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Sample records for postsegregational killer loci

  1. Combining the hok/sok, parDE, and pnd postsegregational killer loci to enhance plasmid stability.

    PubMed

    Pecota, D C; Kim, C S; Wu, K; Gerdes, K; Wood, T K

    1997-05-01

    To enhance plasmid segregational stability in bacterial cells, two pairs of independent postsegregational killing loci (genes which induce host killing upon plasmid loss) isolated from plasmids R1, R483, or RP4 (hok+/sok+ pnd+ or hok+/sok+ parDE+) were cloned into a common site of the beta-galactosidase expression vector pMJR1750 (ptac::lacZ+) to form a series of plasmids in which the effect of one or two stability loci on segregational plasmid stability could be discerned. Adding two antisense killer loci (hok+/sok+ pnd+) decreased the specific growth rate by 50% though they were more effective at reducing segregational instability than hok+/sok+ alone. With the ptac promoter induced fully (2.0 mM isopropyl-beta-D-thiogalactopyranoside) and no antibiotic selection pressure, the combination of a proteic killer locus (parDE+) with antisense killer loci (hok+/sok+) had a negligible impact on specific growth rate, maintained high beta-galactosidase expression, and led to a 30 and 190% increase in segregational stability (based on stable generations) as compared to plasmids containing either hok+/sok+ or parDE+ alone, respectively. Use of hok+/sok+ or parDE+ alone with high cloned-gene expression led to ninefold and fourfold increases in the number of stable generations, respectively. Two convenient cloning cassettes have been constructed to facilitate cloning the dual hok+/sok+ parDE+ and hok+/sok+ pnd+ killer systems. PMID:9143123

  2. Invertebrate Post-Segregation Distorters: A New Embryo-Killing Gene

    PubMed Central

    Sinkins, Steven P.

    2011-01-01

    Cytoplasmic incompatibility induced by inherited intracellular bacteria of arthropods, and Medea elements found in flour beetles, are both forms of postsegregation distortion involving the killing of embryos in order to increase the ratio of progeny that inherit them. The recently described peel-zeel element of Caenorhabditis elegans also uses this mechanism; like Medea the genes responsible are in the nuclear genome but it shares a paternal mode of action with the bacteria. The peel-1 gene has now been shown to encode a potent toxin that is delivered by sperm, and rescued by zygotic transcription of the linked zeel-1. The predominance of self-fertilization in C. elegans has produced an unusual distribution pattern for a selfish genetic element; further population and functional studies will shed light on its evolution. The element might also have potential for use in disease control. PMID:21814492

  3. Post-Slavery? Post-Segregation? Post-Racial? A History of the Impact of Slavery, Segregation, and Racism on the Education of African Americans

    ERIC Educational Resources Information Center

    Span, Christopher M.

    2015-01-01

    This chapter details how slavery, segregation, and racism impacted the educational experiences of African Americans from the colonial era to the present. It argues that America has yet to be a truly post-slavery and post-segregation society, let alone a post-racial society.

  4. Active stable maintenance functions in low copy-number plasmids of Gram-positive bacteria II. Post-segregational killing systems.

    PubMed

    Dmowski, Michał; Jagura-Burdzy, Grazyna

    2013-01-01

    Active support is needed for low copy-number plasmids to be stably maintained in bacterial cells. The mechanisms that fulfill this role are (i) partition systems (PAR) acting to separate plasmid molecules to daughter cells and (ii) toxin-andidote (TA) (post-segregational killing-PSK) systems which arrest cell growth until the plasmid reaches the correct copy-number or kill the cells that have not inherited the plasmid. Our knowledge of toxin-antidote systems comes mainly from studies on Gram-negative bacteria. However, some addiction systems of Gram-positive bacteria have been characterized in detail or recently identified. Altogether, they bring new interesting data on toxin-antidote functioning in bacteria.

  5. Suicide in serial killers.

    PubMed

    Lester, David; White, John

    2010-02-01

    In a sample of 248 killers of two victims in America from 1900 to 2005, obtained from an encyclopedia of serial killers by Newton (2006), those completing suicide did not differ in sex, race, or the motive for the killing from those who were arrested.

  6. Suicide in serial killers.

    PubMed

    Lester, David; White, John

    2010-02-01

    In a sample of 248 killers of two victims in America from 1900 to 2005, obtained from an encyclopedia of serial killers by Newton (2006), those completing suicide did not differ in sex, race, or the motive for the killing from those who were arrested. PMID:20402450

  7. Classifying serial killers.

    PubMed

    Promish, D I; Lester, D

    1999-11-01

    We attempted to match the appearance and demeanor of 27 serial killers to the postmortem 'signatures' found on their victims' bodies. Our results suggest that a link may exist between postmortem signatures and two complementary appearance-demeanor types.

  8. Yeast killer systems.

    PubMed Central

    Magliani, W; Conti, S; Gerloni, M; Bertolotti, D; Polonelli, L

    1997-01-01

    The killer phenomenon in yeasts has been revealed to be a multicentric model for molecular biologists, virologists, phytopathologists, epidemiologists, industrial and medical microbiologists, mycologists, and pharmacologists. The surprisingly widespread occurrence of the killer phenomenon among taxonomically unrelated microorganisms, including prokaryotic and eukaryotic pathogens, has engendered a new interest in its biological significance as well as its theoretical and practical applications. The search for therapeutic opportunities by using yeast killer systems has conceptually opened new avenues for the prevention and control of life-threatening fungal diseases through the idiotypic network that is apparently exploited by the immune system in the course of natural infections. In this review, the biology, ecology, epidemiology, therapeutics, serology, and idiotypy of yeast killer systems are discussed. PMID:9227858

  9. The Violence of Collection: "Indian Killer"'s Archives

    ERIC Educational Resources Information Center

    Dean, Janet

    2008-01-01

    At the close of Sherman Alexie's "Indian Killer," in a final chapter titled "Creation Story," a killer carries a backpack containing, among other things, "dozens of owl feathers, a scrapbook, and two bloody scalps in a plastic bag." Readers schooled in the psychopathologies of real and fictional serial killers will be familiar with the detail:…

  10. Grass and weed killer poisoning

    MedlinePlus

    Weedoff poisoning; Roundup poisoning ... Glyphosate is the poisonous ingredient in some weed killers. ... Glyphosate is in weed killers with these brand names: Roundup Bronco Glifonox Kleen-up Rodeo Weedoff Other ...

  11. Biology Myth-Killers

    ERIC Educational Resources Information Center

    Lampert, Evan

    2014-01-01

    "Biology Myth-Killers" is an activity designed to identify and correct common misconceptions for high school and college introductory biology courses. Students identify common myths, which double as biology misconceptions, and use appropriate sources to share the "truth" about the myths. This learner-centered activity is a fun…

  12. Clemency Pogue: Fairy Killer

    ERIC Educational Resources Information Center

    Petty, J. T.

    2004-01-01

    This young adult author claims his most enjoyable task as a writer is "intellectual danger, getting into other people's trouble." He asks his readers not to trust him, and then, as evidence, tempts us with a look at a chapter from "Clemency Pogue: Fairy Killer."

  13. Classifying serial killers.

    PubMed

    Promish, D I; Lester, D

    1999-11-01

    We attempted to match the appearance and demeanor of 27 serial killers to the postmortem 'signatures' found on their victims' bodies. Our results suggest that a link may exist between postmortem signatures and two complementary appearance-demeanor types. PMID:10643649

  14. Delaware's first serial killer.

    PubMed

    Inguito, G B; Sekula-Perlman, A; Lynch, M J; Callery, R T

    2000-11-01

    The violent murder of Shirley Ellis on November 29, 1987, marked the beginning of the strange and terrible tale of Steven Bryan Pennell's reign as the state of Delaware's first convicted serial killer. Three more bodies followed the first victim, and all had been brutally beaten and sadistically tortured. The body of a fifth woman has never been found. State and county police collaborated with the FBI to identify and hunt down their suspect, forming a task force of over 100 officers and spending about one million dollars. Through their knowledge and experience with other serial killers, the FBI was able to make an amazingly accurate psychological profile of Delaware's serial killer. After months of around-the-clock surveillance, Steven Pennell was arrested on November 29, 1988, one year to the day after the first victim was found. Pennell was found guilty in the deaths of the first two victims on November 29, 1989, and plead no contest to the murder of two others on October 30, 1991. Still maintaining his innocence, he asked for the death penalty so that he could spare his family further agony. Steven Pennell was executed by lethal injection on March 15, 1992.

  15. Delaware's first serial killer.

    PubMed

    Inguito, G B; Sekula-Perlman, A; Lynch, M J; Callery, R T

    2000-11-01

    The violent murder of Shirley Ellis on November 29, 1987, marked the beginning of the strange and terrible tale of Steven Bryan Pennell's reign as the state of Delaware's first convicted serial killer. Three more bodies followed the first victim, and all had been brutally beaten and sadistically tortured. The body of a fifth woman has never been found. State and county police collaborated with the FBI to identify and hunt down their suspect, forming a task force of over 100 officers and spending about one million dollars. Through their knowledge and experience with other serial killers, the FBI was able to make an amazingly accurate psychological profile of Delaware's serial killer. After months of around-the-clock surveillance, Steven Pennell was arrested on November 29, 1988, one year to the day after the first victim was found. Pennell was found guilty in the deaths of the first two victims on November 29, 1989, and plead no contest to the murder of two others on October 30, 1991. Still maintaining his innocence, he asked for the death penalty so that he could spare his family further agony. Steven Pennell was executed by lethal injection on March 15, 1992. PMID:11125664

  16. Suppressing the killer instinct.

    PubMed

    Campbell, Kerry S

    2016-05-24

    Natural killer (NK) cells are innate lymphoid cells that have adopted activating and inhibitory signaling mechanisms enabling them to be tolerant of normal cells but to distinguish and eliminate tumor cells and virus-infected cells. In this issue of Science Signaling, Matalon et al show how inhibitory receptors disrupt NK cell activation by stimulating dephosphorylation of the adaptor protein LAT (linker of activated T cells) and phospholipase C-γ by the phosphatase SHP-1 [Src homology 2 (SH2) domain-containing protein tyrosine phosphatase 1], as well as ubiquitylation of LAT by Cbl family E3 ubiquitin ligases.

  17. Natural Killer Cell Memory.

    PubMed

    O'Sullivan, Timothy E; Sun, Joseph C; Lanier, Lewis L

    2015-10-20

    Natural killer (NK) cells have historically been considered short-lived cytolytic cells that can rapidly respond against pathogens and tumors in an antigen-independent manner and then undergo cell death. Recently, however, NK cells have been shown to possess traits of adaptive immunity and can acquire immunological memory in a manner similar to that of T and B cells. In this review, we discuss evidence of NK cell memory and the mechanisms involved in the generation and survival of these innate lymphocytes.

  18. Arsenic: The Silent Killer

    SciTech Connect

    Foster, Andrea

    2006-02-28

    Andrea Foster uses x-rays to determine the forms of potentially toxic elements in environmentally-important matrices such as water, sediments, plants, and microorganisms. In this free public lecture, Foster will discuss her research on arsenic, which is called the silent killer because dissolved in water, it is colorless, odorless, and tasteless, yet consumption of relatively small doses of this element in its most toxic forms can cause rapid and violent death. Arsenic is a well-known poison, and has been used as such since ancient times. Less well known is the fact that much lower doses of the element, consumed over years, can lead to a variety of skin and internal cancers that can also be fatal. Currently, what has been called the largest mass poisoning in history is occurring in Bangladesh, where most people are by necessity drinking ground water that is contaminated with arsenic far in excess of the maximum amounts determined to be safe by the World Health Organization. This presentation will review the long and complicated history with arsenic, describe how x-rays have helped explain the high yet spatially variable arsenic concentrations in Bangladesh, discuss the ways in which land use in Bangladesh may be exacerbating the problem, and summarize the impact of this silent killer on drinking water systems worldwide.

  19. Immunobiology of natural killer cells

    SciTech Connect

    Lotzova, E.; Herberman, R.B.

    1986-01-01

    This book combines research from many disciplines into a review of natural killer (NK) cell-mediated immunity in humans and experimental animal system. Topics for the volumes include: Volume I: Assays for NK Cell Cytotoxicity; Their Values and Pitfalls. Separation and Characterization of Phenotypically Distinct Subsets of NK Cells. Ultrastructure and Cytochemistry of the Human Large Granular Lymphocytes. Phylogeny and Ontogeny of NK Cells. Tissue and Organ distribution of NK Cells. Genetic Control of NK Cell Activity in Rodents. Phenotype, Functional Heterogeneity, and Lineage of Natural Killer Cells. Target Cell Structures, Recognition Sites, and the Mechanism of NK Cytotoxicity. Natural Killer Cytotoxic Factors (NKCF) Role in Cell-Mediated Cytotoxicity. Characteristics of Cultured NK Cells. Lectin-Dependent Killer Cells. MLC-Induced Cytotoxicity as a Model for the Development and Regulation of NK Cytotoxicity. LGL Lymphoproliferative Diseases in Man and Experimental Animals: The Characteristics of These Cells and Their Potential Experimental Uses. Index.

  20. Geographic patterns of genetic differentiation among killer whales in the northern North Pacific.

    PubMed

    Parsons, Kim M; Durban, John W; Burdin, Alexander M; Burkanov, Vladimir N; Pitman, Robert L; Barlow, Jay; Barrett-Lennard, Lance G; LeDuc, Richard G; Robertson, Kelly M; Matkin, Craig O; Wade, Paul R

    2013-01-01

    The difficulties associated with detecting population boundaries have long constrained the conservation and management of highly mobile, wide-ranging marine species, such as killer whales (Orcinus orca). In this study, we use data from 26 nuclear microsatellite loci and mitochondrial DNA sequences (988bp) to test a priori hypotheses about population subdivisions generated from a decade of killer whale surveys across the northern North Pacific. A total of 462 remote skin biopsies were collected from wild killer whales primarily between 2001 and 2010 from the northern Gulf of Alaska to the Sea of Okhotsk, representing both the piscivorous "resident" and the mammal-eating "transient" (or Bigg's) killer whales. Divergence of the 2 ecotypes was supported by both mtDNA and microsatellites. Geographic patterns of genetic differentiation were supported by significant regions of genetic discontinuity, providing evidence of population structuring within both ecotypes and corroborating direct observations of restricted movements of individual whales. In the Aleutian Islands (Alaska), subpopulations, or groups with significantly different mtDNA and microsatellite allele frequencies, were largely delimited by major oceanographic boundaries for resident killer whales. Although Amchitka Pass represented a major subdivision for transient killer whales between the central and western Aleutian Islands, several smaller subpopulations were evident throughout the eastern Aleutians and Bering Sea. Support for seasonally sympatric transient subpopulations around Unimak Island suggests isolating mechanisms other than geographic distance within this highly mobile top predator.

  1. Geographic patterns of genetic differentiation among killer whales in the northern North Pacific.

    PubMed

    Parsons, Kim M; Durban, John W; Burdin, Alexander M; Burkanov, Vladimir N; Pitman, Robert L; Barlow, Jay; Barrett-Lennard, Lance G; LeDuc, Richard G; Robertson, Kelly M; Matkin, Craig O; Wade, Paul R

    2013-01-01

    The difficulties associated with detecting population boundaries have long constrained the conservation and management of highly mobile, wide-ranging marine species, such as killer whales (Orcinus orca). In this study, we use data from 26 nuclear microsatellite loci and mitochondrial DNA sequences (988bp) to test a priori hypotheses about population subdivisions generated from a decade of killer whale surveys across the northern North Pacific. A total of 462 remote skin biopsies were collected from wild killer whales primarily between 2001 and 2010 from the northern Gulf of Alaska to the Sea of Okhotsk, representing both the piscivorous "resident" and the mammal-eating "transient" (or Bigg's) killer whales. Divergence of the 2 ecotypes was supported by both mtDNA and microsatellites. Geographic patterns of genetic differentiation were supported by significant regions of genetic discontinuity, providing evidence of population structuring within both ecotypes and corroborating direct observations of restricted movements of individual whales. In the Aleutian Islands (Alaska), subpopulations, or groups with significantly different mtDNA and microsatellite allele frequencies, were largely delimited by major oceanographic boundaries for resident killer whales. Although Amchitka Pass represented a major subdivision for transient killer whales between the central and western Aleutian Islands, several smaller subpopulations were evident throughout the eastern Aleutians and Bering Sea. Support for seasonally sympatric transient subpopulations around Unimak Island suggests isolating mechanisms other than geographic distance within this highly mobile top predator. PMID:23846984

  2. Keiko, Killer Whale. [Lesson Plan].

    ERIC Educational Resources Information Center

    Discovery Communications, Inc., Bethesda, MD.

    This lesson plan presents activities designed to help students understand that Keiko, the killer whale, lived for a long time in an aquarium and had to be taught to live independently; and that computer users can get updates on how Keiko is doing. The main activity of the lesson involves middle school students working in small groups to produce a…

  3. Killer behavior within the Candida parapsilosis complex.

    PubMed

    Robledo-Leal, Efrén; Elizondo-Zertuche, Mariana; Villarreal-Treviño, Licet; Treviño-Rangel, Rogelio de J; García-Maldonado, Nancy; Adame-Rodríguez, Juan M; González, Gloria M

    2014-11-01

    A group of 29 isolates of Candida parapsilosis sensu stricto, 29 of Candida orthopsilosis, and 4 of Candida metapsilosis were assayed for the presence of killer activity using Saccharomyces cerevisiae ATCC 26609 as a sensitive strain. All C. metapsilosis isolates showed killer activity at 25 °C while strains of C. parapsilosis sensu stricto or C. orthopsilosis did not exhibit this activity. Sensitivity to killer toxins was evaluated using a set of previously reported killer strains of clinical origin. Only 11 isolates of the C. parapsilosis complex were inhibited by at least one killer isolate without resulting in any clear pattern, except for C. parapsilosis sensu stricto ATCC 22019, which was inhibited by every killer strain with the exception of C. parapsilosis and Candida utilis. The lack of sensitivity to killer activity among isolates of the genus Candida suggests that their toxins belong to the same killer type. Differentiation of species within the C. parapsilosis complex using the killer system may be feasible if a more taxonomically diverse panel of killer strains is employed.

  4. The DNA methylation profile of activated human natural killer cells.

    PubMed

    Wiencke, John K; Butler, Rondi; Hsuang, George; Eliot, Melissa; Kim, Stephanie; Sepulveda, Manuel A; Siegel, Derick; Houseman, E Andres; Kelsey, Karl T

    2016-05-01

    Natural killer (NK) cells are now recognized to exhibit characteristics akin to cells of the adaptive immune system. The generation of adaptive memory is linked to epigenetic reprogramming including alterations in DNA methylation. The study herein found reproducible genome wide DNA methylation changes associated with human NK cell activation. Activation led predominately to CpG hypomethylation (81% of significant loci). Bioinformatics analysis confirmed that non-coding and gene-associated differentially methylated sites (DMS) are enriched for immune related functions (i.e., immune cell activation). Known DNA methylation-regulated immune loci were also identified in activated NK cells (e.g., TNFA, LTA, IL13, CSF2). Twenty-one loci were designated high priority and further investigated as potential markers of NK activation. BHLHE40 was identified as a viable candidate for which a droplet digital PCR assay for demethylation was developed. The assay revealed high demethylation in activated NK cells and low demethylation in naïve NK, T- and B-cells. We conclude the NK cell methylome is plastic with potential for remodeling. The differentially methylated region signature of activated NKs revealed similarities with T cell activation, but also provided unique biomarker candidates of NK activation, which could be useful in epigenome-wide association studies to interrogate the role of NK subtypes in global methylation changes associated with exposures and/or disease states. PMID:26967308

  5. Comparative Genomics of Natural Killer Cell Receptor Gene Clusters

    PubMed Central

    Kelley, James; Walter, Lutz; Trowsdale, John

    2005-01-01

    Many receptors on natural killer (NK) cells recognize major histocompatibility complex class I molecules in order to monitor unhealthy tissues, such as cells infected with viruses, and some tumors. Genes encoding families of NK receptors and related sequences are organized into two main clusters in humans: the natural killer complex on Chromosome 12p13.1, which encodes C-type lectin molecules, and the leukocyte receptor complex on Chromosome 19q13.4, which encodes immunoglobulin superfamily molecules. The composition of these gene clusters differs markedly between closely related species, providing evidence for rapid, lineage-specific expansions or contractions of sets of loci. The choice of NK receptor genes is polarized in the two species most studied, mouse and human. In mouse, the C-type lectin-related Ly49 gene family predominates. Conversely, the single Ly49 sequence is a pseudogene in humans, and the immunoglobulin superfamily KIR gene family is extensive. These different gene sets encode proteins that are comparable in function and genetic diversity, even though they have undergone species-specific expansions. Understanding the biological significance of this curious situation may be aided by studying which NK receptor genes are used in other vertebrates, especially in relation to species-specific differences in genes for major histocompatibility complex class I molecules. PMID:16132082

  6. Phototoxic effects of lysosome-associated genetically encoded photosensitizer KillerRed

    NASA Astrophysics Data System (ADS)

    Serebrovskaya, Ekaterina O.; Ryumina, Alina P.; Boulina, Maria E.; Shirmanova, Marina V.; Zagaynova, Elena V.; Bogdanova, Ekaterina A.; Lukyanov, Sergey A.; Lukyanov, Konstantin A.

    2014-07-01

    KillerRed is a unique phototoxic red fluorescent protein that can be used to induce local oxidative stress by green-orange light illumination. Here we studied phototoxicity of KillerRed targeted to cytoplasmic surface of lysosomes via fusion with Rab7, a small GTPase that is known to be attached to membranes of late endosomes and lysosomes. It was found that lysosome-associated KillerRed ensures efficient light-induced cell death similar to previously reported mitochondria- and plasma membrane-localized KillerRed. Inhibitory analysis demonstrated that lysosomal cathepsins play an important role in the manifestation of KillerRed-Rab7 phototoxicity. Time-lapse monitoring of cell morphology, membrane integrity, and nuclei shape allowed us to conclude that KillerRed-Rab7-mediated cell death occurs via necrosis at high light intensity or via apoptosis at lower light intensity. Potentially, KillerRed-Rab7 can be used as an optogenetic tool to direct target cell populations to either apoptosis or necrosis.

  7. Modus operandi of female serial killers.

    PubMed

    Wilson, W; Hilton, T

    1998-04-01

    The modus operandi of female serial killers was examined from a chronology of 58 cases in America and 47 cases in 17 other countries, compiled over 25-year intervals. Female serial killers in other countries accounted for a disproportionately greater number of victims, but those in America managed a longer killing career when associated with a low profile modus operandi.

  8. Modus operandi of female serial killers.

    PubMed

    Wilson, W; Hilton, T

    1998-04-01

    The modus operandi of female serial killers was examined from a chronology of 58 cases in America and 47 cases in 17 other countries, compiled over 25-year intervals. Female serial killers in other countries accounted for a disproportionately greater number of victims, but those in America managed a longer killing career when associated with a low profile modus operandi. PMID:9621726

  9. Structural Basis for Phototoxicity of the Genetically Encoded Photosensitizer KillerRed

    SciTech Connect

    Pletnev, Sergei; Gurskaya, Nadya G.; Pletneva, Nadya V.; Lukyanov, Konstantin A.; Chudakov, Dmitri M.; Martynov, Vladimir I.; Popov, Vladimir O.; Kovalchuk, Mikhail V.; Wlodawer, Alexander; Dauter, Zbigniew; Pletnev, Vladimir

    2009-11-23

    KillerRed is the only known fluorescent protein that demonstrates notable phototoxicity, exceeding that of the other green and red fluorescent proteins by at least 1,000-fold. KillerRed could serve as an instrument to inactivate target proteins or to kill cell populations in photodynamic therapy. However, the nature of KillerRed phototoxicity has remained unclear, impeding the development of more phototoxic variants. Here we present the results of a high resolution crystallographic study of KillerRed in the active fluorescent and in the photobleached non-fluorescent states. A unique and striking feature of the structure is a water-filled channel reaching the chromophore area from the end cap of the {beta}-barrel that is probably one of the key structural features responsible for phototoxicity. A study of the structure-function relationship of KillerRed, supported by structure-based, site-directed mutagenesis, has also revealed the key residues most likely responsible for the phototoxic effect. In particular, Glu68 and Ser119, located adjacent to the chromophore, have been assigned as the primary trigger of the reaction chain.

  10. Persistence in the shadow of killers

    PubMed Central

    Sinclair, Robert M.

    2014-01-01

    Killing is perhaps the most definite form of communication possible. Microbes such as yeasts and gut bacteria have been shown to exhibit killer phenotypes. The killer strains are able to kill other microbes occupying the same ecological niche, and do so with impunity. It would therefore be expected that, wherever a killer phenotype has arisen, all members of the population would soon be killers or dead. Surprisingly, (1) one can find both killer and sensitive strains in coexistence, both in the wild and in in vitro experiments, and (2) the absolute fitness cost of the killer phenotype often seems to be very small. We present an explicit model of such coexistence in a fragmented or discrete environment. A killer strain may kill all sensitive cells in one patch (one piece of rotting fruit, one cave or one human gut, for example), allowing sensitives to exist only in the absence of killer strains on the same patch. In our model, populations spread easily between patches, but in a stochastic manner: one can imagine spores borne by the wind over a field of untended apple trees, or enteric disease transmission in a region in which travel is effectively unrestricted. What we show is that coexistence is not only possible, but that it is possible even if the absolute fitness advantage of the sensitive strain over the killer strain is arbitrarily small. We do this by performing a specifically targeted mathematical analysis on our model, rather than via simulations. Our model does not assume large population densities, and may thus be useful in the context of understanding the ecology of extreme environments. PMID:25071753

  11. Deficient natural killer cell function in preeclampsia

    SciTech Connect

    Alanen, A.; Lassila, O.

    1982-11-01

    Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour /sup 51/Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder.

  12. Killer whales and whaling: the scavenging hypothesis.

    PubMed

    Whitehead, Hal; Reeves, Randall

    2005-12-22

    Killer whales (Orcinus orca) frequently scavenged from the carcasses produced by whalers. This practice became especially prominent with large-scale mechanical whaling in the twentieth century, which provided temporally and spatially clustered floating carcasses associated with loud acoustic signals. The carcasses were often of species of large whale preferred by killer whales but that normally sink beyond their diving range. In the middle years of the twentieth century floating whaled carcasses were much more abundant than those resulting from natural mortality of whales, and we propose that scavenging killer whales multiplied through diet shifts and reproduction. During the 1970s the numbers of available carcasses fell dramatically with the cessation of most whaling (in contrast to a reasonably stable abundance of living whales), and the scavenging killer whales needed an alternative source of nutrition. Diet shifts may have triggered declines in other prey species, potentially affecting ecosystems, as well as increasing direct predation on living whales.

  13. A Novel Saccharomyces cerevisiae Killer Strain Secreting the X Factor Related to Killer Activity and Inhibition of S. cerevisiae K1, K2 and K28 Killer Toxins.

    PubMed

    Melvydas, Vytautas; Bružauskaitė, Ieva; Gedminienė, Genovaitė; Šiekštelė, Rimantas

    2016-09-01

    It was determined that Kx strains secrete an X factor which can inhibit all known Saccharomyces cerevisiae killer toxins (K1, K2, K28) and some toxins of other yeast species-the phenomenon not yet described in the scientific literature. It was shown that Kx type yeast strains posess a killer phenotype producing small but clear lysis zones not only on the sensitive strain α'1 but also on the lawn of S. cerevisiae K1, K2 and K28 type killer strains at temperatures between 20 and 30 °C. The pH at which killer/antikiller effect of Kx strain reaches its maximum is about 5.0-5.2. The Kx yeast were identified as to belong to S. cerevisiae species. Another newly identified S. cerevisiae killer strain N1 has killer activity but shows no antikilller properties against standard K1, K2 and K28 killer toxins. The genetic basis for Kx killer/antikiller phenotype was associated with the presence of M-dsRNA which is bigger than M-dsRNA of standard S. cerevisiae K1, K2, K28 type killer strains. Killer and antikiller features should be encoded by dsRNA. The phenomenon of antikiller (inhibition) properties was observed against some killer toxins of other yeast species. The molecular weight of newly identified killer toxins which produces Kx type strains might be about 45 kDa.

  14. Nuclear and mitochondrial patterns of population structure in North Pacific false killer whales (Pseudorca crassidens).

    PubMed

    Martien, Karen K; Chivers, Susan J; Baird, Robin W; Archer, Frederick I; Gorgone, Antoinette M; Hancock-Hanser, Brittany L; Mattila, David; McSweeney, Daniel J; Oleson, Erin M; Palmer, Carol; Pease, Victoria L; Robertson, Kelly M; Schorr, Gregory S; Schultz, Mark B; Webster, Daniel L; Taylor, Barbara L

    2014-01-01

    False killer whales (Pseudorca crassidens) are large delphinids typically found in deep water far offshore. However, in the Hawaiian Archipelago, there are 2 resident island-associated populations of false killer whales, one in the waters around the main Hawaiian Islands (MHI) and one in the waters around the Northwestern Hawaiian Islands (NWHI). We use mitochondrial DNA (mtDNA) control region sequences and genotypes from 16 nuclear DNA (nucDNA) microsatellite loci from 206 individuals to examine levels of differentiation among the 2 island-associated populations and offshore animals from the central and eastern North Pacific. Both mtDNA and nucDNA exhibit highly significant differentiation between populations, confirming limited gene flow in both sexes. The mtDNA haplotypes exhibit a strong pattern of phylogeographic concordance, with island-associated populations sharing 3 closely related haplotypes not found elsewhere in the Pacific. However, nucDNA data suggest that NWHI animals are at least as differentiated from MHI animals as they are from offshore animals. The patterns of differentiation revealed by the 2 marker types suggest that the island-associated false killer whale populations likely share a common colonization history, but have limited contemporary gene flow. PMID:24831238

  15. Nuclear and mitochondrial patterns of population structure in North Pacific false killer whales (Pseudorca crassidens).

    PubMed

    Martien, Karen K; Chivers, Susan J; Baird, Robin W; Archer, Frederick I; Gorgone, Antoinette M; Hancock-Hanser, Brittany L; Mattila, David; McSweeney, Daniel J; Oleson, Erin M; Palmer, Carol; Pease, Victoria L; Robertson, Kelly M; Schorr, Gregory S; Schultz, Mark B; Webster, Daniel L; Taylor, Barbara L

    2014-01-01

    False killer whales (Pseudorca crassidens) are large delphinids typically found in deep water far offshore. However, in the Hawaiian Archipelago, there are 2 resident island-associated populations of false killer whales, one in the waters around the main Hawaiian Islands (MHI) and one in the waters around the Northwestern Hawaiian Islands (NWHI). We use mitochondrial DNA (mtDNA) control region sequences and genotypes from 16 nuclear DNA (nucDNA) microsatellite loci from 206 individuals to examine levels of differentiation among the 2 island-associated populations and offshore animals from the central and eastern North Pacific. Both mtDNA and nucDNA exhibit highly significant differentiation between populations, confirming limited gene flow in both sexes. The mtDNA haplotypes exhibit a strong pattern of phylogeographic concordance, with island-associated populations sharing 3 closely related haplotypes not found elsewhere in the Pacific. However, nucDNA data suggest that NWHI animals are at least as differentiated from MHI animals as they are from offshore animals. The patterns of differentiation revealed by the 2 marker types suggest that the island-associated false killer whale populations likely share a common colonization history, but have limited contemporary gene flow.

  16. Killer systems of the yeast Saccharomyces cerevisiae

    SciTech Connect

    Nesterova, G.F.

    1989-01-01

    The killer systems of Saccharomyces cerevisiae are an unusual class of cytoplasmic symbionts of primitive eukaryotes. The genetic material of these symbionts is double-stranded RNA. They are characterized by the linearity of the genome, its fragmentation into a major and a minor fraction, which replicate separately, and their ability to control the synthesis of secretory mycocin proteins possessing a toxic action on closely related strains. The secretion of mycocins at the same time ensures acquiring of resistance to them. Strains containing killer symbionts are toxigenic and resistant to the action of their own toxin, but strains that are free of killer double-stranded RNAs are sensitive to the action of mycocins. The killer systems of S. cerevisiae have retained features relating them to viruses and are apparently the result of evolution of infectious viruses. The occurrences of such systems among monocellular eukaryotic organisms is an example of complication of the genome by means of its assembly from virus-like components. We discuss the unusual features of replication and the expression of killer systems and their utilization in the construction of vector molecules.

  17. Population genomics of the killer whale indicates ecotype evolution in sympatry involving both selection and drift.

    PubMed

    Moura, Andre E; Kenny, John G; Chaudhuri, Roy; Hughes, Margaret A; J Welch, Andreanna; Reisinger, Ryan R; de Bruyn, P J Nico; Dahlheim, Marilyn E; Hall, Neil; Hoelzel, A Rus

    2014-11-01

    The evolution of diversity in the marine ecosystem is poorly understood, given the relatively high potential for connectivity, especially for highly mobile species such as whales and dolphins. The killer whale (Orcinus orca) has a worldwide distribution, and individual social groups travel over a wide geographic range. Even so, regional populations have been shown to be genetically differentiated, including among different foraging specialists (ecotypes) in sympatry. Given the strong matrifocal social structure of this species together with strong resource specializations, understanding the process of differentiation will require an understanding of the relative importance of both genetic drift and local adaptation. Here we provide a high-resolution analysis based on nuclear single-nucleotide polymorphic markers and inference about differentiation at both neutral loci and those potentially under selection. We find that all population comparisons, within or among foraging ecotypes, show significant differentiation, including populations in parapatry and sympatry. Loci putatively under selection show a different pattern of structure compared to neutral loci and are associated with gene ontology terms reflecting physiologically relevant functions (e.g. related to digestion). The pattern of differentiation for one ecotype in the North Pacific suggests local adaptation and shows some fixed differences among sympatric ecotypes. We suggest that differential habitat use and resource specializations have promoted sufficient isolation to allow differential evolution at neutral and functional loci, but that the process is recent and dependent on both selection and drift. PMID:25244680

  18. Population genomics of the killer whale indicates ecotype evolution in sympatry involving both selection and drift.

    PubMed

    Moura, Andre E; Kenny, John G; Chaudhuri, Roy; Hughes, Margaret A; J Welch, Andreanna; Reisinger, Ryan R; de Bruyn, P J Nico; Dahlheim, Marilyn E; Hall, Neil; Hoelzel, A Rus

    2014-11-01

    The evolution of diversity in the marine ecosystem is poorly understood, given the relatively high potential for connectivity, especially for highly mobile species such as whales and dolphins. The killer whale (Orcinus orca) has a worldwide distribution, and individual social groups travel over a wide geographic range. Even so, regional populations have been shown to be genetically differentiated, including among different foraging specialists (ecotypes) in sympatry. Given the strong matrifocal social structure of this species together with strong resource specializations, understanding the process of differentiation will require an understanding of the relative importance of both genetic drift and local adaptation. Here we provide a high-resolution analysis based on nuclear single-nucleotide polymorphic markers and inference about differentiation at both neutral loci and those potentially under selection. We find that all population comparisons, within or among foraging ecotypes, show significant differentiation, including populations in parapatry and sympatry. Loci putatively under selection show a different pattern of structure compared to neutral loci and are associated with gene ontology terms reflecting physiologically relevant functions (e.g. related to digestion). The pattern of differentiation for one ecotype in the North Pacific suggests local adaptation and shows some fixed differences among sympatric ecotypes. We suggest that differential habitat use and resource specializations have promoted sufficient isolation to allow differential evolution at neutral and functional loci, but that the process is recent and dependent on both selection and drift.

  19. Stochastic modeling of a serial killer.

    PubMed

    Simkin, M V; Roychowdhury, V P

    2014-08-21

    We analyze the time pattern of the activity of a serial killer, who during 12 years had murdered 53 people. The plot of the cumulative number of murders as a function of time is of "Devil's staircase" type. The distribution of the intervals between murders (step length) follows a power law with the exponent of 1.4. We propose a model according to which the serial killer commits murders when neuronal excitation in his brain exceeds certain threshold. We model this neural activity as a branching process, which in turn is approximated by a random walk. As the distribution of the random walk return times is a power law with the exponent 1.5, the distribution of the inter-murder intervals is thus explained. We illustrate analytical results by numerical simulation. Time pattern activity data from two other serial killers further substantiate our analysis.

  20. Stochastic modeling of a serial killer

    PubMed Central

    Simkin, M.V.; Roychowdhury, V.P.

    2014-01-01

    We analyze the time pattern of the activity of a serial killer, who during twelve years had murdered 53 people. The plot of the cumulative number of murders as a function of time is of “Devil’s staircase” type. The distribution of the intervals between murders (step length) follows a power law with the exponent of 1.4. We propose a model according to which the serial killer commits murders when neuronal excitation in his brain exceeds certain threshold. We model this neural activity as a branching process, which in turn is approximated by a random walk. As the distribution of the random walk return times is a power law with the exponent 1.5, the distribution of the inter-murder intervals is thus explained. We illustrate analytical results by numerical simulation. Time pattern activity data from two other serial killers further substantiate our analysis. PMID:24721476

  1. Remote Symbolic Computation of Loci

    ERIC Educational Resources Information Center

    Abanades, Miguel A.; Escribano, Jesus; Botana, Francisco

    2010-01-01

    This article presents a web-based tool designed to compute certified equations and graphs of geometric loci specified using standard Dynamic Geometry Systems (DGS). Complementing the graphing abilities of the considered DGS, the equations of the loci produced by the application are remotely computed using symbolic algebraic techniques from the…

  2. Killer toxin from a novel killer yeast Pichia kudriavzevii RY55 with idiosyncratic antibacterial activity.

    PubMed

    Bajaj, Bijender Kumar; Raina, Sandeepu; Singh, Satbir

    2013-08-01

    The killer phenomenon of yeast may have technological implications in many areas like beverage fermentation, food technology, biological control in agriculture, and in medicine. In the present study the killer phenomenon in Pichia kudriavzevii (P. kudriavzevii RY55) is being reported for the first time. The P. kudriavzevii RY55 toxin exhibited excellent antibacterial activity against several pathogens of human health significance such as Escherichia coli, Enterococcus faecalis, Klebsiella sp., Staphylococcus aureus, Pseudomonas aeruginosa and Pseudomonas alcaligenes. Killer toxin was purified to homogeneity by using ammonium sulphate precipitation and ion exchange chromatography and characterized for few properties. P. kudriavzevii RY55 killer toxin may be of vast significance in the development of novel antimicrobial chemotherapeutic agents, new bio-based safer candidates for food preservation and biocontrol, and starter cultures for fermentation industries. PMID:22961241

  3. Killer toxin from a novel killer yeast Pichia kudriavzevii RY55 with idiosyncratic antibacterial activity.

    PubMed

    Bajaj, Bijender Kumar; Raina, Sandeepu; Singh, Satbir

    2013-08-01

    The killer phenomenon of yeast may have technological implications in many areas like beverage fermentation, food technology, biological control in agriculture, and in medicine. In the present study the killer phenomenon in Pichia kudriavzevii (P. kudriavzevii RY55) is being reported for the first time. The P. kudriavzevii RY55 toxin exhibited excellent antibacterial activity against several pathogens of human health significance such as Escherichia coli, Enterococcus faecalis, Klebsiella sp., Staphylococcus aureus, Pseudomonas aeruginosa and Pseudomonas alcaligenes. Killer toxin was purified to homogeneity by using ammonium sulphate precipitation and ion exchange chromatography and characterized for few properties. P. kudriavzevii RY55 killer toxin may be of vast significance in the development of novel antimicrobial chemotherapeutic agents, new bio-based safer candidates for food preservation and biocontrol, and starter cultures for fermentation industries.

  4. Natural born killers?: the development of the sexually sadistic serial killer.

    PubMed

    Johnson, B R; Becker, J V

    1997-01-01

    Today's society seems enthralled with serial killers in the news and the media. Forensic psychiatrists often interview serial killers after they have been caught. There are retrospective studies and case reports of individuals who have committed sexually sadistic serial murders. However, there exists a dearth of case reports on adolescents who have expressed serious fantasies about becoming serial killer prior to actualizing their fantasy. This article presents nine clinical cases of 14- to 18-year-olds who have clinically significant fantasies of becoming a serial killer. Similarities exist in these adolescent cases when compared with retrospective studies and case reports of serial killers on the role of sexually sadistic fantasies and actual killings. Since it has been established that sexual paraphilias may develop at a young age, one can surmise that sadistic paraphilias may also develop in some adolescents. The question is posed, can we predict which of these adolescents may go on to actually become serial killers? This article focuses on how the sexually sadistic fantasy can eventually be acted out and possible motives for the act to be repeated multiple times. Finally, recommendations are made about assessing and treating a youngster who expresses violent sexually sadistic killing fantasies so that attempts can be made to interrupt the progression to actual killing.

  5. Natural born killers?: the development of the sexually sadistic serial killer.

    PubMed

    Johnson, B R; Becker, J V

    1997-01-01

    Today's society seems enthralled with serial killers in the news and the media. Forensic psychiatrists often interview serial killers after they have been caught. There are retrospective studies and case reports of individuals who have committed sexually sadistic serial murders. However, there exists a dearth of case reports on adolescents who have expressed serious fantasies about becoming serial killer prior to actualizing their fantasy. This article presents nine clinical cases of 14- to 18-year-olds who have clinically significant fantasies of becoming a serial killer. Similarities exist in these adolescent cases when compared with retrospective studies and case reports of serial killers on the role of sexually sadistic fantasies and actual killings. Since it has been established that sexual paraphilias may develop at a young age, one can surmise that sadistic paraphilias may also develop in some adolescents. The question is posed, can we predict which of these adolescents may go on to actually become serial killers? This article focuses on how the sexually sadistic fantasy can eventually be acted out and possible motives for the act to be repeated multiple times. Finally, recommendations are made about assessing and treating a youngster who expresses violent sexually sadistic killing fantasies so that attempts can be made to interrupt the progression to actual killing. PMID:9323659

  6. The School: A Killer of Giftedness?

    ERIC Educational Resources Information Center

    van der Walt, J. L.

