimorphism in skull morphology is absent, such as in P. b. sumatranus and P. b. borneoensis. External body measurement comparisons also indicate the low degree of sexual dimorphism. Apart from the gonads, the longer hind

  17. Annual variations of carbonaceous PM2.5 in Malaysia: influence by Indonesian peatland fires

    NASA Astrophysics Data System (ADS)

    Fujii, Y.; Tohno, S.; Amil, N.; Latif, M. T.; Oda, M.; Matsumoto, J.; Mizohata, A.

    2015-08-01

    In this study, we quantified carbonaceous PM2.5 in Malaysia through annual observations of PM2.5, focusing on organic compounds derived from biomass burning. We determined organic carbon (OC), elemental carbon (EC) and concentrations of solvent-extractable organic compounds (biomarkers derived from biomass burning sources and n-alkanes). We observed seasonal variations in the concentrations of pyrolyzed OC (OP), levoglucosan (LG), mannosan (MN), galactosan, syringaldehyde, vanillic acid (VA) and cholesterol. The average concentrations of OP, LG, MN, galactosan, VA and cholesterol were higher during the southwest monsoon season (June-September) than during the northeast monsoon season (December-March), and these differences were statistically significant. Conversely, the syringaldehyde concentration during the southwest monsoon season was lower. The PM2.5 OP/OC4 mass ratio allowed distinguishing the seven samples, which have been affected by the Indonesian peatland fires (IPFs). In addition, we observed significant differences in the concentrations between the IPF and other samples of many chemical species. Thus, the chemical characteristics of PM2.5 in Malaysia appeared to be significantly influenced by IPFs during the southwest monsoon season. Furthermore, we evaluated two indicators, the vanillic acid/syringic acid (VA/SA) and LG/MN mass ratios, which have been suggested as indicators of IPFs. The LG/MN mass ratio ranged from 14 to 22 in the IPF samples and from 11 to 31 in the other samples. Thus, the respective variation ranges partially overlapped. Consequently, this ratio did not satisfactorily reflect the effects of IPFs in Malaysia. In contrast, the VA/SA mass ratio may serve as a good indicator, since it significantly differed between the IPF and other samples. However, the OP/OC4 mass ratio provided more remarkable differences than the VA/SA mass ratio, offering an even better indicator. Finally, we extracted biomass burning emissions' sources such as IPF

  18. Variations in leopard cat (Prionailurus bengalensis) skull morphology and body size: sexual and geographic influences.

    PubMed

    Sicuro, Fernando L; Oliveira, Luiz Flamarion B

    2015-01-01

    The leopard cat, Prionailurus bengalensis (Kerr, 1792), is one of the most widespread Asian cats, occurring in continental eastern and southeastern Asia. Since 1929, several studies have focused on the morphology, ecology, and taxonomy of leopard cats. Nevertheless, hitherto there has been no agreement on basic aspects of leopard cat biology, such as the presence or absence of sexual dimorphism, morphological skull and body differences between the eleven recognized subspecies, and the biogeography of the different morphotypes. Twenty measurements on 25 adult leopard cat skulls from different Asian localities were analyzed through univariate and multivariate statistical approaches. Skull and external body measurements from studies over the last 77 years were assembled and organized in two categories: full data and summary data. Most of this database comprises small samples, which have never been statistically tested and compared with each other. Full data sets were tested with univariate and multivariate statistical analyses; summary data sets (i.e., means, SDs, and ranges) were analyzed through suitable univariate approaches. The independent analyses of the data from these works confirmed our original results and improved the overview of sexual dimorphism and geographical morphological variation among subspecies. Continental leopard cats have larger skulls and body dimensions. Skulls of Indochinese morphotypes have broader and higher features than those of continental morphotypes, while individuals from the Sunda Islands have skulls with comparatively narrow and low profiles. Cranial sexual dimorphism is present in different degrees among subspecies. Most display subtle sex-related variations in a few skull features. However, in some cases, sexual dimorphism in skull morphology is absent, such as in P. b. sumatranus and P. b. borneoensis. External body measurement comparisons also indicate the low degree of sexual dimorphism. Apart from the gonads, the longer hind

  19. The Binding of Antigenic Peptides to HLA-DR Is Influenced by Interactions between Pocket 6 and Pocket 91

    PubMed Central

    James, Eddie A.; Moustakas, Antonis K.; Bui, John; Nouv, Randi; Papadopoulos, George K.; Kwok, William W.

    2013-01-01

    Peptide binding to class II MHC protein is commonly viewed as a combination of discrete anchor residue preferences for pockets 1, 4, 6/7, and 9. However, previous studies have suggested cooperative effects during the peptide binding process. Investigation of the DRB1*0901 binding motif demonstrated a clear interaction between peptide binding pockets 6 and 9. In agreement with prior studies, pockets 1 and 4 exhibited clear binding preferences. Previously uncharacterized pockets 6 and 7 accommodated a wide variety of residues. However, although it was previously reported that pocket 9 is completely permissive, several substitutions at this position were unable to bind. Structural modeling revealed a probable interaction between pockets 6 and 9 through β9Lys. Additional binding studies with doubly substituted peptides confirmed that the amino acid bound within pocket 6 profoundly influences the binding preferences for pocket 9 of DRB1*0901, causing complete permissiveness of pocket 9 when a small polar residue is anchored in pocket 6 but accepting relatively few residues when a basic residue is anchored in pocket 6. The β9Lys residue is unique to DR9 alleles. However, similar studies with doubly substituted peptides confirmed an analogous interaction effect for DRA1/B1*0301, a β9Glu allele. Accounting for this interaction resulted in improved epitope prediction. These findings provide a structural explanation for observations that an amino acid in one pocket can influence binding elsewhere in the MHC class II peptide binding groove. PMID:19648278

  20. Seasonal variation influences outcomes following lung cancer resections⋆, ⋆⋆

    PubMed Central

    LaPar, Damien J.; Nagji, Alykhan S.; Bhamidipati, Castigliano M.; Kozower, Benjamin D.; Lau, Christine L.; Ailawadi, Gorav; Jones, David R.