    Criticisms of the school as a killer of giftedness in children are cited. After defining giftedness and talent, the problem of educating the gifted child is raised, and opinions of "new left" educational theorists are presented. Accusations against the school, based on its failure to meet the individual needs and the mental or cognitive…

  7. Young Killers: The Challenge of Juvenile Homicide.

    ERIC Educational Resources Information Center

    Heide, Kathleen M.

    This book assembles and synthesizes some of the latest available information, research findings, and informed opinions regarding the parameters of homicide by youths and concerning the nature of young killers themselves. It provides a framework for understanding youths who kill, for moving forward with treatment, and for reducing violence in…

  8. Chasing Killer Statements From The Classroom

    ERIC Educational Resources Information Center

    Simon, Marianne

    1975-01-01

    This teacher discusses techniques she uses to rid the classroom of "killer statements", which are negative statements that express some kind of anger or distress and are unthinking outgrowths of the desire to get back at the world when feeling needy or deprived.

  9. The KP4 killer protein gene family

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Killer protein 4 (KP4) is a well studied toxin secreted by the maize smut fungus Ustilago maydis that kills sensitive Ustilago strains as well as inhibits Fusarium and plant root growth. This small, cysteine rich protein is encoded by a virus that depends on host survival for replication. KP4 functi...

  10. Natural killer cells in hepatitis B virus infection.

    PubMed

    Wu, Shao-fei; Wang, Wen-jing; Gao, Yue-qiu

    2015-01-01

    Natural killer cells are a unique type of lymphocytes with cytotoxic capacity, and play important roles against tumors and infections. Recently, natural killer cells have been increasingly valued in their effects in hepatitis B virus infection. Since hepatitis B virus is not cytopathic, the subsequent antiviral immune responses of the host are responsible for sustaining the liver injury, which may result in cirrhosis and even hepatocellular carcinoma. Many studies have confirmed that natural killer cells participate in anti-hepatitis B virus responses both in the early phase after infection and in the chronic phase via cytolysis, degranulation, and cytokine secretion. However, natural killer cells play dichotomic roles: they exert antiviral and immunoregulatory functions whilst contribute to the pathogenesis of liver injury. Here, we review the roles of natural killer cells in hepatitis B virus infection, introducing novel therapeutic strategies for controlling hepatitis B virus infection via the modulation of natural killer cells.

  11. Travel from a supercomputer to killer micros

    SciTech Connect

    Werner, N.E.

    1991-03-01

    I describe my effort to convert a Fortran application that runs on a parallel supercomputer (Cray Y/MP) to run on a set of BBN TC2000 killer micros. I used both shared memory parallel processing options available at MPCI for the BBN TC2000, the Parallel Fortran Preprocessor (PFP) and the Uniform System extended Fortran compiler (US). I describe how I used the BBN Xtra programming tools for analysis and debugging during this conversion process. My ultimate goal for this hands on experiment was to gain insight into the type of tools that might be helpful for porting existing programs from a supercomputer environment to a killer micro environment. 5 refs., 9 figs.

  12. The Human Natural Killer Cell Immune Synapse

    NASA Astrophysics Data System (ADS)

    Davis, Daniel M.; Chiu, Isaac; Fassett, Marlys; Cohen, George B.; Mandelboim, Ofer; Strominger, Jack L.

    1999-12-01

    Inhibitory killer Ig-like receptors (KIR) at the surface of natural killer (NK) cells induced clustering of HLA-C at the contacting surface of target cells. In this manner, inhibitory immune synapses were formed as human NK cells surveyed target cells. At target/NK cell synapses, HLA-C/KIR distributed into rings around central patches of intercellular adhesion molecule-1/lymphocyte function-associated antigen-1, the opposite orientation to mature murine T cell-activating synapses. This organization of protein was stable for at least 20 min. Cells could support multiple synapses simultaneously, and clusters of HLA-C moved as NK cells crawled over target cells. Clustering required a divalent metal cation, explaining how metal chelators inhibit KIR function. Surprisingly, however, formation of inhibitory synapses was unaffected by ATP depletion and the cytoskeletal inhibitors, colchicine and cytochalsins B and D. Clearly, supramolecular organization within plasma membranes is critical for NK cell immunosurveillance.

  13. Representation of the serial killer on the Italian Internet.

    PubMed

    Villano, P; Bastianoni, P; Melotti, G

    2001-10-01

    The representation of serial killers was examined from the analysis of 317 Web pages in the Italian language to study how the psychological profiles of serial killers are described on the Italian Internet. The correspondence analysis of the content of these Web pages shows that in Italy the serial killer is associated with words such as "monster" and "horror," which suggest and imply psychological perversion and aberrant acts. These traits are peculiar for the Italian scenario.

  14. Representation of the serial killer on the Italian Internet.

    PubMed

    Villano, P; Bastianoni, P; Melotti, G

    2001-10-01

    The representation of serial killers was examined from the analysis of 317 Web pages in the Italian language to study how the psychological profiles of serial killers are described on the Italian Internet. The correspondence analysis of the content of these Web pages shows that in Italy the serial killer is associated with words such as "monster" and "horror," which suggest and imply psychological perversion and aberrant acts. These traits are peculiar for the Italian scenario. PMID:11783573

  15. Is killer whale dialect evolution random?

    PubMed

    Filatova, Olga A; Burdin, Alexandr M; Hoyt, Erich

    2013-10-01

    The killer whale is among the few species in which cultural change accumulates over many generations, leading to cumulative cultural evolution. Killer whales have group-specific vocal repertoires which are thought to be learned rather than being genetically coded. It is supposed that divergence between vocal repertoires of sister groups increases gradually over time due to random learning mistakes and innovations. In this case, the similarity of calls across groups must be correlated with pod relatedness and, consequently, with each other. In this study we tested this prediction by comparing the patterns of call similarity between matrilines of resident killer whales from Eastern Kamchatka. We calculated the similarity of seven components from three call types across 14 matrilines. In contrast to the theoretical predictions, matrilines formed different clusters on the dendrograms made by different calls and even by different components of the same call. We suggest three possible explanations for this phenomenon. First, the lack of agreement between similarity patterns of different components may be the result of constraints in the call structure. Second, it is possible that call components change in time with different speed and/or in different directions. Third, horizontal cultural transmission of call features may occur between matrilines.

  16. A psychological profile of a serial killer: a case report.

    PubMed

    Dogra, T D; Leenaars, Antoon A; Chadha, R K; Manju, Mehta; Lalwani, Sanjeev; Sood, Mamta; Lester, David; Raina, Anupuma; Behera, C

    2012-01-01

    Serial killers have always fascinated society. A serial killer is typically defined as a perpetrator who murders three or more people over a period of time. Most reported cases of serial killers come from the United States and Canada. In India, there are few reported cases. We present, to the best of our knowledge, the first Indian case in the literature. The present case is of a 28-year-old man, Surinder Koli. The Department of Forensic Medicine & Toxicology, All India Institute of Medical Sciences, New Delphi handled the forensic study. We present a most unique psychological investigation into the mind of a serial killer.

  17. A psychological profile of a serial killer: a case report.

    PubMed

    Dogra, T D; Leenaars, Antoon A; Chadha, R K; Manju, Mehta; Lalwani, Sanjeev; Sood, Mamta; Lester, David; Raina, Anupuma; Behera, C

    2012-01-01

    Serial killers have always fascinated society. A serial killer is typically defined as a perpetrator who murders three or more people over a period of time. Most reported cases of serial killers come from the United States and Canada. In India, there are few reported cases. We present, to the best of our knowledge, the first Indian case in the literature. The present case is of a 28-year-old man, Surinder Koli. The Department of Forensic Medicine & Toxicology, All India Institute of Medical Sciences, New Delphi handled the forensic study. We present a most unique psychological investigation into the mind of a serial killer. PMID:23115894

  18. The structure of stereotyped calls reflects kinship and social affiliation in resident killer whales ( Orcinus orca)

    NASA Astrophysics Data System (ADS)

    Deecke, Volker B.; Barrett-Lennard, Lance G.; Spong, Paul; Ford, John K. B.

    2010-05-01

    A few species of mammals produce group-specific vocalisations that are passed on by learning, but the function of learned vocal variation remains poorly understood. Resident killer whales live in stable matrilineal groups with repertoires of seven to 17 stereotyped call types. Some types are shared among matrilines, but their structure typically shows matriline-specific differences. Our objective was to analyse calls of nine killer whale matrilines in British Columbia to test whether call similarity primarily reflects social or genetic relationships. Recordings were made in 1985-1995 in the presence of focal matrilines that were either alone or with groups with non-overlapping repertoires. We used neural network discrimination performance to measure the similarity of call types produced by different matrilines and determined matriline association rates from 757 encounters with one or more focal matrilines. Relatedness was measured by comparing variation at 11 microsatellite loci for the oldest female in each group. Call similarity was positively correlated with association rates for two of the three call types analysed. Similarity of the N4 call type was also correlated with matriarch relatedness. No relationship between relatedness and association frequency was detected. These results show that call structure reflects relatedness and social affiliation, but not because related groups spend more time together. Instead, call structure appears to play a role in kin recognition and shapes the association behaviour of killer whale groups. Our results therefore support the hypothesis that increasing social complexity plays a role in the evolution of learned vocalisations in some mammalian species.

  19. Metabolic imaging of the tumor treated by KillerRed fluorescent protein-based photodynamic therapy in mice

    NASA Astrophysics Data System (ADS)

    Sha, Shuang; Qin, Lingsong; Wang, Anle; Liu, Zheng; Yang, Fei; Jin, Honglin; Zhang, Zhihong

    2014-02-01

    KillerRed is a unique red fluorescent protein exhibiting excellent phototoxic properties. It has the ability to produce reactive oxygen species (ROS), for killing tumor cells in vitro upon laser irradiation and has the potential to act as a photosensitizer in the application of tumor therapy. Here, we investigated the effects of KillerRed-based photodynamic therapy (PDT) on tumor growth in vivo and examined the subsequent tumor metabolic states including the changes of pyridine nucleotide (PN) and flavoprotein (Fp), two important metabolic coenzymes of tumor cells. Results showed that the tumor was scabbed in response to 561 nm laser irradiation at 80 mV for 3 min, and the tumor growth had been significantly inhibited by KillerRed-based PDT treatment compared to control groups. More importantly, a home-made cryo-imaging redox scanner was used to measure intrinsic fluorescence and exogenous KillerRed fluorescence signals in tumors. The flavoprotein was remarkable elevated and the PN was seldom increased with concomitant photobleaching of KillerRed fluorescence after irradiation, suggesting that flavoprotein and PN were oxidized in the course of KillerRed-based PDT.

  20. Killer cell immunoglobulin-like receptor (KIR) locus profiles in the Tunisian population.

    PubMed

    Meriem, Bani; Jihen, Seket; Houda, Kaabi; Ghaya, Cherif; Manel, Chaabane; Hedi, Bellali; Slama, Hmida

    2015-05-01

    Killer cell immunoglobulin-like receptors (KIRs) are a family of inhibitory and activatory receptors that are expressed by most natural killer (NK) cells. The KIR gene family is polymorphic: genomic diversity is achieved through differences in gene content and allelic polymorphism. The number of KIR loci has been reported to vary among individuals, resulting in different KIR haplotypes. In this study we report the genotypic structure of KIRs in 267 unrelated and healthy Tunisian subjects by polymerase chain reaction-sequence-specific primer (PCR-SSP) method. All 16 KIR genes were observed in the population with different frequencies; framework genes KIR3DP1 and KIR3DL2 and the nonframework genes KIR2DL1 and KIR2DP1 were present in all individuals. A total of 26 different KIR gene profiles and 54 subgenotypes were observed in the tested population samples. Genotype 1, with a frequency of 36.6%, is the most commonly observed in the Tunisian population. Our results showed that the Tunisian population possesses the previously reported general features of the Caucasian as well as African populations, with some additional interesting differences. Such knowledge of the KIR gene distribution in populations is very useful in the study of associations with diseases and in selection of donors for haploidentical bone marrow transplantation.

  1. The virally encoded killer proteins from Ustilago maydis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several strains of Ustilago maydis, a causal agent of corn smut disease, exhibit a 'killer' phenotype that is due to persistent infection by double-stranded RNA Totiviruses. These viruses produce potent killer proteins that are secreted by the host. This is a rare example of virus/host symbiosis in ...

  2. Optimization of killer assays for yeast selection protocols.

    PubMed

    Lopes, C A; Sangorrín, M P

    2010-01-01

    A new optimized semiquantitative yeast killer assay is reported for the first time. The killer activity of 36 yeast isolates belonging to three species, namely, Metschnikowia pulcherrima, Wickerhamomyces anomala and Torulaspora delbrueckii, was tested with a view to potentially using these yeasts as biocontrol agents against the wine spoilage species Pichia guilliermondii and Pichia membranifaciens. The effectiveness of the classical streak-based (qualitative method) and the new semiquantitative techniques was compared. The percentage of yeasts showing killer activity was found to be higher by the semiquantitative technique (60%) than by the qualitative method (45%). In all cases, the addition of 1% NaCl into the medium allowed a better observation of the killer phenomenon. Important differences were observed in the killer capacity of different isolates belonging to a same killer species. The broadest spectrum of action was detected in isolates of W. anomala NPCC 1023 and 1025, and M. pulcherrima NPCC 1009 and 1013. We also brought experimental evidence supporting the importance of the adequate selection of the sensitive isolate to be used in killer evaluation. The new semiquantitative method proposed in this work enables to visualize the relationship between the number of yeasts tested and the growth of the inhibition halo (specific productivity). Hence, this experimental approach could become an interesting tool to be taken into account for killer yeast selection protocols.

  3. Natural Killer Cell Reduction and Uteroplacental Vasculopathy.

    PubMed

    Golic, Michaela; Haase, Nadine; Herse, Florian; Wehner, Anika; Vercruysse, Lisbeth; Pijnenborg, Robert; Balogh, Andras; Saether, Per Christian; Dissen, Erik; Luft, Friedrich C; Przybyl, Lukasz; Park, Joon-Keun; Alnaes-Katjavivi, Patji; Staff, Anne Cathrine; Verlohren, Stefan; Henrich, Wolfgang; Muller, Dominik N; Dechend, Ralf

    2016-10-01

    Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum-treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum-treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth.

  4. Natural Killer Cell Reduction and Uteroplacental Vasculopathy.

    PubMed

    Golic, Michaela; Haase, Nadine; Herse, Florian; Wehner, Anika; Vercruysse, Lisbeth; Pijnenborg, Robert; Balogh, Andras; Saether, Per Christian; Dissen, Erik; Luft, Friedrich C; Przybyl, Lukasz; Park, Joon-Keun; Alnaes-Katjavivi, Patji; Staff, Anne Cathrine; Verlohren, Stefan; Henrich, Wolfgang; Muller, Dominik N; Dechend, Ralf

    2016-10-01

    Uterine natural killer cells are important for uteroplacental development and pregnancy maintenance. Their role in pregnancy disorders, such as preeclampsia, is unknown. We reduced the number of natural killer cells by administering rabbit anti-asialo GM1 antiserum in an established rat preeclamptic model (female human angiotensinogen×male human renin) and evaluated the effects at the end of pregnancy (day 21), compared with preeclamptic control rats receiving normal rabbit serum. In 100% of the antiserum-treated, preeclamptic rats (7/7), we observed highly degenerated vessel cross sections in the mesometrial triangle at the end of pregnancy. This maternal uterine vasculopathy was characterized by a total absence of nucleated/living cells in the vessel wall and perivascularly and prominent presence of fibrosis. Furthermore, there were no endovascular trophoblast cells within the vessel lumen. In the control, normal rabbit serum-treated, preeclamptic rats, only 20% (1/5) of the animals displayed such vasculopathy. We confirmed the results in healthy pregnant wild-type rats: after anti-asialo GM1 treatment, 67% of maternal rats displayed vasculopathy at the end of pregnancy compared with 0% in rabbit serum-treated control rats. This vasculopathy was associated with a significantly lower fetal weight in wild-type rats and deterioration of fetal brain/liver weight ratio in preeclamptic rats. Anti-asialo GM1 application had no influence on maternal hypertension and albuminuria during pregnancy. Our results show a new role of natural killer cells during hypertensive pregnancy in maintaining vascular integrity. In normotensive pregnancy, this integrity seems important for fetal growth. PMID:27550919

  5. Viral Evasion of Natural Killer Cell Activation

    PubMed Central

    Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

    2016-01-01

    Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections. PMID:27077876

  6. Viral Evasion of Natural Killer Cell Activation.

    PubMed

    Ma, Yi; Li, Xiaojuan; Kuang, Ersheng

    2016-04-12

    Natural killer (NK) cells play a key role in antiviral innate defenses because of their abilities to kill infected cells and secrete regulatory cytokines. Additionally, NK cells exhibit adaptive memory-like antigen-specific responses, which represent a novel antiviral NK cell defense mechanism. Viruses have evolved various strategies to evade the recognition and destruction by NK cells through the downregulation of the NK cell activating receptors. Here, we review the recent findings on viral evasion of NK cells via the impairment of NK cell-activating receptors and ligands, which provide new insights on the relationship between NK cells and viral actions during persistent viral infections.

  7. Photobleaching and phototoxicity of KillerRed in tumor spheroids induced by continuous wave and pulsed laser illumination.

    PubMed

    Kuznetsova, Daria S; Shirmanova, Marina V; Dudenkova, Varvara V; Subochev, Pavel V; Turchin, Ilya V; Zagaynova, Elena V; Lukyanov, Sergey A; Shakhov, Boris E; Kamensky, Vladislav A

    2015-11-01

    The purpose of this study was to evaluate photobleaching of the genetically encoded photosensitizer KillerRed in tumor spheroids upon pulsed and continuous wave (CW) laser irradiation and to analyze the mechanisms of cancer cell death after the treatment. We observed the light-dose dependent mechanism of KillerRed photobleaching over a wide range of fluence rates. Loss of fluorescence was limited to 80% at light doses of 150 J/cm(2) and more. Based on the bleaching curves, six PDT regimes were applied for irradiation using CW and pulsed regimes at a power density of 160 mW/cm(2) and light doses of 140 J/cm(2) , 170 J/cm(2) and 200 J/cm(2). Irradiation of KillerRed-expressing spheroids in the pulsed mode (pulse duration 15 ns, pulse repetition rate 10 Hz) induced predominantly apoptotic cell death, while in the case of CW mode the cancer cells underwent necrosis. In general, these results improve our understanding of photobleaching mechanisms in GFP-like proteins and show the importance of appropriate selection of treatment mode for PDT with KillerRed. Representative fluorescence image of two KillerRed-expressing spheroids before and immediately after CW irradiation.

  8. From Pichia anomala killer toxin through killer antibodies to killer peptides for a comprehensive anti-infective strategy.

    PubMed

    Polonelli, Luciano; Magliani, Walter; Ciociola, Tecla; Giovati, Laura; Conti, Stefania

    2011-01-01

    "Antibiobodies", antibodies (Abs) with antibiotic activity, internal image of a Pichia anomala killer toxin (PaKT) characterized by microbicidal activity against microorganisms expressing β-glucans cell-wall receptors (PaKTRs), were produced by idiotypic vaccination with a PaKT-neutralizing monoclonal Ab (PaKT-like Abs) or induced by a protein-conjugated β-glucan. Human natural PaKT-like Abs (PaKTAbs) were found in the vaginal fluid of women infected with KT-sensitive microorganisms. Monoclonal and recombinant PaKT-like Abs, and PaKTAbs proved to be protective against experimental candidiasis, cryptococcosis and aspergillosis. A killer decapeptide (KP), synthesized from the sequence of a recombinant PaKT-like Ab or produced in transgenic plants, showed a microbicidal activity in vitro, neutralized by β-glucans, a therapeutic effect in vivo, against experimental mucosal and systemic mycoses, and a prophylactic role in planta, against phytopathogenic microorganisms, respectively. KP showed fungicidal properties against all the defective mutants of a Saccharomyces cerevisiae library, inclusive of strains recognized to be resistant to conventional antifungal drugs. KP inhibited in vitro, ex vivo and/or in vivo HIV-1 and Influenza A virus replication, owing to down-regulation of CCR5 co-receptors, physical block of the gp120-receptor interaction and reduction in the synthesis of glycoproteins, HA and M1 in particular. KP modulated the expression of costimulatory and MHC molecules on murine dendritic cells, improving their capacity to induce lymphocyte proliferation. KP, proven to be devoid of cytotoxicity on human cells, showed self-assembly-releasing hydrogel-like properties, catalyzed by β 1,3 glucan. PaKT's biotechnological derivatives may represent the prototypes of novel antifungal vaccines and anti-infective drugs characterized by different mechanisms of action. PMID:20714805

  9. Evidence for Natural Killer Cell Memory

    PubMed Central

    Marcus, Assaf; Raulet, David H.

    2013-01-01

    Natural killer (NK) cells are generally considered part of the innate immune system. However, over the past few years, evidence has accumulated suggesting that NK cells have certain features characteristic of the adaptive immune system. NK cells reportedly respond in an antigen-specific manner to a variety of small molecules and certain viruses, and mediate enhanced responses to these antigens upon re-challenge. In infections with mouse cytomegalovirus (MCMV), MCMV-specific NK cells undergo clonal expansion, and display increased effector function after the resolution of the infection. In addition, inflammatory conditions resulting from exposure to certain cytokines seem to cause prolonged effector function in NK cells in an antigen non-specific fashion. Taken together, these studies reveal new aspects of NK biology, and suggest that NK cells, like T and B cells, may carry out memory responses, and may also exhibit greater capacity to distinguish antigens than was previously recognized. PMID:24028966

  10. Natural killer cells: In health and disease.

    PubMed

    Mandal, Arundhati; Viswanathan, Chandra

    2015-06-01

    Natural killer (NK) cells constitute our bodies' frontline defense system, guarding against tumors and launching attacks against infections. The activities of NK cells are regulated by the interaction of various receptors expressed on their surfaces with cell surface ligands. While the role of NK cells in controlling tumor activity is relatively clear, the fact that they are also linked to various other disease conditions is now being highlighted. Here, we present an overview of the role of NK cells during normal body state as well as under diseased state. We discuss the possible utilization of these powerful cells as immunotherapeutic agents in combating diseases such as asthma, autoimmune diseases, and HIV-AIDS. This review also outlines current challenges in NK cell therapy.

  11. Immunobiology of natural killer cells. Volume II

    SciTech Connect

    Lotzova, E.; Herberman, R.B.

    1986-01-01

    This book provides a review of natural killer (NK) cell-mediated immunity in humans and experimental animal system. Topics for the volume include: In vivo activities of NK cells against primary and metastatic tumors in experimental animals; involvement of NK cells in human malignant disease; impaired NK cell profile in leukemia patients; in vivo modulation of NK activity in cancer patients; implications of aberrant NK cell activity in nonmalignant, chronic diseases; NK cell role in regulation of the growth and functions of hemopoietic and lymphoid cells; NK cells active against viral, bacterial, protozoan, and fungal infections; cytokine secretion and noncytotoxic functions of human large granular lymphocytes; augmentation of NK activity; regulation of NK cell activity by suppressor cells; NK cell cloning technology and characteristics of NK cell clones; comparison of antibody-dependent cellular cytotoxicity (ADCC) and NK activity, and index.

  12. Radiology: "killer app" for next generation networks?

    PubMed

    McNeill, Kevin M

    2004-03-01

    The core principles of digital radiology were well developed by the end of the 1980 s. During the following decade tremendous improvements in computer technology enabled realization of those principles at an affordable cost. In this decade work can focus on highly distributed radiology in the context of the integrated health care enterprise. Over the same period computer networking has evolved from a relatively obscure field used by a small number of researchers across low-speed serial links to a pervasive technology that affects nearly all facets of society. Development directions in network technology will ultimately provide end-to-end data paths with speeds that match or exceed the speeds of data paths within the local network and even within workstations. This article describes key developments in Next Generation Networks, potential obstacles, and scenarios in which digital radiology can become a "killer app" that helps to drive deployment of new network infrastructure. PMID:15255516

  13. Targeting natural killer cells in cancer immunotherapy.

    PubMed

    Guillerey, Camille; Huntington, Nicholas D; Smyth, Mark J

    2016-08-19

    Alteration in the expression of cell-surface proteins is a common consequence of malignant transformation. Natural killer (NK) cells use an array of germline-encoded activating and inhibitory receptors that scan for altered protein-expression patterns, but tumor evasion of detection by the immune system is now recognized as one of the hallmarks of cancer. NK cells display rapid and potent immunity to metastasis or hematological cancers, and major efforts are now being undertaken to fully exploit NK cell anti-tumor properties in the clinic. Diverse approaches encompass the development of large-scale NK cell-expansion protocols for adoptive transfer, the establishment of a microenvironment favorable to NK cell activity, the redirection of NK cell activity against tumor cells and the release of inhibitory signals that limit NK cell function. In this Review we detail recent advances in NK cell-based immunotherapies and discuss the advantages and limitations of these strategies. PMID:27540992

  14. Metabolic regulation of natural killer cells.

    PubMed

    Finlay, David K

    2015-08-01

    Natural killer (NK) cells have key roles in anti-viral and anti-tumour immune responses. Recent research demonstrates that cellular metabolism is an important determinant for the function of pro-inflammatory immune cells, including activated NK cells. The mammalian target of rapamcyin (mTOR) complex 1 (mTORC1) has been identified as a key metabolic regulator that promotes glycolytic metabolism in multiple immune cell subsets. Glycolysis is integrally linked to pro-inflammatory immune responses such that activated NK cells and effector T-cell subsets are reliant on sufficient glucose availability for maximal effector function. This article will discuss the regulation of cellular metabolism in NK cells as compared with that of T lymphocytes and discuss the implications for NK cell responses to viral infection and cancer.

  15. The antileukemic potential of natural killer cells.

    PubMed

    Torelli, Giovanni F; Peragine, Nadia; Mariglia, Paola; Foà, Robin

    2016-01-01

    The antileukemic potential of natural killer (NK) cells has over the years raised considerable interest and new immune-based treatment protocols characterized by the infusion of freshly isolated or ex vivo activated and expanded effectors have been designed. Several aspects still need to be addressed, including the optimal timing of NK infusion during the course of the disease, the best preparative regimen, the origin of NK cells and the possible need of ex vivo NK cell manipulation before the infusion. The aims of this review are to discuss the experimental and clinical data available on the role played by NK cells for leukemia patients and to revise the different good manufacturing practice protocols for ex vivo manipulation of these effector cells.

  16. Killer whales are capable of vocal learning

    PubMed Central

    Foote, Andrew D; Griffin, Rachael M; Howitt, David; Larsson, Lisa; Miller, Patrick J.O; Rus Hoelzel, A

    2006-01-01

    The production learning of vocalizations by manipulation of the sound production organs to alter the physical structure of sound has been demonstrated in only a few mammals. In this natural experiment, we document the vocal behaviour of two juvenile killer whales, Orcinus orca, separated from their natal pods, which are the only cases of dispersal seen during the three decades of observation of their populations. We find mimicry of California sea lion (Zalophus californianus) barks, demonstrating the vocal production learning ability for one of the calves. We also find differences in call usage (compared to the natal pod) that may reflect the absence of a repertoire model from tutors or some unknown effect related to isolation or context. PMID:17148275

  17. Towards PDT with Genetically Encoded Photosensitizer KillerRed: A Comparison of Continuous and Pulsed Laser Regimens in an Animal Tumor Model.

    PubMed

    Shirmanova, Marina; Yuzhakova, Diana; Snopova, Ludmila; Perelman, Gregory; Serebrovskaya, Ekaterina; Lukyanov, Konstantin; Turchin, Ilya; Subochev, Pavel; Lukyanov, Sergey; Kamensky, Vladislav; Zagaynova, Elena

    2015-01-01

    The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT) of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm) and pulsed laser (584 nm, 10 Hz, 18 ns) modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation. PMID:26657001

  18. Towards PDT with Genetically Encoded Photosensitizer KillerRed: A Comparison of Continuous and Pulsed Laser Regimens in an Animal Tumor Model.

    PubMed

    Shirmanova, Marina; Yuzhakova, Diana; Snopova, Ludmila; Perelman, Gregory; Serebrovskaya, Ekaterina; Lukyanov, Konstantin; Turchin, Ilya; Subochev, Pavel; Lukyanov, Sergey; Kamensky, Vladislav; Zagaynova, Elena

    2015-01-01

    The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT) of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm) and pulsed laser (584 nm, 10 Hz, 18 ns) modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation.

  19. The eyeball killer: serial killings with postmortem globe enucleation.

    PubMed

    Coyle, Julie; Ross, Karen F; Barnard, Jeffrey J; Peacock, Elizabeth; Linch, Charles A; Prahlow, Joseph A

    2015-05-01

    Although serial killings are relatively rare, they can be the cause of a great deal of anxiety while the killer remains at-large. Despite the fact that the motivations for serial killings are typically quite complex, the psychological analysis of a serial killer can provide valuable insight into how and why certain individuals become serial killers. Such knowledge may be instrumental in preventing future serial killings or in solving ongoing cases. In certain serial killings, the various incidents have a variety of similar features. Identification of similarities between separate homicidal incidents is necessary to recognize that a serial killer may be actively killing. In this report, the authors present a group of serial killings involving three prostitutes who were shot to death over a 3-month period. Scene and autopsy findings, including the unusual finding of postmortem enucleation of the eyes, led investigators to recognize the serial nature of the homicides.

  20. Fewer Drugs in Pipeline to Treat World's No. 1 Killer

    MedlinePlus

    ... 160676.html Fewer Drugs in Pipeline to Treat World's No. 1 Killer While number of cancer drugs ... 29, 2016 (HealthDay News) -- Heart disease remains the world's leading cause of death, but development of drugs ...

  1. Killer cell lines against Shope carcinoma cells in rabbits.

    PubMed

    Takahashi, M; Yamade, I; Seto, A

    1991-09-01

    Killer cell activity against Shope carcinoma cells was not detected in PBL nor in spleen cells from tumor-bearing B/J rabbits, but was induced by in vitro culture of these cells in the presence of IL-2 and X-irradiated carcinoma cells. HTLV-I-transformed killer cell lines were successfully obtained by the culturing of PBL from an HTLV-I-infected and tumor-bearing Chbb:HM rabbit. These killer cells included large cells with azurophilic granules in the cytoplasm and with a reniform nucleus, thus resembling large granular lymphocytes. The killer activity was similar against the Vx2K cell line from a random-bred rabbit and SCB cell lines from an B/J rabbit, suggesting the absence of MHC restriction. PMID:1655241

  2. The eyeball killer: serial killings with postmortem globe enucleation.

    PubMed

    Coyle, Julie; Ross, Karen F; Barnard, Jeffrey J; Peacock, Elizabeth; Linch, Charles A; Prahlow, Joseph A

    2015-05-01

    Although serial killings are relatively rare, they can be the cause of a great deal of anxiety while the killer remains at-large. Despite the fact that the motivations for serial killings are typically quite complex, the psychological analysis of a serial killer can provide valuable insight into how and why certain individuals become serial killers. Such knowledge may be instrumental in preventing future serial killings or in solving ongoing cases. In certain serial killings, the various incidents have a variety of similar features. Identification of similarities between separate homicidal incidents is necessary to recognize that a serial killer may be actively killing. In this report, the authors present a group of serial killings involving three prostitutes who were shot to death over a 3-month period. Scene and autopsy findings, including the unusual finding of postmortem enucleation of the eyes, led investigators to recognize the serial nature of the homicides. PMID:25682709

  3. Killer whale ecotypes: is there a global model?

    PubMed

    de Bruyn, P J N; Tosh, Cheryl A; Terauds, Aleks

    2013-02-01

    Killer whales, Orcinus orca, are top predators occupying key ecological roles in a variety of ecosystems and are one of the most widely distributed mammals on the planet. In consequence, there has been significant interest in understanding their basic biology and ecology. Long-term studies of Northern Hemisphere killer whales, particularly in the eastern North Pacific (ENP), have identified three ecologically distinct communities or ecotypes in that region. The success of these prominent ENP studies has led to similar efforts at clarifying the role of killer whale ecology in other regions, including Antarctica. In the Southern Hemisphere, killer whales present a range of behavioural, social and morphological characteristics to biologists, who often interpret this as evidence to categorize individuals or groups, and draw general ecological conclusions about these super-predators. Morphologically distinct forms (Type A, B, C, and D) occur in the Southern Ocean and studies of these different forms are often presented in conjunction with evidence for specialised ecology and behaviours. Here we review current knowledge of killer whale ecology and ecotyping globally and present a synthesis of existing knowledge. In particular, we highlight the complexity of killer whale ecology in the Southern Hemisphere and examine this in the context of comparatively well-studied Northern Hemisphere populations. We suggest that assigning erroneous or prefatory ecotypic status in the Southern Hemisphere could be detrimental to subsequent killer whale studies, because unsubstantiated characteristics may be assumed as a result of such classification. On this basis, we also recommend that ecotypic status classification for Southern Ocean killer whale morphotypes be reserved until more evidence-based ecological and taxonomic data are obtained.

  4. Molecular dissection of Neurospora Spore killer meiotic drive elements

    PubMed Central

    Hammond, Thomas M.; Rehard, David G.; Xiao, Hua; Shiu, Patrick K. T.

    2012-01-01

    Meiotic drive is a non-Mendelian inheritance phenomenon in which certain selfish genetic elements skew sexual transmission in their own favor. In some cases, progeny or gametes carrying a meiotic drive element can survive preferentially because it causes the death or malfunctioning of those that do not carry it. In Neurospora, meiotic drive can be observed in fungal spore killing. In a cross of Spore killer (Sk) × WT (Sk-sensitive), the ascospores containing the Spore killer allele survive, whereas the ones with the sensitive allele degenerate. Sk-2 and Sk-3 are the most studied meiotic drive elements in Neurospora, and they each theoretically contain two essential components: a killer element and a resistance gene. Here we report the identification and characterization of the Sk resistance gene, rsk (resistant to Spore killer). rsk seems to be a fungal-specific gene, and its deletion in a killer strain leads to self-killing. Sk-2, Sk-3, and naturally resistant isolates all use rsk for resistance. In each killer system, rsk sequences from an Sk strain and a resistant isolate are highly similar, suggesting that they share the same origin. Sk-2, Sk-3, and sensitive rsk alleles differ from each other by their unique indel patterns. Contrary to long-held belief, the killer targets not only late but also early ascospore development. The WT RSK protein is dispensable for ascospore production and is not a target of the spore-killing mechanism. Rather, a resistant version of RSK likely neutralizes the killer element and prevents it from interfering with ascospore development. PMID:22753473

  5. Natural killer cell lymphoma of the parotid gland.

    PubMed

    Furukawa, Masayuki; Suzuki, Hideaki; Tohmiya, Yasuo; Matsuura, Kazuto; Takahashi, Etsu; Ichinohasama, Ryo; Kobayashi, Toshimitsu

    2003-01-01

    The majority of all parotid lymphomas are of the non-Hodgkin type and of B-cell origin. Primary natural killer cell lymphomas of the parotid gland are extremely rare. We present a case of natural killer cell lymphoma in a 34-year-old woman. The disease was refractory to chemotherapy, and the patient eventually succumbed due to lymphoma-associated hemophagocytic syndrome. PMID:14564097

  6. The role of natural killer cells in chronic myeloid leukemia

    PubMed Central

    Danier, Anna Carolyna Araújo; de Melo, Ricardo Pereira; Napimoga, Marcelo Henrique; Laguna-Abreu, Maria Theresa Cerávolo

    2011-01-01

    Chronic myeloid leukemia is a neoplasia resulting from a translocation between chromosomes 9 and 22 producing the BCR-ABL hybrid known as the Philadelphia chromosome (Ph). In chronic myeloid leukemia a proliferation of malignant myeloid cells occurs in the bone marrow due to excessive tyrosine kinase activity. In order to maintain homeostasis, natural killer cells, by means of receptors, identify the major histocompatibility complex on the surface of tumor cells and subsequently induce apoptosis. The NKG2D receptor in the natural killer cells recognizes the transmembrane proteins related to major histocompatibility complex class I chain-related genes A and B (MICA and MICB), and it is by the interaction between NKG2D and MICA that natural killer cells exert cytotoxic activity against chronic myeloid leukemia tumor cells. However, in the case of chronic exposure of the NKG2D receptor, the MICA ligand releases soluble proteins called sMICA from the tumor cell surface, which negatively modulate NKG2D and enable the tumor cells to avoid lysis mediated by the natural killer cells. Blocking the formation of sMICA may be an important antitumor strategy. Treatment using tyrosine kinase inhibitors induces modulation of NKG2DL expression, which could favor the activity of the natural killer cells. However this mechanism has not been fully described in chronic myeloid leukemia. In the present study, we analyze the role of natural killer cells to reduce proliferation and in the cellular death of tumor cells in chronic myeloid leukemia. PMID:23049299

  7. KillerOrange, a Genetically Encoded Photosensitizer Activated by Blue and Green Light

    PubMed Central

    Bozhanova, Nina G.; Sharonov, George V.; Staroverov, Dmitriy B.; Egorov, Evgeny S.; Ryabova, Anastasia V.; Solntsev, Kyril M.; Mishin, Alexander S.; Lukyanov, Konstantin A.

    2015-01-01

    Genetically encoded photosensitizers, proteins that produce reactive oxygen species when illuminated with visible light, are increasingly used as optogenetic tools. Their applications range from ablation of specific cell populations to precise optical inactivation of cellular proteins. Here, we report an orange mutant of red fluorescent protein KillerRed that becomes toxic when illuminated with blue or green light. This new protein, KillerOrange, carries a tryptophan-based chromophore that is novel for photosensitizers. We show that KillerOrange can be used simultaneously and independently from KillerRed in both bacterial and mammalian cells offering chromatic orthogonality for light-activated toxicity. PMID:26679300

  8. KillerRed and miniSOG as genetically encoded photosensitizers for photodynamic therapy of cancer

    NASA Astrophysics Data System (ADS)

    Shirmanova, Marina V.; Serebrovskaya, Ekaterina O.; Snopova, Ludmila B.; Kuznetsova, Maria M.; Ryumina, Alina P.; Turchin, Ilya V.; Sergeeva, Ekaterina A.; Ignatova, Nadezhda I.; Klementieva, Natalia V.; Lukyanov, Konstantin A.; Lukyanov, Sergey A.; Zagaynova, Elena V.

    2013-06-01

    Despite of the success of photodynamic therapy (PDT) in cancer treatment, the problems of low selective accumulation of a photosensitizer in a tumor and skin phototoxicity have not resolved yet. The idea of encoding of a photosensitizer in genome of cancer cells is attractive, particularly because it can provide highly selective light induced cell killing. This work is aimed at the development of new approach to PDT of cancer, namely to using genetically encoded photosensitizers. A phototoxicity of red fluorescent GFP-like protein KillerRed and FMN-binding protein miniSOG was investigated on HeLa tumor xenografts in nude mice. The tumors were generated by subcutaneous injection of HeLa cells stably expressing the phototoxic proteins. The tumors were irradiated with 594 nm or 473 nm laser at 150 mW/cm2 for 20 or 30 min, repeatedly. Fluorescence intensity of the tumors was measured in vivo before and after each treatment procedure. Detailed pathomorphological analysis was performed 24 h after the therapy. On the epi-fluorescence images in vivo photobleaching of both proteins was observed indicating photodynamic reaction. Substantial pathomorphological abnormalities were found in the treated KillerRed-expressing tumor tissue, such as vacuolization of cytoplasm, cellular and nuclear membrane destruction, activation of apoptosis. In contrast, miniSOG-expressing tumors displayed no reaction to PDT, presumably due to the lack of FMN cofactor needed for fluorescence recovery of the flavoprotein. The results are of interest for photodynamic therapy as a proof of possibility to induce photodamages in cancer cells in vivo using genetically encoded photosensitizers.

  9. Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies

    PubMed Central

    Pittari, Gianfranco; Filippini, Perla; Gentilcore, Giusy; Grivel, Jean-Charles; Rutella, Sergio

    2015-01-01

    Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies. PMID:26029215

  10. Natural Killer Cells: Key Players in Endometriosis.

    PubMed

    Thiruchelvam, Uma; Wingfield, Mary; O'Farrelly, Cliona

    2015-10-01

    Endometriosis affects more than 10% of women, causing significant pain and morbidity. It is also a significant cause of infertility. The aetiology of the disease remains an enigma, and the mechanisms responsible for the associated infertility are unclear. A role for immune cells in endometriosis has been postulated, with attention directed towards natural killer (NK) cells and macrophages. NK cells kill tumours and infected cells but also have roles in tissue remodelling in several organs including the uterus and are key to successful pregnancy. Here, we explore evidence (from peer-reviewed published articles) of phenotypic and functional abnormalities in NK cell subpopulations of women with endometriosis. It is clear that peripheral blood NK cells and peritoneal NK cells have reduced cytotoxic function in women with endometriosis. Uterine NK cells have a vital role in infertility, but very little research has been carried out in this area. We propose that abnormal u NK cell activity may contribute to the pathogenesis of endometriosis and its associated infertility and that future research should focus on this complex area.

  11. Natural killer cells in viral arthritis.

    PubMed Central

    Aaskov, J G; Dalglish, D A; Harper, J J; Douglas, J F; Donaldson, M D; Hertzog, P J

    1987-01-01

    Changes in natural killer (NK) cell activity were studied in patients with polyarthritis associated with rubella or Ross River virus infections. In 30 of 32 Ross River virus patients, peripheral NK cell activity was depressed at some stage of the disease but returned to normal levels as patients recovered from arthritic symptoms. Similar changes did not occur in rubella patients and no difference was found between changes in peripheral NK activity and serum interferon (IFN) levels in rubella patients with arthritis and those without. Neither the peak of NK cell activity in peripheral blood lymphocytes (PBL) recovered early in Ross River virus and rubella infections, nor the depression of NK cell activity late in Ross River virus infections could be correlated with changes in serum IFN levels. The decrease in PBL-NK cell activity in epidemic polyarthritis (EPA) patients could not be attributed solely to loss of NK cells from the peripheral circulation because limiting-cell-dilution (LCD) analyses indicated changes in peripheral NK cell activity were due to changes in both the number and lytic activity of NK cells. Despite the association between HLA-DR7 and EPA no differences were found in levels of peripheral NK cell activity in DR7+ and DR7- EPA patients. The demonstration that peripheral NK cells could kill autologous synovial cells suggested that NK cells in joints of EPA patients may contribute to the arthritis associated with Ross River virus infection. PMID:2443284

  12. Natural Killer Cells for Therapy of Leukemia

    PubMed Central

    Suck, Garnet; Linn, Yeh Ching; Tonn, Torsten

    2016-01-01

    Summary Clinical application of natural killer (NK) cells against leukemia is an area of intense investigation. In human leukocyte antigen-mismatched allogeneic hematopoietic stem cell transplantations (HSCT), alloreactive NK cells exert powerful anti-leukemic activity in preventing relapse in the absence of graft-versus-host disease, particularly in acute myeloid leukemia patients. Adoptive transfer of donor NK cells post-HSCT or in non-transplant scenarios may be superior to the currently widely used unmanipulated donor lymphocyte infusion. This concept could be further improved through transfusion of activated NK cells. Significant progress has been made in good manufacturing practice (GMP)-compliant large-scale production of stimulated effectors. However, inherent limitations remain. These include differing yields and compositions of the end-product due to donor variability and inefficient means for cryopreservation. Moreover, the impact of the various novel activation strategies on NK cell biology and in vivo behavior are barely understood. In contrast, reproduction of the third-party NK-92 drug from a cryostored GMP-compliant master cell bank is straightforward and efficient. Safety for the application of this highly cytotoxic cell line was demonstrated in first clinical trials. This novel ‘off-the-shelf’ product could become a treatment option for a broad patient population. For specific tumor targeting chimeric-antigen-receptor-engineered NK-92 cells have been designed. PMID:27226791

  13. Ten microsatellite loci from Zamia integrifolia (Zamiaceae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ten microsatellite loci isolated from Zamia integrifolia are described. All 10 are polymorphic, with three to ten alleles across 36 members of a single population from South Florida. Heterozygosity ranged from 0.067 to 1. Two loci depart significantly from Hardy Weinberg Equilibrium, and exhibit het...

  14. Cytolysis of oligodendrocytes is mediated by killer (K) cells but not by natural killer (NK) cells.

    PubMed

    Satoh, J; Kim, S U; Kastrukoff, L F

    1991-03-01

    The cytotoxic activity of killer (K) cells against enriched cultures of bovine oligodendrocytes (BOL) was investigated in multiple sclerosis (MS) and controls. Human K cells mediated cytotoxicity to primary cultures of BOL in the presence of anti-BOL antiserum in all study groups, while BOL were resistant to human natural killer (NK) cells. Cytotoxic activity was significantly reduced in MS when compared to age-matched normal controls but not when compared to other neurologic disease (OND) patients. K cell-mediated lysis of BOL could also be induced with anti-galactocerebroside antibody but not with other antibodies including those specific for OL antigens (myelin basic protein, proteolipid apoprotein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase). Enrichment of the effector population indicated that antibody-dependent cell-mediated cytotoxicity (ADCC) to BOL was mediated by large granular lymphocytes, and the effector population was further characterized by flow cytometry. The effector cells mediating ADCC could be inhibited by protein A of Staphylococcus aureus, and by K562 cells in cold competition assay. These observations indicate that oligodendrocytes are resistant to NK cells but are susceptible to cytolysis mediated by K cells. This may represent a potentially important immune mechanism in the pathogenesis of MS.

  15. Suppression of newborn natural killer cell activity by prostaglandin E2

    SciTech Connect

    Milch, P.O.; Salvatore, W.; Luft, B.; Baker, D.A.

    1988-10-01

    The effect of prostaglandin E2 on natural killer cell activity of cord blood was examined. Natural killer cell activity, determined by chromium 51 release, was significantly reduced after prostaglandin E2 (1 microgram/ml) treatment. Prostaglandin E2 has been found to enhance the cellular spread of herpesvirus. Thus prostaglandins may enhance viral infections indirectly by suppressing natural killer cell activity.

  16. Biotyping of Malassezia pachydermatis strains using the killer system.

    PubMed

    Coutinho, S D; Paula, C R

    1998-06-01

    The killer phenomenon has been used as epidemiological marker for Candida albicans, where hundreds of biotypes can be obtained. The objective of this study is to observe the behaviour of 30 strains of Malassezia pachydermatis isolated from dogs with otitis (15) or dermatitis (15) against 9 killer yeasts, which, when grouped in triplets produced a 3 digit code (biotype). The growth inhibition of the 30 strains of M. pachydermatis due to the effect of the killer yeasts used permitted the determination of the following biotypes: 888 (33.3%), 212 (26.7%), 111 (16.7%), 312 (6.7%), 512 (6.7%), 242 (3.3%), 311 (3.3%) and 411 (3.3%). Biotypes 888, 212 and 111 occurred most frequently in both ear canal and skin samples. PMID:17655416

  17. Natural killer cells and natural killer T cells in Lyme arthritis

    PubMed Central

    2013-01-01

    Introduction Natural killer (NK) and natural killer T (NKT) cells provide a first line of defense against infection. However, these cells have not yet been examined in patients with Lyme arthritis, a late disease manifestation. Lyme arthritis usually resolves with antibiotic treatment. However, some patients have persistent arthritis after spirochetal killing, which may result from excessive inflammation, immune dysregulation and infection-induced autoimmunity. Methods We determined the frequencies and phenotypes of NK cells and invariant NKT (iNKT) cells in paired peripheral blood (PB) and synovial fluid (SF) samples from eight patients with antibiotic-responsive arthritis and fifteen patients with antibiotic-refractory arthritis using flow cytometry and cytokine analyses. Results In antibiotic-responsive patients, who were seen during active infection, high frequencies of CD56bright NK cells were found in SF, the inflammatory site, compared with PB (P <0.001); at both sites, a high percentage of cells expressed the activation receptor NKG2D and the chaperone CD94, a low percentage expressed inhibitory killer immunoglobulin-like receptors (KIR), and a high percentage produced IFN-γ. In antibiotic-refractory patients, who were usually evaluated near the conclusion of antibiotics when few if any live spirochetes remained, the phenotype of CD56bright cells in SF was similar to that in patients with antibiotic-responsive arthritis, but the frequency of these cells was significantly less (P = 0.05), and the frequencies of CD56dim NK cells tended to be higher. However, unlike typical NKdim cells, these cells produced large amounts of IFN-γ, suggesting that they were not serving a cytotoxic function. Lastly, iNKT cell frequencies in the SF of antibiotic-responsive patients were significantly greater compared with that of antibiotic-refractory patients where these cells were often absent (P = 0.003). Conclusions In patients with antibiotic-responsive arthritis

  18. Adaptive prolonged postreproductive life span in killer whales.

    PubMed

    Foster, Emma A; Franks, Daniel W; Mazzi, Sonia; Darden, Safi K; Balcomb, Ken C; Ford, John K B; Croft, Darren P

    2012-09-14

    Prolonged life after reproduction is difficult to explain evolutionarily unless it arises as a physiological side effect of increased longevity or it benefits related individuals (i.e., increases inclusive fitness). There is little evidence that postreproductive life spans are adaptive in nonhuman animals. By using multigenerational records for two killer whale (Orcinus orca) populations in which females can live for decades after their final parturition, we show that postreproductive mothers increase the survival of offspring, particularly their older male offspring. This finding may explain why female killer whales have evolved the longest postreproductive life span of all nonhuman animals.

  19. Ultrasonic whistles of killer whales (Orcinus orca) recorded in the North Pacific (L).

    PubMed

    Filatova, Olga A; Ford, John K B; Matkin, Craig O; Barrett-Lennard, Lance G; Burdin, Alexander M; Hoyt, Erich

    2012-12-01

    Ultrasonic whistles were previously found in North Atlantic killer whales and were suggested to occur in eastern North Pacific killer whales based on the data from autonomous recorders. In this study ultrasonic whistles were found in the recordings from two encounters with the eastern North Pacific offshore ecotype killer whales and one encounter with the western North Pacific killer whales of unknown ecotype. All ultrasonic whistles were highly stereotyped and all but two had downsweep contours. These results demonstrate that specific sound categories can be shared by killer whales from different ocean basins.

  20. Spectrum of diseases associated with increased proportions or absolute numbers of peripheral blood natural killer cells.

    PubMed

    Okuno, S H; Tefferi, A; Hanson, C A; Katzmann, J A; Li, C Y; Witzig, T E

    1996-06-01

    In a retrospective review of 1501 lymphoid flow cytometric studies of peripheral blood, we identified an increased proportion of natural killer cells in 125 cases (8%), 49 (3%) of which had a concomitant increase in absolute number of natural killer cells. Of the latter, the most frequent associated disorder was chronic natural killer cell lymphocytosis. Substantial quantitative increases in natural killer cells were also observed in some patients with lymphoma, leukaemia, immune thrombocytopenic purpura, or myelodysplastic syndrome. Our study provides incidence figures and clinical associations of an increased number of natural killer cells in the peripheral blood.

  1. Effect of different levels of alcohol consumption on natural killer and lymphokine activated killer cells

    SciTech Connect

    Klassen, L.W.; DeVasure, J.M.; Lemley-Gillespie, S.D.; Thiele, G.M. Omaha VA Hospital, NE )

    1991-03-11

    The effect of alcohol consumption on natural killer (NK) cell activity is controversial as both increased and decreased levels have been reported. It was the purpose of this study to determine the effects of feeding BDF1 mice different levels of alcohol on NK and lymphokine activated killer (LAK) cell activity. After four-six weeks of chronic alcohol feeding, mice were sacrificed, spleen cells obtained and assayed for NK and IL-2 boosted NK activity against YAC-1 cells in a traditional {sup 51}chromium release assay. Cells were also cultured in the presence of IL-2 for five days and tested for cytolytic activity using P815 cells as targets. Cells from each group were passed over a nylon wool column and the adherent (AD) and nonadherent (NAD) populations collected and tested as above. Increased NK, 24 hour IL-2 boosted NK and 5 day LAK activity were observed only in the spleen cells obtained from mice on 20% alcohol. Also, NAD populations had a 2-4 fold higher lytic unit values (LU{sub 20}) at all levels of alcohol consumption and in all assays, as compared with the unseparated spleen cells. Analysis of cell surface markers on these three populations of cells show that there were differences in MAC-2, Asialo GM-1, Thy 1.2, B220 and NK 1.1 that may correlate with the differences observed in the cytolytic assays. These data suggest that different levels of alcohol affect the cytolytic activity of NK and LAK cells and may result from alterations in the cell subset populations.

  2. A method for selective ablation of neurons in C. elegans using the phototoxic fluorescent protein, KillerRed.

    PubMed

    Kobayashi, Junya; Shidara, Hisashi; Morisawa, Yuma; Kawakami, Maki; Tanahashi, Yuta; Hotta, Kohji; Oka, Kotaro

    2013-08-26

    Specific neuron ablation with laser microbeam has been used in behavioral analysis of Caenorhabditis elegans. However, this method is hard to acquire many ablated worms, and is unable to compare behavioral changes just before and after ablation. Here, we developed an ablation method by using genetically encoded photosensitizer protein, KillerRed, which produces reactive oxygen species by green light irradiation. Ablation of AWA sensory neurons abolished the chemotaxis to AWA specific sensitive attractant, diacetyl, and no functional effect on the other sensory neuron, AWC, which senses benzaldehyde. This ablation method can be useful for analyzing neural in situ. PMID:23748043

  3. Expression of Meiotic Drive Elements Spore Killer-2 and Spore Killer-3 in Asci of Neurospora Tetrasperma

    PubMed Central

    Raju, N. B.; Perkins, D. D.

    1991-01-01

    It was shown previously that when a chromosomal Spore killer factor is heterozygous in Neurospora species with eight-spored asci, the four sensitive ascospores in each ascus die and the four survivors are all killers. Sk-2(K) and Sk-3(K) are nonrecombining haplotypes that segregate with the centromere of linkage group III. No killing occurs when either one of these killers is homozygous, but each is sensitive to killing by the other in crosses of Sk-2(K) X Sk-3(K). In the present study, Sk-2(K) and Sk-3(K) were transferred by recurrent backcrosses from the eight-spored species Neurospora crassa into Neurospora tetrasperma, a pseudohomothallic species which normally makes asci with four large spores, each heterokaryotic for mating type and for any other centromere-linked genes that are heterozygous in the cross. The action of Sk-2(K) and Sk-3(K) in N. tetrasperma is that predicted from their behavior in eight-spored species. A sensitive nucleus is protected from killing if it is enclosed in the same ascospore with a killer nucleus. Crosses of Sk-2(K) X Sk-2(S), Sk-3(K) X Sk-3(S), and Sk-2(K) X Sk-3(K) all produce four-spored asci that are wild type in appearance, with the ascospores heterokaryotic and viable. The Eight-spore gene E, which shows variable penetrance, was used to obtain N. tetrasperma asci in which two to eight spores are small and homokaryotic. When killer and sensitive alleles are segregating in the presence of E, only those ascospores that contain a killer allele survive. Half of the small ascospores are killed. In crosses of Sk-2(K) X Sk-3(K) (with E heterozygous), effectively all small ascospores are killed. The ability of N. tetrasperma to carry killer elements in cryptic condition suggests a possible role for Spore killers in the origin of pseudohomothallism, with adoption of the four-spored mode restoring ascospore viability of crosses in which killing would otherwise occur. PMID:1834522

  4. Impaired cytotoxicity associated with defective natural killer cell differentiation in myelodysplastic syndromes.

    PubMed

    Hejazi, Maryam; Manser, Angela R; Fröbel, Julia; Kündgen, Andrea; Zhao, Xiaoyi; Schönberg, Kathrin; Germing, Ulrich; Haas, Rainer; Gattermann, Norbert; Uhrberg, Markus

    2015-05-01

    Natural killer cells are well known to mediate anti-leukemic responses in myeloid leukemia but their role in myelodysplastic syndromes is not well understood. Here, in a cohort of newly diagnosed patients (n=75), widespread structural and functional natural killer cell defects were identified. One subgroup of patients (13%) had a selective deficiency of peripheral natural killer cells (count <10/mm(3) blood) with normal frequencies of T and natural killer-like T cells. Natural killer cell-deficient patients were predominantly found in high-risk subgroups and deficiency of these cells was significantly associated with poor prognosis. In the second subgroup, comprising the majority of patients (76%), natural killer cells were present but exhibited poor cytotoxicity. The defect was strongly associated with reduced levels of perforin and granzyme B. Notably, natural killer cell function and arming of cytotoxic granules could be fully reconstituted by in vitro stimulation. Further phenotypic analysis of these patients revealed an immature natural killer cell compartment that was biased towards CD56(bright) cells. The residual CD56(dim) cells exhibited a significant increase of the unlicensed NKG2A(-)KIR(-) subset and a striking reduction in complexity of the repertoire of killer cell immunoglobulin-like receptors. Taken together, these results suggest that the widespread defects in natural killer cell function occurring in patients with myelodysplastic syndromes are mostly due to either unsuccessful or inefficient generation of mature, functionally competent natural killer cells, which might contribute to disease progression through impaired immune surveillance.

  5. The occurrence of killer activity in yeasts isolated from natural habitats.

    PubMed

    Wójcik, Monika; Kordowska-Wiater, Monika

    2015-01-01

    Yeast's ability to restrict the growth and kill other yeasts, fungi and bacteria has been known for over 50 years. Killer activity was detected in yeasts deposited in the world collections or isolated from natural habitats. In this study, isolates from the forest environment, leaves of fruit trees, flower petals, cereals and frozen fruit have been screened in terms of their killer activities. Killer activity was tested on strains belonging to six yeast species: Candida, Rhodotorula, Pichia, Pachysolen, Yarrowia, Trichosporon. The reference strains were Kluyveromyces lactis Y-6682 and Kluyveromyces marxinanus Y-8281, well-known to be sensitive to yeast killer toxins. Among one hundred and two tested strains, 24 (23.5% of isolates) showed positive killer action, and 10 (9.8% of the isolates) a weak killer action against at least one sensitive reference strain. The highest killer activity was observed among isolates from forest soil and flowers. PMID:26636138

  6. Quantifying Missing Heritability at Known GWAS Loci

    PubMed Central

    Gusev, Alexander; Bhatia, Gaurav; Zaitlen, Noah; Vilhjalmsson, Bjarni J.; Diogo, Dorothée; Stahl, Eli A.; Gregersen, Peter K.; Worthington, Jane; Klareskog, Lars; Raychaudhuri, Soumya; Plenge, Robert M.; Pasaniuc, Bogdan; Price, Alkes L.

    2013-01-01

    Recent work has shown that much of the missing heritability of complex traits can be resolved by estimates of heritability explained by all genotyped SNPs. However, it is currently unknown how much heritability is missing due to poor tagging or additional causal variants at known GWAS loci. Here, we use variance components to quantify the heritability explained by all SNPs at known GWAS loci in nine diseases from WTCCC1 and WTCCC2. After accounting for expectation, we observed all SNPs at known GWAS loci to explain more heritability than GWAS-associated SNPs on average (). For some diseases, this increase was individually significant: for Multiple Sclerosis (MS) () and for Crohn's Disease (CD) (); all analyses of autoimmune diseases excluded the well-studied MHC region. Additionally, we found that GWAS loci from other related traits also explained significant heritability. The union of all autoimmune disease loci explained more MS heritability than known MS SNPs () and more CD heritability than known CD SNPs (), with an analogous increase for all autoimmune diseases analyzed. We also observed significant increases in an analysis of Rheumatoid Arthritis (RA) samples typed on ImmunoChip, with more heritability from all SNPs at GWAS loci () and more heritability from all autoimmune disease loci () compared to known RA SNPs (including those identified in this cohort). Our methods adjust for LD between SNPs, which can bias standard estimates of heritability from SNPs even if all causal variants are typed. By comparing adjusted estimates, we hypothesize that the genome-wide distribution of causal variants is enriched for low-frequency alleles, but that causal variants at known GWAS loci are skewed towards common alleles. These findings have important ramifications for fine-mapping study design and our understanding of complex disease architecture. PMID:24385918

  7. Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection.

    PubMed

    Gillespie, Alyssa Lundgren; Teoh, Jeffrey; Lee, Heather; Prince, Jessica; Stadnisky, Michael D; Anderson, Monique; Nash, William; Rival, Claudia; Wei, Hairong; Gamache, Awndre; Farber, Charles R; Tung, Kenneth; Brown, Michael G

    2016-02-01

    The MHC class I D(k) molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds D(k), are required to control viral spread. The extent of D(k)-dependent host resistance, however, differs significantly amongst related strains of mice, C57L and MA/My. As a result, we predicted that relatively small-effect modifier genetic loci might together shape immune cell features, NK cell reactivity, and the host immune response to MCMV. A robust D(k)-dependent genetic effect, however, has so far hindered attempts to identify additional host resistance factors. Thus, we applied genomic mapping strategies and multicolor flow cytometric analysis of immune cells in naive and virus-infected hosts to identify genetic modifiers of the host immune response to MCMV. We discovered and validated many quantitative trait loci (QTL); these were mapped to at least 19 positions on 16 chromosomes. Intriguingly, one newly discovered non-MHC locus (Cmv5) controlled splenic NK cell accrual, secondary lymphoid organ structure, and lymphoid follicle development during MCMV infection. We infer that Cmv5 aids host resistance to MCMV infection by expanding NK cells needed to preserve and protect essential tissue structural elements, to enhance lymphoid remodeling and to increase viral clearance in spleen. PMID:26845690

  8. Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection.

    PubMed

    Gillespie, Alyssa Lundgren; Teoh, Jeffrey; Lee, Heather; Prince, Jessica; Stadnisky, Michael D; Anderson, Monique; Nash, William; Rival, Claudia; Wei, Hairong; Gamache, Awndre; Farber, Charles R; Tung, Kenneth; Brown, Michael G

    2016-02-01

    The MHC class I D(k) molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds D(k), are required to control viral spread. The extent of D(k)-dependent host resistance, however, differs significantly amongst related strains of mice, C57L and MA/My. As a result, we predicted that relatively small-effect modifier genetic loci might together shape immune cell features, NK cell reactivity, and the host immune response to MCMV. A robust D(k)-dependent genetic effect, however, has so far hindered attempts to identify additional host resistance factors. Thus, we applied genomic mapping strategies and multicolor flow cytometric analysis of immune cells in naive and virus-infected hosts to identify genetic modifiers of the host immune response to MCMV. We discovered and validated many quantitative trait loci (QTL); these were mapped to at least 19 positions on 16 chromosomes. Intriguingly, one newly discovered non-MHC locus (Cmv5) controlled splenic NK cell accrual, secondary lymphoid organ structure, and lymphoid follicle development during MCMV infection. We infer that Cmv5 aids host resistance to MCMV infection by expanding NK cells needed to preserve and protect essential tissue structural elements, to enhance lymphoid remodeling and to increase viral clearance in spleen.

  9. Life history evolution: what does a menopausal killer whale do?

    PubMed

    Whitehead, Hal

    2015-03-16

    Menopause evolved in humans and whales, presumably because older females can help their kin. But how do they help? New research shows that post-menopausal female killer whales lead foraging groups. This leadership is most significant when food is scarce. PMID:25784039

  10. West Nile virus infection in killer whale, Texas, USA, 2007.

    PubMed

    St Leger, Judy; Wu, Guang; Anderson, Mark; Dalton, Les; Nilson, Erika; Wang, David

    2011-08-01

    In 2007, nonsuppurative encephalitis was identified in a killer whale at a Texas, USA, marine park. Panviral DNA microarray of brain tissue suggested West Nile virus (WNV); WNV was confirmed by reverse transcription PCR and sequencing. Immunohistochemistry demonstrated WNV antigen within neurons. WNV should be considered in cases of encephalitis in cetaceans. PMID:21801643

  11. Life history evolution: what does a menopausal killer whale do?

    PubMed

    Whitehead, Hal

    2015-03-16

    Menopause evolved in humans and whales, presumably because older females can help their kin. But how do they help? New research shows that post-menopausal female killer whales lead foraging groups. This leadership is most significant when food is scarce.

  12. Whistle sequences in wild killer whales (Orcinus orca).

    PubMed

    Riesch, Rüdiger; Ford, John K B; Thomsen, Frank

    2008-09-01

    Combining different stereotyped vocal signals into specific sequences increases the range of information that can be transferred between individuals. The temporal emission pattern and the behavioral context of vocal sequences have been described in detail for a variety of birds and mammals. Yet, in cetaceans, the study of vocal sequences is just in its infancy. Here, we provide a detailed analysis of sequences of stereotyped whistles in killer whales off Vancouver Island, British Columbia. A total of 1140 whistle transitions in 192 whistle sequences recorded from resident killer whales were analyzed using common spectrographic analysis techniques. In addition to the stereotyped whistles described by Riesch et al., [(2006). "Stability and group specificity of stereotyped whistles in resident killer whales, Orcinus orca, off British Columbia," Anim. Behav. 71, 79-91.] We found a new and rare stereotyped whistle (W7) as well as two whistle elements, which are closely linked to whistle sequences: (1) stammers and (2) bridge elements. Furthermore, the frequency of occurrence of 12 different stereotyped whistle types within the sequences was not randomly distributed and the transition patterns between whistles were also nonrandom. Finally, whistle sequences were closely tied to close-range behavioral interactions (in particular among males). Hence, we conclude that whistle sequences in wild killer whales are complex signal series and propose that they are most likely emitted by single individuals.

  13. Killer Queens: screen representations of the gay psychopath.

    PubMed

    Hanlon, Daniel J

    2009-06-01

    Killer Queen is a well-known term with a developing definition. Over the last century attitudes have changed considerably towards both homosexuality and mental illness but in rather different ways. In exploring the depiction of this characterization in film and how it has evolved, consideration is given to whether or which of these changes might be responsible. PMID:19459106

  14. Glioblastoma Invoking "Killer" Rabbits of the Middle Ages.

    PubMed

    Massoud, Tarik F; Kalnins, Aleksandrs

    2016-08-01

    We present the unusual appearance on brain magnetic resonance imaging of a glioblastoma with an uncanny shape of a rabbit. By invoking fearsome "killer" rabbits depicted in the art and literature of the Middle Ages, this image is an eerie reminder of the current lethality of this disease. There is a pressing need for more effective treatments for glioblastoma. PMID:27157288

  15. Killer beacons for combined cancer imaging and therapy.

    PubMed

    Stefflova, Klara; Chen, Juan; Zheng, Gang

    2007-01-01

    Precisely localizing therapeutic agents in neoplastic areas would greatly improve their efficacy for killing tumor cells and reduce their toxicity to normal cells. Photodynamic therapy (PDT) is a promising cancer treatment modality, and near-infrared fluorescence imaging (NIRF-I) is a sensitive and noninvasive approach for in vivo cancer detection. This review focuses on the current efforts to engineer single molecule constructs that allow these two modalities to be combined to achieve a high level of selectivity for cancer treatment. The primary component of these so called killer beacons is a fluorescent photosensitizer responsible for both imaging and therapy. By attaching other components, e.g. various DNA- or peptide-based linkers, quenchers or cancer cell-specific delivery vehicles, their primary diagnostic and therapeutic functions as well as their target specificity and pharmacological properties can be modulated. This modular design makes these agents customizable, offering the ability to assemble a few simple and often interchangeable functional modules into beacons with totally different functions. This review will summarize following three types of killer beacons: photodynamic molecular beacons, traceable beacons and beacons with built-in apoptosis sensor. Despite the rapid progress in killer beacon development, numerous challenges remain before these beacons can be translated into clinics, such as photobleaching, delivery efficiency and cancer-specificity. In this review we outline the basic principles of killer beacons, the current achievements and future directions, including possible cancer targets and different therapeutic applications.

  16. Radiosensitivity of human natural killer cells: Binding and cytotoxic activities of natural killer cell subsets

    SciTech Connect

    Rana, R.; Vitale, M.; Mazzotti, G.; Manzoli, L.; Papa, S. )

    1990-10-01

    The sensitivity of human natural killer (NK) cell activities (both binding and killing) after exposure of peripheral blood mononuclear cells to different doses of gamma radiation was studied. A panel of monoclonal antibodies was used to identify the NK and T-lymphocyte subsets and to evaluate their radiosensitivity. Peripheral blood mononuclear cells were irradiated with low (2-6 Gy) and high (10-30 Gy) doses and NK cell binding and cytotoxic activity against K562 target cells were studied after 3 h and 48 h in culture. The primary damage to NK cell activity was identified at the postbinding level and affected mainly the lytic machinery. After 48 h culture postirradiation, an overall depression of cytotoxic activity was observed, but ionizing radiation produced either a selection of the more cytotoxic NK cell subsets, which therefore might be considered more resistant to radiation damage than the less cytotoxic NK cells, or a long-term stimulation of cytotoxic activity in surviving cells.

  17. GWAS identifies four novel eosinophilic esophagitis loci.

    PubMed

    Sleiman, Patrick M A; Wang, Mei-Lun; Cianferoni, Antonella; Aceves, Seema; Gonsalves, Nirmala; Nadeau, Kari; Bredenoord, Albert J; Furuta, Glenn T; Spergel, Jonathan M; Hakonarson, Hakon

    2014-11-19

    Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the oesophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune diseases, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the oesophagus. The identification of five EoE loci, not only expands our aetiological understanding of the disease but may also represent new therapeutic targets to treat the most debilitating aspect of EoE, oesophageal inflammation and remodelling.

  18. Phylogenomics of the killer whale indicates ecotype divergence in sympatry.

    PubMed

    Moura, A E; Kenny, J G; Chaudhuri, R R; Hughes, M A; Reisinger, R R; de Bruyn, P J N; Dahlheim, M E; Hall, N; Hoelzel, A R

    2015-01-01

    For many highly mobile species, the marine environment presents few obvious barriers to gene flow. Even so, there is considerable diversity within and among species, referred to by some as the 'marine speciation paradox'. The recent and diverse radiation of delphinid cetaceans (dolphins) represents a good example of this. Delphinids are capable of extensive dispersion and yet many show fine-scale genetic differentiation among populations. Proposed mechanisms include the division and isolation of populations based on habitat dependence and resource specializations, and habitat release or changing dispersal corridors during glacial cycles. Here we use a phylogenomic approach to investigate the origin of differentiated sympatric populations of killer whales (Orcinus orca). Killer whales show strong specialization on prey choice in populations of stable matrifocal social groups (ecotypes), associated with genetic and phenotypic differentiation. Our data suggest evolution in sympatry among populations of resource specialists. PMID:25052415

  19. Phylogenomics of the killer whale indicates ecotype divergence in sympatry.

    PubMed

    Moura, A E; Kenny, J G; Chaudhuri, R R; Hughes, M A; Reisinger, R R; de Bruyn, P J N; Dahlheim, M E; Hall, N; Hoelzel, A R

    2015-01-01

    For many highly mobile species, the marine environment presents few obvious barriers to gene flow. Even so, there is considerable diversity within and among species, referred to by some as the 'marine speciation paradox'. The recent and diverse radiation of delphinid cetaceans (dolphins) represents a good example of this. Delphinids are capable of extensive dispersion and yet many show fine-scale genetic differentiation among populations. Proposed mechanisms include the division and isolation of populations based on habitat dependence and resource specializations, and habitat release or changing dispersal corridors during glacial cycles. Here we use a phylogenomic approach to investigate the origin of differentiated sympatric populations of killer whales (Orcinus orca). Killer whales show strong specialization on prey choice in populations of stable matrifocal social groups (ecotypes), associated with genetic and phenotypic differentiation. Our data suggest evolution in sympatry among populations of resource specialists.

  20. Sounds produced by Norwegian killer whales, Orcinus orca, during capture

    NASA Astrophysics Data System (ADS)

    van Parijs, Sofie M.; Leyssen, Teo; Similä, Tiu

    2004-07-01

    To date very little is still known about the acoustic behavior of Norwegian killer whales, in particular that of individual whales. In this study a unique opportunity was presented to document the sounds produced by five captured killer whales in the Vestfjord area, northern Norway. Individuals produced 14 discrete and 7 compound calls. Two call types were used both by individuals 16178 and 23365 suggesting that they may belong to the same pod. Comparisons with calls documented in Strager (1993) showed that none of the call types used by the captured individuals were present. The lack of these calls in the available literature suggests that call variability within individuals is likely to be large. This short note adds to our knowledge of the vocal repertoire of this population and demonstrates the need for further studies to provide behavioural context to these sounds.

  1. Lineage-specific diversification of killer cell Ig-like receptors in the owl monkey, a New World primate.

    PubMed

    Cadavid, Luis F; Lun, Cheng-Man

    2009-01-01

    Killer cell Ig-like receptors (KIRs) modulate the cytotoxic effects of natural killer cells. In primates, the KIRs are highly diverse as a consequence of variation in gene content, alternative domain composition, and loci polymorphism. We analyzed a bacterial artificial chromosome (BAC) clone draft sequence spanning the owl monkey KIR cluster. The draft sequence had seven ordered yet unconnected contigs containing six full-length and two partial gene models, flanked by the LILRB and FcAR framework genes. Gene models were predicted to encode KIRs with inhibitory, activating, or dual functionality. Four gene models encoded three Ig domain receptors, while three others encoded molecules with four Ig domains. The additional domain resulted from an insertion in tandem of a 2,101 bp fragment containing the last 289 bp of intron 2, exon 3, and intron 3, resulting in molecules with two D0 domains. Re-screening of the owl monkey BAC library and sequencing of partial cDNAs from an owl monkey yielded five additional KIRs, four of which encoded receptors with short cytoplasmic domains with premature stop codons due to either a single nucleotide substitution or deletion or the absence of exon 8. Phylogenetic analysis by domains showed that owl monkey KIRs were monophyletic, clustering independently from other primate KIR lineages. Retroelements found in introns, however, were shared by KIRs from different primate lineages. This suggests that the owl monkey inherited a KIR cluster with a rich history of exon shuffling upon which positive selection for ligand binding operated to diversify the receptors in a lineage-specific fashion.

  2. Which serial killers commit suicide? An exploratory study.

    PubMed

    Lester, David; White, John

    2012-11-30

    In a sample of 483 serial killers, 6.2% were documented to have committed suicide. Those who committed suicide were found to come from more dysfunctional homes characterized by more psychiatric disturbance in the parents. The sexual acts involved in the murders by the suicides seemed to be more deviant in some aspects, such as committing more bizarre sexual acts or more often taping the murder.

  3. [A serial killer as exemplified by T. R. Bundy].

    PubMed

    Gałeska-Sliwka, Anita

    2008-01-01

    The question of serial homicides and their perpetrators poses a considerable problem of both a definitional and practical nature. T R. Bundy is the first perpetrator who was officially termed a "serial killer". Since that time, this concept has been commonly used and sometimes even overused, e.g. in reference to mass murderers. However, the definitions established for Bundy's case have been preserved and continue to be used in practice.

  4. Which serial killers commit suicide? An exploratory study.

    PubMed

    Lester, David; White, John

    2012-11-30

    In a sample of 483 serial killers, 6.2% were documented to have committed suicide. Those who committed suicide were found to come from more dysfunctional homes characterized by more psychiatric disturbance in the parents. The sexual acts involved in the murders by the suicides seemed to be more deviant in some aspects, such as committing more bizarre sexual acts or more often taping the murder. PMID:23131308

  5. Interferon induces natural killer cell blastogenesis in vivo

    NASA Technical Reports Server (NTRS)

    Biron, C. A.; Sonnenfeld, G.; Welsh, R. M.

    1984-01-01

    Interferon (IFN), types beta and gamma, and IFN inducers polyinosinic-polycytidylic acid and lymphocytic choriomeningitis virus, all stimulated the generation of blast-natural killer (NK) cells in mouse spleens, Blast-NK cells were characterized on the basis of size, 3H-thymidine uptake, and NK cell markers These data indicate that in addition to augmenting NK cell-mediated lysis, IFN may regulate NK cell proliferation in vivo.

  6. Comparison of KIR gene content profiles revealed a difference between northern and southern Persians in the distribution of KIR2DS5 and its linked loci.

    PubMed

    Solgi, Ghasem; Ghafari, Hamidreza; Ashouri, Elham; Alimoghdam, Kamran; Rajalingam, Raja; Amirzargar, Aliakbar

    2011-11-01

    Killer cell immunoglobulin-like receptors (KIR) are the key receptors of human natural killer (NK) cells that mount an early immune response against infection and tumors. The number and type of KIR genes are substantially variable between individuals and populations. Recently we reported KIR gene content diversity in a Persian population living in the southern province of Fars, which is comparable to that of European Caucasians. These results are consistent with the ethnic ancestry and affinity between Persians and Caucasians. Herein we analyzed another Persian population living in the northern province of Tehran and discovered an unexpected increase in the distribution of KIR2DS5 and its linked loci KIR3DS1, -2DS1, and -2DL5 in northern Persians compared with that reported in the southern Persian population. Although the geographic barriers may have limited the gene flow, the impact of the local environment on the natural selection of KIR2DS5 and its linked loci in the northern Persians cannot be completely ruled out. The difference in northern and southern populations in activating KIR gene content creates an appealing hypothesis that KIR2DS5-enriched northern Persians are more resistant to developing clinical conditions demonstrated to be associated with KIR2DS5, such as psoriasis vulgaris, endometriosis, ankylosing spondylitis, and acute rejection of kidney grafts, compared with those living in the southern part of the country. PMID:21867738

  7. Offshore killer whale tracking using multiple hydrophone arrays.

    PubMed

    Gassmann, Martin; Henderson, E Elizabeth; Wiggins, Sean M; Roch, Marie A; Hildebrand, John A

    2013-11-01

    To study delphinid near surface movements and behavior, two L-shaped hydrophone arrays and one vertical hydrophone line array were deployed at shallow depths (<125 m) from the floating instrument platform R/P FLIP, moored northwest of San Clemente Island in the Southern California Bight. A three-dimensional propagation-model based passive acoustic tracking method was developed and used to track a group of five offshore killer whales (Orcinus orca) using their emitted clicks. In addition, killer whale pulsed calls and high-frequency modulated (HFM) signals were localized using other standard techniques. Based on these tracks sound source levels for the killer whales were estimated. The peak to peak source levels for echolocation clicks vary between 170-205 dB re 1 μPa @ 1 m, for HFM calls between 185-193 dB re 1 μPa @ 1 m, and for pulsed calls between 146-158 dB re 1 μPa @ 1 m.

  8. Experimental evidence for action imitation in killer whales (Orcinus orca).

    PubMed

    Abramson, José Z; Hernández-Lloreda, Victoria; Call, Josep; Colmenares, Fernando

    2013-01-01

    Comparative experimental studies of imitative learning have focused mainly on primates and birds. However, cetaceans are promising candidates to display imitative learning as they have evolved in socioecological settings that have selected for large brains, complex sociality, and coordinated predatory tactics. Here we tested imitative learning in killer whales, Orcinus orca. We used a 'do-as-other-does' paradigm in which 3 subjects witnessed a conspecific demonstrator's performance that included 15 familiar and 4 novel behaviours. The three subjects (1) learned the copy command signal 'Do that' very quickly, that is, 20 trials on average; (2) copied 100 % of the demonstrator's familiar and novel actions; (3) achieved full matches in the first attempt for 8-13 familiar behaviours (out of 15) and for the 2 novel behaviours (out of 2) in one subject; and (4) took no longer than 8 trials to accurately copy any familiar behaviour, and no longer than 16 trials to copy any novel behaviour. This study provides experimental evidence for body imitation, including production imitation, in killer whales that is comparable to that observed in dolphins tested under similar conditions. These findings suggest that imitative learning may underpin some of the group-specific traditions reported in killer whales in the field.

  9. Toxicity of a plant based mosquito repellent/killer

    PubMed Central

    Singh, Prakash Raj; Mohanty, Manoj Kumar

    2012-01-01

    The mission to make humans less attractive to mosquitoes has fuelled decades of scientific research on mosquito behaviour and control. The search for the perfect topical insect repellent/killer continues. This analysis was conducted to review and explore the scientific information on toxicity produced by the ingredients/contents of a herbal product. In this process of systemic review the following methodology was applied. By doing a MEDLINE search with key words of selected plants, plant based insect repellents/killers pertinent articles published in journals and authentic books were reviewed. The World Wide Web and the Extension Toxicity Network database (IPCS-ITOX) were also searched for toxicology data and other pertinent information. Repellents do not all share a single mode of action and surprisingly little is known about how repellents act on their target insects. Moreover, different mosquito species may react differently to the same repellent. After analysis of available data and information on the ingredient, of the product in relation to medicinal uses, acute and chronic toxicity of the selected medicinal plants, it can be concluded that the ingredients included in the herbal product can be used as active agents against mosquitoes. If the product which contains the powder of the above said plants is applied with care and safety, it is suitable fo use as a mosquito repellent/killer. PMID:23554562

  10. Effect of spaceflight on natural killer cell activity

    NASA Technical Reports Server (NTRS)

    Rykova, Marina P.; Sonnenfeld, Gerald; Lesniak, A. T.; Taylor, Gerald R.; Meshkov, Dimitrii O.; Mandel, Adrian D.; Medvedev, Andrei E.; Berry, Wallace D.; Fuchs, Boris B.; Konstantinova, Irina V.

    1992-01-01

    The effects of spaceflight on immune cell function were determined in rats flown on Cosmos 2044. Control groups included vivarium, synchronous, and antiorthostatically suspended rats. The ability of natural killer cells to lyse two different target cell lines was determined. Spleen and bone marrow cells obtained from flight rats showed significantly inhibited cytotoxicity for YAC-1 target cells compared with cells from synchronous control rats. This could have been due to exposure of the rats to microgravity. Antiorthostatic suspension did not affect the level of cytotoxicity from spleen cells of suspended rats for YAC-1 cells. On the other hand, cells from rats flown in space showed no significant differences from vivarium and synchronous control rats in cytotoxicity for K-562 target cells. Binding of natural killer cells to K-562 target cells was unaffected by spaceflight. Antiorthostatic suspension resulted in higher levels of cytotoxicity from spleen cells for Cr-51-labeled K-562 cells. The results indicate differential effects of spaceflight on function of natural killer cells. This shows that spaceflight has selective effects on the immune response.

  11. Present and Future of Allogeneic Natural Killer Cell Therapy

    PubMed Central

    Lim, Okjae; Jung, Mi Young; Hwang, Yu Kyeong; Shin, Eui-Cheol

    2015-01-01

    Natural killer (NK) cells are innate lymphocytes that are capable of eliminating tumor cells and are therefore used for cancer therapy. Although many early investigators used autologous NK cells, including lymphokine-activated killer cells, the clinical efficacies were not satisfactory. Meanwhile, human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation revealed the antitumor effect of allogeneic NK cells, and HLA-haploidentical, killer cell immunoglobulin-like receptor ligand-mismatched allogeneic NK cells are currently used for many protocols requiring NK cells. Moreover, allogeneic NK cells from non-HLA-related healthy donors have been recently used in cancer therapy. The use of allogeneic NK cells from non-HLA-related healthy donors allows the selection of donor NK cells with higher flexibility and to prepare expanded, cryopreserved NK cells for instant administration without delay for ex vivo expansion. In cancer therapy with allogeneic NK cells, optimal matching of donors and recipients is important to maximize the efficacy of the therapy. In this review, we summarize the present state of allogeneic NK cell therapy and its future directions. PMID:26089823

  12. Offshore killer whale tracking using multiple hydrophone arrays.

    PubMed

    Gassmann, Martin; Henderson, E Elizabeth; Wiggins, Sean M; Roch, Marie A; Hildebrand, John A

    2013-11-01

    To study delphinid near surface movements and behavior, two L-shaped hydrophone arrays and one vertical hydrophone line array were deployed at shallow depths (<125 m) from the floating instrument platform R/P FLIP, moored northwest of San Clemente Island in the Southern California Bight. A three-dimensional propagation-model based passive acoustic tracking method was developed and used to track a group of five offshore killer whales (Orcinus orca) using their emitted clicks. In addition, killer whale pulsed calls and high-frequency modulated (HFM) signals were localized using other standard techniques. Based on these tracks sound source levels for the killer whales were estimated. The peak to peak source levels for echolocation clicks vary between 170-205 dB re 1 μPa @ 1 m, for HFM calls between 185-193 dB re 1 μPa @ 1 m, and for pulsed calls between 146-158 dB re 1 μPa @ 1 m. PMID:24180762

  13. Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity.