    2011-01-01

    Objective The effect of seasonal variation on postoperative outcomes following lung cancer resections is unknown. We hypothesized that postoperative outcomes following surgical resection for lung cancer within the United States would not be impacted by operative season. Methods From 2002 to 2007, 182 507 isolated lung cancer resections (lobectomy (n = 147 937), sublobar resection (n = 21 650), and pneumonectomy (n = 13 916)) were evaluated using the Nationwide Inpatient Sample (NIS) database. Patients were stratified according to operative season: spring (n = 47 382), summer (n = 46 131), fall (n = 45 370) and winter (n = 43 624). Multivariate regression models were applied to assess the effect of operative season on adjusted postoperative outcomes. Results Patient co-morbidities and risk factors were similar despite the operative season. Lobectomy was the most common operation performed: spring (80.0%), summer (81.3%), fall (81.8%), and winter (81.1%). Lung cancer resections were more commonly performed at large, high-volume (>75th percentile operative volume) centers (P < 0.001). Unadjusted mortality was lowest during the spring (2.6%, P < 0.001) season compared with summer (3.1%), fall (3.0%) and winter (3.2%), while complications were most common in the fall (31.7%, P < 0.001). Hospital length of stay was longest for operations performed in the winter season (8.92 ± 0.11 days, P < 0.001). Importantly, multivariable logistic regression revealed that operative season was an independent predictor of in-hospital mortality (P < 0.001) and of postoperative complications (P < 0.001). Risk-adjusted odds of in-hospital mortality were increased for lung cancer resections occurring during all other seasons compared with those occurring in the spring. Conclusions Outcomes following surgical resection for lung cancer are independently influenced by time of year. Risk-adjusted in-hospital mortality and hospital length of stay were lowest during the spring season. PMID

  1. Influence of the interplanetary shock on the heliocentric radial variations of gradual SEP events

    NASA Astrophysics Data System (ADS)

    Aran, Angels; Jacobs, Carla; Sanahuja, Blai; Poedts, Stefaan; Lario, David; Rodriguez-Gasen, Rosa

    The inclusion of a travelling shock as a source of energetic particles during gradual solar ener-getic particle (SEP) events is a key element to assess the radiation encountered by a mission in the inner heliosphere. We have developed, in the frame of the Solar Energetic Particle Envi-ronment Model (SEPEM) project, a new two dimensional (2D) magnetohydrodynamic (MHD) model to describe the shock propagation from 4 solar radii up to 1.6 AU. The outputs of this model are used to simulate the transport of SEPs from the shock front up to a given observer. The combination of the shock and particle transport models allows us to study the influence of both the shock properties and the observer's magnetic connection on the radial and longitudinal variation of proton peak intensities and fluences in gradual SEP events. We have simulated the propagation of six shocks characterized by three different transit times to 1 AU and two different angular widths (narrow and wide). Two sets of spacecraft are placed along two nominal interplanetary magnetic field lines in the undisturbed solar wind but at different radial distances from the Sun. The two observers at 1 AU are located at central meridian and western positions with respect to the nose of each shock. For each spacecraft, synthetic proton time-intensity profiles at several energies (1.0 < E < 128 MeV) are produced. By tracking the shock from close to the Sun, we obtain the peak intensity of high energy particles at the prompt component of the SEP events, without assuming ad-hoc conditions for particle injection at the corona. We discuss how the resulting power-law dependences of the peak intensities (and fluences) on the observer's radial distance vary with the particle energy, the characteristics of the shock, and the different evolving conditions for particle injection at the cobpoint.

  2. The Influence of Social Systems on Patterns of Mitochondrial DNA Variation in Baboons.

    PubMed

    Kopp, G H; Ferreira da Silva, M J; Fischer, J; Brito, J C; Regnaut, S; Roos, C; Zinner, D

    2014-01-01

    Behavior is influenced by genes but can also shape the genetic structure of natural populations. Investigating this link is of great importance because behavioral processes can alter the genetic diversity on which selection acts. Gene flow is one of the main determinants of the genetic structure of a population and dispersal is the behavior that mediates gene flow. Baboons (genus Papio) are among the most intensely studied primate species and serve as a model system to investigate the evolution of social systems using a comparative approach. The general mammalian pattern of male dispersal and female philopatry has thus far been found in baboons, with the exception of hamadryas baboons (Papio hamadryas). As yet, the lack of data on Guinea baboons (Papio papio) creates a taxonomic gap in genus-wide comparative analyses. In our study we investigated the sex-biased dispersal pattern of Guinea baboons in comparison to hamadryas, olive, yellow, and chacma baboons using sequences of the maternally transmitted mitochondrial hypervariable region I. Analyzing whole-range georeferenced samples (N = 777), we found strong evidence for female-biased gene flow in Guinea baboons and confirmed this pattern for hamadryas baboons, as shown by a lack of genetic-geographic structuring. In addition, most genetic variation was found within and not among demes, in sharp contrast to the pattern observed in matrilocal primates including the other baboon taxa. Our results corroborate the notion that the Guinea baboons' social system shares some important features with that of hamadryas baboons, suggesting similar evolutionary forces have acted to distinguish them from all other baboons. PMID:24523566

  3. Influence of in situ stress variations on acoustic emissions: a numerical study

    NASA Astrophysics Data System (ADS)

    Zhao, Qi; Tisato, Nicola; Grasselli, Giovanni; Mahabadi, Omid K.; Lisjak, Andrea; Liu, Qinya

    2015-11-01

    The study of acoustic emissions (AEs) is of paramount importance to understand rock deformation processes. AE recorded during laboratory experiments mimics, in a controlled geometry and environment, natural and induced seismicity. However, these experiments are destructive, time consuming and require a significant amount of resources. Lately, significant progresses have been made in numerical simulations of rock failure processes, providing detailed insights into AE. We utilized the 2-D combined finite-discrete element method to simulate the deformation of Stanstead Granite under varying confining pressure (Pc) and demonstrated that the increase of confining pressure, Pc, (i) shifts failures from tensile towards shear dominated and (ii) enhance the macroscopic ductility. We quantitatively describe the AE activity associated with the fracturing process by assessing the spatial fractal dimension (D-value), the temporal distribution (AE rate) and the slope of the frequency-magnitude distribution (b-value). Based on the evaluation of D-value and AE rate, we defined two distinct deformation phases: Phase I and Phase II. The influence of Pc on the spatial distribution of AE varies according to the deformation phase: for increasing Pc, D-value decreases and increases during Phases I and II, respectively. In addition, b-value decreases with increasing Pc during the entire experiment. Our numerical results show for the first time that variations of D- and b-values as a function of in situ stress can be simulated using the combined finite-discrete element approach. We demonstrate that the examination of seismicity should be carried out carefully, taking into consideration the deformation phase and in situ stress conditions.