    PubMed

    Shavit, Y; Lewis, J W; Terman, G W; Gale, R P; Liebeskind, J C

    1984-01-13

    The cytotoxic activity of natural killer cells was investigated in rats subjected to one of two inescapable footshock stress paradigms, both of which induce analgesia, but only one via activation of opioid mechanisms. Splenic natural killer cell activity was suppressed by the opioid, but not the nonopioid, form of stress. This suppression was blocked by the opioid antagonist naltrexone. Similar suppression of natural killer activity was induced by high doses of morphine. These results suggest that endogenous opioid peptides mediate the suppressive effect of certain forms of stress on natural killer cell cytotoxicity.

  14. Destructive hostility: the Jeffrey Dahmer case. A psychiatric and forensic study of a serial killer.

    PubMed

    Jentzen, J; Palermo, G; Johnson, L T; Ho, K C; Stormo, K A; Teggatz, J

    1994-12-01

    We were involved as forensic experts in the case of the serial killer Jeffrey Dahmer. We discuss the scene and victim autopsy findings, with a brief consideration of the basic emotion of hostility. These findings support the thesis that at the basis of this serial killer's behavior were primary unconscious feelings of hate that he had channeled into a sadistic programmed destruction of 17 young men. The interview of the serial killer, the photographic scene documentation, and the autopsy findings stress the ambivalent homosexuality of the killer, his sexual sadism, his obsessive fetishism, and his possible cannibalism and necrophilia.

  15. Prostate cancer susceptibility loci: finding the genes.

    PubMed

    Ostrander, Elanie A; Johannesson, Bo

    2008-01-01

    Studies to date suggest that PC is a genetically very heterogeneous disease. High-risk families, in which multiple men are affected likely, reflect the contributions of a number of genes, some that are rare and highly penetrant, while others are more common and weakly penetrant. In this review, we have discussed only the first type of loci, and found that the identification of such genomic regions is a formidable problem. Replication between seemingly similar data sets is weak, likely reflecting the older age of onset associated with the disease, the inability to collect affected individuals from more than two generations in a family, and the variation seen in disease presentation, in addition to the underlying locus heterogeneity. Indeed, the definition of PC is ever changing, as diagnostic criteria and tools for pinpointing early lesions improve. Are we making progress? Clearly the answer is yes. The ability to divide large data sets into homogenous subset of families likely to share common genetic under-pinnings has improved power to identify loci and reproducibility between loci is now more common. Indeed, several groups report linkage to loci on chromosomes 1, 17, 19, and 22. Key to our continued success is our ever increasing ability to understand the disease. Identifying the subset of men who are likely to get clinically significant disease is the goal of genetic studies like these, and identifying the underlying loci is the key for developing diagnostics. The willingness of the community to work together has been an important factor in the successes the community has enjoyed to date, and will likely be as important as we move forward to untangle the genetics of this complex and common disorder.

  16. Microsatellite loci for genetic mapping in the turkey (Meleagris gallopavo).

    PubMed

    Reed, K M; Chaves, L D; Hall, M K; Knutson, T P; Rowe, J A; Torgerson, A J

    2003-11-01

    New microsatellite loci for the turkey (Meleagris gallopavo) were developed from two small insert DNA libraries. Polymorphism at these new loci was examined in domestic birds and two resource populations designed for genetic linkage mapping. The majority of loci (152 of 168) was polymorphic in domestic turkeys and informative in two mapping resource populations and thus will be useful for genetic linkage mapping.

  17. Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation.

    PubMed

    Levanon, Ditsa; Negreanu, Varda; Lotem, Joseph; Bone, Karen Rae; Brenner, Ori; Leshkowitz, Dena; Groner, Yoram

    2014-03-01

    Natural killer cells belong to the family of innate lymphoid cells comprising the frontline defense against infected and transformed cells. Development and activation of natural killer cells is highly dependent on interleukin-15 signaling. However, very little is known about the transcription program driving this process. The transcription factor Runx3 is highly expressed in natural killer cells, but its function in these cells is largely unknown. We show that loss of Runx3 impaired interleukin-15-dependent accumulation of mature natural killer cells in vivo and under culture conditions and pregnant Runx3(-/-) mice completely lack the unique population of interleukin-15-dependent uterine natural killer cells. Combined chromatin immunoprecipitation sequencing and differential gene expression analysis of wild-type versus Runx3-deficient in vivo activated splenic natural killer cells revealed that Runx3 cooperates with ETS and T-box transcription factors to drive the interleukin-15-mediated transcription program during activation of these cells. Runx3 functions as a nuclear regulator during interleukin-15-dependent activation of natural killer cells by regulating the expression of genes involved in proliferation, maturation, and migration. Similar studies with additional transcription factors will allow the construction of a more detailed transcriptional network that controls natural killer cell development and function.

  18. 50 CFR 226.206 - Critical habitat for the Southern Resident killer whale (Orcinus orca).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Critical habitat for the Southern... DESIGNATED CRITICAL HABITAT § 226.206 Critical habitat for the Southern Resident killer whale (Orcinus orca). Critical habitat is designated for the Southern Resident killer whale as described in this section....

  19. 50 CFR 226.206 - Critical habitat for the Southern Resident killer whale (Orcinus orca).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Critical habitat for the Southern... DESIGNATED CRITICAL HABITAT § 226.206 Critical habitat for the Southern Resident killer whale (Orcinus orca). Critical habitat is designated for the Southern Resident killer whale as described in this section....

  20. 50 CFR 226.206 - Critical habitat for the Southern Resident killer whale (Orcinus orca).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Critical habitat for the Southern... DESIGNATED CRITICAL HABITAT § 226.206 Critical habitat for the Southern Resident killer whale (Orcinus orca). Critical habitat is designated for the Southern Resident killer whale as described in this section....

  1. 50 CFR 226.206 - Critical habitat for the Southern Resident killer whale (Orcinus orca).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Critical habitat for the Southern Resident... CRITICAL HABITAT § 226.206 Critical habitat for the Southern Resident killer whale (Orcinus orca). Critical habitat is designated for the Southern Resident killer whale as described in this section. The...

  2. One-Year Prediction of Pain Killer Use among At-Risk Older Teens and Emerging Adults

    ERIC Educational Resources Information Center

    Sussman, Steve; Rohrbach, Louise A.; Spruijt-Metz, Donna; Barnett, Elizabeth; Lisha, Nadra; Sun, Ping

    2012-01-01

    The leading substance of misuse among teens after tobacco, alcohol, and marijuana is the use of pain killers. Very few longitudinal studies on prediction of pain killer use have been conducted among teens. This study examined the 1-year prediction of self-reported last 30-day pain killer use controlling for baseline 30-day painkiller use among…

  3. Radiation-induced mutation at minisatellite loci

    SciTech Connect

    Dubrova, Y.E. |; Nesterov, V.N.; Krouchinsky, N.G.

    1997-10-01

    We are studying the radiation-induced increase of mutation rate in minisatellite loci in mice and humans. Minisatellite mutations were scored by multilocus DNA fingerprint analysis in the progeny of {gamma}-irradiated and non-irradiated mice. The frequency of mutation in offspring of irradiated males was 1.7 higher that in the control group. Germline mutation at human minisatellite loci was studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation assayed both by DNA fingerprinting and by eight single locus probes was found to be two times higher in the exposed families than in the control group. Furthermore, mutation rate was correlated with the parental radiation dose for chronic exposure {sup 137}Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed.

  4. Construction of Killer Industrial Yeast Saccharomyces Cerevisiae Hau-1 and its Fermentation Performance

    PubMed Central

    Bajaj, Bijender K.; Sharma, S.

    2010-01-01

    Saccharomyces cerevisiae HAU-1, a time tested industrial yeast possesses most of the desirable fermentation characteristics like fast growth and fermentation rate, osmotolerance, high ethanol tolerance, ability to ferment molasses, and to ferment at elevated temperatures etc. However, this yeast was found to be sensitive against the killer strains of Saccharomyces cerevisiae. In the present study, killer trait was introduced into Saccharomyces cerevisiae HAU-1 by protoplast fusion with Saccharomyces cerevisiae MTCC 475, a killer strain. The resultant fusants were characterized for desirable fermentation characteristics. All the technologically important characteristics of distillery yeast Saccharomyces cerevisiae HAU-1 were retained in the fusants, and in addition the killer trait was also introduced into them. Further, the killer activity was found to be stably maintained during hostile conditions of ethanol fermentations in dextrose or molasses, and even during biomass recycling. PMID:24031519

  5. Killer cell immunoglobulin-like receptor gene association with cryptorchidism.

    PubMed

    Niepiekło-Miniewska, Wanda; Kuśnierczyk, Piotr; Havrylyuk, Anna; Kamieniczna, Marzena; Nakonechnyy, Andrij; Chopyak, Valentyna; Kurpisz, Maciej

    2015-12-01

    Cryptorchidism is a condition where a testis persists in the abdominal cavity. Thus, due to elevated temperature we may expect induction of aberrant immune reactions depending on genetic constitution of individual. This may be reflected by development of anti-sperm antibodies (ASA) in cryptorchid males. Also, natural killer (NK) cells which belong to innate immunity may control adaptive immunity. Therefore, the gene system encoding polymorphic NK cell immunoglobulin receptors (KIRs) has been studied. 109 prepubertal boys with cryptorchidism and 136 ethnically matched young male donors were selected to study NK cell KIRs. DNA was isolated using automatic Maxwell(®) system from the peripheral venous blood drawn onto anticoagulant. Olerup SSP KIR Genotyping kit including Taq polymerase was used for detection of KIR genes. Human leukocyte antigen-C (HLA-C) groups, C1 and C2 were established using a Olerup SSP KIR HLA Ligand kit. KIR2DL2 (killer immunoglobulin-like receptor two-domain long 2) and KIR2DS2 (killer immunoglobulin-like receptor two-domain short 2) genes were less frequent in patients than in control individuals (corrected p values: 0.0110 and 0.0383, respectively). However, no significant differences were observed between ASA-positive and ASA-negative patients, or between bilateral or unilateral cryptorchidism. No association between KIR ligands C1 and C2, alone or together with KIR2DL2, was found. However, the results suggest that KIR2DL2+/KIR2DS2+ genotype may be, to some extent, protective against cryptorchidism.

  6. Characterization of microsatellite loci isolated in trumpeter swan (Cygnus buccinator)

    USGS Publications Warehouse

    John, J. St; Ransler, F.A.; Quinn, T.W.; Oyler-McCance, S.J.

    2006-01-01

    Primers for 16 microsatellite loci were developed for the trumpeter swan (Cygnus buccinator), a species recovering from a recent population bottleneck. In a screen of 158 individuals, the 16 loci were found to have levels of variability ranging from two to seven alleles. No loci were found to be linked, although two loci repeatedly revealed significant departures from Hardy-Weinberg equilibrium. Amplification in the closely related tundra swan (Cygnus columbianus) was successful for all except one locus. These microsatellite loci will be applicable for population genetic analyses and ultimately aid in management efforts. ?? 2006 The Authors.

  7. Classification of vocalizations of killer whales using dynamic time warping.

    PubMed

    Brown, Judith C; Hodgins-Davis, Andrea; Miller, Patrick J O

    2006-03-01

    A large number of killer whale sounds have recently been classified perceptually into Call Types. [A. Hodgins-Davis, thesis, Wellesley College (2004)]. The repetition rate of the pulsed component of five or more examples of each call type has been calculated using a modified form of the FFT based comb-filter method. A dissimilarity or distance matrix for these sounds was calculated using dynamic time warping to compare their melodic contours. These distances were transformed into a component space using multidimensional scaling and the resulting points were clustered with a kmeans algorithm. In grouping 57 sounds into 9 call types, a single discrepancy between the perceptual and the automated methods occurred.

  8. Isolation and identification of normal killer cells from Syrian hamsters

    SciTech Connect

    Matveeva, V.A.; Klyuchareva, T.E.

    1986-09-01

    This paper gives data on isolation of normal killer cells from the blood and various tissues of Syrian hamsters in a Percoll density gradient and their identification on the basis of morphologic criteria and cytotoxic activity (CTA). CTA of the isolated cells was studied in the cytotoxic test with target cells of a human MOLT-4 thymoma cell labeled with /sup 51/Cr. Isolation of large granular lymphocytes from blood, spleen, and bone marrow of Syrian hamsters in Percoll density gradient is shown in the results of five experiments used for cells of each type.

  9. A killer micro attack on 3D neutron transport

    SciTech Connect

    Dorr, M.R.; Ferguson, J.M.

    1990-11-01

    We describe the deterministic solution of the neutron transport equation and the computation of the effective criticality of three-dimensional assemblies using the BBN TC2000 killer micros. We observe that the performance of our research code PTRAN running on 48 processors of the TC2000 is competitive with the partially vectorizable version running on a single Cray Y/MP processor. This performance scales well with the number of processors on real problems, including those that are not load balanced a priori. To obtain this performance, we explicitly specify and exploit data locality and data dependence using domain decomposition and dynamic job scheduling. 3 refs., 4 figs., 2 tabs.

  10. Three faces of mortalin: a housekeeper, guardian and killer.

    PubMed

    Kaul, Sunil C; Deocaris, Custer C; Wadhwa, Renu

    2007-04-01

    Mortalin was first cloned as a mortality factor that existed in the cytoplasmic fractions of normal, but not in immortal, mouse fibroblasts. A decade of efforts have expanded its persona from a house keeper protein involved in mitochondrial import, energy generation and chaperoning of misfolded proteins, to a guardian of stress that has multiple binding partners and to a killer protein that contributes to carcinogenesis on one hand and to old age disorders on the other. Being proved to be an attractive target for cancer therapy, it also warrants attention from the perspectives of management of old age diseases and healthy aging.

  11. Bringing natural killer cells to the clinic: ex vivo manipulation.

    PubMed

    Childs, Richard W; Berg, Maria

    2013-01-01

    Recently, there has been a substantial gain in our understanding of the role that natural killer (NK) cells play in mediating innate host immune responses against viruses and cancer. Although NK cells have long been known to be capable of killing cancer cells independently of antigen recognition, the full therapeutic potential of NK cell-based immunotherapy has yet to be realized. Here we review novel methods to activate and expand human NK cells ex vivo for adoptive transfer in humans, focusing on the important phenotypic and functional differences observed among freshly isolated, cytokine activated, and ex vivo-expanded NK populations. PMID:24319186

  12. Role of human leukocyte antigen, killer-cell immunoglobulin-like receptors, and cytokine gene polymorphisms in leptospirosis.

    PubMed

    Fialho, Raquel Nunes; Martins, Luís; Pinheiro, João Paulo; Bettencourt, Bruno Filipe; Couto, Ana Rita; Santos, Margarida Rodrigues; Peixoto, Maria José; Garrett, Francisco; Leal, João; Tomás, Ana Maria; Bruges-Armas, Jácome

    2009-11-01

    Leptospirosis is an emerging zoonotic disease caused by pathogenic species of the genus Leptospira. It has a broad range of clinical presentations in humans. Although progress has been made in the characterization of the host immune system factors that may affect disease progression and outcome, to date few reports have addressed the role of genetic polymorphisms in the susceptibility to leptospirosis. In this work a group of patients with a history of leptospiral infection and a control group were compared for polymorphisms in the human leukocyte antigen (HLA), in killer-cell immunoglobulin-like receptors (KIR), and in cytokine genes. Alleles in the HLA-A and -B loci were associated with susceptibility, as were the class I haplotype A*01-B*08-Cw*07 and the 8.1 ancestral haplotype (A*01-B*08-Cw*07-DRB1*03-DQB1*02). Single nucleotide polymorphisms in the interleukin (IL)-4 and IL-4Ralpha genes also had significantly higher frequencies in the patient group. No association was reported between KIR gene profile and leptospirosis. This work highlights the importance of using genetic polymorphisms to better understand the mechanisms involved in the immune response to leptospirosis.

  13. Energy Security: From Deal Killers to Game Changers

    NASA Astrophysics Data System (ADS)

    Cooke, Charlie

    2010-03-01

    Five energy security ``deal killers" are identified: 1) Global warming and CO2 emissions from fossil fuel combustion; 2) Intermittent energy sources (wind, solar) and the presence and stability of the grid; 3) Penetration of plant defenses to produce transportation fuels from biomass; 4) Mimicking nature: artificial photosynthesis for solar energy to fuels; and 5) Spent fuel from nuclear power reactors. Transformational basic research is required to successfully change the ground rules, to transform these ``deal killers" into ``game changers." T hey are: 1) Offsetting carbon capture and storage costs through enhanced oil recovery and methane generation from high temperature geothermal saline aquifers; 2) Electrical energy storage, through batteries and super-capacitors; 3) Genetic modification of plant cell walls, and catalytic methods for transforming plant sugars into fuels; 4) Separation of solar-induced electrons from holes, and catalysis to produce fuels; and 5) Closing the nuclear fuel cycle. Basic research can revolutionize our approach to carbon-free energy by enhancing nature to achieve energy security.

  14. Echolocation signals of foraging killer whales (Orcinus orca)

    NASA Astrophysics Data System (ADS)

    Au, Whitlow W. L.; Ford, John K. B.; Allman, Kelly A.

    2002-05-01

    Fish eating resident killer whales that frequent the coastal waters of Vancouver Island, Canada have a strong preference for chinook salmon. The whales in Johnston Strait often forage along the steep cliffs that extend into the water, echolocating their prey. Echolocation signals were measured with a four hydrophone symmetrical star array and the signals were simultaneous digitized at a sample rate of 500 kHz using a lunch-box PC. A portable VCR recorded the images from an underwater camera located close to the array center. Only signals emanated from close to the beam axis (1185 total) were chosen for a detailed analysis. Killer whales project very broad band echolocation signals (Q 1.3 to 1.5) that tend to have a bimodal frequency structure. Ninety seven percent of the signals had center frequencies between 45 and 80 kHz with a band-width between 35 and 50 kHz. The peak-to-peak source level of the echolocation signal decreased as a function of the one way transmission loss to the array. Source levels varied between 200 and 225 dB re 1 μPa. Using a model of target strength for chinook salmons, the echo levels from the echolocation signals are estimated for different ranges between whale and salmon.

  15. Cord Blood as a Source of Natural Killer Cells.

    PubMed

    Mehta, Rohtesh S; Shpall, Elizabeth J; Rezvani, Katayoun

    2015-01-01

    Cord blood (CB) offers several unique advantages as a graft source for hematopoietic stem cell transplantation (HSCT). The risk of relapse and graft vs. host disease after cord blood transplantation (CBT) is lower than what is typically observed after other graft sources with a similar degree of human leukocyte antigen mismatch. Natural killer (NK) cells have a well-defined role in both innate and adaptive immunity and as the first lymphocytes to reconstitute after HSCT and CBT, and they play a significant role in protection against early relapse. In this article, we highlight the uses of CB NK cells in transplantation and adoptive immunotherapy. First, we will describe differences in the phenotype and functional characteristics of NK cells in CB as compared with peripheral blood. Then, we will review some of the obstacles we face in using resting CB NK cells for adoptive immunotherapy, and discuss methods to overcome them. We will review the current literature on killer-cell immunoglobulin-like receptors ligand mismatch and outcomes after CBT. Finally, we will touch on current strategies for the use of CB NK cells in cellular immunotherapy. PMID:26779484

  16. Immunosuppression of pulmonary natural killer activity by exposure to ozone

    SciTech Connect

    Burleson, G.R.; Keyes, L.L.; Stutzman, J.D. )

    1989-01-01

    Ozone is an oxidant gas and an ubiquitous oxidant air pollutant with the potential to adversely affect pulmonary immune function with a consequent increase in disease susceptibility. Pulmonary natural killer (NK) activity was measured in order to assess the pulmonary immunotoxicity of continuous ozone exposure. Continuous ozone exposures at 1.0 ppm were performed for 23.5 hours per day for either 1, 5, 7, or 10 consecutive days. Pulmonary immune function was assessed by measuring natural killer (NK) activity from whole-lung homogenates of male Fischer-344 rats. Results of this study indicated that continuous ozone exposure for 1, 5, or 7 days resulted in a significant decrease in pulmonary NK activity. This suppressed pulmonary NK activity returned to control levels after continuous exposure to ozone for 10 days. The suppressed pulmonary NK response was thus attenuated and returned to normal values in the continued presence of ozone gas. This attenuation process is dynamic, complex, and doubtless involves several cell types and/or products of these cells. Pulmonary NK activity was also suppressed at 0.5 ppm ozone, but not at 0.1 ppm ozone, following 23.5 hours of exposure. NK activity is important for defense against viral, bacterial, and neoplastic disease. The depressed NK activity resulting from continuous ozone exposure could therefore result in a compromised ability to defend against pulmonary diseases.

  17. Reduced killer cell activity of lymphocytes from patients with asbestosis.

    PubMed Central

    Kubota, M; Kagamimori, S; Yokoyama, K; Okada, A

    1985-01-01

    Immunological abnormalities in 30 patients with asbestosis were investigated by examining the cytoxicity of natural killer (NK) cells and antibody dependent cellular cytotoxicity by killer (K) cells from peripheral blood lymphocytes; the effects of interferon on NK activity was also examined. Fifteen men and 15 women (mean age 58; range 40-72) with asbestosis but who were free of complications such as tuberculosis, carcinoma, or steroid treatment were the subjects for study. There were nine cases of type 1, 19 cases of type 2, and two cases of type 3 disease as described in the ILO classification of pneumoconiosis. They were all textile workers with a mean duration of 18 years (3-40 years) since first exposure to chrysotile. Controls matched for age and sex were selected from a population without occupational exposure to asbestos. The activity of the NK and K cells in patients with asbestosis was significantly lower than in the control group, but the populations of NK and K cells in the peripheral blood lymphocytes were not significantly different in the two groups. An in vitro experiment showed that the increase in the cytotoxicity of the NK cell after treatment with interferon-alpha was significantly lower in the subjects than in the controls. These results indicate that one of the defence mechanisms in relation to cancer is deficient in patients with asbestosis. PMID:3978049

  18. Accumulation and transfer of contaminants in killer whales (Orcinus orca) from Norway: indications for contaminant metabolism.

    PubMed

    Wolkers, Hans; Corkeron, Peter J; Van Parijs, Sofie M; Similä, Tiu; Van Bavel, Bert

    2007-08-01

    Blubber tissue of one subadult and eight male adult killer whales was sampled in Northern Norway in order to assess the degree and type of contaminant exposure and transfer in the herring-killer whale link of the marine food web. A comprehensive selection of contaminants was targeted, with special attention to toxaphenes and polybrominated diphenyl ethers (PBDEs). In addition to assessing exposure and food chain transfer, selective accumulation and metabolism issues also were addressed. Average total polychlorinated biphenyl (PCB) and pesticide levels were similar, approximately 25 microg/g lipid, and PBDEs were approximately 0.5 microg/g. This makes killer whales one of the most polluted arctic animals, with levels exceeding those in polar bears. Comparing the contamination of the killer whale's diet with the diet of high-arctic species such as white whales reveals six to more than 20 times higher levels in the killer whale diet. The difference in contaminant pattern between killer whales and their prey and the metabolic index calculated suggested that these cetaceans have a relatively high capacity to metabolize contaminants. Polychlorinated biphenyls, chlordanes, and dichlorodiphenyldichloro-ethylene (DDE) accumulate to some degree in killer whales, although toxaphenes and PBDEs might be partly broken down.

  19. Killer toxin from several food-derived Debaryomyces hansenii strains effective against pathogenic Candida yeasts.

    PubMed

    Banjara, Nabaraj; Nickerson, Kenneth W; Suhr, Mallory J; Hallen-Adams, Heather E

    2016-04-01

    Candida yeasts are the dominant fungi in the healthy human microbiome, but are well-known for causing disease following a variety of perturbations. Evaluation of fungal populations from the healthy human gut revealed a significant negative correlation between the foodborne yeast, Debaryomyces hansenii, and Candida species. D. hansenii is reported to produce killer toxins (mycocins) effective against other yeast species. In order to better understand this phenomenon, a collection of 42 D. hansenii isolates was obtained from 22 cheeses and evaluated for killer activity against Candida albicans and Candida tropicalis over a range of temperatures and pH values. Twenty three strains demonstrated killer activity against both C. albicans and C. tropicalis, which was pH- and temperature-dependent, with no killer activity observed for any strain at pH6.5 or higher, or at ≥ 35 °C (physiological conditions in the human gastrointestinal tract). A cell-free mycocin preparation showed transient killer activity against C. albicans at 35 °C and a cheese sample containing a killer D. hansenii strain demonstrated sustained killer activity against both C. albicans and C. tropicalis. Together, these observations raise the possibility that D. hansenii could influence Candida populations in the gut.

  20. Low-frequency signals produced by Northeast Atlantic killer whales (Orcinus orca).

    PubMed

    Samarra, Filipa I P; Deecke, Volker B; Miller, Patrick J O

    2016-03-01

    Killer whale acoustic behavior has been extensively investigated; however, most studies have focused on pulsed calls and whistles. This study reports the production of low-frequency signals by killer whales at frequencies below 300 Hz. Recordings were made in Iceland and Norway when killer whales were observed feeding on herring and no other marine mammal species were nearby. Low-frequency sounds were identified in Iceland and ranged in duration between 0.14 and 2.77 s and in frequency between 50 and 270 Hz, well below the previously reported lower limit for killer whale tonal sounds of 500 Hz. Low-frequency sounds appeared to be produced close in time to tail slaps, which are indicative of feeding attempts, suggesting that these sounds may be related to a feeding context. However, their precise function is unknown, and they could be the by-product of a non-vocal behavior rather than a vocal signal deliberately produced by the whales. Although killer whales in Norway exhibit similar feeding behavior, this sound has not been detected in recordings from Norway to date. This study suggests that, like other delphinids, killer whales produce low-frequency sounds, but further studies will be required to understand whether similar sounds exist in other killer whale populations. PMID:27036251

  1. Low-frequency signals produced by Northeast Atlantic killer whales (Orcinus orca).

    PubMed

    Samarra, Filipa I P; Deecke, Volker B; Miller, Patrick J O

    2016-03-01

    Killer whale acoustic behavior has been extensively investigated; however, most studies have focused on pulsed calls and whistles. This study reports the production of low-frequency signals by killer whales at frequencies below 300 Hz. Recordings were made in Iceland and Norway when killer whales were observed feeding on herring and no other marine mammal species were nearby. Low-frequency sounds were identified in Iceland and ranged in duration between 0.14 and 2.77 s and in frequency between 50 and 270 Hz, well below the previously reported lower limit for killer whale tonal sounds of 500 Hz. Low-frequency sounds appeared to be produced close in time to tail slaps, which are indicative of feeding attempts, suggesting that these sounds may be related to a feeding context. However, their precise function is unknown, and they could be the by-product of a non-vocal behavior rather than a vocal signal deliberately produced by the whales. Although killer whales in Norway exhibit similar feeding behavior, this sound has not been detected in recordings from Norway to date. This study suggests that, like other delphinids, killer whales produce low-frequency sounds, but further studies will be required to understand whether similar sounds exist in other killer whale populations.

  2. Yeast killer toxins, molecular mechanisms of their action and their applications.

    PubMed

    Liu, Guang-Lei; Chi, Zhe; Wang, Guang-Yuan; Wang, Zhi-Peng; Li, Yang; Chi, Zhen-Ming

    2015-06-01

    Killer toxins secreted by some yeast strains are the proteins that kill sensitive cells of the same or related yeast genera. In recent years, many new yeast species have been found to be able to produce killer toxins against the pathogenic yeasts, especially Candida albicans. Some of the killer toxins have been purified and characterized, and the genes encoding the killer toxins have been cloned and characterized. Many new targets including different components of cell wall, plasma membrane, tRNA, DNA and others in the sensitive cells for the killer toxin action have been identified so that the new molecular mechanisms of action have been elucidated. However, it is still unknown how some of the newly discovered killer toxins kill the sensitive cells. Studies on the killer phenomenon in yeasts have provided valuable insights into a number of fundamental aspects of eukaryotic cell biology and interactions of different eukaryotic cells. Elucidation of the molecular mechanisms of their action will be helpful to develop the strategies to fight more and more harmful yeasts.

  3. Expression quantitative trait loci: present and future

    PubMed Central

    Nica, Alexandra C.; Dermitzakis, Emmanouil T.

    2013-01-01

    The last few years have seen the development of large efforts for the analysis of genome function, especially in the context of genome variation. One of the most prominent directions has been the extensive set of studies on expression quantitative trait loci (eQTLs), namely, the discovery of genetic variants that explain variation in gene expression levels. Such studies have offered promise not just for the characterization of functional sequence variation but also for the understanding of basic processes of gene regulation and interpretation of genome-wide association studies. In this review, we discuss some of the key directions of eQTL research and its implications. PMID:23650636

  4. Increased killer immunoglobulin-like receptor expression and functional defects in natural killer cells in lung cancer.

    PubMed

    Al Omar, Suliman Y; Marshall, Ernie; Middleton, Derek; Christmas, Stephen E

    2011-05-01

    Frequencies of natural killer (NK) cells from patients with non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) did not differ from healthy controls. A higher proportion of NK cells from NSCLC patients expressed the killer immunoglobulin-like receptor (KIR) CD158b than in controls (P = 0.0004), in the presence or absence of its ligand, HLA-C1. A similar result was obtained for CD158e in the presence of its ligand HLA-Bw4 in NSCLC patients (P = 0.003); this was entirely attributable to the Bw4I group of alleles in the presence of which a fivefold higher percentage of CD158e(+) NK cells was found in NSCLC patients than controls. Proportions of CD158b(+) NK cells declined with advancing disease in NSCLC patients. Expression of NKp46, CD25 and perforin A, and production of interferon-γ following stimulation with interleukin-12 and interleukin-18, were all significantly lower in NK cells from NSCLC patients than in controls. Both NK cell cytotoxicity and granzyme B expression were also reduced in lung cancer patients. Increased inhibitory KIR expression would decrease NK cell cytotoxic function against tumour cells retaining class I HLA expression. Furthermore, the reduced ability to produce interferon-γ would restrict the ability of NK cells to stimulate T-cell responses in patients with lung cancer.

  5. Speaking up: Killer whales (Orcinus orca) increase their call amplitude in response to vessel noise.

    PubMed

    Holt, Marla M; Noren, Dawn P; Veirs, Val; Emmons, Candice K; Veirs, Scott

    2009-01-01

    This study investigated the effects of anthropogenic sound exposure on the vocal behavior of free-ranging killer whales. Endangered Southern Resident killer whales inhabit areas including the urban coastal waters of Puget Sound near Seattle, WA, where anthropogenic sounds are ubiquitous, particularly those from motorized vessels. A calibrated recording system was used to measure killer whale call source levels and background noise levels (1-40 kHz). Results show that whales increased their call amplitude by 1 dB for every 1 dB increase in background noise levels. Furthermore, nearby vessel counts were positively correlated with these observed background noise levels. PMID:19173379

  6. [Nasal type natural killer/T cell lymphoma: case series and literature review].

    PubMed

    Düzlü, Mehmet; Ant, Ayça; Tutar, Hakan; Karamert, Recep; Şahin, Melih; Sayar, Erolcan; Cesur, Nesibe

    2016-01-01

    Nasal type natural killer/T-cell lymphoma is a rare type of extranodal non-Hodgkin lymphoma which originates from nasal cavity and paranasal sinuses. Exact diagnosis of nasal natural killer/T-cell lymphoma, which is a rapidly progressive clinical condition, may be established by immunohistochemical analysis on biopsy material after clinical suspicion. In this article, we report four cases of nasal natural killer/T-cell lymphoma who were followed-up in our clinic and discuss the diagnosis and treatment of the disease in light of the literature data. PMID:27405082

  7. Environmental isolates of fungi from aquarium pools housing killer whales (Orcinus orca).

    PubMed

    Kohata, Erina; Kano, Rui; Akune, Yuichiro; Ohno, Yoshito; Soichi, Makoto; Yanai, Tokuma; Hasegawa, Atsuhiko; Kamata, Hiroshi

    2013-12-01

    Systemic mycoses in killer whales (Orcinus orca) are rare diseases, but have been reported. Two killer whales died by fungal infections at the Port of Nagoya Public Aquarium in Japan. In this study, the fungal flora of the pool environment at the aquarium was characterized. Alternaria spp., Aspergillus spp. (A. fumigatus, A. niger, A. versicolor), Fusarium spp. and Penicillium spp. were isolated from the air and the pool surroundings. The other isolates were identified as fungal species non-pathogenic for mammals. However, the species of fungi isolated from the environmental samples in this study were not the same as those isolated from the cases of disease in killer whales previously reported.

  8. Mapping of hybrid incompatibility loci in Nasonia.

    PubMed Central

    Gadau, J; Page, R E; Werren, J H

    1999-01-01

    According to theory, F(2) hybrid breakdown (lethality or sterility) is due to incompatibilities between interacting genes of the different species (i.e., the breaking up of coadapted gene complexes). Detection of such incompatibilities is particularly straightforward in haplodiploid species, because virgin F(1) hybrid females will produce haploid recombinant F(2) males. This feature allows for screening of the complete genome for recessive genetic incompatibilities. Crosses were performed between Nasonia vitripennis (v) and its sibling species N. giraulti (g). First, a linkage map was produced using RAPD markers. RAPD markers showed an overall bias toward vitripennis alleles, a pattern not predicted by the basic two-interactor Dobzhansky-Muller model. Recovery patterns of visible markers were consistent with those of linked RAPD markers. If particular genetic interactions between two loci are causing hybrid lethality, then those genotypes should be underrepresented or absent among adult F(2) males. Four sets of significant incompatibilities were detected by performing pairwise comparisons of markers on different chromosomes. Likely explanations for the observed patterns are maternal effect-zygotic gene incompatibilities or clustering of incompatibility loci. Due to the short generation time, advantages of haplodiploidy, and availability of markers, Nasonia promises to be a productive system for investigating the genetics of hybrid inviability. PMID:10581280

  9. Quantitative Trait Loci for Murine Growth

    PubMed Central

    Cheverud, J. M.; Routman, E. J.; Duarte, FAM.; van-Swinderen, B.; Cothran, K.; Perel, C.

    1996-01-01

    Body size is an archetypal quantitative trait with variation due to the segregation of many gene loci, each of relatively minor effect, and the environment. We examine the effects of quantitative trait loci (QTLs) on age-specific body weights and growth in the F(2) intercross of the LG/J and SM/J strains of inbred mice. Weekly weights (1-10 wk) and 75 microsatellite genotypes were obtained for 535 mice. Interval mapping was used to locate and measure the genotypic effects of QTLs on body weight and growth. QTL effects were detected on 16 of the 19 autosomes with several chromosomes carrying more than one QTL. The number of QTLs for age-specific weights varied from seven at 1 week to 17 at 10 wk. The QTLs were each of relatively minor, subequal effect. QTLs affecting early and late growth were generally distinct, mapping to different chromosomal locations indicating separate genetic and physiological systems for early and later murine growth. PMID:8846907

  10. A population study of killer viruses reveals different evolutionary histories of two closely related Saccharomyces sensu stricto yeasts.

    PubMed

    Chang, Shang-Lin; Leu, Jun-Yi; Chang, Tien-Hsien

    2015-08-01

    Microbes have evolved ways of interference competition to gain advantage over their ecological competitors. The use of secreted killer toxins by yeast cells through acquiring double-stranded RNA viruses is one such prominent example. Although the killer behaviour has been well studied in laboratory yeast strains, our knowledge regarding how killer viruses are spread and maintained in nature and how yeast cells co-evolve with viruses remains limited. We investigated these issues using a panel of 81 yeast populations belonging to three Saccharomyces sensu stricto species isolated from diverse ecological niches and geographic locations. We found that killer strains are rare among all three species. In contrast, killer toxin resistance is widespread in Saccharomyces paradoxus populations, but not in Saccharomyces cerevisiae or Saccharomyces eubayanus populations. Genetic analyses revealed that toxin resistance in S. paradoxus is often caused by dominant alleles that have independently evolved in different populations. Molecular typing identified one M28 and two types of M1 killer viruses in those killer strains. We further showed that killer viruses of the same type could lead to distinct killer phenotypes under different host backgrounds, suggesting co-evolution between the viruses and hosts in different populations. Taken together, our data suggest that killer viruses vary in their evolutionary histories even within closely related yeast species.

  11. Energy Security: From Deal Killers to Game Changers

    NASA Astrophysics Data System (ADS)

    Orbach, Raymond L.

    2010-03-01

    Five ``deal killers'' for achieving energy security will be addressed: 1) Global warming and CO2 emissions from fossil fuel combustion, 2) Intermittent energy sources (wind, solar) and the presence and stability of the grid, 3) Penetration of plant defenses to produce transportation fuels from biomass, 4) Mimicking nature: artificial photosynthesis for solar energy-to-fuels, and 5) Spent fuel from nuclear power reactors. Basic research can lead to ``game changers'' for these five fields: 1) Carbon capture and storage through enhanced oil and gas recovery, 2) Electrical energy storage for base-load electricity through batteries and supercapacitors, 3) Genetic modification of the plant cell wall, and catalytic methods for conversion of plant sugars to fuels, 4) Separation of solar-induced electrons from holes, and catalysis to produce fuels, and 5) Closing the nuclear fuel cycle. The present state for each of these game changers will be summarized, and future research opportunities discussed.

  12. Automatic classification of killer whale vocalizations using dynamic time warping.

    PubMed

    Brown, Judith C; Miller, Patrick J O

    2007-08-01

    A set of killer whale sounds from Marineland were recently classified automatically [Brown et al., J. Acoust. Soc. Am. 119, EL34-EL40 (2006)] into call types using dynamic time warping (DTW), multidimensional scaling, and kmeans clustering to give near-perfect agreement with a perceptual classification. Here the effectiveness of four DTW algorithms on a larger and much more challenging set of calls by Northern Resident whales will be examined, with each call consisting of two independently modulated pitch contours and having considerable overlap in contours for several of the perceptual call types. Classification results are given for each of the four algorithms for the low frequency contour (LFC), the high frequency contour (HFC), their derivatives, and weighted sums of the distances corresponding to LFC with HFC, LFC with its derivative, and HFC with its derivative. The best agreement with the perceptual classification was 90% attained by the Sakoe-Chiba algorithm for the low frequency contours alone.

  13. Vulnerability of a killer whale social network to disease outbreaks

    NASA Astrophysics Data System (ADS)

    Guimarães, Paulo R., Jr.; de Menezes, Márcio Argollo; Baird, Robin W.; Lusseau, David; Guimarães, Paulo; Dos Reis, Sérgio F.

    2007-10-01

    Emerging infectious diseases are among the main threats to conservation of biological diversity. A crucial task facing epidemiologists is to predict the vulnerability of populations of endangered animals to disease outbreaks. In this context, the network structure of social interactions within animal populations may affect disease spreading. However, endangered animal populations are often small and to investigate the dynamics of small networks is a difficult task. Using network theory, we show that the social structure of an endangered population of mammal-eating killer whales is vulnerable to disease outbreaks. This feature was found to be a consequence of the combined effects of the topology and strength of social links among individuals. Our results uncover a serious challenge for conservation of the species and its ecosystem. In addition, this study shows that the network approach can be useful to study dynamical processes in very small networks.

  14. Novel targets for natural killer/T-cell lymphoma immunotherapy.

    PubMed

    Kumai, Takumi; Kobayashi, Hiroya; Harabuchi, Yasuaki

    2016-01-01

    Extranodal natural killer/T-cell lymphoma, nasal type (NKTL) is a rare but highly aggressive Epstein-Barr virus-related malignancy, which mainly occurs in nasopharyngeal and nasal/paranasal areas. In addition to its high prevalence in Asian, Central American and South American populations, its incidence rate has been gradually increasing in Western countries. The current mainstay of treatment is a combination of multiple chemotherapies and irradiation. Although chemoradiotherapy can cure NKTL, it often causes severe and fatal adverse events. Because a growing body of evidence suggests that immunotherapy is effective against hematological malignancies, this treatment could provide an alternative to chemoradiotherapy for treatment of NKTL. In this review, we focus on how recent findings could be used to develop efficient immunotherapies against NKTL. PMID:26642249

  15. Cytotoxic and natural killer cell stimulatory constituents of Phyllanthus songboiensis

    PubMed Central

    Ren, Yulin; Yuan, Chunhua; Deng, Youcai; Kanagasabai, Ragu; Ninh, Tran Ngoc; Tu, Vuong Tan; Chai, Hee-Byung; Soejarto, Djaja D.; Fuchs, James R.; Yalowich, Jack C.; Yu, Jianhua; Kinghorn, A. Douglas

    2014-01-01

    A dichapetalin-type triterpenoid and a dibenzylbutyrolactone-type lignan, together with five known lignans, a known aromatic diterpenoid, and a known acylated phytosterol, were isolated from the aerial parts of Phyllanthus songboiensis, collected in Vietnam. Their structures were determined by interpretation of the spectroscopic data, and the inhibitory activity toward the HT-29 human colon cancer cells of all isolates was evaluated by a cytotoxicity assay. The known arylnaphthalene lignan, (+)-acutissimalignan A, was highly cytotoxic toward HT-29 cells, with an IC50 value of 19 nM, but this compound was inactive as a DNA topoisomerase IIα (topo IIα) poison. The known phytosterol, (−)-β-sitosterol-3-O-β-D-(6-O-palmitoyl)glucopyranoside, was found to stimulate natural killer (NK) cells at a concentration of 10 μM in the presence of interleukin 12 (IL-12). PMID:25596805

  16. A killer micro attack on 3D neutron transport

    SciTech Connect

    Dorr, M.R.; Ferguson, J.M.

    1990-11-16

    In this paper, we describe the deterministic solution of the neutron transport equation and the computation of the effective criticality of three-dimensional assemblies using the BBN TC2000 killer micros. We observe that the performance of our research code PTRAN running on 48 processors of the TC2000 is competitive with the partially vectorizable version running on a single Cray Y/MP processor. This performance scales well with the number of processors on real problems, including those that are not load balanced a priori. To obtain this performance, we explicitly specify and exploit data locality and data dependence using domain decomposition and dynamic job scheduling. From the results obtained here, it appears that, at least for this application, a production machine based on the TC2000 architecture with more powerful processors and a commensurate increase in switch speed could yield a significant gain in our design capability. 2 refs., 5 figs., 2 tabs.

  17. Operational Performance Analysis of Passive Acoustic Monitoring for Killer Whales

    SciTech Connect

    Matzner, Shari; Fu, Tao; Ren, Huiying; Deng, Zhiqun; Sun, Yannan; Carlson, Thomas J.

    2011-09-30

    For the planned tidal turbine site in Puget Sound, WA, the main concern is to protect Southern Resident Killer Whales (SRKW) due to their Endangered Species Act status. A passive acoustic monitoring system is proposed because the whales emit vocalizations that can be detected by a passive system. The algorithm for detection is implemented in two stages. The first stage is an energy detector designed to detect candidate signals. The second stage is a spectral classifier that is designed to reduce false alarms. The evaluation presented here of the detection algorithm incorporates behavioral models of the species of interest, environmental models of noise levels and potential false alarm sources to provide a realistic characterization of expected operational performance.

  18. Stressin and natural killer cell activity in professional soldiers.

    PubMed

    Lauc, G; Dabelić; Dumić, J; Flögel, M

    1998-06-30

    Chronic stress causes multiple biochemical and physiological changes in the human organism. Recently we have identified stressin, a human serum glycoprotein that was significantly increased in sera of prisoners released from Serbian concentration camps. To eliminate malnutrition and maltreatment as possible causes for the increased stressin concentration, we have analyzed stressin in sera of 40 professional soldiers after involvement in major military activity and compared it to stressin in sera of 20 control individuals. As expected, the sera of professional soldiers contained more than 2.2 times higher concentrations of stressin than control sera. It is interesting that, contrary to expectations, the natural killer cell activity of professional soldiers was normal or even increased. We hypothesize that this might be an effect of winning the war that could have, at least temporarily, erased the immunosuppressive effects of stress.

  19. Novel targets for natural killer/T-cell lymphoma immunotherapy.

    PubMed

    Kumai, Takumi; Kobayashi, Hiroya; Harabuchi, Yasuaki

    2016-01-01

    Extranodal natural killer/T-cell lymphoma, nasal type (NKTL) is a rare but highly aggressive Epstein-Barr virus-related malignancy, which mainly occurs in nasopharyngeal and nasal/paranasal areas. In addition to its high prevalence in Asian, Central American and South American populations, its incidence rate has been gradually increasing in Western countries. The current mainstay of treatment is a combination of multiple chemotherapies and irradiation. Although chemoradiotherapy can cure NKTL, it often causes severe and fatal adverse events. Because a growing body of evidence suggests that immunotherapy is effective against hematological malignancies, this treatment could provide an alternative to chemoradiotherapy for treatment of NKTL. In this review, we focus on how recent findings could be used to develop efficient immunotherapies against NKTL.

  20. Endocytosis and Intracellular Trafficking of Human Natural Killer Cell Receptors

    PubMed Central

    Masilamani, Madhan; Peruzzi, Giovanna; Borrego, Francisco; Coligan, John E.

    2009-01-01

    Natural killer (NK) cells play a vital role in the defense against viral infections and tumor development. NK cell function is primarily regulated by the sum of signals from a broad array of activation and inhibitory receptors. Key to generating the input level of either activating or inhibitory signals is the maintenance of receptor expression levels on the cell surface. Although the mechanisms of endocytosis and trafficking for some cell surface receptors, such as transferrin receptor, and certain immune receptors, are very well known, that is not the situation for receptors expressed by NK cells. Recent studies have uncovered that endocytosis and trafficking routes characteristic for specific activation and inhibitory receptors can regulate the functional responses of NK cells. In this review, we summarize the current knowledge of receptor endocytosis and trafficking, and integrate this with our current understanding of NK cell receptor trafficking. PMID:19719476

  1. Osteoporosis: incidence, prevention, and treatment of the silent killer.

    PubMed

    Parsons, Lynn C

    2005-03-01

    Osteoporosis is a nationwide health care concern affecting millions of Americans. Health care dollars to prevent and treat osteoporosis are needed. Osteoporosis-related injuries and resulting disabilities, and consequent admissions to hospitals, nursing homes, and long-term care facilities is costing billions of dollars for care and treatment. Healthy lifestyle choices including vitamin and mineral therapy; safe home environments; a diet replete with calcium, vitamin D, and protein; weight-bearing and resistance exercises; and fall prevention programs for home-bound and hospitalized elders are needed to prevent osteoporosis-related fractures and injuries. Nurses must educate the public on osteoporosis and osteoporosis-prevention activities. Research in nursing, pharmacy, and allied health fields such as physical therapy and nutrition must expand to improve understanding of the risks associated with osteoporosis and to evaluate health-promotion and disease- prevention activities. Interdisciplinary partnerships should be established to study the issues, prevention, and treatment modalities of this "silent killer."

  2. The effects of IL-17 upon human natural killer cells.

    PubMed

    Al Omar, Suliman; Flanagan, Brian F; Almehmadi, Mazen; Christmas, Stephen E

    2013-04-01

    These experiments were designed to investigate the effects of IL-17 upon the phenotype and function of human Natural Killer (NK) cells. Peripheral blood mononuclear cells from healthy subjects were cultured in the presence or absence of different combinations of IL-17s and changes in relative numbers and cell surface phenotype of NK cells and CD56+CD3+ cells measured by flow cytometry. Real time PCR was used to measure changes in expression of the cytotoxicity-related genes perforin A and granzymes A and B and IL-17 receptors. A chromium release assay was used to measure cytotoxic function against K562 tumour cells. IL-17D, IL-17A, IL-17F or the combination of both of the latter had little effect upon NK cell surface expression of Killer Immunoglobulin-like Receptors, although IL-17A modestly increased NK cell numbers. Slight but not significant increases in expression of perforin and granzymes were induced by IL-17A and/or IL-17F. Both IL-17A and D significantly increased cytotoxic function of NK cells at some E:T ratios. Similarly, numbers of NK cells induced to express CD107a after interaction with K562 cells were increased, but not significantly, by all combinations of IL-17s tested. IL-17RC was not found at the NK cell surface but was expressed at the message level and the protein detected intracellularly. NK cells are known to produce IL-17 but here we report that there is little response to this cytokine although some isoforms may moderately enhance cytotoxic function. There may therefore be some enhancement of NK cell function resulting from Th17 cell activation.

  3. On the communicative significance of whistles in wild killer whales (Orcinus orca)

    NASA Astrophysics Data System (ADS)

    Thomsen, Frank; Franck, Dierk; Ford, John

    2002-08-01

    Killer whales (Orcinus orca) use pulsed calls and whistles in underwater communication. Unlike pulsed calls, whistles have received little study and thus their function is poorly known. In this study, whistle activities of groups of individually known killer whales were compared quantitatively across behavioural categories. Acoustic recordings and simultaneous behavioural observations were made of northern resident killer whales off Vancouver Island in 1996 and 1997. Whistles were produced at greater rates than discrete calls during close-range behavioural activities than during long-range activities. They were the predominant sound-type recorded during socializing. The number of whistles per animal per minute was significantly higher during close-range behavioural activities than during long-range activities. Evidently, whistles play an important role in the close-range acoustic communication in northern resident killer whales.

  4. Killers in the Brain - Essays in Science and Technology from the Royal Institution

    NASA Astrophysics Data System (ADS)

    Day, Peter

    1999-09-01

    This fascinating and diverse selection of essays from the Royal Institution provides a glimpse of some of the most current and exciting scientific research, ranging from the global increase in asthma and allergies to neurodegenerative diseases known as "brain killers."

  5. Competing conservation objectives for predators and prey: estimating killer whale prey requirements for Chinook salmon.

    PubMed

    Williams, Rob; Krkošek, Martin; Ashe, Erin; Branch, Trevor A; Clark, Steve; Hammond, Philip S; Hoyt, Erich; Noren, Dawn P; Rosen, David; Winship, Arliss

    2011-01-01

    Ecosystem-based management (EBM) of marine resources attempts to conserve interacting species. In contrast to single-species fisheries management, EBM aims to identify and resolve conflicting objectives for different species. Such a conflict may be emerging in the northeastern Pacific for southern resident killer whales (Orcinus orca) and their primary prey, Chinook salmon (Oncorhynchus tshawytscha). Both species have at-risk conservation status and transboundary (Canada-US) ranges. We modeled individual killer whale prey requirements from feeding and growth records of captive killer whales and morphometric data from historic live-capture fishery and whaling records worldwide. The models, combined with caloric value of salmon, and demographic and diet data for wild killer whales, allow us to predict salmon quantities needed to maintain and recover this killer whale population, which numbered 87 individuals in 2009. Our analyses provide new information on cost of lactation and new parameter estimates for other killer whale populations globally. Prey requirements of southern resident killer whales are difficult to reconcile with fisheries and conservation objectives for Chinook salmon, because the number of fish required is large relative to annual returns and fishery catches. For instance, a U.S. recovery goal (2.3% annual population growth of killer whales over 28 years) implies a 75% increase in energetic requirements. Reducing salmon fisheries may serve as a temporary mitigation measure to allow time for management actions to improve salmon productivity to take effect. As ecosystem-based fishery management becomes more prevalent, trade-offs between conservation objectives for predators and prey will become increasingly necessary. Our approach offers scenarios to compare relative influence of various sources of uncertainty on the resulting consumption estimates to prioritise future research efforts, and a general approach for assessing the extent of conflict

  6. Target Strength of Southern Resident Killer Whales (Orcinus orca): Measurement and Modeling

    SciTech Connect

    Xu, Jinshan; Deng, Zhiqun; Carlson, Thomas J.; Moore, Brian

    2012-04-04

    A major criterion for tidal power licensing in Washington’s Puget Sound is the management of the risk of injury to killer whales due to collision with moving turbine blades. An active monitoring system is being proposed for killer whale detection, tracking, and alerting that links to and triggers temporary turbine shutdown when there is risk of collision. Target strength (TS) modeling of the killer whale is critical to the design and application of any active monitoring system. A 1996 study performed a high-resolution measurement of acoustic reflectivity as a function of frequency of a female bottlenose dolphin (2.2 m length) at broadside aspect and TS as a function of incident angle at 67 kHz frequency. Assuming that killer whales share similar morphology structure with the bottlenose dolphin, we extrapolated the TS of an adult killer whale 7.5 m in length at 67 kHz frequency with -8 dB at broadside aspect and -28 dB at tail side. The backscattering data from three Southern Resident killer whales were analyzed to obtain the TS measurement. These data were collected at Lime Kiln State Park using a split-beam system deployed from a boat. The TS of the killer whale at higher frequency (200 kHz) was estimated based on a three-layer model for plane wave reflection from the lung of the whale. The TS data of killer whales were in good agreement with our model. In this paper, we also discuss and explain possible causes for measurement estimation error.

  7. Competing Conservation Objectives for Predators and Prey: Estimating Killer Whale Prey Requirements for Chinook Salmon

    PubMed Central

    Williams, Rob; Krkošek, Martin; Ashe, Erin; Branch, Trevor A.; Clark, Steve; Hammond, Philip S.; Hoyt, Erich; Noren, Dawn P.; Rosen, David; Winship, Arliss

    2011-01-01

    Ecosystem-based management (EBM) of marine resources attempts to conserve interacting species. In contrast to single-species fisheries management, EBM aims to identify and resolve conflicting objectives for different species. Such a conflict may be emerging in the northeastern Pacific for southern resident killer whales (Orcinus orca) and their primary prey, Chinook salmon (Oncorhynchus tshawytscha). Both species have at-risk conservation status and transboundary (Canada–US) ranges. We modeled individual killer whale prey requirements from feeding and growth records of captive killer whales and morphometric data from historic live-capture fishery and whaling records worldwide. The models, combined with caloric value of salmon, and demographic and diet data for wild killer whales, allow us to predict salmon quantities needed to maintain and recover this killer whale population, which numbered 87 individuals in 2009. Our analyses provide new information on cost of lactation and new parameter estimates for other killer whale populations globally. Prey requirements of southern resident killer whales are difficult to reconcile with fisheries and conservation objectives for Chinook salmon, because the number of fish required is large relative to annual returns and fishery catches. For instance, a U.S. recovery goal (2.3% annual population growth of killer whales over 28 years) implies a 75% increase in energetic requirements. Reducing salmon fisheries may serve as a temporary mitigation measure to allow time for management actions to improve salmon productivity to take effect. As ecosystem-based fishery management becomes more prevalent, trade-offs between conservation objectives for predators and prey will become increasingly necessary. Our approach offers scenarios to compare relative influence of various sources of uncertainty on the resulting consumption estimates to prioritise future research efforts, and a general approach for assessing the extent of conflict

  8. Fourier models and the loci of adaptation.

    PubMed

    Makous, W L

    1997-09-01

    First measures of sensitivity and the need for a model to interpret them are addressed. Then modeling in the Fourier domain is promoted by a demonstration of how much an approach explains spatial sensitization and its dependence on luminance. Then the retinal illuminance and receptor absorptions produced by various stimuli are derived to foster interpretation of the neural mechanisms underlying various psychophysical phenomena. Finally, the sequence and the anatomical loci of the processes controlling visual sensitivity are addressed. It is concluded that multiplicative adaptation often has effects identical to response compression followed by subtractive adaptation and that, perhaps as a consequence, there is no evidence of retinal gain changes in human cone vision until light levels are well above those available in natural scenes and in most contemporary psychophysical experiments; that contrast gain control fine tunes sensitivity to patterns at all luminances; and that response compression, modulated by subtractive adaptation, predominates in the control of sensitivity in human cone vision.

  9. Pollen Killer Gene S35 Function Requires Interaction with an Activator That Maps Close to S24, Another Pollen Killer Gene in Rice.

    PubMed

    Kubo, Takahiko; Yoshimura, Atsushi; Kurata, Nori

    2016-01-01

    Pollen killer genes disable noncarrier pollens, and are responsible for male sterility and segregation distortion in hybrid populations of distantly related plant species. The genetic networks and the molecular mechanisms underlying the pollen killer system remain largely unknown. Two pollen killer genes, S24 and S35, have been found in an intersubspecific cross of Oryza sativa ssp. indica and japonica The effect of S24 is counteracted by an unlinked locus EFS Additionally, S35 has been proposed to interact with S24 to induce pollen sterility. These genetic interactions are suggestive of a single S24-centric genetic pathway (EFS-S24-S35) for the pollen killer system. To examine this hypothetical genetic pathway, the S35 and the S24 regions were further characterized and genetically dissected in this study. Our results indicated that S35 causes pollen sterility independently of both the EFS and S24 genes, but is dependent on a novel gene close to the S24 locus, named incentive for killing pollen (INK). We confirmed the phenotypic effect of the INK gene separately from the S24 gene, and identified the INK locus within an interval of less than 0.6 Mb on rice chromosome 5. This study characterized the genetic effect of the two independent genetic pathways of INK-S35 and EFS-S24 in indica-japonica hybrid progeny. Our results provide clear evidence that hybrid male sterility in rice is caused by several pollen killer networks with multiple factors positively and negatively regulating pollen killer genes.

  10. Pollen Killer Gene S35 Function Requires Interaction with an Activator That Maps Close to S24, Another Pollen Killer Gene in Rice

    PubMed Central

    Kubo, Takahiko; Yoshimura, Atsushi; Kurata, Nori

    2016-01-01

    Pollen killer genes disable noncarrier pollens, and are responsible for male sterility and segregation distortion in hybrid populations of distantly related plant species. The genetic networks and the molecular mechanisms underlying the pollen killer system remain largely unknown. Two pollen killer genes, S24 and S35, have been found in an intersubspecific cross of Oryza sativa ssp. indica and japonica. The effect of S24 is counteracted by an unlinked locus EFS. Additionally, S35 has been proposed to interact with S24 to induce pollen sterility. These genetic interactions are suggestive of a single S24-centric genetic pathway (EFS–S24–S35) for the pollen killer system. To examine this hypothetical genetic pathway, the S35 and the S24 regions were further characterized and genetically dissected in this study. Our results indicated that S35 causes pollen sterility independently of both the EFS and S24 genes, but is dependent on a novel gene close to the S24 locus, named incentive for killing pollen (INK). We confirmed the phenotypic effect of the INK gene separately from the S24 gene, and identified the INK locus within an interval of less than 0.6 Mb on rice chromosome 5. This study characterized the genetic effect of the two independent genetic pathways of INK–S35 and EFS–S24 in indica–japonica hybrid progeny. Our results provide clear evidence that hybrid male sterility in rice is caused by several pollen killer networks with multiple factors positively and negatively regulating pollen killer genes. PMID:27172610

  11. Differences in acoustic features of vocalizations produced by killer whales cross-socialized with bottlenose dolphins.

    PubMed

    Musser, Whitney B; Bowles, Ann E; Grebner, Dawn M; Crance, Jessica L

    2014-10-01

    Limited previous evidence suggests that killer whales (Orcinus orca) are capable of vocal production learning. However, vocal contextual learning has not been studied, nor the factors promoting learning. Vocalizations were collected from three killer whales with a history of exposure to bottlenose dolphins (Tursiops truncatus) and compared with data from seven killer whales held with conspecifics and nine bottlenose dolphins. The three whales' repertoires were distinguishable by a higher proportion of click trains and whistles. Time-domain features of click trains were intermediate between those of whales held with conspecifics and dolphins. These differences provided evidence for contextual learning. One killer whale spontaneously learned to produce artificial chirps taught to dolphins; acoustic features fell within the range of inter-individual differences among the dolphins. This whale also produced whistles similar to a stereotyped whistle produced by one dolphin. Thus, results provide further support for vocal production learning and show that killer whales are capable of contextual learning. That killer whales produce similar repertoires when associated with another species suggests substantial vocal plasticity and motivation for vocal conformity with social associates. PMID:25324098

  12. K2 killer toxin-induced physiological changes in the yeast Saccharomyces cerevisiae.

    PubMed

    Orentaite, Irma; Poranen, Minna M; Oksanen, Hanna M; Daugelavicius, Rimantas; Bamford, Dennis H

    2016-03-01

    Saccharomyces cerevisiae cells produce killer toxins, such as K1, K2 and K28, that can modulate the growth of other yeasts giving advantage for the killer strains. Here we focused on the physiological changes induced by K2 toxin on a non-toxin-producing yeast strain as well as K1, K2 and K28 killer strains. Potentiometric measurements were adjusted to observe that K2 toxin immediately acts on the sensitive cells leading to membrane permeability. This correlated with reduced respiration activity, lowered intracellular ATP content and decrease in cell viability. However, we did not detect any significant ATP leakage from the cells treated by killer toxin K2. Strains producing heterologous toxins K1 and K28 were less sensitive to K2 than the non-toxin producing one suggesting partial cross-protection between the different killer systems. This phenomenon may be connected to the observed differences in respiratory activities of the killer strains and the non-toxin-producing strain at low pH. This might also have practical consequences in wine industry; both as beneficial ones in controlling contaminating yeasts and non-beneficial ones causing sluggish fermentation.

  13. Habitat-based PCB environmental quality criteria for the protection of endangered killer whales (Orcinus orca).

    PubMed

    Alava, Juan José; Ross, Peter S; Lachmuth, Cara; Ford, John K B; Hickie, Brendan E; Gobas, Frank A P C

    2012-11-20

    The development of an area-based polychlorinated biphenyl (PCB) food-web bioaccumulation model enabled a critical evaluation of the efficacy of sediment quality criteria and prey tissue residue guidelines in protecting fish-eating resident killer whales of British Columbia and adjacent waters. Model-predicted and observed PCB concentrations in resident killer whales and Chinook salmon were in good agreement, supporting the model's application for risk assessment and criteria development. Model application shows that PCB concentrations in the sediments from the resident killer whale's Critical Habitats and entire foraging range leads to PCB concentrations in most killer whales that exceed PCB toxicity threshold concentrations reported for marine mammals. Results further indicate that current PCB sediment quality and prey tissue residue criteria for fish-eating wildlife are not protective of killer whales and are not appropriate for assessing risks of PCB-contaminated sediments to high trophic level biota. We present a novel methodology for deriving sediment quality criteria and tissue residue guidelines that protect biota of high trophic levels under various PCB management scenarios. PCB concentrations in sediments and in prey that are deemed protective of resident killer whale health are much lower than current criteria values, underscoring the extreme vulnerability of high trophic level marine mammals to persistent and bioaccumulative contaminants. PMID:23098163

  14. [Additive effect of marihuana and retrovirus in the anergy of natural killer cells in mice].

    PubMed

    Ongrádi, J; Specter, S; Horváth, A; Friedman, H

    1999-01-10

    Among the immunosuppressive effects of marijuana, impairment of natural killer cell activity is significant. HIV also inhibits these cells. Friend leukemia virus complex and its helper component Rowson-Parr virus induce early immunosuppression in mice resembling human AIDS, and late leukemia, providing a small animal AIDS model. Leukemia susceptible BALB/c and resistant C57BL/6 mice were infected with these viruses. At different time points, their natural killer cells separated from spleens were treated with 0 to 10 micrograms/ml tetrahydrocannabinol, subsequently mixed with Yac-1 target cells for 4 and 18 h. The natural killer cell activity in both mouse strains infected by either virus complex or helper virus weakened on days 2 to 4 postinfection, normalized by day 8 and enhanced on days 11 to 14. Natural killer cell activity upon the effect of low concentration (1.0 to 2.5 micrograms/ml) of tetrahydrocannabinol slightly increased in BALB/c, was unaffected in C57BL/6, especially in 18 h assays. In the combined effects of marijuana and retrovirus, damages by marijuana dominated over those of retroviruses. Inhibition or reactive enhancement of natural killer cell activity on the effect of viruses are similar to those of infected but marijuana-free counterparts, but on the level of uninfected cells treated with marijuana. The effects of marijuana and retrovirus are additive resulting in anergy of natural killer cells.

  15. Differences in acoustic features of vocalizations produced by killer whales cross-socialized with bottlenose dolphins.

    PubMed

    Musser, Whitney B; Bowles, Ann E; Grebner, Dawn M; Crance, Jessica L

    2014-10-01

    Limited previous evidence suggests that killer whales (Orcinus orca) are capable of vocal production learning. However, vocal contextual learning has not been studied, nor the factors promoting learning. Vocalizations were collected from three killer whales with a history of exposure to bottlenose dolphins (Tursiops truncatus) and compared with data from seven killer whales held with conspecifics and nine bottlenose dolphins. The three whales' repertoires were distinguishable by a higher proportion of click trains and whistles. Time-domain features of click trains were intermediate between those of whales held with conspecifics and dolphins. These differences provided evidence for contextual learning. One killer whale spontaneously learned to produce artificial chirps taught to dolphins; acoustic features fell within the range of inter-individual differences among the dolphins. This whale also produced whistles similar to a stereotyped whistle produced by one dolphin. Thus, results provide further support for vocal production learning and show that killer whales are capable of contextual learning. That killer whales produce similar repertoires when associated with another species suggests substantial vocal plasticity and motivation for vocal conformity with social associates.

  16. Habitat-based PCB environmental quality criteria for the protection of endangered killer whales (Orcinus orca).

    PubMed

    Alava, Juan José; Ross, Peter S; Lachmuth, Cara; Ford, John K B; Hickie, Brendan E; Gobas, Frank A P C

    2012-11-20

    The development of an area-based polychlorinated biphenyl (PCB) food-web bioaccumulation model enabled a critical evaluation of the efficacy of sediment quality criteria and prey tissue residue guidelines in protecting fish-eating resident killer whales of British Columbia and adjacent waters. Model-predicted and observed PCB concentrations in resident killer whales and Chinook salmon were in good agreement, supporting the model's application for risk assessment and criteria development. Model application shows that PCB concentrations in the sediments from the resident killer whale's Critical Habitats and entire foraging range leads to PCB concentrations in most killer whales that exceed PCB toxicity threshold concentrations reported for marine mammals. Results further indicate that current PCB sediment quality and prey tissue residue criteria for fish-eating wildlife are not protective of killer whales and are not appropriate for assessing risks of PCB-contaminated sediments to high trophic level biota. We present a novel methodology for deriving sediment quality criteria and tissue residue guidelines that protect biota of high trophic levels under various PCB management scenarios. PCB concentrations in sediments and in prey that are deemed protective of resident killer whale health are much lower than current criteria values, underscoring the extreme vulnerability of high trophic level marine mammals to persistent and bioaccumulative contaminants.

  17. Comparison of echolocation clicks from geographically sympatric killer whales and long-finned pilot whales (L).

    PubMed

    Eskesen, Ida G; Wahlberg, Magnus; Simon, Malene; Larsen, Ole Næsbye

    2011-07-01

    The source characteristics of biosonar signals from sympatric killer whales and long-finned pilot whales in a Norwegian fjord were compared. A total of 137 pilot whale and more than 2000 killer whale echolocation clicks were recorded using a linear four-hydrophone array. Of these, 20 pilot whale clicks and 28 killer whale clicks were categorized as being recorded on-axis. The clicks of pilot whales had a mean apparent source level of 196 dB re 1 μPa pp and those of killer whales 203 dB re 1 μPa pp. The duration of pilot whale clicks was significantly shorter (23 μs, S.E.=1.3) and the centroid frequency significantly higher (55 kHz, S.E.=2.1) than killer whale clicks (duration: 41 μs, S.E.=2.6; centroid frequency: 32 kHz, S.E.=1.5). The rate of increase in the accumulated energy as a function of time also differed between clicks from the two species. The differences in duration, frequency, and energy distribution may have a potential to allow for the distinction between pilot and killer whale clicks when using automated detection routines for acoustic monitoring.

  18. Hungarian population data on seven PCR-based loci.

    PubMed

    Budowle, B; Woller, J; Koons, B W; Furedi, S; Errera, J D; Padar, Z

    1996-07-01

    Hungarian population data for the loci LDLR, GYPA, HBGG, D7S8, Gc, HLA-DQA1, and D1S80 were generated. The genotype frequency distributions for the loci do not deviate from Hardy Weinberg expectations. Furthermore, there was little evidence for departures from expectations of independence between the loci. Using a test for homogeneity all the loci were similar between two Hungarian population samples and only the HLA-DQA1 locus was statistically different between Hungarians and US Caucasians. There generally would be little forensic differences, whether a Hungarian or a US Caucasian database was used, for estimating multiple locus profile frequencies for the seven PCR-based loci. PMID:8754580

  19. Development of eighteen microsatellite loci in walleye (Sander vitreus)

    USGS Publications Warehouse

    Coykendall, Dolly K.; Morrison, Cheryl L.; Stott, Wendy; Springmann, Marcus J.

    2014-01-01

    A suite of tri- and tetra-nucleotide microsatellite loci were developed for walleye (Sander vitreus) from 454 pyrosequencing data. Eighteen of the 50 primer sets tested amplified consistently in 35 walleye from two lakes on Isle Royale, Lake Superior: Chickenbone Lake and Whittlesey Lake. The loci displayed moderate levels of allelic diversity (average 5.5 alleles/locus) and heterozygosity (average 35.8 %). Levels of genetic diversity were sufficient to produce unique multi-locus genotypes and detect phylogeographic structuring as individuals assigned back to their population of origin. Cross-species amplification within S. canadensis (sauger) was successful for 15 loci, and 11 loci were diagnostic to species. The loci characterized here will be useful for detecting fine-scale spatial structuring, resolving the taxonomic status of Sander species and sub-species, and detecting walleye/sauger hybrids.

  20. Killer activity of Saccharomyces cerevisiae strains: partial characterization and strategies to improve the biocontrol efficacy in winemaking.

    PubMed

    de Ullivarri, Miguel Fernández; Mendoza, Lucía M; Raya, Raúl R

    2014-11-01

    Killer yeasts are considered potential biocontrol agents to avoid or reduce wine spoilage by undesirable species. In this study two Saccharomyces cerevisiae strains (Cf8 and M12) producing killer toxin were partially characterized and new strategies to improve their activity in winemaking were evaluated. Killer toxins were characterized by biochemical tests and growth inhibition of sensitive yeasts. Also genes encoding killer toxin were detected in the chromosomes of both strains by PCR. Both toxins showed optimal activity and production at conditions used during the wine-making process (pH 3.5 and temperatures of 15-25 °C). In addition, production of both toxins was higher when a nitrogen source was added. To improve killer activity different strategies of inoculation were studied, with the sequential inoculation of killer strains the best combination to control the growth of undesired yeasts. Sequential inoculation of Cf8-M12 showed a 45 % increase of killer activity on sensitive S. cerevisiae and spoilage yeasts. In the presence of ethanol (5-12 %) and SO2 (50 mg/L) the killer activity of both toxins was increased, especially for toxin Cf8. Characteristics of both killer strains support their future application as starter cultures and biocontrol agents to produce wines of controlled quality.

  1. Longitudinal evaluation of leukocyte transcripts in killer whales (Orcinus Orca)

    USGS Publications Warehouse

    Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra; McBain, James; Dold, Christopher; Stott, Jeffrey L.

    2016-01-01

    Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify “insults” and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The

  2. Longitudinal evaluation of leukocyte transcripts in killer whales (Orcinus Orca).

    PubMed

    Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra T; McBain, James; Dold, Christopher; Stott, Jeffrey L

    2016-07-01

    Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify "insults" and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The immunologic

  3. Longitudinal evaluation of leukocyte transcripts in killer whales (Orcinus Orca).

    PubMed

    Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra T; McBain, James; Dold, Christopher; Stott, Jeffrey L

    2016-07-01

    Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify "insults" and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The immunologic

  4. Therapeutic depletion of natural killer cells controls persistent infection.

    PubMed

    Waggoner, Stephen N; Daniels, Keith A; Welsh, Raymond M

    2014-02-01

    Persistent viral infections are associated with host and viral factors that impair effective antiviral immunity. Natural killer (NK) cells contribute to establishment of persistent lymphocytic choriomeningitis virus (LCMV) infection in mice through suppression of virus-specific T cell responses during the first few days of infection, but NK cell depletion during those early time points can enable severe T cell-mediated immune pathology and death of the host. Here we show that long after their peak in cytolytic activation, NK cells continue to support viral persistence at later times of infection. Delayed depletion of NK cells, 2 to 3 weeks after infection, enhanced virus-specific T cell responses and viral control. This enhancing effect of delayed NK cell depletion on antiviral immunity, in contrast to early NK cell depletion, was not associated with increased morbidity and mortality, and mice quickly regained weight after treatment. The efficacy of the depletion depended in part upon the size of the original virus inoculum, the viral load at the time of depletion, and the presence of CD4 T cells. Each of these factors is an important contributor to the degree of CD8 T cell dysfunction during viral persistence. Thus, NK cells may continuously contribute to exhaustion of virus-specific T cells during chronic infection, possibly by depleting CD4 T cells. Targeting of NK cells could thus be considered in combination with blockade of other immunosuppressive pathways, such as the interleukin-10 (IL-10) and programmed death 1 (PD-1) pathways, as a therapy to cure chronic human infections, including those with HIV or hepatitis C virus. IMPORTANCE Persistent virus infections are a major threat to global human health. The capacity of viruses, including HIV and hepatitis C virus, to overwhelm or subvert host immune responses contributes to a prolonged state of dampened antiviral immune functionality, which in turn facilitates viral persistence. Recent efforts have focused on

  5. Design and operation specifications of an active monitoring system for detecting southern resident killer whales

    SciTech Connect

    Deng, Zhiqun; Carlson, Thomas J.; Xu, Jinshan; Martinez, Jayson J.; Weiland, Mark A.; Mueller, Robert P.; Myers, Joshua R.; Jones, Mark E.

    2011-09-30

    Before final approval is given to the Snohomish County Public Utility District No. 1 for deploying the first tidal power devices in the United States in an open water environment, a system to manage the potential risk of injury to killer whales due to collision with moving turbine blades must be demonstrated. The Pacific Northwest National Laboratory (PNNL) is tasked with establishing the performance requirements for, constructing, and testing a prototype marine animal alert system for triggering temporary turbine shutdown when there is risk of collision with a killer whale. To develop a system that relies on active sonar two critical areas must be investigated - the target strength of killer whales and the frequency content of commercially available active sonar units. PNNL studied three target strength models: a simple model, the Fourier matching model, and the Kirchoff-ray mode model. Using target strength measurements of bottlenose dolphins obtained by previous researchers and assuming killer whales share similar morphology and structure, PNNL extrapolated the target strength of an adult killer whale 7.5 m in length at a frequency of 67 kHz. To study the frequency content of a commercially available sonar unit, direct measurements of the signal transmitted by the sonar were obtained by using a hydrophone connected to a data acquisition system in both laboratory and field conditions. The measurements revealed that in addition to the primary frequency of 200 kHz, there is a secondary frequency component at 90 kHz, which is within the hearing range of killer whales. The amplitude of the 90-kHz frequency component is above the hearing threshold of killer whales but below the threshold for potential injuries.

  6. Genetic loci for retinal arteriolar microcirculation.

    PubMed

    Sim, Xueling; Jensen, Richard A; Ikram, M Kamran; Cotch, Mary Frances; Li, Xiaohui; MacGregor, Stuart; Xie, Jing; Smith, Albert Vernon; Boerwinkle, Eric; Mitchell, Paul; Klein, Ronald; Klein, Barbara E K; Glazer, Nicole L; Lumley, Thomas; McKnight, Barbara; Psaty, Bruce M; de Jong, Paulus T V M; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; van Duijn, Cornelia M; Aspelund, Thor; Eiriksdottir, Gudny; Harris, Tamara B; Jonasson, Fridbert; Launer, Lenore J; Attia, John; Baird, Paul N; Harrap, Stephen; Holliday, Elizabeth G; Inouye, Michael; Rochtchina, Elena; Scott, Rodney J; Viswanathan, Ananth; Li, Guo; Smith, Nicholas L; Wiggins, Kerri L; Kuo, Jane Z; Taylor, Kent D; Hewitt, Alex W; Martin, Nicholas G; Montgomery, Grant W; Sun, Cong; Young, Terri L; Mackey, David A; van Zuydam, Natalie R; Doney, Alex S F; Palmer, Colin N A; Morris, Andrew D; Rotter, Jerome I; Tai, E Shyong; Gudnason, Vilmundur; Vingerling, Johannes R; Siscovick, David S; Wang, Jie Jin; Wong, Tien Y

    2013-01-01

    Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.

  7. New basal cell carcinoma susceptibility loci

    PubMed Central

    Stacey, Simon N.; Helgason, Hannes; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A.; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G.; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M.; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T.; Halldorsson, Bjarni V.; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I.; Gudbjartsson, Daniel F.; Olafsson, Jon H.; Stefansson, Kari

    2015-01-01

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10−12), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10−9), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10−12) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10−16). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained. PMID:25855136

  8. Naturally segregating loci exhibit epistasis for fitness

    PubMed Central

    Monnahan, Patrick J.; Kelly, John K.

    2015-01-01

    The extent to which gene interaction or epistasis contributes to fitness variation within populations remains poorly understood, despite its importance to a myriad of evolutionary questions. Here, we report a multi-year field study estimating fitness of Mimulus guttatus genetic lines in which pairs of naturally segregating loci exist in an otherwise uniform background. An allele at QTL x5b—a locus originally mapped for its effect on flower size—positively affects survival if combined with one genotype at quantitative trait locus x10a (aa) but has negative effects when combined with the other genotypes (Aa and AA). The viability differences between genotypes parallel phenotypic differences for the time and node at which a plant flowers. Viability is negatively correlated with fecundity across genotypes, indicating antagonistic pleiotropy for fitness components. This trade-off reduces the genetic variance for total fitness relative to the individual fitness components and thus may serve to maintain variation. Additionally, we find that the effects of each locus and their interaction often vary with the environment. PMID:26246336

  9. Genetic loci for retinal arteriolar microcirculation.

    PubMed

    Sim, Xueling; Jensen, Richard A; Ikram, M Kamran; Cotch, Mary Frances; Li, Xiaohui; MacGregor, Stuart; Xie, Jing; Smith, Albert Vernon; Boerwinkle, Eric; Mitchell, Paul; Klein, Ronald; Klein, Barbara E K; Glazer, Nicole L; Lumley, Thomas; McKnight, Barbara; Psaty, Bruce M; de Jong, Paulus T V M; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; van Duijn, Cornelia M; Aspelund, Thor; Eiriksdottir, Gudny; Harris, Tamara B; Jonasson, Fridbert; Launer, Lenore J; Attia, John; Baird, Paul N; Harrap, Stephen; Holliday, Elizabeth G; Inouye, Michael; Rochtchina, Elena; Scott, Rodney J; Viswanathan, Ananth; Li, Guo; Smith, Nicholas L; Wiggins, Kerri L; Kuo, Jane Z; Taylor, Kent D; Hewitt, Alex W; Martin, Nicholas G; Montgomery, Grant W; Sun, Cong; Young, Terri L; Mackey, David A; van Zuydam, Natalie R; Doney, Alex S F; Palmer, Colin N A; Morris, Andrew D; Rotter, Jerome I; Tai, E Shyong; Gudnason, Vilmundur; Vingerling, Johannes R; Siscovick, David S; Wang, Jie Jin; Wong, Tien Y

    2013-01-01

    Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5×10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11×10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined. PMID:23776548

  10. Multiplicity and plasticity of natural killer cell signaling pathways

    PubMed Central

    Chiesa, Sabrina; Mingueneau, Michael; Fuseri, Nicolas; Malissen, Bernard; Raulet, David H.; Malissen, Marie; Vivier, Eric; Tomasello, Elena

    2006-01-01

    Natural killer (NK) cells express an array of activating receptors that associate with DAP12 (KARAP), CD3ζ, and/or FcRγ ITAM (immunoreceptor tyrosine-based activation motif)–bearing signaling subunits. In T and mast cells, ITAM-dependent signals are integrated by critical scaffolding elements such as LAT (linker for activation of T cells) and NTAL (non–T-cell activation linker). Using mice that are deficient for ITAM-bearing molecules, LAT or NTAL, we show that NK cell cytotoxicity and interferon-γ secretion are initiated by ITAM-dependent and -independent as well as LAT/NTAL-dependent and -independent pathways. The role of these various signaling circuits depends on the target cell as well as on the activation status of the NK cell. The multiplicity and the plasticity of the pathways that initiate NK cell effector functions contrast with the situation in T cells and B cells and provide an explanation for the resiliency of NK cell effector functions to various pharmacologic inhibitors and genetic mutations in signaling molecules. PMID:16291591

  11. Natural killer cell activity in cigarette smokers and asbestos workers

    SciTech Connect

    Ginns, L.C.; Ryu, J.H.; Rogol, P.R.; Sprince, N.L.; Oliver, L.C.; Larsson, C.J.

    1985-06-01

    In order to evaluate the effects of cigarette smoking and asbestos exposure on cellular immunity, the authors tested a group of cigarette smokers and asbestos workers for natural killer (NK) activity in the peripheral blood. The mean NK activity in cigarette smokers was lower than in normal subjects (13.7 +/- 1.6 versus 29.0 +/- 3%; p less than 0.05). As a group, the mean NK activity for the asbestos-exposed group was also reduced compared with that of the nonsmoking control group (22.6 +/- 3.2%; p less than 0.05). When divided according to the smoking status, the asbestos workers who were nonsmokers or ex-smokers showed similar decreases in NK activity compared with normal subjects (19.5 +/- 6.2 and 21.2 +/- 4.5%, respectively; p less than 0.05). A subgroup of asbestos-exposed subjects who currently smoked showed no decrease in NK activity. The data show that NK activity is reduced in the peripheral blood of cigarette smokers and asbestos workers. The relatively normal NK activity found in asbestos workers who also smoked is unexplained. Impairment of NK activity is a potential mechanism for the increased incidence of infection and cancer in smokers and neoplasia in asbestos workers.

  12. Newtonian cell interactions shape natural killer cell education.

    PubMed

    Goodridge, Jodie P; Önfelt, Björn; Malmberg, Karl-Johan

    2015-09-01

    Newton's third law of motion states that for every action on a physical object there is an equal and opposite reaction. The dynamic change in functional potential of natural killer (NK) cells during education bears many features of such classical mechanics. Cumulative physical interactions between cells, under a constant influence of homeostatic drivers of differentiation, lead to a reactive spectrum that ultimately shapes the functionality of each NK cell. Inhibitory signaling from an array of self-specific receptors appear not only to suppress self-reactivity but also aid in the persistence of effector functions over time, thereby allowing the cell to gradually build up a functional potential. Conversely, the frequent non-cytolytic interactions between normal cells in the absence of such inhibitory signaling result in continuous stimulation of the cells and attenuation of effector function. Although an innate cell, the degree to which the fate of the NK cell is predetermined versus its ability to adapt to its own environment can be revealed through a Newtonian view of NK cell education, one which is both chronological and dynamic. As such, the development of NK cell functional diversity is the product of qualitatively different physical interactions with host cells, rather than simply the sum of their signals or an imprint based on intrinsically different transcriptional programs.

  13. Mathematics of pulsed vocalizations with application to killer whale biphonation.

    PubMed

    Brown, Judith C

    2008-05-01

    Formulas for the spectra of pulsed vocalizations for both the continuous and discrete cases are rigorously derived from basic formulas for Fourier analysis, a topic discussed qualitatively in Watkins' classic paper on "the harmonic interval" ["The harmonic interval: Fact or artifact in spectral analysis of pulse trains," in Marine Bioacoustics 2, edited by W. N. Tavogla (Pergamon, New York, 1967), pp. 15-43]. These formulas are summarized in a table for easy reference, along with most of the corresponding graphs. The case of a "pulse tone" is shown to involve multiplication of two temporal wave forms, corresponding to convolution in the frequency domain. This operation is discussed in detail and shown to be equivalent to a simpler approach using a trigonometric formula giving sum and difference frequencies. The presence of a dc component in the temporal wave form, which implies physically that there is a net positive pressure at the source, is discussed, and examples of the corresponding spectra are calculated and shown graphically. These have application to biphonation (two source signals) observed for some killer whale calls and implications for a source mechanism. A MATLAB program for synthesis of a similar signal is discussed and made available online.