  4. Metabarcoding reveals environmental factors influencing spatio-temporal variation in pelagic micro-eukaryotes.

    PubMed

    Brannock, Pamela M; Ortmann, Alice C; Moss, Anthony G; Halanych, Kenneth M

    2016-08-01

    Marine environments harbour a vast diversity of micro-eukaryotic organisms (protists and other small eukaryotes) that play important roles in structuring marine ecosystems. However, micro-eukaryote diversity is not well understood. Likewise, knowledge is limited regarding micro-eukaryote spatial and seasonal distribution, especially over long temporal scales. Given the importance of this group for mobilizing energy from lower trophic levels near the base of the food chain to larger organisms, assessing community stability, diversity and resilience is important to understand ecosystem health. Herein, we use a metabarcoding approach to examine pelagic micro-eukaryote communities over a 2.5-year time series. Bimonthly surface sampling (July 2009 to December 2011) was conducted at four locations within Mobile Bay (Bay) and along the Alabama continental shelf (Shelf). Alpha-diversity only showed significant differences in Shelf sites, with the greatest differences observed between summer and winter. Beta-diversity showed significant differences in community composition in relation to season and the Bay was dominated by diatoms, while the Shelf was characterized by dinoflagellates and copepods. The northern Gulf of Mexico is heavily influenced by the Mobile River Basin, which brings low-salinity nutrient-rich water mostly during winter and spring. Community composition was correlated with salinity, temperature and dissolved silicate. However, species interactions (e.g. predation and parasitism) may also contribute to the observed variation, especially on the Shelf, which warrants further exploration. Metabarcoding revealed clear patterns in surface pelagic micro-eukaryote communities that were consistent over multiple years, demonstrating how these techniques could be greatly beneficial to ecological monitoring and management over temporal scales. PMID:27238767

  5. Sequence Variations and Protein Expression Levels of the Two Immune Evasion Proteins Gpm1 and Pra1 Influence Virulence of Clinical Candida albicans Isolates

    PubMed Central

    Luo, Shanshan; Hipler, Uta-Christina; Münzberg, Christin; Skerka, Christine; Zipfel, Peter F.

    2015-01-01

    Candida albicans, the important human fungal pathogen uses multiple evasion strategies to control, modulate and inhibit host complement and innate immune attack. Clinical C. albicans strains vary in pathogenicity and in serum resistance, in this work we analyzed sequence polymorphisms and variations in the expression levels of two central fungal complement evasion proteins, Gpm1 (phosphoglycerate mutase 1) and Pra1 (pH-regulated antigen 1) in thirteen clinical C. albicans isolates. Four nucleotide (nt) exchanges, all representing synonymous exchanges, were identified within the 747-nt long GPM1 gene. For the 900-nt long PRA1 gene, sixteen nucleotide exchanges were identified, which represented synonymous, as well as non-synonymous exchanges. All thirteen clinical isolates had a homozygous exchange (A to G) at position 73 of the PRA1 gene. Surface levels of Gpm1 varied by 8.2, and Pra1 levels by 3.3 fold in thirteen tested isolates and these differences influenced fungal immune fitness. The high Gpm1/Pra1 expressing candida strains bound the three human immune regulators more efficiently, than the low expression strains. The difference was 44% for Factor H binding, 51% for C4BP binding and 23% for plasminogen binding. This higher Gpm1/Pra1 expressing strains result in enhanced survival upon challenge with complement active, Factor H depleted human serum (difference 40%). In addition adhesion to and infection of human endothelial cells was increased (difference 60%), and C3b surface deposition was less effective (difference 27%). Thus, variable expression levels of central immune evasion protein influences immune fitness of the human fungal pathogen C. albicans and thus contribute to fungal virulence. PMID:25692293

  6. Adjuvant Effect of Cationic Liposomes for Subunit Influenza Vaccine: Influence of Antigen Loading Method, Cholesterol and Immune Modulators

    PubMed Central

    Barnier-Quer, Christophe; Elsharkawy, Abdelrahman; Romeijn, Stefan; Kros, Alexander; Jiskoot, Wim

    2013-01-01

    Cationic liposomes are potential adjuvants for influenza vaccines. In a previous study we reported that among a panel of cationic liposomes loaded with influenza hemagglutinin (HA), DC-Chol:DPPC (1:1 molar ratio) liposomes induced the strongest immune response. However, it is not clear whether the cholesterol (Chol) backbone or the tertiary amine head group of DC-Chol was responsible for this. Therefore, in the present work we studied the influence of Chol in the lipid bilayer of cationic liposomes. Moreover, we investigated the effect of the HA loading method (adsorption versus encapsulation) and the encapsulation of immune modulators in DC-Chol liposomes on the immunogenicity of HA. Liposomes consisting of a neutral lipid (DPPC or Chol) and a cationic compound (DC-Chol, DDA, or eDPPC) were produced by film hydration-extrusion with/without an encapsulated immune modulator (CpG or imiquimod). The liposomes generally showed comparable size distribution, zeta potential and HA loading. In vitro studies with monocyte-derived human dendritic cells and immunization studies in C57Bl/6 mice showed that: (1) liposome-adsorbed HA is more immunogenic than encapsulated HA; (2) the incorporation of Chol in the bilayer of cationic liposomes enhances their adjuvant effect; and (3) CpG loaded liposomes are more efficient at enhancing HA-specific humoral responses than plain liposomes or Alhydrogel. PMID:24300513

  7. Cell Surface Expression Level Variation between Two Common Human Leukocyte Antigen Alleles, HLA-A2 and HLA-B8, Is Dependent on the Structure of the C Terminal Part of the Alpha 2 and the Alpha 3 Domains