  14. Type I natural killer T cells: naturally born for fighting

    PubMed Central

    Tan, Jin-quan; Xiao, Wei; Wang, Lan; He, Yu-ling

    2010-01-01

    Type І natural killer T cells (NKT cells), a subset of CD1d-restricted T cells with invariant Vαβ TCR, are characterized by prompt production of large amounts of Th1 and/or Th2 cytokines upon primary stimulation through the TCR complex. The rapid release of cytokines implies that type І NKT cells may play a critical role in modulating the upcoming immune responses, such as anti-tumor response, protection against infection, and autoimmunity. As a bridge between innate and adaptive immunity, type І NKT cells differentiate and mature upon stimulations to achieve and maintain a homeostasis. Orchestrating with other arms of adaptive immunity, type І NKT cells show strong cytotoxic effects in response to various tumors in a direct and/or indirect manner(s). This review will focus primarily on type І NKT cell development, homeostasis, and effector functions, especially in anti-tumor immunity, and followed by their potential applications in treatment of cancers. PMID:20694020

  15. The influence of natural killer cells in neuroblastoma.

    PubMed

    Reynolds, J V; Shou, J; Choi, H; Sigal, R; Ziegler, M M; Daly, J M

    1989-02-01

    Human neuroblastoma (NRB) cell lines are markedly sensitive to natural killer (NK) cell lysis in vitro, but patients with NRBs have low or absent NK activity. This study evaluated the NK sensitivity of murine NRBs (C1300 and TBJ) in the regulation of NRB growth and determined the effects of recombinant (r) interferon gamma and recombinant interleukin 2 (rIL-2). Both basal (8% +/- 3% specific cytotoxicity) and induced (20% +/- 3%) NK lyses of C1300-NRB were observed. In vivo depletion of NK cells with anti-asialo GM-1 significantly enhanced growth of C1300-NRB and decreased survival. Treatment with r-interferon gamma or rIL-2 on days 1 through 3 after C1300-NRB inoculation significantly prolonged the mean tumor latency period, decreased the tumor growth rate, and enhanced in vitro NK killing of C1300-NRB and YAC-1. The effects of r-interferon gamma and IL-2 were abrogated by pretreatment with anti-asialo GM-1. These results demonstrated that NK cells form one important component of regulation of a murine NRB, but immunomodulation with potent lymphokines requires cooperation of more than one cell type.

  16. Natural killer cells regulate eosinophilic inflammation in chronic rhinosinusitis

    PubMed Central

    Kim, Ji Heui; Choi, Go Eun; Lee, Bong-Jae; Kwon, Seog Woon; Lee, Seung-Hyo; Kim, Hun Sik; Jang, Yong Ju

    2016-01-01

    Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD2, is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD2 and its metabolite, but not PGE2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD2-dependent, rather than PGE2-dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD2, as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS. PMID:27271931

  17. Natural killer cell biology: an update and future directions.

    PubMed

    Campbell, Kerry S; Hasegawa, Jun

    2013-09-01

    Natural killer (NK) cells constitute a minor subset of normal lymphocytes that initiate innate immune responses toward tumor and virus-infected cells. They can mediate spontaneous cytotoxicity toward these abnormal cells and rapidly secrete numerous cytokines and chemokines to promote subsequent adaptive immune responses. Significant progress has been made in the past 2 decades to improve our understanding of NK cell biology. Here we review recent discoveries, including a better comprehension of the "education" of NK cells to achieve functional competence during their maturation and the discovery of "memory" responses by NK cells, suggesting that they might also contribute to adaptive immunity. The improved understanding of NK cell biology has forged greater awareness that these cells play integral early roles in immune responses. In addition, several promising clinical therapies have been used to exploit NK cell functions in treating patients with cancer. As our molecular understanding improves, these and future immunotherapies should continue to provide promising strategies to exploit the unique functions of NK cells to treat cancer, infections, and other pathologic conditions.

  18. Newtonian cell interactions shape natural killer cell education.

    PubMed

    Goodridge, Jodie P; Önfelt, Björn; Malmberg, Karl-Johan

    2015-09-01

    Newton's third law of motion states that for every action on a physical object there is an equal and opposite reaction. The dynamic change in functional potential of natural killer (NK) cells during education bears many features of such classical mechanics. Cumulative physical interactions between cells, under a constant influence of homeostatic drivers of differentiation, lead to a reactive spectrum that ultimately shapes the functionality of each NK cell. Inhibitory signaling from an array of self-specific receptors appear not only to suppress self-reactivity but also aid in the persistence of effector functions over time, thereby allowing the cell to gradually build up a functional potential. Conversely, the frequent non-cytolytic interactions between normal cells in the absence of such inhibitory signaling result in continuous stimulation of the cells and attenuation of effector function. Although an innate cell, the degree to which the fate of the NK cell is predetermined versus its ability to adapt to its own environment can be revealed through a Newtonian view of NK cell education, one which is both chronological and dynamic. As such, the development of NK cell functional diversity is the product of qualitatively different physical interactions with host cells, rather than simply the sum of their signals or an imprint based on intrinsically different transcriptional programs. PMID:26284479

  19. Utilizing Chimeric Antigen Receptors to Direct Natural Killer Cell Activity

    PubMed Central

    Hermanson, David L.; Kaufman, Dan S.

    2015-01-01

    Natural killer (NK) cells represent an attractive lymphocyte population for cancer immunotherapy due to their ability to lyse tumor targets without prior sensitization and without need for human leukocyte antigens-matching. Chimeric antigen receptors (CARs) are able to enhance lymphocyte targeting and activation toward diverse malignancies. CARs consist of an external recognition domain (typically a small chain variable fragment) directed at a specific tumor antigen that is linked with one or more intracellular signaling domains that mediate lymphocyte activation. Most CAR studies have focused on their expression in T cells. However, use of CARs in NK cells is starting to gain traction because they provide a method to redirect these cells more specifically to target refractory cancers. CAR-mediated anti-tumor activity has been demonstrated using NK cell lines, as well as NK cells isolated from peripheral blood, and NK cells produced from human pluripotent stem cells. This review will outline the CAR constructs that have been reported in NK cells with a focus on comparing the use of different signaling domains in combination with other co-activating domains. PMID:25972867

  20. Natural Killer Cell Mediated Cytotoxic Responses in the Tasmanian Devil

    PubMed Central

    Brown, Gabriella K.; Kreiss, Alexandre; Lyons, A. Bruce; Woods, Gregory M.

    2011-01-01

    The Tasmanian devil (Sarcophilus harrisii), the world's largest marsupial carnivore, is under threat of extinction following the emergence of an infectious cancer. Devil facial tumour disease (DFTD) is spread between Tasmanian devils during biting. The disease is consistently fatal and devils succumb without developing a protective immune response. The aim of this study was to determine if Tasmanian devils were capable of forming cytotoxic antitumour responses and develop antibodies against DFTD cells and foreign tumour cells. The two Tasmanian devils immunised with irradiated DFTD cells did not form cytotoxic or humoral responses against DFTD cells, even after multiple immunisations. However, following immunisation with xenogenic K562 cells, devils did produce cytotoxic responses and antibodies against this foreign tumour cell line. The cytotoxicity appeared to occur through the activity of natural killer (NK) cells in an antibody dependent manner. Classical NK cell responses, such as innate killing of DFTD and foreign cancer cells, were not observed. Cells with an NK-like phenotype comprised approximately 4 percent of peripheral blood mononuclear cells. The results of this study suggest that Tasmanian devils have NK cells with functional cytotoxic pathways. Although devil NK cells do not directly recognise DFTD cancer cells, the development of antibody dependent cell-mediated cytotoxicity presents a potential pathway to induce cytotoxic responses against the disease. These findings have positive implications for future DFTD vaccine research. PMID:21957452

  1. Advantages and applications of CAR-expressing natural killer cells

    PubMed Central

    Glienke, Wolfgang; Esser, Ruth; Priesner, Christoph; Suerth, Julia D.; Schambach, Axel; Wels, Winfried S.; Grez, Manuel; Kloess, Stephan; Arseniev, Lubomir; Koehl, Ulrike

    2015-01-01

    In contrast to donor T cells, natural killer (NK) cells are known to mediate anti-cancer effects without the risk of inducing graft-versus-host disease (GvHD). In order to improve cytotoxicity against resistant cancer cells, auspicious efforts have been made with chimeric antigen receptor (CAR) expressing T- and NK cells. These CAR-modified cells express antigen receptors against tumor-associated surface antigens, thus redirecting the effector cells and enhancing tumor-specific immunosurveillance. However, many cancer antigens are also expressed on healthy tissues, potentially leading to off tumor/on target toxicity by CAR-engineered cells. In order to control such potentially severe side effects, the insertion of suicide genes into CAR-modified effectors can provide a means for efficient depletion of these cells. While CAR-expressing T cells have entered successfully clinical trials, experience with CAR-engineered NK cells is mainly restricted to pre-clinical investigations and predominantly to NK cell lines. In this review we summarize the data on CAR expressing NK cells focusing on the possible advantage using these short-lived effector cells and discuss the necessity of suicide switches. Furthermore, we address the compliance of such modified NK cells with regulatory requirements as a new field in cellular immunotherapy. PMID:25729364

  2. Natural killer cells in patients with polycythemia vera.

    PubMed

    Sanchez, Carole; Baier, Céline; Colle, Julien G; Chelbi, Rabie; Rihet, Pascal; Le Treut, Thérèse; Imbert, Jean; Sébahoun, Gérard; Venton, Geoffroy; Costello, Régis T

    2015-09-01

    Natural killer cells (NK) are pivotal cells of innate immunity. They are potent antileukemic cytotoxic effectors. A defect in their cytotoxicity has been described in some hematopoietic malignancies such as acute myeloid leukemia, multiple myeloma and myelodysplastic syndromes. This defect is at least partially linked to a decreased or absent expression of some activating NK cells molecules, more particularly the so-called natural cytotoxicity receptors. In the present study, we more particularly focused our attention on NK cells of polycythemia vera, a myeloproliferative disease characterized by the presence of mutated JAK2 tyrosine kinase. The polymerase chain reaction analysis of NK cells from patients showed that they expressed the mutated form of JAK2. In polycythemia vera the proportion of NK was increased compared to healthy donors. The proliferative and cytotoxic abilities of NK cells from patients were similar to healthy donors. Expression of activating or inhibitory receptors was comparable in patients and donors, with nonetheless an imbalance for the inhibitory form of the CD158a,h couple of receptors in patients. Finally, the transcriptomic profile analysis clearly identified a discriminant signature between NK cells from patients and donors that could putatively be the consequence of abnormal continuous activation of mutated JAK2.

  3. rRNA fragmentation induced by a yeast killer toxin.

    PubMed

    Kast, Alene; Klassen, Roland; Meinhardt, Friedhelm

    2014-02-01

    Virus like dsDNA elements (VLE) in yeast were previously shown to encode the killer toxins PaT and zymocin, which target distinct tRNA species via specific anticodon nuclease (ACNase) activities. Here, we characterize a third member of the VLE-encoded toxins, PiT from Pichia inositovora, and identify PiOrf4 as the cytotoxic subunit by conditional expression in Saccharomyces cerevisiae. In contrast to the tRNA targeting toxins, however, neither a change of the wobble uridine modification status by introduction of elp3 or trm9 mutations nor tRNA overexpression rescued from PiOrf4 toxicity. Consistent with a distinct RNA target, expression of PiOrf4 causes specific fragmentation of the 25S and 18S rRNA. A stable cleavage product comprising the first ∼ 130 nucleotides of the 18S rRNA was purified and characterized by linker ligation and subsequent reverse transcription; 3'-termini were mapped to nucleotide 131 and 132 of the 18S rRNA sequence, a region showing some similarity to the anticodon loop of tRNA(Glu)(UUC), the zymocin target. PiOrf4 residues Glu9 and His214, corresponding to catalytic sites Glu9 and His209 in the ACNase subunit of zymocin are essential for in vivo toxicity and rRNA fragmentation, raising the possibility of functionally conserved RNase modules in both proteins. PMID:24308908

  4. Determination of natural killer cell function by flow cytometry.

    PubMed Central

    Kane, K L; Ashton, F A; Schmitz, J L; Folds, J D

    1996-01-01

    Natural killer cells (NK cells) are a subset of peripheral blood lymphocytes that mediate non-major histocompatibility complex-restricted cytotoxicity of foreign target cells. The "gold standard" assay for NK cell activity has been the chromium release assay. This method is not easily performed in the clinical laboratory because of difficulties with disposal of radioactive and hazardous materials, short reagent half-lives, expense, and difficulties with assay standardization. We describe a flow cytometric assay for the clinical measurement of NK cell activity. This study compared the chromium release assay and the flow cytometric assay by using clinically relevant specimens. There were no significant differences between the two assays in the measurement of lytic activity for 17 peripheral blood specimens or in reproducibility in repeated samplings of healthy individuals. We also established a normal range of values for NK activity in healthy adults and identified a small cluster of individuals who have exceptionally high or low levels of NK activity. The flow cytometric assay was validated by testing specimens from subjects expected to have abnormally low levels of NK activity (pregnant women) and specimens from healthy individuals in whom the activity of NK cells was enhanced by exposure to interleukin-2 or alpha interferon. Treatment with these agents was associated with a significant increase in NK activity. These results confirm and extend those of others, showing that the flow cytometric assay is a viable alternative to the chromium release assay for measuring NK cell activity. PMID:8705672

  5. Human natural killer cell development in secondary lymphoid tissues.

    PubMed

    Freud, Aharon G; Yu, Jianhua; Caligiuri, Michael A

    2014-04-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34(+)CD45RA(+) hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field.

  6. Characterization of tumor infiltrating natural killer cell subset.

    PubMed

    Levi, Inbar; Amsalem, Hagai; Nissan, Aviram; Darash-Yahana, Merav; Peretz, Tamar; Mandelboim, Ofer; Rachmilewitz, Jacob

    2015-05-30

    The presence of tumor-infiltrating Natural Killer (NK) within a tumor bed may be indicative of an ongoing immune response toward the tumor. However, many studies have shown that an intense NK infiltration, is associated with advanced disease and may even facilitate cancer development. The exact role of the tumor infiltrating NK cells and the correlation between their presence and poor prognosis remains unclear. Interestingly, during pregnancy high numbers of a specific NK subset, CD56(bright)CD16(dim), are accumulated within first trimester deciduas. These decidual NK (dNK) cells are unique in their gene expression pattern secret angiogenic factors that induce vascular growth. In the present study we demonstrate a significant enrichment of a CD56(brigh)CD16(dim) NK cells within tumors. These NK cells express several dNK markers including VEGF. Hence, this study adds new insights into the identity of tumor residual NK cells, which has clear implications for the treatment of human cancer. PMID:26079948

  7. Variation in call pitch among killer whale ecotypes.

    PubMed

    Foote, Andrew D; Nystuen, Jeffrey A

    2008-03-01

    Vocal structure can vary between populations due to variation in ecology-dependent selection pressures, such as masking by background noise and the presence of eavesdroppers. Signalers can overcome these obstacles to effective communication by avoiding frequencies that overlap with background noise or the audible range of eavesdroppers. In the Northeastern Pacific three "ecotypes" of killer whale coexist in sympatry, but differ from one another in their diet and habitat use. The minimum frequency (F(min)) and the frequency containing the peak energy between 0 and 10 kHz (F(peak)) of a random sample of calls produced by a population of each ecotype was measured. The offshore ecotype produced calls with a significantly higher F(min) than the other ecotypes, which could be a strategy to avoid masking by low frequency chronic bandlimited wind noise found in the offshore environment. The resident ecotype produced calls with a significantly higher F(min) and F(peak) than the transient ecotype. This could be to reduce detection by their salmonid prey, which has a narrow band, low frequency auditory range.

  8. Natural killer (NK) cell cytotoxicity in athymic (nude) rats.

    PubMed

    Grzelak, I; Olszewski, W L; Fossum, S; Engeset, A

    1984-01-01

    The in vitro and in vivo natural killer (NK) cell activity of congenitally athymic, nude (ATH) rats and of normal, euthymic (EUTH) rats was compared. We found: a) a higher level of in vitro NK cell activity in blood, spleen and lymph nodes of ATH rats compared with their heterozygous littermates, b) in the spleen the number of NK lytic units per organ was not higher in ATH compared with EUTH whereas it was significantly higher in lymph nodes, c) a lack of age-dependence of in vitro NK cell activity tested in culture with heat inactivated fetal calf serum, d) a higher rate of in vivo elimination of target tumor cells in 4-week ATH rats compared with EUTH rats, e) an age-dependent decrease in the rate of in vivo target cell elimination in both groups, and finally, f) an age-dependent increase in the inhibitory effect of autologous serum on NK cell activity in vitro in both groups. These findings show that the blood and lymphoid organs of athymic rats contain a substantially higher proportion of NK cells, active both in vitro and in vivo against K562 tumor cells, than their euthymic littermates. In the spleen this increased proportion can be attributed to the lack of T cells, whereas in the ATH rat lymph nodes there is an absolute increase in NK cell activity, and that the decrease of cytotoxicity in vivo with age reflects the increasing inhibitory properties of autologous serum both in nude and in normal rats.

  9. Immunotherapeutic strategies targeting natural killer T cell responses in cancer.

    PubMed

    Shissler, Susannah C; Bollino, Dominique R; Tiper, Irina V; Bates, Joshua P; Derakhshandeh, Roshanak; Webb, Tonya J

    2016-08-01

    Natural killer T (NKT) cells are a unique subset of lymphocytes that bridge the innate and adaptive immune system. NKT cells possess a classic αβ T cell receptor (TCR) that is able to recognize self and foreign glycolipid antigens presented by the nonclassical class I major histocompatibility complex (MHC) molecule, CD1d. Type I NKT cells (referred to as invariant NKT cells) express a semi-invariant Vα14Jα18 TCR in mice and Vα24Jα18 TCR in humans. Type II NKT cells are CD1d-restricted T cells that express a more diverse set of TCR α chains. The two types of NKT cells often exert opposing effects especially in tumor immunity, where type II cells generally suppress tumor immunity while type I NKT cells can enhance anti-tumor immune responses. In this review, we focus on the role of NKT cells in cancer. We discuss their effector and suppressive functions, as well as describe preclinical and clinical studies utilizing therapeutic strategies focused on harnessing their potent anti-tumor effector functions, and conclude with a discussion on potential next steps for the utilization of NKT cell-targeted therapies for the treatment of cancer. PMID:27393665

  10. Functional heterogeneity among cytotoxic clones derived from natural killer cells.

    PubMed

    Christmas, S E; Moore, M

    1987-01-01

    Clones were obtained from highly purified populations of human peripheral blood natural killer (NK) cells propagated in the presence of interleukin-2 and phytohaemagglutinin. Almost all clones were cytotoxic against standard NK targets and many were also able to kill the B lymphoblastoid cell line BSM. This latter property was not necessarily a result of the incorporation of this cell line into the feeder mixture used to derive the clones. In most cloning experiments there was a high degree of concordance between the killing of the NK targets K562 and Molt 4 by panels of clones. In some cases this extended to the killing of BSM targets but in other instances there was no relationship or even an inverse correlation between killing of BSM and other targets. In a single cloning experiment there was no relationship between killing of BSM and Raji targets. In some cases a panel of clones could be divided into two or more distinct groups based on their differential activity towards BSM and K562. Such differences were not solely due to inter-donor variation. These findings were extended by cold target inhibition experiments in which at least three types of clone were identified. In one group of clones, which was nonreactive towards BSM, cold BSM significantly enhanced the killing of K562 in a dose-dependent fashion. These experiments provide evidence for a limited degree of functional heterogeneity among clones derived from human peripheral blood NK cells.

  11. Natural killer cells in hepatitis C: Current progress

    PubMed Central

    Yoon, Joo Chun; Yang, Chang Mo; Song, Youkyong; Lee, Jae Myun

    2016-01-01

    Patients infected with the hepatitis C virus (HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairment of HCV-specific T cells is associated with the evolution of an acute infection to chronic hepatitis. While T cells are the important effector cells in adaptive immunity, natural killer (NK) cells are the critical effector cells in innate immunity to virus infections. The findings of recent studies on NK cells in hepatitis C suggest that NK cell responses are indeed important in each phase of HCV infection. In the early phase, NK cells are involved in protective immunity to HCV. The immune evasion strategies used by HCV may target NK cells and might contribute to the progression to chronic hepatitis C. NK cells may control HCV replication and modulate hepatic fibrosis in the chronic phase. Further investigations are, however, needed, because a considerable number of studies observed functional impairment of NK cells in chronic HCV infection. Interestingly, the enhanced NK cell responses during interferon-α-based therapy of chronic hepatitis C indicate successful treatment. In spite of the advances in research on NK cells in hepatitis C, establishment of more physiological HCV infection model systems is needed to settle unsolved controversies over the role and functional status of NK cells in HCV infection. PMID:26819513

  12. Isolation and characterization of microsatellite loci in Quercus fabri (Fagaceae).

    PubMed

    Xiao, Z Z; Chen, W W; Bao, W; Wang, R; Li, Y Y

    2016-01-01

    Quercus fabri is a pioneer species of secondary succession in evergreen broadleaved forests in China. In this study, we isolated and developed 12 polymorphic and 2 monomorphic microsatellite loci for Q. fabri using the biotin-streptavidin capture method. We characterized 12 polymorphic loci in 52 individuals from two populations. The number of alleles per locus ranged from 3 to 23. The observed and expected heterozygosities per locus were 0.033-0.773 and 0.138-0.924, respectively. These microsatellite loci will facilitate the studies on genetic variation, mating system, and gene flow of Q. fabri. PMID:27420954

  13. Characterization of microsatellite loci isolated in Mountain Plover (Charadrius montanus)

    USGS Publications Warehouse

    John, J. St; Kysela, R.F.; Oyler-McCance, S.J.

    2007-01-01

    Primers for 15 microsatellite loci were developed for Mountain Plover, a species whose distribution and abundance have been reduced drastically in the past 30 years. In a screen of 126 individuals collected from four breeding locales across the species' range, levels of polymorphism ranged from two to 13 alleles per locus. No two loci were found to be linked, although one locus revealed significant departures from Hardy-Weinberg equilibrium. These microsatellite loci can be used in population genetic studies, ultimately aiding in management efforts for Mountain Plover. Additionally, these markers can potentially be used in studies investigating the mating system of Mountain Plover. ?? 2007 Blackwell Publishing Ltd.

  14. Polymorphic microsatellite loci for the crimson snapper (Lutjanus erythropterus).

    PubMed

    Liu, L; Lin, L; Li, C H; Xu, S N; Liu, Y; Zhou, Y B

    2014-07-24

    We isolated and characterized 22 polymorphic microsatellite loci in Lutjanus erythropterus using a (GT)13-enriched genomic library. We found between 2 and 8 alleles per locus, with a mean of 4.85. The observed and expected heterozygosities ranged from 0.065 to 0.867 and from 0.085 to 0.832, respectively, with means of 0.461 and 0.529, respectively. Allele frequencies in three loci were found to deviate from Hardy-Weinberg equilibrium. Evidence for null alleles was found for three loci. These markers will be useful for distinguishing released captive-bred L. erythropterus individuals from wild individuals.

  15. Killer whale call frequency is similar across the oceans, but varies across sympatric ecotypes.

    PubMed

    Filatova, Olga A; Miller, Patrick J O; Yurk, Harald; Samarra, Filipa I P; Hoyt, Erich; Ford, John K B; Matkin, Craig O; Barrett-Lennard, Lance G

    2015-07-01

    Killer whale populations may differ in genetics, morphology, ecology, and behavior. In the North Pacific, two sympatric populations ("resident" and "transient") specialize on different prey (fish and marine mammals) and retain reproductive isolation. In the eastern North Atlantic, whales from the same populations have been observed feeding on both fish and marine mammals. Fish-eating North Pacific "residents" are more genetically related to eastern North Atlantic killer whales than to sympatric mammal-eating "transients." In this paper, a comparison of frequency variables in killer whale calls recorded from four North Pacific resident, two North Pacific transient, and two eastern North Atlantic populations is reported to assess which factors drive the large-scale changes in call structure. Both low-frequency and high-frequency components of North Pacific transient killer whale calls have significantly lower frequencies than those of the North Pacific resident and North Atlantic populations. The difference in frequencies could be related to ecological specialization or to the phylogenetic history of these populations. North Pacific transient killer whales may have genetically inherited predisposition toward lower frequencies that may shape their learned repertoires. PMID:26233024

  16. The utilization of forensic science and criminal profiling for capturing serial killers.

    PubMed

    White, John H; Lester, David; Gentile, Matthew; Rosenbleeth, Juliana

    2011-06-15

    Movies and nightly television shows appear to emphasize highly efficient regimens in forensic science and criminal investigative analysis (profiling) that result in capturing serial killers and other perpetrators of homicide. Although some of the shows are apocryphal and unrealistic, they reflect major advancements that have been made in the fields of forensic science and criminal psychology during the past two decades that have helped police capture serial killers. Some of the advancements are outlined in this paper. In a study of 200 serial killers, we examined the variables that led to police focusing their attention on specific suspects. We developed 12 categories that describe how serial killers come to the attention of the police. The results of the present study indicate that most serial killers are captured as a result of citizens and surviving victims contributing information that resulted in police investigations that led to an arrest. The role of forensic science appears to be important in convicting the perpetrator, but not necessarily in identifying the perpetrator.

  17. Killer whale call frequency is similar across the oceans, but varies across sympatric ecotypes.

    PubMed

    Filatova, Olga A; Miller, Patrick J O; Yurk, Harald; Samarra, Filipa I P; Hoyt, Erich; Ford, John K B; Matkin, Craig O; Barrett-Lennard, Lance G

    2015-07-01

    Killer whale populations may differ in genetics, morphology, ecology, and behavior. In the North Pacific, two sympatric populations ("resident" and "transient") specialize on different prey (fish and marine mammals) and retain reproductive isolation. In the eastern North Atlantic, whales from the same populations have been observed feeding on both fish and marine mammals. Fish-eating North Pacific "residents" are more genetically related to eastern North Atlantic killer whales than to sympatric mammal-eating "transients." In this paper, a comparison of frequency variables in killer whale calls recorded from four North Pacific resident, two North Pacific transient, and two eastern North Atlantic populations is reported to assess which factors drive the large-scale changes in call structure. Both low-frequency and high-frequency components of North Pacific transient killer whale calls have significantly lower frequencies than those of the North Pacific resident and North Atlantic populations. The difference in frequencies could be related to ecological specialization or to the phylogenetic history of these populations. North Pacific transient killer whales may have genetically inherited predisposition toward lower frequencies that may shape their learned repertoires.

  18. Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells.

    PubMed

    Torelli, Giovanni F; Peragine, Nadia; Raponi, Sara; Pagliara, Daria; De Propris, Maria S; Vitale, Antonella; Bertaina, Alice; Barberi, Walter; Moretta, Lorenzo; Basso, Giuseppe; Santoni, Angela; Guarini, Anna; Locatelli, Franco; Foà, Robin

    2014-07-01

    In this study, we aimed to investigate the pathways of recognition of acute lymphoblastic leukemia blasts by natural killer cells and to verify whether differences in natural killer cell activating receptor ligand expression among groups defined by age of patients, or presence of cytogenetic/molecular aberrations correlate with the susceptibility to recognition and killing. We analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and 57 children. Pediatric blasts showed a significantly higher expression of Nec-2 (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The differential expression of these ligands between adults and children was confined to B-lineage acute lymphoblastic leukemia with no known molecular alterations. Within molecularly defined subgroups of patients, a high surface expression of NKG2D and DNAM1 ligands was found on BCR-ABL(+) blasts, regardless of patient age. Accordingly, BCR-ABL(+) blasts proved to be significantly more susceptible to natural killer-dependent lysis than B-lineage blasts without molecular aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological explanation of the different roles played by alloreactive natural killer cells in pediatric versus adult acute lymphoblastic leukemia and suggest that new natural killer-based strategies targeting specific subgroups of patients, particularly those BCR-ABL(+), are worth pursuing further.

  19. [Rapid identification and susceptibility to killer toxins of yeasts isolated from non-systemic mycoses].

    PubMed

    Sangorrín, M P; Lopes, C A; Rivero, A; Caballero, A C

    2007-01-01

    Rapid identification and susceptibility to killer toxins of yeasts isolated from non-systemic mycoses. The use of quick and reliable yeast identification methods, as well as the development of new antifungal agents with more specific targets, will enable a more efficient treatment of mycoses. In the present work, a total of 53 clinical isolates obtained from non-systemic infections in Neuquén Hospitals and an ophthalmologic clinic in Buenos Aires during 2005, were identified by means of a rapid molecular method (ITS1-5.8S ADNr-ITS2 PCR-RFLP). Additionally, the killer susceptibility of the isolates was tested against reference and indigenous killer yeasts on plate tests. Eight yeast species were identified among the clinical isolates: Candida albicans (52%), Candida parapsilosis (17%), Candida tropicalis (10%), Candida krusei (5%), Candida glabrata (4%), Candida guilliermondii (4%), Kluyveromyces lactis (4%) and Saccharomyces cerevisiae (4%). Sixty-nine percent of the isolates corresponding to the predominant species (C. albicans) were related to vaginal infections. On the other hand, 61% of the yeasts associated with ocular infections were identified as C. parapsilosis. Two indigenous killer isolates DVMais5 and HCMeiss5, belonging to Pichia anomala and P. kluyveri respectively, exhibited the broadest killer spectrum against clinical isolates.

  20. The utilization of forensic science and criminal profiling for capturing serial killers.

    PubMed

    White, John H; Lester, David; Gentile, Matthew; Rosenbleeth, Juliana

    2011-06-15

    Movies and nightly television shows appear to emphasize highly efficient regimens in forensic science and criminal investigative analysis (profiling) that result in capturing serial killers and other perpetrators of homicide. Although some of the shows are apocryphal and unrealistic, they reflect major advancements that have been made in the fields of forensic science and criminal psychology during the past two decades that have helped police capture serial killers. Some of the advancements are outlined in this paper. In a study of 200 serial killers, we examined the variables that led to police focusing their attention on specific suspects. We developed 12 categories that describe how serial killers come to the attention of the police. The results of the present study indicate that most serial killers are captured as a result of citizens and surviving victims contributing information that resulted in police investigations that led to an arrest. The role of forensic science appears to be important in convicting the perpetrator, but not necessarily in identifying the perpetrator. PMID:21333473

  1. The direct effects of male killer infection on fitness of ladybird hosts (Coleoptera: Coccinellidae).

    PubMed

    Elnagdy, S; Majerus, M E N; Gardener, M; Lawson Handley, L-J

    2013-08-01

    Male killing bacteria are common in insects and are thought to persist in host populations primarily by indirect fitness benefits to infected females, whereas direct fitness effects are generally assumed to be neutral or deleterious. Here, we estimated the effect of male killer infection on direct fitness (number of eggs laid, as a measure of fecundity, together with survival) and other life-history traits (development time and body size) in seven ladybird host/male killer combinations. Effects of male killers on fecundity ranged, as expected, from costly to neutral; however, we found evidence of reduced development time and increased survival and body size in infected strains. Greater body size in Spiroplasma-infected Harmonia axyridis corresponded to greater ovariole number and therefore higher potential fecundity. To our knowledge, this is the first report of direct benefits of male killer infection after explicitly controlling for indirect fitness effects. Neutral or deleterious fitness effects of male killer infection should not therefore be automatically assumed. PMID:23869568

  2. The direct effects of male killer infection on fitness of ladybird hosts (Coleoptera: Coccinellidae).

    PubMed

    Elnagdy, S; Majerus, M E N; Gardener, M; Lawson Handley, L-J

    2013-08-01

    Male killing bacteria are common in insects and are thought to persist in host populations primarily by indirect fitness benefits to infected females, whereas direct fitness effects are generally assumed to be neutral or deleterious. Here, we estimated the effect of male killer infection on direct fitness (number of eggs laid, as a measure of fecundity, together with survival) and other life-history traits (development time and body size) in seven ladybird host/male killer combinations. Effects of male killers on fecundity ranged, as expected, from costly to neutral; however, we found evidence of reduced development time and increased survival and body size in infected strains. Greater body size in Spiroplasma-infected Harmonia axyridis corresponded to greater ovariole number and therefore higher potential fecundity. To our knowledge, this is the first report of direct benefits of male killer infection after explicitly controlling for indirect fitness effects. Neutral or deleterious fitness effects of male killer infection should not therefore be automatically assumed.

  3. Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Franceschi, Danilo Santana Alessio; de Souza, Cármino Antonio; Aranha, Francisco José Penteado; Cardozo, Daniela Maira; Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

    2011-01-01

    Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA) compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients) can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein. PMID:23284260

  4. Multiple interval mapping for quantitative trait loci.

    PubMed Central

    Kao, C H; Zeng, Z B; Teasdale, R D

    1999-01-01

    A new statistical method for mapping quantitative trait loci (QTL), called multiple interval mapping (MIM), is presented. It uses multiple marker intervals simultaneously to fit multiple putative QTL directly in the model for mapping QTL. The MIM model is based on Cockerham's model for interpreting genetic parameters and the method of maximum likelihood for estimating genetic parameters. With the MIM approach, the precision and power of QTL mapping could be improved. Also, epistasis between QTL, genotypic values of individuals, and heritabilities of quantitative traits can be readily estimated and analyzed. Using the MIM model, a stepwise selection procedure with likelihood ratio test statistic as a criterion is proposed to identify QTL. This MIM method was applied to a mapping data set of radiata pine on three traits: brown cone number, tree diameter, and branch quality scores. Based on the MIM result, seven, six, and five QTL were detected for the three traits, respectively. The detected QTL individually contributed from approximately 1 to 27% of the total genetic variation. Significant epistasis between four pairs of QTL in two traits was detected, and the four pairs of QTL contributed approximately 10.38 and 14.14% of the total genetic variation. The asymptotic variances of QTL positions and effects were also provided to construct the confidence intervals. The estimated heritabilities were 0.5606, 0.5226, and 0. 3630 for the three traits, respectively. With the estimated QTL effects and positions, the best strategy of marker-assisted selection for trait improvement for a specific purpose and requirement can be explored. The MIM FORTRAN program is available on the worldwide web (http://www.stat.sinica.edu.tw/chkao/). PMID:10388834

  5. Expression of different lipoprotein receptors in natural killer cells and their effect on natural killer proliferative and cytotoxic activity.

    PubMed Central

    De Sanctis, J B; Blanca, I; Bianco, N E

    1995-01-01

    Natural killer (NK) cells take up chylomicrons (CM), very low density (VLDL), low density (LDL), high density (HDL) and acetyl-modified low density (AcLDL) lipoproteins through different receptors, VLDL being the lipoprotein with the highest uptake and HDL the lowest. The uptake of LDL can be selectively blocked by the anti-LDL receptor, which does not affect the uptake of CM, VLDL, HDL and AcLDL. Although the uptake of lipoproteins assessed by flow cytometry using DiI is not very high, the lipoproteins are able to induce an increase in proliferative responses, VLDL, AcLDL and HDL being the most important ones with 12- and 17-fold increments, respectively. CM, VLDL and LDL at low concentrations increase NK cytotoxic activity, while HDL and AcLDL inhibit, in a dose-dependent fashion, the killing of NK cells against K562. These results suggest the presence of four different receptors that are responsible for the cytotoxic and proliferative responses observed. PMID:8550077

  6. HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells

    PubMed Central

    Van den Bergh, Johan M J; Guerti, Khadija; Willemen, Yannick; Lion, Eva; Cools, Nathalie; Goossens, Herman; Vorsters, Alex; Van Tendeloo, Viggo F I; Anguille, Sébastien; Van Damme, Pierre; Smits, Evelien L J M

    2014-01-01

    Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposure of IL-15 DC to the HPV vaccine results in increased expression of phenotypic maturation markers, pro-inflammatory cytokine production and cytotoxic activity against HPV-positive tumour cells. These effects are mediated by the vaccine adjuvant, partly through Toll-like receptor 4 activation. Next, we demonstrate that vaccine-exposed IL-15 DC in turn induce phenotypic activation of NK cells, resulting in a synergistic cytotoxic action against HPV-infected tumour cells. Our study thus identifies a novel mode of action of the HPV vaccine in boosting innate immunity, including killing of HPV-infected cells by DC and NK cells. PMID:24979331

  7. Killer yeasts inhibit the growth of the phytopathogen Moniliophthora perniciosa, the causal agent of Witches' Broom disease.

    PubMed

    de Souza Cabral, Anderson; de Carvalho, Patricia Maria Barroso; Pinotti, Tatiana; Hagler, Allen Norton; Mendonça-Hagler, Leda Cristina Santana; Macrae, Andrew

    2009-01-01

    Fruit and soil yeasts isolated from the Amazon, Atlantic Rainforests and an organic farm were screened for killer activity against yeasts. Killer yeasts were then tested against the phytopathogen Moniliophthora perniciosa (syn. Crinipellis perniciosa) and a Dipodascus capitatus strain and a Candida sp strain inhibited its growth.

  8. 75 FR 17377 - Endangered and Threatened Species; Initiation of 5-Year Review for Southern Resident Killer Whales

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-06

    ... in November 2006 (71 FR 69054) and includes 2,560 square miles (6,630 sq km) of marine habitat in... of 5-Year Review for Southern Resident Killer Whales AGENCY: National Marine Fisheries Service (NMFS... Southern Resident killer whale distinct population segment (DPS) currently listed as endangered (70...

  9. Discovery and Refinement of Loci Associated with Lipid Levels

    PubMed Central

    Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M.; Do, Ron; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tõnu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian’an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Müller-Nurasyid, Martina; Nolte, Ilja M.; O’Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Döring, Angela; Elliott, Paul; Epstein, Stephen E.; Ingi Eyjolfsson, Gudmundur; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J.F.; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; März, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njølstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.; Ripatti, Samuli; Cupples, L. Adrienne; Sandhu, Manjinder S.; Rich, Stephen S.

    2013-01-01

    Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and total cholesterol are heritable, modifiable, risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,578 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5×10−8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian, and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipids are often associated with cardiovascular and metabolic traits including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio, and body mass index. Our results illustrate the value of genetic data from individuals of diverse ancestries and provide insights into biological mechanisms regulating blood lipids to guide future genetic, biological, and therapeutic research. PMID:24097068

  10. Physical Modeling of Dynamic Coupling between Chromosomal Loci.

    PubMed

    Lampo, Thomas J; Kennard, Andrew S; Spakowitz, Andrew J

    2016-01-19

    The motion of chromosomal DNA is essential to many biological processes, including segregation, transcriptional regulation, recombination, and packaging. Physical understanding of these processes would be dramatically enhanced through predictive, quantitative modeling of chromosome dynamics of multiple loci. Using a polymer dynamics framework, we develop a prediction for the correlation in the velocities of two loci on a single chromosome or otherwise connected by chromatin. These predictions reveal that the signature of correlated motion between two loci can be identified by varying the lag time between locus position measurements. In general, this theory predicts that as the lag time interval increases, the dual-loci dynamic behavior transitions from being completely uncorrelated to behaving as an effective single locus. This transition corresponds to the timescale of the stress communication between loci through the intervening segment. This relatively simple framework makes quantitative predictions based on a single timescale fit parameter that can be directly compared to the in vivo motion of fluorescently labeled chromosome loci. Furthermore, this theoretical framework enables the detection of dynamically coupled chromosome regions from the signature of their correlated motion.

  11. Discovery and refinement of loci associated with lipid levels.

    PubMed

    Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M; Do, Ron; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Müller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Döring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J F; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stancáková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S; Boehnke, Michael; Deloukas, Panos; Kathiresan, Sekar; Mohlke, Karen L; Ingelsson, Erik; Abecasis, Gonçalo R

    2013-11-01

    Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

  12. Linkage Mapping of 1454 New Maize Candidate Gene Loci

    PubMed Central

    Falque, Matthieu; Décousset, Laurent; Dervins, Delphine; Jacob, Anne-Marie; Joets, Johann; Martinant, Jean-Pierre; Raffoux, Xavier; Ribière, Nicolas; Ridel, Céline; Samson, Delphine; Charcosset, Alain; Murigneux, Alain

    2005-01-01

    Bioinformatic analyses of maize EST sequences have highlighted large numbers of candidate genes putatively involved in agriculturally important traits. To contribute to ongoing efforts toward mapping of these genes, we used two populations of intermated recombinant inbred lines (IRILs), which allow a higher map resolution than nonintermated RILs. The first panel (IBM), derived from B73 × Mo17, is publicly available from the Maize Genetics Cooperation Stock Center. The second panel (LHRF) was developed from F2 × F252 to map loci monomorphic on IBM. We built framework maps of 237 loci from the IBM panel and 271 loci from the LHRF panel. Both maps were used to place 1454 loci (1056 on map IBM_Gnp2004 and 398 on map LHRF_Gnp2004) that corresponded to 954 cDNA probes previously unmapped. RFLP was mostly used, but PCR-based methods were also performed for some cDNAs to map SNPs. Unlike in usual IRIL-based maps published so far, corrected meiotic centimorgan distances were calculated, taking into account the number of intermating generations undergone by the IRILs. The corrected sizes of our framework maps were 1825 cM for IBM_Gnp2004 and 1862 cM for LHRF_Gnp2004. All loci mapped on LHRF_Gnp2004 were also projected on a consensus map IBMconsensus_Gnp2004. cDNA loci formed clusters near the centromeres except for chromosomes 1 and 8. PMID:15937132

  13. Linkage mapping of 1454 new maize candidate gene Loci.

    PubMed

    Falque, Matthieu; Décousset, Laurent; Dervins, Delphine; Jacob, Anne-Marie; Joets, Johann; Martinant, Jean-Pierre; Raffoux, Xavier; Ribière, Nicolas; Ridel, Céline; Samson, Delphine; Charcosset, Alain; Murigneux, Alain

    2005-08-01

    Bioinformatic analyses of maize EST sequences have highlighted large numbers of candidate genes putatively involved in agriculturally important traits. To contribute to ongoing efforts toward mapping of these genes, we used two populations of intermated recombinant inbred lines (IRILs), which allow a higher map resolution than nonintermated RILs. The first panel (IBM), derived from B73 x Mo17, is publicly available from the Maize Genetics Cooperation Stock Center. The second panel (LHRF) was developed from F2 x F252 to map loci monomorphic on IBM. We built framework maps of 237 loci from the IBM panel and 271 loci from the LHRF panel. Both maps were used to place 1454 loci (1056 on map IBM_Gnp2004 and 398 on map LHRF_Gnp2004) that corresponded to 954 cDNA probes previously unmapped. RFLP was mostly used, but PCR-based methods were also performed for some cDNAs to map SNPs. Unlike in usual IRIL-based maps published so far, corrected meiotic centimorgan distances were calculated, taking into account the number of intermating generations undergone by the IRILs. The corrected sizes of our framework maps were 1825 cM for IBM_Gnp2004 and 1862 cM for LHRF_Gnp2004. All loci mapped on LHRF_Gnp2004 were also projected on a consensus map IBMconsensus_Gnp2004. cDNA loci formed clusters near the centromeres except for chromosomes 1 and 8.

  14. Physical Modeling of Dynamic Coupling between Chromosomal Loci.

    PubMed

    Lampo, Thomas J; Kennard, Andrew S; Spakowitz, Andrew J

    2016-01-19

    The motion of chromosomal DNA is essential to many biological processes, including segregation, transcriptional regulation, recombination, and packaging. Physical understanding of these processes would be dramatically enhanced through predictive, quantitative modeling of chromosome dynamics of multiple loci. Using a polymer dynamics framework, we develop a prediction for the correlation in the velocities of two loci on a single chromosome or otherwise connected by chromatin. These predictions reveal that the signature of correlated motion between two loci can be identified by varying the lag time between locus position measurements. In general, this theory predicts that as the lag time interval increases, the dual-loci dynamic behavior transitions from being completely uncorrelated to behaving as an effective single locus. This transition corresponds to the timescale of the stress communication between loci through the intervening segment. This relatively simple framework makes quantitative predictions based on a single timescale fit parameter that can be directly compared to the in vivo motion of fluorescently labeled chromosome loci. Furthermore, this theoretical framework enables the detection of dynamically coupled chromosome regions from the signature of their correlated motion. PMID:26789757

  15. Serial killers with military experience: applying learning theory to serial murder.

    PubMed

    Castle, Tammy; Hensley, Christopher

    2002-08-01

    Scholars have endeavored to study the motivation and causality behind serial murder by researching biological, psychological, and sociological variables. Some of these studies have provided support for the relationship between these variables and serial murder. However, the study of serial murder continues to be an exploratory rather than explanatory research topic. This article examines the possible link between serial killers and military service. Citing previous research using social learning theory for the study of murder, this article explores how potential serial killers learn to reinforce violence, aggression, and murder in military boot camps. As with other variables considered in serial killer research, military experience alone cannot account for all cases of serial murder. Future research should continue to examine this possible link.

  16. Paths to destruction: the lives and crimes of two serial killers.

    PubMed

    Wolf, Barbara C; Lavezzi, Wendy A

    2007-01-01

    Although research into the phenomenon of serial murder has revealed that serial killers frequently do not fit the initially described paradigm in terms of their physical and psychological profiles, backgrounds, and motives to kill, the media continues to sensationalize the figures of such killers and the investigators who attempt to analyze them on the basis of aspects of their crimes. Although the so-called "typical" profile of the serial murderer has proven accurate in some instances, in many other cases the demographics and behaviors of these killers have deviated widely from the generalized assumptions. This report details two unusual cases in which five and eight murders were committed in upstate New York. The lives and crimes of these offenders illustrate the wide spectrum of variations in the backgrounds, demographics, motivations, and actions witnessed among serial murderers, and highlight the limitations and dangers of profiling based on generalities.

  17. A versatile pitch tracking algorithm: from human speech to killer whale vocalizations.

    PubMed

    Shapiro, Ari Daniel; Wang, Chao

    2009-07-01

    In this article, a pitch tracking algorithm [named discrete logarithmic Fourier transformation-pitch detection algorithm (DLFT-PDA)], originally designed for human telephone speech, was modified for killer whale vocalizations. The multiple frequency components of some of these vocalizations demand a spectral (rather than temporal) approach to pitch tracking. The DLFT-PDA algorithm derives reliable estimations of pitch and the temporal change of pitch from the harmonic structure of the vocal signal. Scores from both estimations are combined in a dynamic programming search to find a smooth pitch track. The algorithm is capable of tracking killer whale calls that contain simultaneous low and high frequency components and compares favorably across most signal to noise ratio ranges to the peak-picking and sidewinder algorithms that have been used for tracking killer whale vocalizations previously.

  18. Super natural killer cells that target metastases in the tumor draining lymph nodes.

    PubMed

    Chandrasekaran, Siddarth; Chan, Maxine F; Li, Jiahe; King, Michael R

    2016-01-01

    Tumor draining lymph nodes are the first site of metastasis in most types of cancer. The extent of metastasis in the lymph nodes is often used in staging cancer progression. We previously showed that nanoscale TRAIL liposomes conjugated to human natural killer cells enhance their endogenous therapeutic potential in killing cancer cells cultured in engineered lymph node microenvironments. In this work, it is shown that liposomes decorated with apoptosis-inducing ligand TRAIL and an antibody against a mouse natural killer cell marker are carried to the tumor draining inguinal lymph nodes and prevent the lymphatic spread of a subcutaneous tumor in mice. It is shown that targeting natural killer cells with TRAIL liposomes enhances their retention time within the tumor draining lymph nodes to induce apoptosis in cancer cells. It is concluded that this approach can be used to kill cancer cells within the tumor draining lymph nodes to prevent the lymphatic spread of cancer.

  19. Making the giant leap with augmented cognition technologies : what will be the first %22killer app?'.

    SciTech Connect

    Forsythe, James Chris

    2007-08-01

    This paper highlights key topic areas to be discussed the authors in a panel format during the Augmented Cognition thematic area paper session: 'Augmented Cognition Lessons Learned and Future Directions for Enabling 'Anyone, Anytime, Anywhere' Applications'. The term 'killer app' has been part of the vernacular in the commercial computer software and electronic devices industry to refer to breakthrough technologies [2]. A 'killer app' generally emerges with the development of related technologies that extends over some time and involves numerous variations on a basic concept. Hypotheses may be offered with respect to the conditions that will be needed to enable a similar situation with augmented cognition technologies. This paper and resulting panel session will address the numerous concepts that have emerged from the augmented cognition field to date and postulate how and when this field's first 'killer app' may emerge (e.g., 5, 10, 15, or more years from now).

  20. Environmental isolates of fungi from aquarium pools housing killer whales (Orcinus orca).

    PubMed

    Kohata, Erina; Kano, Rui; Akune, Yuichiro; Ohno, Yoshito; Soichi, Makoto; Yanai, Tokuma; Hasegawa, Atsuhiko; Kamata, Hiroshi

    2013-12-01

    Systemic mycoses in killer whales (Orcinus orca) are rare diseases, but have been reported. Two killer whales died by fungal infections at the Port of Nagoya Public Aquarium in Japan. In this study, the fungal flora of the pool environment at the aquarium was characterized. Alternaria spp., Aspergillus spp. (A. fumigatus, A. niger, A. versicolor), Fusarium spp. and Penicillium spp. were isolated from the air and the pool surroundings. The other isolates were identified as fungal species non-pathogenic for mammals. However, the species of fungi isolated from the environmental samples in this study were not the same as those isolated from the cases of disease in killer whales previously reported. PMID:24045935

  1. Serial killers with military experience: applying learning theory to serial murder.

    PubMed

    Castle, Tammy; Hensley, Christopher

    2002-08-01

    Scholars have endeavored to study the motivation and causality behind serial murder by researching biological, psychological, and sociological variables. Some of these studies have provided support for the relationship between these variables and serial murder. However, the study of serial murder continues to be an exploratory rather than explanatory research topic. This article examines the possible link between serial killers and military service. Citing previous research using social learning theory for the study of murder, this article explores how potential serial killers learn to reinforce violence, aggression, and murder in military boot camps. As with other variables considered in serial killer research, military experience alone cannot account for all cases of serial murder. Future research should continue to examine this possible link. PMID:12150084

  2. Paths to destruction: the lives and crimes of two serial killers.

    PubMed

    Wolf, Barbara C; Lavezzi, Wendy A

    2007-01-01

    Although research into the phenomenon of serial murder has revealed that serial killers frequently do not fit the initially described paradigm in terms of their physical and psychological profiles, backgrounds, and motives to kill, the media continues to sensationalize the figures of such killers and the investigators who attempt to analyze them on the basis of aspects of their crimes. Although the so-called "typical" profile of the serial murderer has proven accurate in some instances, in many other cases the demographics and behaviors of these killers have deviated widely from the generalized assumptions. This report details two unusual cases in which five and eight murders were committed in upstate New York. The lives and crimes of these offenders illustrate the wide spectrum of variations in the backgrounds, demographics, motivations, and actions witnessed among serial murderers, and highlight the limitations and dangers of profiling based on generalities. PMID:17209938

  3. The Cmv1 host resistance locus is closely linked to the Ly49 multigene family within the natural killer cell gene complex on mouse chromosome 6

    SciTech Connect

    Forbes, C.A.; Shellam, G.R.; Scalzo, A.A.

    1997-05-01

    Natural killer (NK) cells play important roles in controlling tumor cells and against a range of infectious organisms. Recent studies of mouse NK cell surface receptors, which may be involved in the specificity of NK cells, have shown that many of these molecules are encoded by the Ly49 and Ly55 (Nkrp1) multigene families that map to distal mouse chromosome 6. Also mapping to this NK cell gene complex (NKC) is the resistance locus, Cmv1, which is involved in genetically determined resistance to murine cytomegalovirus (MCMV). The aim of this study was to localize Cmv1 more precisely in relation to other NKC loci by generating a high-resolution genetic map of the region. We have analyzed 1250 backcross mice comprising panels of 700 (BALB/c x C57BL/6J)F{sub 1} X BALB/c and 550 (A/J X C57BL/6J)F{sub 1} X A/J progeny. A total of 25 polymorphic genes or microsatellite markers were analyzed over a region of 10 map units from D6Mit134 to D6Mit59. The Cmv1 phenotypes of mice recombinant in this interval were tested by infection with MCMV. The results obtained indicate that the functionally important NKC region is a tightly linked cluster of loci spanning at least 0.4 map units. Furthermore, Cmv1 maps distal to, but very closely linked to, the Ly49 multigene family (< 0.2 map units), suggesting that MCMV resistance may be conferred by MHC class I-specific NK cell receptors. 49 refs., 4 figs., 1 tab.

  4. Psychosocial resources, aging, and natural killer cell terminal maturity

    PubMed Central

    Segerstrom, Suzanne C.; Al-Attar, Ahmad; Lutz, Charles T.

    2012-01-01

    Psychosocial factors may influence aspects of immunological aging. The present study tested the hypothesis that psychosocial resources correlate with the expression of the cell surface maker CD57 on natural killer (NK) immune cells. CD57 is a marker of terminal maturation and senescence in this cell subset. The study further tested the relative contribution of specific resources in the social, psychological, financial, and status-skill domains, given the potential differential value of different resources for younger and older adults, and the contribution of relative vs. absolute resources. Younger (N=38) and older (N=34) women completed measures of relative and absolute resources and had blood drawn. Examined both between groups and within the older women, older age and fewer total relative resources were associated with more CD57 expression on NK cells. One SD in resources was the equivalent of 5 years of aging among the older women. Among the specific resource types, a preponderance of financial resources, both relative and absolute, was associated with less CD57 expression on NK cells, and these relationships did not significantly vary between younger and older women. There was no evidence that depressive symptoms mediated the effects of resources on CD57 expression on NK cells. These findings provide support for the hypothesis that the sense that one has substantial resources, particular with regard to finances and possessions, may retard age-associated aspects of the microenvironment in which NK cells develop and mature, independent of effects on distress, and this process may begin in younger adulthood. PMID:22708535

  5. Dyson Dots & Geoengineering: The Killer App Ad Astra

    NASA Astrophysics Data System (ADS)

    Kennedy, R. G.; Hughes, Eric; Roy, Kenneth I.; Fields, David E.

    No study of coping with climate change is complete without considering geoengineering. A "Dyson Dot" is one or more large (area ~700 K km2, >200 megatonne) lightsail(s) in a radiation-levitated non-Keplerian orbit(s) just sunward of the Sun-Earth Lagrange-1 point. The purpose of this syncretic concept is twofold: (I) As a parasol, it would reduce insolation on Earth by at least one-quarter of a percent (-3.4 W m-2), same as what caused 1.5°C drop during the "Little Ice Age" (~1550-1850) and same as the IPCC Third Report's mid-range value for global warming by 2050. The parasol transforms the "solar constant" to a controlled solar variable. (II) Hosting a ~50K km2 photovoltaic power station on its sunny side and relaying beamed power via maser to rectennas on a circumpolar Dymaxion grid, the system could displace over 300 EJ/a (~100 trillion kWh/yr) of fossil-fired power (total global demand for electricity forecast by 2050), while providing USD trillions in revenue from cheap clean energy sales (@1-3¢/kWh) to amortize the scheme. Total system efficiency compares favorably to automobiles; total system power density is comparable to nuclear power. This approach -- self-funding, "pay-as-you-go", minimally intrusive, scalable, complementary with a portfolio of other measures and above all reversible is not precluded by international treaty. Indeed geoengineering may be the best "killer app" to bootstrap orbital industry and humanity ad astra, because the terawattscale product is comparable to the power required for interstellar travel. If Tellurian spacefaring civilization bootstraps its exponential growth with multi-terawatt maser beams from such lightsails, there might eventually be enough of them to have a detectable effect on Sol's apparent luminosity at certain wavelengths, as seen from far away, similar to the eponymous Dyson Sphere, hence the moniker.

  6. A Killer Asteroids Research Project for Undergraduate Non-Majors

    NASA Astrophysics Data System (ADS)

    Puckett, Andrew W.; Rector, T. A.

    2009-01-01

    We present a progress report on the development and testing of our Killer Asteroids Research Project, which enables the assessment of asteroid impact risk in the undergraduate classroom. This is part of an NSF CCLI grant to develop Research Based Science Education (RBSE) curricula for non-majors. Our curricula include six projects covering astrometric, photometric, and spectroscopic techniques, which are being tested at multiple schools of varying sizes around the country. We report on the second semester of testing this project with undergraduates at the University of Alaska Anchorage. Students use our Polaris Plugin for ImageJ to perform both astrometry and aperture photometry on research-grade astronomical images. The output is fed into Find_Orb, which uses a Monte Carlo method to compute orbital elements for thousands of possible orbits. The resulting orbit database is then fed into a planetarium program, which allows students to visualize the uncertainty region and to observe how that region changes with time and/or additional data. For potentially hazardous asteroids, impact risk is assessed by counting the number of "clone” orbits that strike a planet's surface. Alternatively, the output from our plugin can be used directly to measure the lightcurves of minor planets, leading to an improved understanding of their shapes. This plugin is the first FITS reader to produce correct time-stamps for minor planet observations found in the SDSS, which observes in drift-scan mode. Recent progress is promising. We are in dialogue with software engineers behind both Starry Night and Guide, helping to improve these planetarium programs as research tools. We are also constantly improving the Polaris Plugin, most recently to make it compatible with the astrometry format used by the websites NeoDys and AstDys.

  7. Regulation of Natural Killer Cell Function by STAT3

    PubMed Central

    Cacalano, Nicholas A.

    2016-01-01

    Natural killer (NK) cells, key members of a distinct hematopoietic lineage, innate lymphoid cells, are not only critical effectors that mediate cytotoxicity toward tumor and virally infected cells but also regulate inflammation, antigen presentation, and the adaptive immune response. It has been shown that NK cells can regulate the development and activation of many other components of the immune response, such as dendritic cells, which in turn, modulate the function of NK cells in multiple synergistic feed back loops driven by cell–cell contact, and the secretion of cytokines and chemokines that control effector function and migration of cells to sites of immune activation. The signal transducer and activator of transcription (STAT)-3 is involved in driving almost all of the pathways that control NK cytolytic activity as well as the reciprocal regulatory interactions between NK cells and other components of the immune system. In the context of tumor immunology, NK cells are a first line of defense that eliminates pre-cancerous and transformed cells early in the process of carcinogenesis, through a mechanism of “immune surveillance.” Even after tumors become established, NK cells are critical components of anticancer immunity: dysfunctional NK cells are often found in the peripheral blood of cancer patients, and the lack of NK cells in the tumor microenvironment often correlates to poor prognosis. The pathways and soluble factors activated in tumor-associated NK cells, cancer cells, and regulatory myeloid cells, which determine the outcome of cancer immunity, are all critically regulated by STAT3. Using the tumor microenvironment as a paradigm, we present here an overview of the research that has revealed fundamental mechanisms through which STAT3 regulates all aspects of NK cell biology, including NK development, activation, target cell killing, and fine tuning of the innate and adaptive immune responses. PMID:27148255

  8. Potassium channels mediate killing by human natural killer cells

    SciTech Connect

    Schlichter, L.; Sidell N.; Hagiwara, S.

    1986-01-01

    Human natural killer (NK) cells in peripheral blood spontaneously recognize and kill a wide variety of target cells. It has been suggested that ion channels are involved in the killing process because there is a Ca-dependent stage and because killing by presensitized cytotoxic T lymphocytes, which in many respects resembles NK killing, is associated with changes in K and Na transport in the target cell. Using the whole-cell variation of the patch-clamp technique, the authors found a voltage-dependent potassium (K/sup +/) current in NK cells. The K/sup +/ current was reduced in a dose-dependent manner by the K-channel blockers 4-aminopyridine and quinidine and by the traditional Ca-channel blockers verapamil and Cd/sup 2 +/. They tested the effects of ion-channel blockers on killing of two commonly used target cell lines: K562, which is derived from a human myeloid leukemia, and U937, which is derived from a human histiocytic leukemia. Killing of K562 target cells, determined in a standard /sup 51/Cr-release assay, was inhibited in a dose-dependent manner by verapamil, quinidine, Cd/sup 2 +/, and 4-aminopyridine at concentrations comparable to those that blocked the K/sup +/ current in NK cells. In K562 target cells only a voltage-dependent Na= current was found and it was blocked by concentrations of tetrodotoxin that had no effect on killing. Killing of U937 target cells was also inhibited by the two ion-channel blockers tested, quinidine and verapamil. In this cell line only a small K/sup +/ current was found that was similar to the one in NK cells. The findings show that there are K channels in NK cells and that these channels play a necessary role in the killing process.

  9. Cardif (MAVS) Regulates the Maturation of Natural Killer Cells

    PubMed Central

    Haynes, LaTeira D.; Verma, Shilpi; McDonald, Bryan; Wu, Runpei; Tacke, Robert; Ekstein, Jennifer; Feuvrier, Ariana; Benedict, Chris A.; Hedrick, Catherine C.

    2015-01-01

    Cardif, also known as IPS-1, VISA and, MAVS, is an intracellular adaptor protein that functions downstream of the RIG-I family of pattern recognition receptors. Cardif is required for the production of type I-IFNs and other inflammatory cytokines after RIG-I like receptors recognize intracellular antigenic RNA. Studies have recently shown that Cardif may have other roles in the immune system in addition to its role in viral immunity. In this study, we find that the absence of Cardif alters normal natural killer cell development and maturation. Cardif−/− mice have a 35% loss of mature CD27−CD11b+ NK cells in the periphery. Additionally, Cardif−/− NK cells have altered surface marker expression, lower cytoxicity, decreased intracellular STAT1 levels, increased apoptosis and decreased proliferation compared to wild-type NK cells. Mixed chimeric mice revealed that the defective maturation and increased apoptotic rate of peripheral Cardif−/− NK cells is cell-intrinsic. However, Cardif−/− mice showed enhanced control of mouse cytomegalovirus (MCMV, a DNA β-herpesvirus) by NK cells, commensurate with increased activation and IFNγ production by these immature NK cell subsets. These results indicate that the skewed differentiation and altered STAT expression of Cardif−/− NK cells can result in their hyper-responsiveness in some settings, and support recent findings that Cardif-dependent signaling can regulate aspects of immune cell development and/or function distinct from its well characterized role in mediating cell-intrinsic defense to RNA viruses. PMID:26232430

  10. Relationship between uterine natural killer cells and unexplained repeated miscarriage

    PubMed Central

    Farghali, Mohamed M.; El-kholy, Abdel-Latif G.; Swidan, Khaled H.; Abdelazim, Ibrahim A.; Rashed, Ahmed R.; El-Sobky, Ezzat; Goma, Mostafa F.

    2015-01-01

    Objective To evaluate the relation between uterine killer (uK) cells and unexplained repeated miscarriage (RM). Material and Methods Eighty women with unexplained repeated miscarriage and missed miscarriage of current pregnancy were studied. Fetal viability and gestational age of the current pregnancy were confirmed by ultrasound, followed by suction evacuation to collect abortion specimens and uterine wall curettage to collect decidua specimens. Abortion specimens were collected for long-term monolayer cell culture and subsequent chromosome analysis using conventional G-banding. Decidua specimens were subjected to immunohistochemical staining using monoclonal antibodies specific to CD56+ and CD16+ expressed by uK cells. Results CD56+ CD16+ uK cells were found in 85% [68/80] of the studied decidua specimens of women with unexplained repeated miscarriage; 88.5% [54/61] had normal abortion karyotyping and 73.7% [14/19] had abnormal abortion karyotyping. Moreover, 73.75% [59/80] of the studied women with a past history of early miscarriage had CD56+ CD16+ uK cells in their decidua specimens, and 66.25% [53/80] of studied women with a past history of late miscarriage had CD56+ CD16+ uK cells in their decidua specimens; the association between early and late miscarriage and CD56+ CD16+ uK cells in decidua specimens was significant. Conclusion CD56+CD16+ uK cells were predominant in the decidua specimens of the studied women with repeated miscarriage. A significant association was found between the presence of CD56+ CD16+ uK cells in the studied decidua specimens and unexplained repeated miscarriage. PMID:26692771

  11. Ozone exposed epithelial cells modify cocultured natural killer cells

    PubMed Central

    Müller, Loretta; Brighton, Luisa E.

    2013-01-01

    Ozone (O3) causes significant adverse health effects worldwide. Nasal epithelial cells (NECs) are among the first sites within the respiratory system to be exposed to inhaled air pollutants. They recruit, activate, and interact with immune cells via soluble mediators and direct cell-cell contacts. Based on our recent observation demonstrating the presence of natural killer (NK) cells in nasal lavages, the goal of this study was to establish a coculture model of NECs and NK cells and examine how exposure to O3 modifies this interaction. Flow cytometry analysis was used to assess immunophenotypes of NK cells cocultured with either air- or O3-exposed NECs. Our data show that coculturing NK cells with O3-exposed NECs decreased intracellular interferon-γ (IFN-γ), enhanced, albeit not statistically significant, IL-4, and increased CD16 expression on NK cells compared with air controls. Additionally, the cytotoxicity potential of NK cells was reduced after coculturing with O3-exposed NECs. To determine whether soluble mediators released by O3-exposed NECs caused this shift, apical and basolateral supernatants of air- and O3-exposed NECs were used to stimulate NK cells. While the conditioned media of O3-exposed NECs alone did not reduce intracellular IFN-γ, O3 enhanced the expression of NK cell ligands ULBP3 and MICA/B on NECs. Blocking ULBP3 and MICA/B reversed the effects of O3-exposed NECs on IFN-γ production in NK cells. Taken together, these data showed that interactions between NECs and NK cells in the context of O3 exposure changes NK cell activity via direct cell-cell interactions and is dependent on ULBP3/MICA/B expressed on NECs. PMID:23241529

  12. Acquisition of enhanced natural killer cell activity under anesthesia.

    PubMed

    Hsueh, C M; Lorden, J F; Hiramoto, R N; Ghanta, V K

    1992-01-01

    An increase in natural killer (NK) cell activity can be conditioned with a one trial learning paradigm to demonstrate the interaction between the central nervous system (CNS) and the immune system. In order to demonstrate learning possibilities during 'non-conscious' state, mice were anesthetized with a ketamin/rompun mixture and underwent one trial learning with odor cue as the conditioned stimulus (CS) preceding the unconditioned stimulus (US). The results indicated that mice that were exposed to camphor odor cue under the influence of anesthesia can associate the signal with the poly I:C unconditioned stimulus and were able to recall the conditioned response upon reexposure to the CS. Secondly, the conditioned association made in a conscious state can be recalled by exposure to the same olfactory odor cue in a 'non-conscious' state. The increase in the conditioned change in NK cell activity of both situations was significantly higher than the control group. The results demonstrate that learning can take place and the learned response can be recalled under the reduced awareness caused by anesthesia. The findings we report are unusual and novel in that they demonstrate that the CNS can learn new associations under conditions where the host is apparently unaware of the signals being linked. Anesthesia combined with the long interstimulus interval indicates that certain neuronal pathways in the CNS are receptive to second signals (elicited by the US) even when the second signal is separated by one day. This means the conditioned learning of a physiological response can take place unconsciously at a separate level and under situations where the host is totally unaware of the events which the brain is processing and linking as incoming information.

  13. Emotional stability, anxiety, and natural killer activity under examination stress.

    PubMed

    Borella, P; Bargellini, A; Rovesti, S; Pinelli, M; Vivoli, R; Solfrini, V; Vivoli, G

    1999-08-01

    This study was performed to evaluate the relation between a stable personality trait, a mood state and immune response to an examination stress. A self-reported measure of emotional stability (BFQ-ES scale) was obtained in a sample (n = 39) randomly selected from 277 cadets; this personality trait was also investigated by completing a neuroticism scale (Eysenck personality inventory) and a trait-anxiety scale (STAI). Natural killer (NK) cell activity was measured at baseline, long before the examination time and the examination day. The state-anxiety scale evaluated the response to the stressful stimulus. Taking subjects all together, the academic task did not result in significant modification over baseline in NK cell activity. Subjects were then divided into three groups based on emotional stability and state-anxiety scores: high emotional stability/low anxiety, medium, and low emotional stability/high anxiety. Examination stress induced significant increases in NK cell activity in the high emotional stability/low anxiety group, no effect in the medium group, and significant decreases in the low emotional stability/high anxiety group. The repeated-measure ANOVA revealed a significant interaction of group x period (baseline vs. examination) for both lytic units and percent cytolysis. The results did not change after introducing coffee and smoking habits as covariates. Our findings suggest that the state-anxiety acts in concert with a stable personality trait to modulate NK response in healthy subjects exposed to a psychological naturalistic stress. The relation between anxiety and poor immune control has been already described, whereas the ability of emotional stability to associate with an immunoenhancement has not yet reported. The peculiarity of our population, a very homogeneous and healthy group for life style and habits, can have highlighted the role of emotional stability, and may account for the difference with other studies.

  14. Evolution of non-cytotoxic uterine natural killer cells.

    PubMed

    Kalkunte, Satyan; Chichester, Clinton O; Gotsch, Francesca; Sentman, Charles L; Romero, Roberto; Sharma, Surendra

    2008-05-01

    The immune tolerance and de novo vascularization are two highly intriguing processes at the maternal-fetal interface that appear to be central to normal pregnancy outcome. Immune tolerance occurs despite the local presence of an active maternal immune system including macrophages, dendritic cells and specialized CD56(bright)CD16(-) uterine natural killer (uNK) cells (65-70%). Recent observations indicate that the phenotypic and functional repertoire of uNK cells is distinct from peripheral blood NK and endometrial NK cells, challenging the understanding of their temporal occurrence and function. Origin and specialized programming of uNK cells continue to be debated. uNK cells, replete with an armamentarium to kill the foreign, tolerate the conceptus and facilitate pregnancy. Why do these uNK cells remain non-cytotoxic? Are these NK cells 'multitasking' in nature harboring beneficial and detrimental roles in pregnancy? Are there distinct subpopulations of NK cells that may populate the decidua? We propose that the endometrium/decidua functions as an 'inducible tertiary lymphoid tissue' that supports the recruitment and expansion of CD56(bright)CD16(-) NK cells and induces transcriptional up-regulation of angiogenic machinery in response to exposure to local hormonal factors, cytokine milieu and perhaps hypoxia. The angiogenic features of uNK cells could further result in a 'multitasking' phenotype that still remains to be characterized. This article discusses the factors and pathways that bridge the angiogenic and non-cytotoxic response machineries at the maternal-fetal interface. PMID:18405313

  15. P-LOCI: a computer program for choosing the most efficient set of loci for parentage assignment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Determining which and how many codominant marker loci are required for accurate parentage assignment is not straightforward because levels of marker polymorphism and linkage, allelic distributions among potential parents and other factors produce differences in the discriminatory power of individual...

  16. IMPAIRED NATURAL KILLER CELL LYSIS IN BREAST CANCER PATIENTS WITH HIGH LEVELS OF PSYCHOLOGICAL STRESS IS ASSOCIATED WITH ALTERED EXPRESSION OF KILLER IMMUNOGLOBULIN-LIKE RECEPTORS

    PubMed Central

    Varker, Kimberly A.; Terrell, Catherine E.; Welt, Marilyn; Suleiman, Samer; Thornton, Lisa; Andersen, Barbara L.; Carson, William E.

    2007-01-01

    Background We previously reported that cancer-related psychological stress is associated with reduced natural killer (NK) cell lysis. We hypothesized that reduced NK cell cytotoxicity in patients with increased levels of stress would correlate with alterations in the expression of inhibitory NK cell receptors (killer immunoglobulin-like receptors, or KIRs). The specific aim of this study was to examine KIR expression in patients with high or low levels of psychologic stress and correlate alterations in KIR expression with NK cell function. Materials and Methods 227 patients underwent baseline evaluation of cancer-related psychological stress and were randomized to psychosocial intervention versus observation. From this population, two groups were defined based on pre-treatment measurements of NK lytic activity, stress levels, and the availability of cryopreserved peripheral blood mononuclear cells (PBMC). Group I (n = 9) had low stress by the Impact of Events Scale (IES), and high NK cell lysis at the 50:1 effector: target ratio (NK50 = 52–89%). Group II (n = 8) had high stress and low NK50 (27–52%). Lymphokine activated killer (LAK) activity, antibody dependent cellular cytotoxicity (ADCC), and expression of cytokine receptors, adhesion molecules, and killer immunoglobulin-like receptors (KIRs) were assessed in PBMC. Results Incubation of PBMC with NK-stimulatory cytokines (IL-2, IL-12, or IL-15) led to significant increases in cytotoxic activity regardless of IES/NK50 scores. There were no significant group differences in NK cell surface expression of the IL-2 receptor components CD25 and CD122, antibody-dependent lysis of HER2/neu-positive SKBr3 cells treated with an anti-HER2/neu monoclonal antibody, expression of adhesion molecules (CD2, CD11a, CD18) and markers of activation (CD69), or expression of the KIRs CD158a, NKG2a, NKB1, and CD161. However, levels of CD158b were significantly higher in Group I after incubation in media alone or with IL-2, and CD94

  17. Killer whale depredation and associated costs to Alaskan sablefish, Pacific halibut and Greenland turbot longliners.

    PubMed

    Peterson, Megan J; Mueter, Franz; Criddle, Keith; Haynie, Alan C

    2014-01-01

    Killer whale (Orcinus orca) depredation (whales stealing or damaging fish caught on fishing gear) adversely impacts demersal longline fisheries for sablefish (Anoplopoma fimbria), Pacific halibut (Hippoglossus stenolepis) and Greenland turbot (Reinhardtius hippoglossoides) in the Bering Sea, Aleutian Islands and Western Gulf of Alaska. These interactions increase direct costs and opportunity costs associated with catching fish and reduce the profitability of longline fishing in western Alaska. This study synthesizes National Marine Fisheries Service observer data, National Marine Fisheries Service sablefish longline survey and fishermen-collected depredation data to: 1) estimate the frequency of killer whale depredation on longline fisheries in Alaska; 2) estimate depredation-related catch per unit effort reductions; and 3) assess direct costs and opportunity costs incurred by longliners in western Alaska as a result of killer whale interactions. The percentage of commercial fishery sets affected by killer whales was highest in the Bering Sea fisheries for: sablefish (21.4%), Greenland turbot (9.9%), and Pacific halibut (6.9%). Average catch per unit effort reductions on depredated sets ranged from 35.1-69.3% for the observed longline fleet in all three management areas from 1998-2012 (p<0.001). To compensate for depredation, fishermen set additional gear to catch the same amount of fish, and this increased fuel costs by an additional 82% per depredated set (average $433 additional fuel per depredated set). In a separate analysis with six longline vessels in 2011 and 2012, killer whale depredation avoidance measures resulted in an average additional cost of $494 per depredated vessel-day for fuel and crew food. Opportunity costs of time lost by fishermen averaged $522 per additional vessel-day on the grounds. This assessment of killer whale depredation costs represents the most extensive economic evaluation of this issue in Alaska to date and will help longline

  18. Killer whale depredation and associated costs to Alaskan sablefish, Pacific halibut and Greenland turbot longliners.

    PubMed

    Peterson, Megan J; Mueter, Franz; Criddle, Keith; Haynie, Alan C

    2014-01-01

    Killer whale (Orcinus orca) depredation (whales stealing or damaging fish caught on fishing gear) adversely impacts demersal longline fisheries for sablefish (Anoplopoma fimbria), Pacific halibut (Hippoglossus stenolepis) and Greenland turbot (Reinhardtius hippoglossoides) in the Bering Sea, Aleutian Islands and Western Gulf of Alaska. These interactions increase direct costs and opportunity costs associated with catching fish and reduce the profitability of longline fishing in western Alaska. This study synthesizes National Marine Fisheries Service observer data, National Marine Fisheries Service sablefish longline survey and fishermen-collected depredation data to: 1) estimate the frequency of killer whale depredation on longline fisheries in Alaska; 2) estimate depredation-related catch per unit effort reductions; and 3) assess direct costs and opportunity costs incurred by longliners in western Alaska as a result of killer whale interactions. The percentage of commercial fishery sets affected by killer whales was highest in the Bering Sea fisheries for: sablefish (21.4%), Greenland turbot (9.9%), and Pacific halibut (6.9%). Average catch per unit effort reductions on depredated sets ranged from 35.1-69.3% for the observed longline fleet in all three management areas from 1998-2012 (p<0.001). To compensate for depredation, fishermen set additional gear to catch the same amount of fish, and this increased fuel costs by an additional 82% per depredated set (average $433 additional fuel per depredated set). In a separate analysis with six longline vessels in 2011 and 2012, killer whale depredation avoidance measures resulted in an average additional cost of $494 per depredated vessel-day for fuel and crew food. Opportunity costs of time lost by fishermen averaged $522 per additional vessel-day on the grounds. This assessment of killer whale depredation costs represents the most extensive economic evaluation of this issue in Alaska to date and will help longline

  19. Decreased non-MHC-restricted (CD56+) killer cell cytotoxicity after spaceflight

    NASA Technical Reports Server (NTRS)

    Mehta, S. K.; Kaur, I.; Grimm, E. A.; Smid, C.; Feeback, D. L.; Pierson, D. L.

    2001-01-01

    Cytotoxic activity of non-major histocompatibility complex-restricted (CD56+) (NMHC) killer cells and cell surface marker expression of peripheral blood mononuclear cells were determined before and after spaceflight. Ten astronauts (9 men, 1 woman) from two space shuttle missions (9- and 10-day duration) participated in the study. Blood samples were collected 10 days before launch, within 3 h after landing, and 3 days after landing. All peripheral blood mononuclear cell preparations were cryopreserved and analyzed simultaneously in a 4-h cytotoxicity (51)Cr release assay using K562 target cells. NMHC killer cell lytic activity was normalized per 1,000 CD56+ cells. When all 10 subjects were considered as one study group, NMHC killer cell numbers did not change significantly during the three sampling periods, but at landing lytic activity had decreased by approximately 40% (P < 0.05) from preflight values. Nine of ten astronauts had decreased lytic activity immediately after flight. NMHC killer cell cytotoxicity of only three astronauts returned toward preflight values by 3 days after landing. Consistent with decreased NMHC killer cell cytotoxicity, urinary cortisol significantly increased after landing compared with preflight levels. Plasma cortisol and ACTH levels at landing were not significantly different from preflight values. No correlation of changes in NMHC killer cell function or hormone levels with factors such as age, gender, mission, or spaceflight experience was found. After landing, expression of the major lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), as determined by flow cytometric analysis, did not show any consistent changes from measurements made before flight.

  20. Killer whale (Orcinus orca) whistles from the western South Atlantic Ocean include high frequency signals.

    PubMed

    Andriolo, Artur; Reis, Sarah S; Amorim, Thiago O S; Sucunza, Federico; de Castro, Franciele R; Maia, Ygor Geyer; Zerbini, Alexandre N; Bortolotto, Guilherme A; Dalla Rosa, Luciano

    2015-09-01

    Acoustic parameters of killer whale (Orcinus orca) whistles were described for the western South Atlantic Ocean and highlight the occurrence of high frequency whistles. Killer whale signals were recorded on December of 2012, when a pod of four individuals was observed harassing a group of sperm whales. The high frequency whistles were highly stereotyped and were modulated mostly at ultrasonic frequencies. Compared to other contour types, the high frequency whistles are characterized by higher bandwidths, shorter durations, fewer harmonics, and higher sweep rates. The results add to the knowledge of vocal behavior of this species.

  1. Killer whale (Orcinus orca) whistles from the western South Atlantic Ocean include high frequency signals.

    PubMed

    Andriolo, Artur; Reis, Sarah S; Amorim, Thiago O S; Sucunza, Federico; de Castro, Franciele R; Maia, Ygor Geyer; Zerbini, Alexandre N; Bortolotto, Guilherme A; Dalla Rosa, Luciano

    2015-09-01

    Acoustic parameters of killer whale (Orcinus orca) whistles were described for the western South Atlantic Ocean and highlight the occurrence of high frequency whistles. Killer whale signals were recorded on December of 2012, when a pod of four individuals was observed harassing a group of sperm whales. The high frequency whistles were highly stereotyped and were modulated mostly at ultrasonic frequencies. Compared to other contour types, the high frequency whistles are characterized by higher bandwidths, shorter durations, fewer harmonics, and higher sweep rates. The results add to the knowledge of vocal behavior of this species. PMID:26428807

  2. Genetic association studies in complex disease: disentangling additional predisposing loci from associated neutral loci using a constrained - permutation approach.

    PubMed

    Spijker, G T; Nolte, I M; Jansen, R C; Te Meerman, G J

    2005-01-01

    In the process of genetically mapping a complex disease, the question may arise whether a certain polymorphism is the only causal variant in a region. A number of methods can answer this question, but unfortunately these methods are optimal for bi-allelic loci only. We wanted to develop a method that is more suited for multi-allelic loci, such as microsatellite markers. We propose the Additional Disease Loci Test (ADLT): the alleles at an additional locus are permuted within the subsample of haplotypes that have identical alleles at the predisposing locus. The hypothesis being tested is, whether the predisposing locus is the sole factor predisposing to the trait that is in LD with the additional locus under study. We applied ADLT to simulated datasets and a published dataset on Type 1 Diabetes, genotyped for microsatellite markers in the HLA-region. The method showed the expected number of false-positive results in the absence of additional loci, but proved to be more powerful than existing methods in the presence of additional disease loci. ADLT was especially superior in datasets with less LD or with multiple predisposing alleles. We conclude that the ADLT can be useful in identifying additional disease loci.

  3. Bone marrow mesenchymal stem cells suppressing activation of allogeneic cytokine-induced killer/natural killer cells either by direct or indirect interaction.

    PubMed

    Li, Yang; Qu, Yu H; Wu, Yan F; Liu, Ling; Lin, Xiang H; Huang, Ke; Wei, Jing

    2015-04-01

    Bone marrow mesenchymal stem cells (MSC) were recently found to be associated with some special immunological characteristics, the immunoregulatory effect of MSC was dose-dependent. Low amount of MSC was associated with mild immunosuppression or even immune activation, while the high amount of that was associated with significant immunosuppressive effect. In this study, by using a transwell system, we explored the effect of MSC on the cell cycle, apoptosis rate and the expression of CD69, an activation marker, on the allogeneic cord blood derived cytokine-induced killer(CIK)/natural killer(NK) cells. The results showed that either by transwell or mixed cell-cell co-culture, the MSC can effect CIK/NK cells on the cell cycle, such as arrested in the G0/G1 phase, diminished the ratio of cells in S, G2/M phase, and increased the apoptosis of them. MSC can also depress the expression of CD69 on these killer cells, as well as increased the ratio of CD4(+) CD25(+) CD127(low) T regulatory (Treg) cells in the CIK/NK cell culture system. We draw conclusions that either by transwell or mixed co-culture, the MSC can suppress activation of allogeneic CB-CIK/NK cells in a dose-dependent manner.

  4. Prediction of causal candidate genes in coronary artery disease loci

    PubMed Central

    Brænne, Ingrid; Civelek, Mete; Vilne, Baiba; Di Narzo, Antonio; Johnson, Andrew D.; Zhao, Yuqi; Reiz, Benedikt; Codoni, Veronica; Webb, Thomas R.; Asl, Hassan Foroughi; Hamby, Stephen E.; Zeng, Lingyao; Trégouët, David-Alexandre; Hao, Ke; Topol, Eric J.; Schadt, Eric E.; Yang, Xia; Samani, Nilesh J.; Björkegren, Johan L.M.; Erdmann, Jeanette; Schunkert, Heribert; Lusis, Aldons J.