    PubMed Central

    Dellgren, Christoffer; Nehlin, Jan O.; Barington, Torben

    2015-01-01

    Constitutive cell surface expression of Human Leukocyte Antigen (HLA) class I antigens vary extremely from tissue to tissue and individual antigens may differ widely in expression levels. Down-regulation of class I expression is a known immune evasive mechanism used by cancer cells and viruses. Moreover, recent observations suggest that even minor differences in expression levels may influence the course of viral infections and the frequency of complications to stem cell transplantation. We have shown that some human multipotent stem cells have high expression of HLA-A while HLA-B is only weakly expressed, and demonstrate here that this is also the case for the human embryonic kidney cell line HEK293T. Using quantitative flow cytometry and quantitative polymerase chain reaction we found expression levels of endogenous HLA-A3 (median 71,204 molecules per cell) 9.2-fold higher than the expression of-B7 (P = 0.002). Transfection experiments with full-length HLA-A2 and -B8 encoding plasmids confirmed this (54,031 molecules per cell vs. 2,466, respectively, P = 0.001) independently of transcript levels suggesting a post-transcriptional regulation. Using chimeric constructs we found that the cytoplasmic tail and the transmembrane region had no impact on the differential cell surface expression. In contrast, ~65% of the difference could be mapped to the six C-terminal amino acids of the alpha 2 domain and the alpha 3 domain (amino acids 176–284), i.e. amino acids not previously shown to be of importance for differential expression levels of HLA class I molecules. We suggest that the differential cell surface expression of two common HLA-A and–B alleles is regulated by a post-translational mechanism that may involve hitherto unrecognized molecules. PMID:26258424

  8. Natural Selection Promotes Antigenic Evolvability

    PubMed Central

    Graves, Christopher J.; Ros, Vera I. D.; Stevenson, Brian; Sniegowski, Paul D.; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed ‘cassettes’ that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections

  9. Circular dichroism, molecular modeling, and serology indicate that the structural basis of antigenic variation in foot-and-mouth disease virus is [alpha]-helix formation

    SciTech Connect

    France, L.L.; Piatti, P.G.; Newman, J.F.E.; Brown, F. ); Toth, I.; Gibbons, W.A. )

    1994-08-30

    Seven antigenic variants obtained from a single field isolate of foot-and-mouth disease virus, serotype A12, differ only at residues 148 and 153 in the immunodominant loop of viral protein VP1. Synthetic peptides corresponding to the region 141-160 are highly immunogenic. UV circular dichroism shows that (i) in aqueous solution of the peptides are nearly identical, but in 100% trifluoroethanol they display helix-forming properties which correlate well with their serological crossreactivities for anti-peptide sera, and (ii) these properties are insensitive to substitutions at position 153, except for proline, but are highly sensitive to substitutions at position 148. This pattern can be explained by the effects of these substitutions on the amphiphilic character and positions of helices postulated in the region 146-156. Molecular models indicate that residues 147, 148, 150, 151, 153-155, and 157 are most likely to interact with residues of the antibody paratopes. The data are consistent with the existence of an inverse [gamma]-turn around Pro-153, and a [beta]-turn at the cell-attachment site at residues 145-147. 31 refs., 5 figs.

  10. Factors influencing the short-term variation in phytoplankton composition and biomass in coral reef waters

    NASA Astrophysics Data System (ADS)

    van Duyl, F.; Gast, G.; Steinhoff, W.; Kloff, S.; Veldhuis, M.; Bak, R.

    2002-09-01

    The short-term temporal dynamics of phytoplankton composition was compared among coral reef waters, the adjacent ocean and polluted harbour water from July until October along the south-western coast of Curaçao, southern Caribbean. Temporal variations in phytoplankton pigment 'fingerprints' (zeaxanthin, chlorophyll b, 19'-hexanoyloxyfucoxanthin, fucoxanthin, 19'-butanoyloxyfucoxanthin, chlorophyll c 2 and c 3 relative to chlorophyll a) in the ocean were also observed in waters overlying the reef. However, with respect to specific pigments and algal-size distribution, the algal composition in reef waters was usually slightly different from that in the oceanic water. Phytoplankton biomass (chlorophyll a) was either higher or lower than in the oceanic water. The relative amount of fucoxanthin and peridinin was usually higher, and the relative and absolute amount of zeaxanthin was significantly lower than in oceanic water. Zeaxanthin-containing Synechococci were significantly reduced in reef water. Average algal cell size increased from the open water to the reef and the harbour entrance. Large centric diatoms (>20 m Ø) were better represented in reef than in oceanic water. In reef-overlying waters, the nitrate and nitrite concentrations were higher than in oceanic water. In front of the town, anthropogenic eutrophication (sewage discharge and ground water seepage) resulted in higher NH4, NO3 and PO4 concentrations than at other reef stations. This concurred with significantly enhanced phytoplankton biomass (chlorophyll a), chlorophyll c 2 and peridinin amounts at Town Reef compared with the other reef stations. Polluted harbour water usually showed the highest phytoplankton biomass of all stations, dominated by diatoms and dinoflagellates. Conditions in reef waters and harbour water promoted the occurrence and the relative abundance of diatoms and dinoflagellates. Harbour water did not influence the phytoplankton composition and biomass at reef stations situated >5

  11. The influence of RBE variations in a clinical proton treatment plan for a hypopharynx cancer

    NASA Astrophysics Data System (ADS)

    Tilly, N.; Johansson, J.; Isacsson, U.; Medin, J.; Blomquist, E.; Grusell, E.; Glimelius, B.

    2005-06-01

    Currently, most clinical range-modulated proton beams are assumed to have a fixed overall relative biological effectiveness (RBE) of 1.1. However, it is well known that the RBE increases with depth in the spread-out Bragg peak (SOBP) and becomes about 10% higher than mid-SOBP RBE at 2 mm from the distal edge (Paganetti 2003 Technol. Cancer Res. Treat. 2 413-26) and can reach values of 1.3-1.4 in vitro at the distal edge (Robertson et al 1975 Cancer 35 1664-77, Courdi et al 1994 Br. J. Radiol. 67 800-4). We present a fast method for applying a variable RBE correction with linear energy transfer (LET) dependent tissue-specific parameters based on the αref/βref ratios suitable for implementation in a treatment planning system. The influence of applying this variable RBE correction on a clinical multiple beam proton dose plan is presented here. The treatment plan is evaluated by RBE weighted dose volume histograms (DVHs) and the calculation of tumour control probability (TCP) and normal tissue complication probability (NTCP) values. The variable RBE correction yields DVHs for the clinical target volumes (CTVs), a primary advanced hypopharynx cancer and subclinical disease in the lymph nodes, that are slightly higher than those achieved by multiplying the absorbed dose with RBE = 1.1. Although, more importantly, the RBE weighted DVH for an organ at risk, the spinal cord is considerably increased for the variable RBE. As the spinal cord in this particular case is located 8 mm behind the planning target volume (PTV) and hence receives only low total doses, the NTCP values are zero in spite of the significant increase in the RBE weighted DVHs for the variable RBE. However, high NTCP values for the non-target normal tissue were obtained when applying the variable RBE correction. As RBE variations tend to be smaller for in vivo systems, this study—based on in vitro data since human tissue RBE values are scarce and have large uncertainties—can be interpreted as showing

  12. Influence of seasonal variations in sea level on the salinity regime of a coastal groundwater-fed wetland.

    PubMed

    Wood, Cameron; Harrington, Glenn A

    2015-01-01

    Seasonal variations in sea level are often neglected in studies of coastal aquifers; however, they may have important controls on processes such as submarine groundwater discharge, sea water intrusion, and groundwater discharge to coastal springs and wetlands. We investigated seasonal variations in salinity in a groundwater-fed coastal wetland (the RAMSAR listed Piccaninnie Ponds in South Australia) and found that salinity peaked during winter, coincident with seasonal sea level peaks. Closer examination of salinity variations revealed a relationship between changes in sea level and changes in salinity, indicating that sea level-driven movement of the fresh water-sea water interface influences the salinity of discharging groundwater in the wetland. Moreover, the seasonal control of sea level on wetland salinity seems to override the influence of seasonal recharge. A two-dimensional variable density model helped validate this conceptual model of coastal groundwater discharge by showing that fluctuations in groundwater salinity in a coastal aquifer can be driven by a seasonal coastal boundary condition in spite of seasonal recharge/discharge dynamics. Because seasonal variations in sea level and coastal wetlands are ubiquitous throughout the world, these findings have important implications for monitoring and management of coastal groundwater-dependent ecosystems. PMID:24571421

  13. Altering the antigenicity of proteins.

    PubMed Central

    Alexander, H; Alexander, S; Getzoff, E D; Tainer, J A; Geysen, H M; Lerner, R A

    1992-01-01

    To better understand the binding interaction between antigen and antibody we need to distinguish protein residues critical to the binding energy and mechanism from residues merely localized in the interface. By analyzing the binding of monoclonal antibodies to recombinant wild-type and mutant myohemerythrin (MHr) proteins, we were able to test the role of individual critical residues at the highly antigenic site MHr-(79-84), within the context of the folded protein. The results directly show the existence of antigenically critical residues, whose mutations significantly reduce antibody binding to the folded protein, thus verifying peptide-based assignments of these critical residues and demonstrating the ability of buried side chains to influence antigenicity. Taken together, these results (i) distinguish the antigenic surface from the solvent-exposed protein surface before binding, (ii) support a two-stage interaction mechanism allowing inducible changes in protein antigens by antibody binding, and (iii) show that protein antigenicity can be significantly reduced by alteration of single critical residues without destroying biological activity. Images PMID:1373498

  14. Variations in the Free Chlorine Content of the Stratosphere (1991-1997): Anthropogenic an Volcanic Influences

    NASA Technical Reports Server (NTRS)

    Froidevaux, L.; Waters, J.; Read, W.; Connell, P.; Kinnison, D.; Russell, J.

    1999-01-01

    Remote sensing of chlorine monoxide (CIO) by the Microwave Limb Sounder (MLS) experiment aboard the Upper Atmosphere Research Satellite (UARS) has provided global measurements of variations in stratospheric free chlorine (for 1991 to 1997).

  15. Solar activity influence on climatic variations of stratosphere and mesosphere in mid-latitudes

    NASA Technical Reports Server (NTRS)

    Taubenheim, J.; Entzian, G.; Voncossart, G.

    1989-01-01

    The direct modulation of temperature of the mid-latitude mesosphere by the solar-cycle EUV variation, which leads to greater heat input at higher solar activity, is well established. Middle atmosphere temperature modulation by the solar cycle is independently confirmed by the variation of reflection heights of low frequency radio waves in the lower ionosphere, which are regularly monitored over about 30 years. As explained elsewhere in detail, these reflection heights depend on the geometric altitude of a certain isobaric surface (near 80 k), and on the solar ionizing Lyman-alpha radiation flux. Knowing the solar cycle variation of Lyman-alpha how much the measured reflection heights would be lowered with the transition from solar minimum to maximum can be calculated, if the vertical baric structure of the neutral atmosphere would remain unchanged. An discrepancy between expected and observed height change must be explained by an uplifting of the isobaric level from solar minimum to maximum, caused by the temperature rise in the mesosphere. By integrating the solar cycle temperature changes over the height region of the middle atmosphere, and assuming that the lower boundary (tropopause) has no solar cycle variation, the magnitude of this uplifting can be estimated. It is given for the Lidar-derived and for the rocket-measured temperature variations. Comparison suggests that the real amplitude of the solar cycle temperature variation in the mesosphere is underestimated when using the rocket data, but probably overestimated with the Lidar data.

  16. Both male and female identity influence variation in male signalling effort

    PubMed Central

    2011-01-01

    Background Male sexual displays play an important role in sexual selection by affecting reproductive success. However, for such displays to be useful for female mate choice, courtship should vary more among than within individual males. In this regard, a potentially important source of within male variation is adjustment of male courtship effort in response to female traits. Accordingly, we set out to dissect sources of variation in male courtship effort in a fish, the desert goby (Chlamydogobius eremius). We did so by designing an experiment that allowed simultaneous estimation of within and between male variation in courtship, while also assessing the importance of the males and females as sources of courtship variation. Results Although males adjusted their courtship depending on the identity of the female (a potentially important source of within-male variation), among-male differences were considerably greater. In addition, male courtship effort towards a pair of females was highly repeatable over a short time frame. Conclusion Despite the plasticity in male courtship effort, courtship displays had the potential to reliably convey information about the male to mate-searching females. Our experiment therefore underscores the importance of addressing the different sources contributing to variation in the expression of sexually-selected traits. PMID:21827657

  17. Influence of glucocorticoids on a time-of-day-dependent variation in intradermal reactivity to histamine in dogs.

    PubMed

    Goto, Shun; Shimizu, Sunao; Watanabe, Miwa; Osada, Hironari; Sasaki, Kazuaki; Shimoda, Minoru; Nagai, Makoto; Shirai, Junsuke; Itoh, Hiroshi; Ohmori, Keitaro

    2016-08-01

    The objectives of this study were to determine daily variation in intradermal reactivity to histamine in dogs and to evaluate a potential influence of glucocorticoids on reactivity. Wheal sizes formed after intradermal injections of histamine were measured every 6 h during a single 24 h period in six healthy dogs. To determine whether glucocorticoids were implicated in daily variation, intradermal reactivity to histamine was evaluated at 9:00 h and at 21:00 h during a single day in dogs that received oral prednisolone (a synthetic glucocorticoid) or oral trilostane (an inhibitor of endogenous glucocorticoid synthesis). Finally, the time required for the histamine reaction to diminish after an intravenous injection of hydrocortisone was also assessed. A significant time-of-day-dependent variation in intradermal reactivity to histamine was detected in dogs, with a larger wheal size observed at 9:00 h than at 21:00 h. Administration of prednisolone or trilostane disrupted this variation. Intradermal reactivity to histamine was significantly reduced 6 h after an intravenous injection of hydrocortisone. These results suggest that glucocorticoid secretion from the adrenal glands could be involved in the regulation of daily variation in histamine-mediated reactions in dogs. PMID:27387732

  18. Understanding the relative influence of climatic variations and agricultural management practices on crop yields at the US county level

    NASA Astrophysics Data System (ADS)

    Leng, G.; Zhang, X.; Huang, M.; Yang, Q.; Rafique, R.; Asrar, G.; Leung, L. R.

    2015-12-01

    Crop yields are largely determined by climate variations and agricultural management practices, such as irrigation, fertilization and residue management. Understanding the role of these factors in regulating crop yield variations is not only important for improved crop yield production, but also equally valuable for future crop yield prediction and food security assessments. Recently, the Community Land Model (CLM) has been augmented and evaluated for simulating corn, soybean and cereals at coarse aerial resolutions of 2 degrees (2000x2000 km). To better understand the underlying mechanisms controlling yield variations, we implemented and validated the agricultural version of CLM (CLM-crop) at a 0.125 degree resolution over the Conterminous United States (CONUS). We conducted a suite of numerical experiments to untangle the relative influence of climatic variations (temperature, precipitation, and radiation) and agricultural management practices on yield variations for the past 30 years at the US county level. Preliminary results show that the model with default parameter settings captures well the temporal variations in crop yields, as compared with the actual yield reported by the US Department of Agriculture (USDA). However, the magnitude of simulated crop yields is substantially higher, especially in the Mid-western US. We find that improved characterization of fertilizers and irrigation practices is key to model performance. Retrospectively (1979-2012), crop yields are more sensitive to changes in climate factors (such as temperature) than to changes in crop management practices. The results of this study advances understanding of the dominant factors in regulating the crop yield variations at the county level, which is essential for credible prediction of crop yields in a changing climate, under different agricultural management practices.

  19. Influence of variation of etching conditions on the sensitivity of PADC detectors with a new evaluation method.

    PubMed

    Fiechtner-Scharrer, A; Mayer, S; Boschung, M; Whitelaw, A

    2011-03-01

    At the Paul Scherrer Institut, a personal neutron dosimetry system based on chemically etched poly allyl diglycol carbonate (PADC) detectors and an automatic track counting (Autoscan 60) for neutron dose evaluations has been in routine use since 1998. Today, the hardware and the software of the Autoscan 60 are out of date, no spare components are available anymore and more sophisticated image-analysis systems are already developed. Therefore, a new evaluation system, the 'TASLIMAGE', was tested thoroughly in 2009 for linearity, reproducibility, influence of etching conditions and so forth, with the intention of replacing the Autoscan 60 in routine evaluations. The TASLIMAGE system is based on a microscope (high-quality Nikon optics) and an ultra-fast three-axis motorised control for scanning the detectors. In this paper, the TASLIMAGE system and its possibilities for neutron dose calculation are explained in more detail and the study of the influence of the variation of etching conditions on the sensitivity and background of the PADC detectors is described. The etching temperature and etching duration were varied, which showed that the etching conditions do not have a significant influence on the results of non-irradiated detectors. However, the sensitivity of irradiated detectors decreases by 5 % per 1°C when increasing the etching temperature. For the variation of the etching duration, the influence on the sensitivity of irradiated detectors is less pronounced. PMID:21212078

  20. Antigenic sites in carcinoembryonic antigen.

    PubMed

    Hammarstrom, S; Shively, J E; Paxton, R J; Beatty, B G; Larsson, A; Ghosh, R; Bormer, O; Buchegger, F; Mach, J P; Burtin, P

    1989-09-01

    The epitope reactivities of 52 well-characterized monoclonal antibodies (Mabs) against carcinoembryonic antigen from 11 different research groups were studied using competitive solid-phase immunoassays. About 60% of all possible combinations of Mabs as inhibitors and as the primary binding antibody were investigated. The inhibition data were analyzed by a specially developed computer program "EPITOPES" which measures concordance and discordance in inhibition patterns between Mabs. The analysis showed that 43 of the 52 Mabs (83%) could be classified into one of five essentially noninteracting epitope groups (GOLD 1-5) containing between four and 15 Mabs each. The epitopes recognized by the Mabs belonging to groups 1 to 5 were peptide in nature. With one or two possible exceptions non-classifiable Mabs were either directed against carbohydrate epitopes (4 Mabs) or were inactive in the tests used. Within epitope groups GOLD 1, 4, and 5 two partially overlapping subgroups were distinguished. Mabs with a high degree of carcinoembryonic antigen specificity generally belonged to epitope groups GOLD 1 and 3. PMID:2474375

  1. Interacting Alleles of the Coinhibitory Immunoreceptor Genes Cytotoxic T-Lymphocyte Antigen 4 and Programmed Cell-Death 1 Influence Risk and Features of Primary Biliary Cirrhosis

    PubMed Central

    Juran, Brian D.; Atkinson, Elizabeth J.; Schlicht, Erik M.; Fridley, Brooke L.; Petersen, Gloria M.; Lazaridis, Konstantinos N.

    2012-01-01

    Autoimmune diseases such as primary biliary cirrhosis (PBC) result from failure in the immune mechanisms that establish and maintain self-tolerance. Evidence suggests that these processes are shared among the spectrum of autoimmune syndromes and are likely genetically determined. Cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell-death 1 (PDCD1) are two genes encoding coinhibitory immunoreceptors that harbor polymorphisms with demonstrated associations to multiple autoimmune disorders. We aimed to assess functional single nucleotide polymorphisms (SNPs) in these two genes for association with PBC. SNPs in CTLA4 and PDCD1 were genotyped in 351 PBC patients and 205 controls. Allele and genotype frequencies were evaluated for association with PBC and/or antimitochondrial antibody (AMA) positivity with logistic regression. Haplotypes were inferred with an expectation-maximization algorithm, and allelic interaction was analyzed by logistic regression modeling. Individual SNPs demonstrated no association to PBC. However, the GG genotype of CTLA4 49AG was significantly associated with AMA positivity among the PBC patients. Also, individual SNPs and a haplotype of CTLA4 as well as a rare genotype of the PDCD1 SNP PD1.3 were associated with orthotopic liver transplantation. As well, we identified the influence of an interaction between the putatively autoimmune-protective CTLA4 49AG:CT60 AA haplotype and autoimmune-risk PDCD1 PD1.3 A allele on development of PBC. Conclusion Our findings illustrate the complex nature of the genetically induced risk of PBC and emphasize the importance of considering definable subphenotypes of disease, such as AMA positivity, or definitive measures of disease severity/progression, like orthotopic liver transplantation, when genetic analyses are being performed. Comprehensive screening of genes involved with immune function will lead to a greater understanding of the genetic component of autoimmunity in PBC while furthering our

  2. Influence of topography on the temperature variation around the tropical tropopause layer

    NASA Astrophysics Data System (ADS)

    Kubokawa, H.; Masaki, S.; Fujiwara, M.; Suzuki, J.

    2015-12-01

    Temperature variations in the Tropical Tropopause Layer (TTL) are an important factor for dehydration in the UTLS region. It is known that Kelvin waves induce large temperature variations in the TTL. We investigated the temperature variations in the TTL using both numerical data produced by the Nonhydrostatic Icosahedral Atmospheric Model (NICAM) and various observational data including satellite data (the Constellation Observing System for Meteorology, Ionosphere, and Climate; COSMIC), the reanalysis data of different resolution (ERA-40-interim, NCEP-CFSR, MERRA, YOTC-ECMWF), and radiosonde data for the Cooperative Indian Ocean experiment on intra-seasonal variability in the Year 2011 (CINDY). We found that all the data shows that the temperature variations become larger over the mountainous regions of the Indonesian maritime continent than over the oceanic regions and that the large temperature variations are associated with Kelvin waves. As, the horizontal resolution of the reanalysis becomes higher, the standard deviations of the TTL temperature near the mountains became larger. When Kelvin waves passed over the Indonesian maritime continent, the amplitude of temperature becomes about 2 K larger over the mountainous regions. The power spectrum for the periods between 7 days and 12 days was larger over the mountainous regions compared with that over the ocean. The sensitivity study using the stretch-NICAM shows that the height of mountains clearly affect the amplitude of temperature near the TTL.

  3. Influence of geometry variations on the gravitational focusing of timelike geodesic congruences

    NASA Astrophysics Data System (ADS)

    Seriu, Masafumi

    2015-10-01

    We derive a set of equations describing the linear response of the convergence properties of a geodesic congruence to arbitrary geometry variations. It is a combination of equations describing the deviations from the standard Raychaudhuri-type equations due to the geodesic shifts and an equation describing the geodesic shifts due to the geometry variations. In this framework, the geometry variations, which can be chosen arbitrarily, serve as probes to investigate the gravitational contraction processes from various angles. We apply the obtained framework to the case of conformal geometry variations, characterized by an arbitrary function f (x ), and see that the formulas get simplified to a great extent. We investigate the response of the convergence properties of geodesics in the latest phase of gravitational contractions by restricting the class of conformal geometry variations to the one satisfying the strong energy condition. We then find out that in the final stage, f and D .D f control the overall contraction behavior and that the contraction rate gets larger when f is negative and |f | is so large as to overwhelm |D .D f |. (Here D .D is the Laplacian operator on the spatial hypersurfaces orthogonal to the geodesic congruence in concern.) To get more concrete insights, we also apply the framework to the time-reversed Friedmann-Robertson-Walker model as the simplest case of the singularity formations.

  4. Characterisation of Sarcoptes scabiei antigens.

    PubMed

    Hejduk, Gloria; Hofstätter, Katja; Löwenstein, Michael; Peschke, Roman; Miller, Ingrid; Joachim, Anja

    2011-02-01

    In pig herds, the status of Sarcoptes scabiei infections is routinely monitored by serodiagnosis. Crude antigen for ELISA is usually prepared from S. scabiei var. canis or other variations and may lead to variations in the outcome of different tests, making assay standardisation difficult. This study was performed to investigate the antigen profiles of S. scabiei, including differences between hydrophilic and more hydrophobic protein fractions, by Western blotting with sera from pigs with defined infection status. Potential cross-reactivity among S. scabiei (var. canis, suis and bovis), Dermatophagoides farinae and Tyrophagus putrescentiae was also analysed. Hydrophobic S. scabiei antigens were detectable in the range of 40-50 kDa, whilst the hydrophilic fraction showed no specific antigenicity. In the hydrophobic fractions of D. farinae and T. putrescentiae, two major protein fractions in a similar size range could be identified, but no cross-reactivity with Sarcoptes-positive sera was detectable. However, examination of the hydrophilic fractions revealed cross-reactivity between Sarcoptes-positive sera and both the house dust mite and the storage mite in the range of 115 and 28/38 kDa. Specific bands in the same range (42 and 48 kDa) could be detected in blots from hydrophobic fractions of all three tested variations of S. scabiei (var. canis, bovis and suis). These results show that there are considerable differences in mange antibody reactivity, including reactions with proteins from free-living mites, which may interfere with tests based on hydrophilic antigens. Further refinement of antigen and the use of specific hydrophobic proteins could improve ELISA performance and standardisation. PMID:20865427

  5. Relationship between serum carcinoembryonic antigen level and epidermal growth factor receptor mutations with the influence on the prognosis of non-small-cell lung cancer patients

    PubMed Central

    Cai, Zuxun

    2016-01-01

    Objective To investigate the relationship between serum carcinoembryonic antigen (CEA) level and epidermal growth factor receptor (EGFR) gene mutations in non-small-cell lung cancer (NSCLC) patients and to analyze the influence of CEA level on postoperative survival time in lung cancer patients. Methods A total of 296 patients who were treated in Thoracic Surgery Department of Henan Provincial Chest Hospital from September 2011 to September 2013 were recruited. The level of tumor markers, such as CEA, was determined before the surgery, and EGFR gene mutations were detected after surgery. Thereby, the relationship between tumor makers, including CEA, and EGFR mutation and its influence on prognosis could be investigated. Results Among 296 patients, the positive rate of EGFR gene mutation was 37.84% (112/296); the mutation occurred more frequently in nonsmokers, adenocarcinoma patients, women, and patients aged <60 years (P<0.05). Both tumor markers and chemosensitivity indicators were related to the profile of EGFR mutations. Elevated squamous cell carcinoma and Cyfra21-1 as well as positively expressed ERCC1 were more common in patients with wild-type EGFR (P<0.05), whereas increased CEA level was observed more frequently in patients with EGFR gene mutation (P=0.012). The positive rate of EGFR gene mutations was higher as the serum CEA level increased, that is, the positive rate in patients with serum CEA level <5, 5–20, and >20 μg/L was 39.81%, 45.32%, and 65.47%, respectively (P=0.004). Logistic regression analysis showed that CEA level was an independent factor in predicting EGFR gene mutations, and serum CEA level was also an independent factor in affecting the prognosis of NSCLC patients, as the overall 2-year survival rate was 73.86% in elevated CEA group and 86.43% in normal group (P<0.01). Conclusion The prognosis of NSCLC patients receiving resection can be predicted according to serum CEA level, which is associated with EGFR mutations in NSCLC patients

  6. Factors influencing the variation in capture rates of shrews in southern California, USA

    USGS Publications Warehouse

    Laakkonen, J.; Fisher, R.N.; Case, T.J.

    2003-01-01

    We examined the temporal variation in capture rates of shrews Notiosorex crawfordi (Coues, 1877) and Sorex ornatus (Merriam, 1895) in 20 sites representing fragmented and continuous habitats in southern California, USA. In N. crawfordi, the temporal variation was significantly correlated with the mean capture rates. Of the 6 landscape variables analyzed (size of the landscape, size of the sample area, altitude, edge, longitude and latitude), sample area was positively correlated with variation in capture rates of N. crawfordi. In S. ornatus, longitude was negatively correlated with variation in capture rates. Analysis of the effect of precipitation on the short- and long-term capture rates at 2 of the sites showed no correlation between rainfall and capture rates of shrews even though peak number of shrews at both sites were reached during the year of highest amount of rainfall. A key problem confounding capture rates of shrews in southern California is the low overall abundance of both shrew species in all habitats and seasons.

  7. Solar influence on meteor rates and atmospheric density variations at meteor heights

    NASA Technical Reports Server (NTRS)

    Ellyett, C.

    1977-01-01

    Lindblad (1967) has concluded that there was an inverse relation between meteor rates and the solar cycle brought about by an increase in atmospheric density gradient at the height of meteor ionization. The present paper investigates Lindblad's conclusion more fully by using three long series of continuous radar meteor data from New Zealand and Canada. The results confirm a clear variation of total rate from year to year, inversely correlated with the annual sunspot number. Although meteor rates call for a density gradient variation inversely related to the solar cycle, direct evidence for such a variation remains nonexistant. Possibly the effect is being obscured by other density changes occurring at these heights. Analysis of meteor rates within the same one-year period in the two hemispheres has established that seasonal rate changes brought about by the variation of the angle between the latitude of the observing station and the apex of the earth's way override change of density gradient in at least one of the hemispheres and possibly both in controlling meteor rates within the year.

  8. Variations in stress and immune responses of cattle: Natural deviations and nutritional influences

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Given the importance of the innate immune response with regard to the overall health and survival of domestic livestock, the primary immunological focus of this manuscript is on variations that exist within the innate immune system, and efforts to selectively and precisely modulate this system in a ...

  9. Influence of Analogy Instruction for Pitch Variation on Perceptual Ratings of Other Speech Parameters

    ERIC Educational Resources Information Center

    Tse, Andy C. Y.; Wong, Andus W-K.; Ma, Estella P-M.; Whitehill, Tara L.; Masters, Rich S. W.

    2013-01-01

    Purpose: "Analogy" is the similarity of different concepts on which a comparison can be based. Recently, an analogy of "waves at sea" was shown to be effective in modulating fundamental frequency (F[subscript 0]) variation. Perceptions of intonation were not examined, as the primary aim of the work was to determine whether…

  10. Brain modularity across the theropod-bird transition: testing the influence of flight on neuroanatomical variation.

    PubMed

    Balanoff, Amy M; Smaers, Jeroen B; Turner, Alan H

    2016-08-01

    Living birds constitute the only vertebrate group whose brain volume relative to body size approaches the uniquely expanded values expressed by mammals. The broad suite of complex behaviors exhibited by crown-group birds, including sociality, vocal learning, parental care, and flying, suggests the origins of their encephalization was likely driven by a mosaic of selective pressures. If true, the historical pattern of brain expansion may be more complex than either a gradual expansion, as proposed by early studies of the avian brain, or a sudden expansion correlating with the appearance of flight. The origins of modern avian neuroanatomy are obscured by the more than 100 million years of evolution along their phylogenetic stem (from the origin of the modern radiation in the Middle Jurassic to the split from crocodile-line archosaurs). Here we use phylogenetic comparative approaches to explore which evolutionary scenarios best explain variation in measured volumes of digitally partitioned endocasts of modern birds and their non-avian ancestors. Our analyses suggest that variation in the relative volumes of the endocranium and cerebrum explain most of the structural variation in this lineage. Generalized multi-regime Ornstein-Uhlenbeck (OU) models suggest that powered flight does not appear to be a driver of observed variation, reinforcing the hypothesis that the deep history of the avian brain is complex, with nuances still to be discovered. PMID:26538376