    2015-01-01

    Objective Genome-wide association studies (GWAS) have so far identified 159 significant and suggestive loci for coronary artery disease (CAD). We now report comprehensive bioinformatics analyses of sequence variation in these loci to predict candidate causal genes. Approach and Results All annotated genes in the loci were evaluated with respect to protein coding SNPs and gene expression parameters. The latter included expression quantitative trait loci, tissue specificity, and miRNA binding. High priority candidate genes were further identified based on literature searches and our experimental data. We conclude that the great majority of causal variations affecting CAD risk occur in non-coding regions, with 41 % affecting gene expression robustly versus 6% leading to amino acid changes. Many of these genes differed from the traditionally annotated genes, which was usually based on proximity to the lead SNP. Indeed, we obtained evidence that genetic variants at CAD loci affect 98 genes which had not been linked to CAD previously. Conclusions Our results substantially revise the list of likely candidates for CAD and suggest that GWAS efforts in other diseases may benefit from similar bioinformatics analyses. PMID:26293461

  5. Plasmodium genetic loci linked to host cytokine and chemokine responses

    PubMed Central

    Pattaradilokrat, Sittiporn; Li, Jian; Wu, Jian; Qi, Yanwei; Eastman, Richard T.; Zilversmit, Martine; Nair, Sethu C.; Huaman, Maria Cecilia; Quinones, Mariam; Jiang, Hongying; Li, Na; Zhu, Jun; Zhao, Keji; Kaneko, Osamu; Long, Carole A.; Su, Xin-zhuan

    2014-01-01

    Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CC) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1β, IP-10, IFN-γ, MCP-1, and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12, and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosome 7 and 13 had significant (p < 0.005) additive effects on IL-1β, IL-5, and IP-10 responses, and the chromosome 9 and 12 loci had significant (p = 0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection. PMID:24452266

  6. Potassium Channels Mediate Killing by Human Natural Killer Cells

    NASA Astrophysics Data System (ADS)

    Schlichter, Lyanne; Sidell, Neil; Hagiwara, Susumu

    1986-01-01

    Human natural killer (NK) cells in peripheral blood spontaneously recognize and kill a wide variety of target cells. It has been suggested that ion channels are involved in the killing process because there is a Ca-dependent stage and because killing by presensitized cytotoxic T lymphocytes, which in many respects resembles NK killing, is associated with changes in K and Na transport in the target cell. However, no direct evidence exists for ion channels in NK cells or in their target cells. Using the whole-cell variation of the patch-clamp technique, we found a voltage-dependent potassium (K+) current in NK cells. The K+ current was reduced in a dose-dependent manner by the K-channel blockers 4-aminopyridine and quinidine and by the traditional Ca-channel blockers verapamil and Cd2+. We tested the effects of ion-channel blockers on killing of two commonly used target cell lines: K562, which is derived from a human myeloid leukemia, and U937, which is derived from a human histiocytic leukemia. Killing of K562 target cells, determined in a standard 51Cr-release assay, was inhibited in a dose-dependent manner by verapamil, quinidine, Cd2+, and 4-aminopyridine at concentrations comparable to those that blocked the K+ current in NK cells. In K562 target cells only a voltage-dependent Na+ current was found and it was blocked by concentrations of tetrodotoxin that had no effect on killing. Killing of U937 target cells was also inhibited by the two ion-channel blockers tested, quinidine and verapamil. In this cell line only a small K+ current was found that was similar to the one in NK cells. We could not find any evidence of a Ca2+ current in target cells or in NK cells; therefore, our results cannot explain the Ca dependence of killing. Our findings show that there are K channels in NK cells and that these channels play a necessary role in the killing process. In contrast, the endogenous channel type in the target cell is probably not a factor in determining target cell

  7. Recognition of Microbial Glycolipids by Natural Killer T Cells.

    PubMed

    Zajonc, Dirk M; Girardi, Enrico

    2015-01-01

    T cells can recognize microbial antigens when presented by dedicated antigen-presenting molecules. While peptides are presented by classical members of the major histocompatibility complex (MHC) family (MHC I and II), lipids, glycolipids, and lipopeptides can be presented by the non-classical MHC member, CD1. The best studied subset of lipid-reactive T cells are type I natural killer T (iNKT) cells that recognize a variety of different antigens when presented by the non-classical MHCI homolog CD1d. iNKT cells have been shown to be important for the protection against various microbial pathogens, including B. burgdorferi, the causative agents of Lyme disease, and S. pneumoniae, which causes pneumococcal meningitis and community-acquired pneumonia. Both pathogens carry microbial glycolipids that can trigger the T cell antigen receptor (TCR), leading to iNKT cell activation. iNKT cells have an evolutionary conserved TCR alpha chain, yet retain the ability to recognize structurally diverse glycolipids. They do so using a conserved recognition mode, in which the TCR enforces a conserved binding orientation on CD1d. TCR binding is accompanied by structural changes within the TCR binding site of CD1d, as well as the glycolipid antigen itself. In addition to direct recognition of microbial antigens, iNKT cells can also be activated by a combination of cytokines (IL-12/IL-18) and TCR stimulation. Many microbes carry TLR antigens, and microbial infections can lead to TLR activation. The subsequent cytokine response in turn lower the threshold of TCR-mediated iNKT cell activation, especially when weak microbial or even self-antigens are presented during the cause of the infection. In summary, iNKT cells can be directly activated through TCR triggering of strong antigens, while cytokines produced by the innate immune response may be necessary for TCR triggering and iNKT cell activation in the presence of weak antigens. Here, we will review the molecular basis of iNKT cell

  8. Recognition of Microbial Glycolipids by Natural Killer T Cells

    PubMed Central

    Zajonc, Dirk M.; Girardi, Enrico

    2015-01-01

    T cells can recognize microbial antigens when presented by dedicated antigen-presenting molecules. While peptides are presented by classical members of the major histocompatibility complex (MHC) family (MHC I and II), lipids, glycolipids, and lipopeptides can be presented by the non-classical MHC member, CD1. The best studied subset of lipid-reactive T cells are type I natural killer T (iNKT) cells that recognize a variety of different antigens when presented by the non-classical MHCI homolog CD1d. iNKT cells have been shown to be important for the protection against various microbial pathogens, including B. burgdorferi, the causative agents of Lyme disease, and S. pneumoniae, which causes pneumococcal meningitis and community-acquired pneumonia. Both pathogens carry microbial glycolipids that can trigger the T cell antigen receptor (TCR), leading to iNKT cell activation. iNKT cells have an evolutionary conserved TCR alpha chain, yet retain the ability to recognize structurally diverse glycolipids. They do so using a conserved recognition mode, in which the TCR enforces a conserved binding orientation on CD1d. TCR binding is accompanied by structural changes within the TCR binding site of CD1d, as well as the glycolipid antigen itself. In addition to direct recognition of microbial antigens, iNKT cells can also be activated by a combination of cytokines (IL-12/IL-18) and TCR stimulation. Many microbes carry TLR antigens, and microbial infections can lead to TLR activation. The subsequent cytokine response in turn lower the threshold of TCR-mediated iNKT cell activation, especially when weak microbial or even self-antigens are presented during the cause of the infection. In summary, iNKT cells can be directly activated through TCR triggering of strong antigens, while cytokines produced by the innate immune response may be necessary for TCR triggering and iNKT cell activation in the presence of weak antigens. Here, we will review the molecular basis of iNKT cell

  9. High-Density Genotyping of Immune Loci in Koreans and Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci

    PubMed Central

    Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K.; Eyre, Steve; Bowes, John; Pappas, Dimitrios A.; Kremer, Joel M.; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P.; Karlson, Elizabeth W.; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Greenberg, Jeffrey D.; Plenge, Robert M.; Bae, Sang-Cheol

    2015-01-01

    Objective A highly polygenic etiology and high degree of allele-sharing between ancestries have been well-elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analyzed Korean rheumatoid arthritis case-control samples using the Immunochip and GWAS array to search for new risk alleles of rheumatoid arthritis with anti-citrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data, for a total sample size of 9,299 Korean and 45,790 European case-control samples. Results We identified 8 new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1–FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10−8), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the 7 new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of SNPs that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusion This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. PMID:24532676

  10. Analysis of GzmbCre as a Model System for Gene Deletion in the Natural Killer Cell Lineage.

    PubMed

    Xu, Yiying; Evaristo, Cesar; Alegre, Maria-Luisa; Gurbuxani, Sandeep; Kee, Barbara L

    2015-01-01

    The analysis of gene function in mature and activated natural killer cells has been hampered by the lack of model systems for Cre-mediated recombination in these cells. Here we have investigated the utility of GzmbCre for recombination of loxp sequences in these cells predicated on the observation that Gzmb mRNA is highly expressed in mature and activated natural killer cells. Using two different reporter strains we determined that gene function could be investigated in mature natural killer cells after GzmbCre mediated recombination in vitro in conditions that lead to natural killer cell activation such as in the cytokine combination of interleukin 2 and interleukin 12. We demonstrated the utility of this model by creating GzmbCre;Rosa26IKKbca mice in which Cre-mediated recombination resulted in expression of constitutively active IKKβ, which results in activation of the NFκB transcription factor. In vivo and in vitro activation of IKKβ in natural killer cells revealed that constitutive activation of this pathway leads to natural killer cell hyper-activation and altered morphology. As a caveat to the use of GzmbCre we found that this transgene can lead to recombination in all hematopoietic cells the extent of which varies with the particular loxp flanked allele under investigation. We conclude that GzmbCre can be used under some conditions to investigate gene function in mature and activated natural killer cells.

  11. Paucity of natural killer and cytotoxic T cells in human neuromyelitis optica lesions.

    PubMed

    Saadoun, Samira; Bridges, Leslie R; Verkman, A S; Papadopoulos, Marios C

    2012-12-19

    Neuromyelitis optica is a severe inflammatory demyelinating disease of the central nervous system. Most patients with neuromyelitis optica have circulating immunoglobulin G (IgG) antibodies against the astrocytic water channel protein aquaporin-4 (AQP4), which are pathogenic. Anti-AQP4 IgG-mediated complement-dependent astrocyte toxicity is a key mechanism of central nervous system damage in neuromyelitis optica, but the role of natural killer and cytotoxic T cells is unknown. Our objective was to determine whether natural killer and cytotoxic T cells play a role in human neuromyelitis optica lesions. We immunostained four actively demyelinating lesions, obtained from patients with anti-AQP4 IgG positive neuromyelitis optica, for Granzyme B and Perforin. The inflammatory cells were perivascular neutrophils, eosinophils and macrophages, with only occasional Granzyme B+ or Perforin+ cells. Greater than 95% of inflamed vessels in each lesion had no surrounding Granzyme B+ or Perforin+ cells. Granzyme B+ or Perforin+ cells were abundant in human spleen (positive control). Although natural killer cells produce central nervous system damage in mice injected with anti-AQP4 IgG, our findings here indicate that natural killer-mediated and T cell-mediated cytotoxicity are probably not involved in central nervous system damage in human neuromyelitis optica.

  12. Methylprednisolone pulse therapy induced fall in natural killer cell activity in rheumatoid arthritis.

    PubMed

    Pedersen, B K; Beyer, J M; Rasmussen, A; Klarlund, K; Pedersen, B N; Helin, P

    1984-10-01

    Natural killer (NK) cell activity was studied in 8 patients with classic or definite rheumatoid arthritis (RA) by investigating the killing of K 562 cells by peripheral blood lymphocytes before, during, and after intravenous methylprednisolone pulse therapy (MPPT). MPPT produced a considerable fall in NK activity and after 3 months NK activity was less than half that before MPPT. PMID:6516854

  13. Susceptibility of species within the Sporothrix schenckii complex to a panel of killer yeasts.

    PubMed

    Stopiglia, Cheila Denise Ottonelli; Heidrich, Daiane; Sorrentino, Julia Medeiros; Vieira, Fabiane Jamono; Landell, Melissa Fontes; Valente, Patrícia; Scroferneker, Maria Lúcia

    2014-06-01

    The Sporothrix schenckii complex is the etiologic agent of sporotrichosis, a subacute or chronic mycosis which can affect humans and animals. Killer yeasts have been used in the medical field for development of novel antimycotics and biotyping of pathogenic fungi. The action of 18 killer yeasts on the growth of 88 characterized S. schenckii, Sporothrix globosa, Sporothrix brasiliensis, and Sporothrix mexicana clinical and environmental isolates was evaluated. Killer studies were performed on Petri dishes containing cheese black starch agar. The yeasts Candida catenulata (QU26, QU31, QU127, LV102); Trichosporon faecale (QU100); Trichosporon japonicum (QU139); Kluyveromyces lactis (QU30, QU99, QU73); Kazachstania unispora (QU49), Trichosporon insectorum (QU89), and Kluyveromyces marxianus (QU103) showed activity against all strains of the S. schenckii complex tested. Observation by optical microscopy of S. brasiliensis 61 within the inhibition haloes around the colonies of the killer yeasts QU100, QU139, and LV102 showed that there was no conidiation, but there was hyphal proliferation. The toxins were fungistatic against S. brasiliensis 61. There was no difference in susceptibility to the toxins among the S. schenckii species complex. Further investigations are necessary to clearly establish the mechanism of action of the toxins.

  14. TdKT, a new killer toxin produced by Torulaspora delbrueckii effective against wine spoilage yeasts.

    PubMed

    Villalba, María Leticia; Susana Sáez, Julieta; Del Monaco, Silvana; Lopes, Christian Ariel; Sangorrín, Marcela Paula

    2016-01-18

    Microbiological spoilage is a major concern throughout the wine industry, and control tools are limited. This paper addresses the identification and partial characterization of a new killer toxin from Torulaspora delbrueckii with potential biocontrol activity of Brettanomyces bruxellensis, Pichia guilliermondii, Pichia manshurica and Pichia membranifaciens wine spoilage. A panel of 18 different wine strains of T. delbrueckii killer yeasts was analysed, and the strain T. delbrueckii NPCC 1033 (TdKT producer) showed a significant inhibitory effect on the growth of all different spoilage yeasts evaluated. The TdKT toxin was then subjected to a partial biochemical characterization. Its estimated molecular weight was N30 kDa and it showed glucanase and chitinase enzymatic activities. The killer activity was stable between pH 4.2 and 4.8 and inactivated at temperature above 40 °C. Pustulan and chitin — but not other cell wall polysaccharides — prevented sensitive yeast cells from being killed by TdKT, suggesting that those may be the first toxin targets in the cell wall. TdKT provoked an increase in necrosis cell death after 3 h treatment and apoptotic cell death after 24 h showing time dependence in its mechanisms of action. Killer toxin extracts were active at oenological conditions, confirming their potential use as a biocontrol tool in winemaking. PMID:26513248

  15. Reactive oxygen species in photochemistry of the red fluorescent protein "Killer Red".

    PubMed

    Vegh, Russell B; Solntsev, Kyril M; Kuimova, Marina K; Cho, Soohee; Liang, Yue; Loo, Bernard L W; Tolbert, Laren M; Bommarius, Andreas S

    2011-05-01

    The fluorescent protein aptly named "Killer Red" (KRed) is capable of killing transfected cells and inactivating fused proteins upon exposure to visible light in the presence of oxygen. We have investigated the source of the bioactive species through a variety of photophysical and photochemical techniques. Our results indicate a Type I (electron transfer mediated) photosensitizing mechanism.

  16. Sipping Coffee with a Serial Killer: On Conducting Life History Interviews with a Criminal Genius

    ERIC Educational Resources Information Center

    Oleson, J. C.

    2004-01-01

    As part of my Ph.D. research on criminal genius, I conducted 44 semi-structured interviews. One of the 44 subjects, in particular, stood out. This noteworthy individual claimed that he had killed 15 people. His story was particularly interesting because--unlike most social research involving serial killers--he claimed that he had never been…

  17. 77 FR 71259 - Taking of Marine Mammals Incidental to Commercial Fishing Operations; False Killer Whale Take...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-29

    ... of this FKWTRP were provided in the proposed rule (76 FR 42082, July 18, 2011) and are not repeated... Team (75 FR 2853, January 19, 2010), the American Samoa stock was not included in the scope of the Team... a False Killer Whale Take Reduction Team and Meeting, 75 FR 2853, January 19, 2010), the...

  18. Rapid multiple-level coevolution in experimental populations of yeast killer and nonkiller strains.

    PubMed

    Pieczynska, Magdalena D; Wloch-Salamon, Dominika; Korona, Ryszard; de Visser, J Arjan G M

    2016-06-01

    Coevolution between different biological entities is considered an important evolutionary mechanism at all levels of biological organization. Here, we provide evidence for coevolution of a yeast killer strain (K) carrying cytoplasmic dsRNA viruses coding for anti-competitor toxins and an isogenic toxin-sensitive strain (S) during 500 generations of laboratory propagation. Signatures of coevolution developed at two levels. One of them was coadaptation of K and S. Killing ability of K first increased quickly and was followed by the rapid invasion of toxin-resistant mutants derived from S, after which killing ability declined. High killing ability was shown to be advantageous when sensitive cells were present but costly when they were absent. Toxin resistance evolved via a two-step process, presumably involving the fitness-enhancing loss of one chromosome followed by selection of a recessive resistant mutation on the haploid chromosome. The other level of coevolution occurred between cell and killer virus. By swapping the killer viruses between ancestral and evolved strains, we could demonstrate that changes observed in both host and virus were beneficial only when combined, suggesting that they involved reciprocal changes. Together, our results show that the yeast killer system shows a remarkable potential for rapid multiple-level coevolution.

  19. Motherlove is a Killer: "Sula,""Beloved," and the Deadly Trinity of Motherlove.

    ERIC Educational Resources Information Center

    Delancey, Dayle B.

    1990-01-01

    Explores the view of motherhood and the concept of mother love as a killer in Toni Morrison's novels "Sula" (1973) and "Beloved" (1987). The triple nature of mother love as destructive materially, emotionally, and literally is examined in the context of African-American women's struggles. (SLD)

  20. "The Killer Angels": A Case Study of Historical Fiction in the Social Studies Curriculum.

    ERIC Educational Resources Information Center

    Bilof, Edwin G.

    1996-01-01

    Describes an interdisciplinary instructional unit using the historical novel "The Killer Angels" to teach about the Civil War. Writing assignments focused on character analysis from the novel bolstered by outside historical research. Student response was overwhelmingly positive. Includes suggested guidelines for developing an interdisciplinary…

  1. Information Literacy, Collaboration, and "Killer Apps": New Challenges for Media Specialists

    ERIC Educational Resources Information Center

    Georges, Fitzgerald

    2004-01-01

    Information literacy is a set of abilities requiring individuals to recognize when information is needed and have the ability to locate, evaluate, and use effectively the needed information. Some of the few strategies that could be adopted for instilling the school's information literacy programming with killer applications such as Public…

  2. Conceptual Change and Killer Whales: Constructing Ecological Values for Animals at the Vancouver Aquarium.

    ERIC Educational Resources Information Center

    Kelsey, Elin

    1991-01-01

    Examines how the aquarium has attempted to move from a transfer view of knowledge to a constructivist approach in its most popular general public program--the killer whale presentation. The process of change that staff underwent is similar to conceptual change processes among learners of science. Describes constructivist strategies of conceptual…

  3. Native Killer Yeasts as Biocontrol Agents of Postharvest Fungal Diseases in Lemons

    PubMed Central

    Garnica, Nydia Mercedes; Fernández-Zenoff, María Verónica; Farías, María Eugenia; Sepulveda, Milena; Ramallo, Jacqueline; Dib, Julián Rafael

    2016-01-01

    Economic losses caused by postharvest diseases represent one of the main problems of the citrus industry worldwide. The major diseases affecting citrus are the "green mold" and "blue mold", caused by Penicillium digitatum and P. italicum, respectively. To control them, synthetic fungicides are the most commonly used method. However, often the emergence of resistant strains occurs and their use is becoming more restricted because of toxic effects and environmental pollution they generate, combined with trade barriers to international markets. The aim of this work was to isolate indigenous killer yeasts with antagonistic activity against fungal postharvest diseases in lemons, and to determine their control efficiency in in vitro and in vivo assays. Among 437 yeast isolates, 8.5% show to have a killer phenotype. According to molecular identification, based on the 26S rDNA D1/D2 domain sequences analysis, strains were identified belonging to the genera Saccharomyces, Wickerhamomyces, Kazachstania, Pichia, Candida and Clavispora. Killers were challenged with pathogenic molds and strains that caused the maximum in vitro inhibition of P. digitatum were selected for in vivo assays. Two strains of Pichia and one strain of Wickerhamomyces depicted a significant protection (p <0.05) from decay by P. digitatum in assays using wounded lemons. Thus, the native killer yeasts studied in this work showed to be an effective alternative for the biocontrol of postharvest fungal infections of lemons and could be promising agents for the development of commercial products for the biological control industry. PMID:27792761

  4. 50 CFR 229.37 - False Killer Whale Take Reduction Plan.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Hawaii Pelagic and Hawaii Insular stocks of false killer whales in the Hawaii-based deep-set and shallow... section have the following meanings: (1) Deep-set or Deep-setting has the same meaning as the definition... this title. (c) Gear requirements. (1) While deep-setting, the owner and operator of a...

  5. 50 CFR 229.37 - False Killer Whale Take Reduction Plan.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Hawaii Pelagic and Hawaii Insular stocks of false killer whales in the Hawaii-based deep-set and shallow... section have the following meanings: (1) Deep-set or Deep-setting has the same meaning as the definition... this title. (c) Gear requirements. (1) While deep-setting, the owner and operator of a...

  6. TdKT, a new killer toxin produced by Torulaspora delbrueckii effective against wine spoilage yeasts.

    PubMed

    Villalba, María Leticia; Susana Sáez, Julieta; Del Monaco, Silvana; Lopes, Christian Ariel; Sangorrín, Marcela Paula

    2016-01-18

    Microbiological spoilage is a major concern throughout the wine industry, and control tools are limited. This paper addresses the identification and partial characterization of a new killer toxin from Torulaspora delbrueckii with potential biocontrol activity of Brettanomyces bruxellensis, Pichia guilliermondii, Pichia manshurica and Pichia membranifaciens wine spoilage. A panel of 18 different wine strains of T. delbrueckii killer yeasts was analysed, and the strain T. delbrueckii NPCC 1033 (TdKT producer) showed a significant inhibitory effect on the growth of all different spoilage yeasts evaluated. The TdKT toxin was then subjected to a partial biochemical characterization. Its estimated molecular weight was N30 kDa and it showed glucanase and chitinase enzymatic activities. The killer activity was stable between pH 4.2 and 4.8 and inactivated at temperature above 40 °C. Pustulan and chitin — but not other cell wall polysaccharides — prevented sensitive yeast cells from being killed by TdKT, suggesting that those may be the first toxin targets in the cell wall. TdKT provoked an increase in necrosis cell death after 3 h treatment and apoptotic cell death after 24 h showing time dependence in its mechanisms of action. Killer toxin extracts were active at oenological conditions, confirming their potential use as a biocontrol tool in winemaking.

  7. An agent-based model of dialect evolution in killer whales.

    PubMed

    Filatova, Olga A; Miller, Patrick J O

    2015-05-21

    The killer whale is one of the few animal species with vocal dialects that arise from socially learned group-specific call repertoires. We describe a new agent-based model of killer whale populations and test a set of vocal-learning rules to assess which mechanisms may lead to the formation of dialect groupings observed in the wild. We tested a null model with genetic transmission and no learning, and ten models with learning rules that differ by template source (mother or matriline), variation type (random errors or innovations) and type of call change (no divergence from kin vs. divergence from kin). The null model without vocal learning did not produce the pattern of group-specific call repertoires we observe in nature. Learning from either mother alone or the entire matriline with calls changing by random errors produced a graded distribution of the call phenotype, without the discrete call types observed in nature. Introducing occasional innovation or random error proportional to matriline variance yielded more or less discrete and stable call types. A tendency to diverge from the calls of related matrilines provided fast divergence of loose call clusters. A pattern resembling the dialect diversity observed in the wild arose only when rules were applied in combinations and similar outputs could arise from different learning rules and their combinations. Our results emphasize the lack of information on quantitative features of wild killer whale dialects and reveal a set of testable questions that can draw insights into the cultural evolution of killer whale dialects.

  8. JEFX 10 demonstration of Cooperative Hunter Killer UAS and upstream data fusion

    NASA Astrophysics Data System (ADS)

    Funk, Brian K.; Castelli, Jonathan C.; Watkins, Adam S.; McCubbin, Christopher B.; Marshall, Steven J.; Barton, Jeffrey D.; Newman, Andrew J.; Peterson, Cammy K.; DeSena, Jonathan T.; Dutrow, Daniel A.; Rodriguez, Pedro A.

    2011-05-01

    The Johns Hopkins University Applied Physics Laboratory deployed and demonstrated a prototype Cooperative Hunter Killer (CHK) Unmanned Aerial System (UAS) capability and a prototype Upstream Data Fusion (UDF) capability as participants in the Joint Expeditionary Force Experiment 2010 in April 2010. The CHK capability was deployed at the Nevada Test and Training Range to prosecute a convoy protection operational thread. It used mission-level autonomy (MLA) software applied to a networked swarm of three Raven hunter UAS and a Procerus Miracle surrogate killer UAS, all equipped with full motion video (FMV). The MLA software provides the capability for the hunter-killer swarm to autonomously search an area or road network, divide the search area, deconflict flight paths, and maintain line of sight communications with mobile ground stations. It also provides an interface for an operator to designate a threat and initiate automatic engagement of the target by the killer UAS. The UDF prototype was deployed at the Maritime Operations Center at Commander Second Fleet, Naval Station Norfolk to provide intelligence analysts and the ISR commander with a common fused track picture from the available FMV sources. It consisted of a video exploitation component that automatically detected moving objects, a multiple hypothesis tracker that fused all of the detection data to produce a common track picture, and a display and user interface component that visualized the common track picture along with appropriate geospatial information such as maps and terrain as well as target coordinates and the source video.

  9. Microsatellite loci analysis for individual identification in Shiba Inu

    PubMed Central

    ARATA, Sayaka; ASAHI, Ai; TAKEUCHI, Yukari; MORI, Yuji

    2015-01-01

    Eighteen autosomal microsatellite loci were examined using 275 Shiba Inus in Japan. Eighteen dogs representing eight trios were obtained from four breeders to calculate mutation rates, and 257 dogs kept by owners were collected through veterinary clinics throughout Japan to calculate population genetic parameters and estimate discrimination power. After two loci (INU005 and AHTk253) were excluded, average expected heterozygosity (He), polymorphic information content (PIC) and fixation index (F) were 0.665, 0.623 and 0.046, respectively. The combined power of discrimination over the 16 microsatellite markers was more than 0.9999. Therefore, it is suggested that these 16 microsatellite loci recommended by the International Society for Animal Genetics (ISAG) are applicable for individual identification and parentage testing of domestic Shiba Inu in Japan. PMID:26537551

  10. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

    PubMed

    Andlauer, Till F M; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A; Loleit, Verena; Luessi, Felix; Meuth, Sven G; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-06-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

  11. Genome-Wide Significant Loci: How Important Are They?

    PubMed Central

    Björkegren, Johan L.M.; Kovacic, Jason C.; Dudley, Joel T.; Schadt, Eric E.

    2015-01-01

    Genome-wide association studies (GWAS) have been extensively used to study common complex diseases such as coronary artery disease (CAD), revealing 153 suggestive CAD loci, of which at least 46 have been validated as having genome-wide significance. However, these loci collectively explain <10% of the genetic variance in CAD. Thus, we must address the key question of what factors constitute the remaining 90% of CAD heritability. We review possible limitations of GWAS, and contextually consider some candidate CAD loci identified by this method. Looking ahead, we propose systems genetics as a complementary approach to unlocking the CAD heritability and etiology. Systems genetics builds network models of relevant molecular processes by combining genetic and genomic datasets to ultimately identify key “drivers” of disease. By leveraging systems-based genetic approaches, we can help reveal the full genetic basis of common complex disorders, enabling novel diagnostic and therapeutic opportunities. PMID:25720628

  12. Multiple loci affect genetic predisposition to hepatocarcinogenesis in mice

    SciTech Connect

    Manenti, G.; Gariboldi, M.; Canzian, F.

    1994-09-01

    The C3H/He mouse represents a good experimental model of genetic predispositoin to hepatocellular tumor development. We analyzed an interspecific test-cross population of 106 urethane-treated male (C3H/He x Mus spretus) x C57BL/6J mice, typed with 222 genetic markers to locate precisely the hepatocellular tumor susceptibility (Hcs) loci. Three regions, on chromosomes 2, 5, and 19, showed a significant linkage with hepatocellular tumor development, as indicated by different quantitative indexes estimating liver tumor size. Liver tumor frequency was not genetically controlled. These loci are different from three other Hcs loci that we have previously mapped in an F2 progeny of the C3H/He mouse crossed with the resistant laboratory strain A/J. The present result indicates a multigenic model of inheritance for hepatocellular tumor susceptibility.

  13. Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans

    PubMed Central

    Keaton, Jacob M.; Hellwege, Jacklyn N.; Ng, Maggie C. Y.; Palmer, Nicholette D.; Pankow, James S.; Fornage, Myriam; Wilson, James G.; Correa, Adolfo; Rasmussen-Torvik, Laura J.; Rotter, Jerome I.; Chen, Yii-Der I.; Taylor, Kent D.; Rich, Stephen S.; Wagenknecht, Lynne E.; Freedman, Barry I.; Bowden, Donald W.

    2016-01-01

    Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with insulin secretion loci. To test this hypothesis, single nucleotide polymorphisms (SNPs) associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n = 492 subjects). These SNPs were tested for interaction, individually and jointly as a genetic risk score (GRS), using genome-wide association study (GWAS) data from five cohorts (ARIC, CARDIA, JHS, MESA, WFSM; n = 2,725 cases, 4,167 controls) with T2D as the outcome. In single variant analyses, suggestively significant (Pinteraction<5×10−6) interactions were observed at several loci including LYPLAL1 (rs10746381), CHN2 (rs7796525), and EXOC1 (rs4289500). Notable AIRg GRS interactions were observed with SAMD4A (rs11627203) and UTRN (rs17074194). These data support the hypothesis that additional genetic factors contributing to T2D risk can be identified by interactions with insulin secretion loci. PMID:27448167

  14. Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans.

    PubMed

    Keaton, Jacob M; Hellwege, Jacklyn N; Ng, Maggie C Y; Palmer, Nicholette D; Pankow, James S; Fornage, Myriam; Wilson, James G; Correa, Adolfo; Rasmussen-Torvik, Laura J; Rotter, Jerome I; Chen, Yii-Der I; Taylor, Kent D; Rich, Stephen S; Wagenknecht, Lynne E; Freedman, Barry I; Bowden, Donald W

    2016-01-01

    Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with insulin secretion loci. To test this hypothesis, single nucleotide polymorphisms (SNPs) associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n = 492 subjects). These SNPs were tested for interaction, individually and jointly as a genetic risk score (GRS), using genome-wide association study (GWAS) data from five cohorts (ARIC, CARDIA, JHS, MESA, WFSM; n = 2,725 cases, 4,167 controls) with T2D as the outcome. In single variant analyses, suggestively significant (Pinteraction<5×10-6) interactions were observed at several loci including LYPLAL1 (rs10746381), CHN2 (rs7796525), and EXOC1 (rs4289500). Notable AIRg GRS interactions were observed with SAMD4A (rs11627203) and UTRN (rs17074194). These data support the hypothesis that additional genetic factors contributing to T2D risk can be identified by interactions with insulin secretion loci. PMID:27448167

  15. Vocalisations of Killer Whales (Orcinus orca) in the Bremer Canyon, Western Australia.

    PubMed

    Wellard, Rebecca; Erbe, Christine; Fouda, Leila; Blewitt, Michelle

    2015-01-01

    To date, there has been no dedicated study in Australian waters on the acoustics of killer whales. Hence no information has been published on the sounds produced by killer whales from this region. Here we present the first acoustical analysis of recordings collected off the Western Australian coast. Underwater sounds produced by Australian killer whales were recorded during the months of February and March 2014 and 2015 in the Bremer Canyon in Western Australia. Vocalisations recorded included echolocation clicks, burst-pulse sounds and whistles. A total of 28 hours and 29 minutes were recorded and analysed, with 2376 killer whale calls (whistles and burst-pulse sounds) detected. Recordings of poor quality or signal-to-noise ratio were excluded from analysis, resulting in 142 whistles and burst-pulse vocalisations suitable for analysis and categorisation. These were grouped based on their spectrographic features into nine Bremer Canyon (BC) "call types". The frequency of the fundamental contours of all call types ranged from 600 Hz to 29 kHz. Calls ranged from 0.05 to 11.3 seconds in duration. Biosonar clicks were also recorded, but not studied further. Surface behaviours noted during acoustic recordings were categorised as either travelling or social behaviour. A detailed description of the acoustic characteristics is necessary for species acoustic identification and for the development of passive acoustic tools for population monitoring, including assessments of population status, habitat usage, migration patterns, behaviour and acoustic ecology. This study provides the first quantitative assessment and report on the acoustic features of killer whales vocalisations in Australian waters, and presents an opportunity to further investigate this little-known population. PMID:26352429

  16. Vocalisations of Killer Whales (Orcinus orca) in the Bremer Canyon, Western Australia.

    PubMed

    Wellard, Rebecca; Erbe, Christine; Fouda, Leila; Blewitt, Michelle

    2015-01-01

    To date, there has been no dedicated study in Australian waters on the acoustics of killer whales. Hence no information has been published on the sounds produced by killer whales from this region. Here we present the first acoustical analysis of recordings collected off the Western Australian coast. Underwater sounds produced by Australian killer whales were recorded during the months of February and March 2014 and 2015 in the Bremer Canyon in Western Australia. Vocalisations recorded included echolocation clicks, burst-pulse sounds and whistles. A total of 28 hours and 29 minutes were recorded and analysed, with 2376 killer whale calls (whistles and burst-pulse sounds) detected. Recordings of poor quality or signal-to-noise ratio were excluded from analysis, resulting in 142 whistles and burst-pulse vocalisations suitable for analysis and categorisation. These were grouped based on their spectrographic features into nine Bremer Canyon (BC) "call types". The frequency of the fundamental contours of all call types ranged from 600 Hz to 29 kHz. Calls ranged from 0.05 to 11.3 seconds in duration. Biosonar clicks were also recorded, but not studied further. Surface behaviours noted during acoustic recordings were categorised as either travelling or social behaviour. A detailed description of the acoustic characteristics is necessary for species acoustic identification and for the development of passive acoustic tools for population monitoring, including assessments of population status, habitat usage, migration patterns, behaviour and acoustic ecology. This study provides the first quantitative assessment and report on the acoustic features of killer whales vocalisations in Australian waters, and presents an opportunity to further investigate this little-known population.

  17. Vocalisations of Killer Whales (Orcinus orca) in the Bremer Canyon, Western Australia

    PubMed Central

    Wellard, Rebecca; Erbe, Christine; Fouda, Leila; Blewitt, Michelle

    2015-01-01

    To date, there has been no dedicated study in Australian waters on the acoustics of killer whales. Hence no information has been published on the sounds produced by killer whales from this region. Here we present the first acoustical analysis of recordings collected off the Western Australian coast. Underwater sounds produced by Australian killer whales were recorded during the months of February and March 2014 and 2015 in the Bremer Canyon in Western Australia. Vocalisations recorded included echolocation clicks, burst-pulse sounds and whistles. A total of 28 hours and 29 minutes were recorded and analysed, with 2376 killer whale calls (whistles and burst-pulse sounds) detected. Recordings of poor quality or signal-to-noise ratio were excluded from analysis, resulting in 142 whistles and burst-pulse vocalisations suitable for analysis and categorisation. These were grouped based on their spectrographic features into nine Bremer Canyon (BC) “call types”. The frequency of the fundamental contours of all call types ranged from 600 Hz to 29 kHz. Calls ranged from 0.05 to 11.3 seconds in duration. Biosonar clicks were also recorded, but not studied further. Surface behaviours noted during acoustic recordings were categorised as either travelling or social behaviour. A detailed description of the acoustic characteristics is necessary for species acoustic identification and for the development of passive acoustic tools for population monitoring, including assessments of population status, habitat usage, migration patterns, behaviour and acoustic ecology. This study provides the first quantitative assessment and report on the acoustic features of killer whales vocalisations in Australian waters, and presents an opportunity to further investigate this little-known population. PMID:26352429

  18. Homothetic transformations and geometric loci: properties of triangles and quadrilaterals

    NASA Astrophysics Data System (ADS)

    Flavia Mammana, Maria

    2016-10-01

    In this paper, we use geometric transformations to find some interesting properties related with geometric loci. In particular, given a triangle or a cyclic quadrilateral, the locus generated by the centroid or by the orthocentre (for triangles) or by the anticentre (for cyclic quadrilaterals) when one vertex moves on the circumcircle of the figure are considered. These loci are studied in paragraphs 3 and 4. By means of the homothetic transformations some properties of triangles and quadrilaterals are found. The study of these properties can be used, with profit, in a classroom activity supported by Dynamic Geometry System.

  19. Isolation and Characterization of Twelve Microsatellite Loci for Rockfish (Sebastes).

    PubMed

    Wimberger; Burr; Gray; Lopez; Bentzen

    1999-05-01

    : We describe the first microsatellites for rockfishes in the diverse genus Sebastes. Clones containing microsatellites were isolated from the genomic library of a quillback rockfish, Sebastes maliger. Twelve microsatellites are characterized; six of these are polymorphic in quillback rockfish, and eight are polymorphic in at least one rockfish species on which they were tested. The number of alleles per variable locus ranged from 4 to 15 and averaged 6.8. The expected heterozygosities ranged from 0.38 to 0.79 and averaged 0.60 in these loci. These loci should prove valuable in studies examining species identification, population genetics, hybridization, paternity, kinship, and microsatellite evolution. PMID:10384005

  20. Generalization of adiposity genetic loci to US Hispanic women

    PubMed Central

    Graff, M; Fernández-Rhodes, L; Liu, S; Carlson, C; Wassertheil-Smoller, S; Neuhouser, M; Reiner, A; Kooperberg, C; Rampersaud, E; Manson, J E; Kuller, L H; Howard, B V; Ochs-Balcom, H M; Johnson, K C; Vitolins, M Z; Sucheston, L; Monda, K; North, K E

    2013-01-01

    BACKGROUND: Obesity is a public health concern. Yet the identification of adiposity-related genetic variants among United States (US) Hispanics, which is the largest US minority group, remains largely unknown. OBJECTIVE: To interrogate an a priori list of 47 (32 overall body mass and 15 central adiposity) index single-nucleotide polymorphisms (SNPs) previously studied in individuals of European descent among 3494 US Hispanic women in the Women's Health Initiative SNP Health Association Resource (WHI SHARe). DESIGN: Cross-sectional analysis of measured body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were inverse normally transformed after adjusting for age, smoking, center and global ancestry. WC and WHR models were also adjusted for BMI. Genotyping was performed using the Affymetrix 6.0 array. In the absence of an a priori selected SNP, a proxy was selected (r2⩾0.8 in CEU). RESULTS: Six BMI loci (TMEM18, NUDT3/HMGA1, FAIM2, FTO, MC4R and KCTD15) and two WC/WHR loci (VEGFA and ITPR2-SSPN) were nominally significant (P<0.05) at the index or proxy SNP in the corresponding BMI and WC/WHR models. To account for distinct linkage disequilibrium patterns in Hispanics and further assess generalization of genetic effects at each locus, we interrogated the evidence for association at the 47 surrounding loci within 1 Mb region of the index or proxy SNP. Three additional BMI loci (FANCL, TFAP2B and ETV5) and five WC/WHR loci (DNM3-PIGC, GRB14, ADAMTS9, LY86 and MSRA) displayed Bonferroni-corrected significant associations with BMI and WC/WHR. Conditional analyses of each index SNP (or its proxy) and the most significant SNP within the 1 Mb region supported the possible presence of index-independent signals at each of these eight loci as well as at KCTD15. CONCLUSION: This study provides evidence for the generalization of nine BMI and seven central adiposity loci in Hispanic women. This study expands the current knowledge of common adiposity

  1. Microsatellite loci discovery from next-generation sequencing data and loci characterization in the epizoic barnacle Chelonibia testudinaria (Linnaeus, 1758).

    PubMed

    Ewers-Saucedo, Christine; Zardus, John D; Wares, John P

    2016-01-01

    Microsatellite markers remain an important tool for ecological and evolutionary research, but are unavailable for many non-model organisms. One such organism with rare ecological and evolutionary features is the epizoic barnacle Chelonibia testudinaria (Linnaeus, 1758). Chelonibia testudinaria appears to be a host generalist, and has an unusual sexual system, androdioecy. Genetic studies on host specificity and mating behavior are impeded by the lack of fine-scale, highly variable markers, such as microsatellite markers. In the present study, we discovered thousands of new microsatellite loci from next-generation sequencing data, and characterized 12 loci thoroughly. We conclude that 11 of these loci will be useful markers in future ecological and evolutionary studies on C. testudinaria. PMID:27231653

  2. Microsatellite loci discovery from next-generation sequencing data and loci characterization in the epizoic barnacle Chelonibia testudinaria (Linnaeus, 1758)

    PubMed Central

    Zardus, John D.; Wares, John P.

    2016-01-01

    Microsatellite markers remain an important tool for ecological and evolutionary research, but are unavailable for many non-model organisms. One such organism with rare ecological and evolutionary features is the epizoic barnacle Chelonibia testudinaria (Linnaeus, 1758). Chelonibia testudinaria appears to be a host generalist, and has an unusual sexual system, androdioecy. Genetic studies on host specificity and mating behavior are impeded by the lack of fine-scale, highly variable markers, such as microsatellite markers. In the present study, we discovered thousands of new microsatellite loci from next-generation sequencing data, and characterized 12 loci thoroughly. We conclude that 11 of these loci will be useful markers in future ecological and evolutionary studies on C. testudinaria. PMID:27231653

  3. Food Web Bioaccumulation Model for Resident Killer Whales from the Northeastern Pacific Ocean as a Tool for the Derivation of PBDE-Sediment Quality Guidelines.

    PubMed

    Alava, Juan José; Ross, Peter S; Gobas, Frank A P C

    2016-01-01

    Resident killer whale populations in the NE Pacific Ocean are at risk due to the accumulation of pollutants, including polybrominated diphenyl ethers (PBDEs). To assess the impact of PBDEs in water and sediments in killer whale critical habitat, we developed a food web bioaccumulation model. The model was designed to estimate PBDE concentrations in killer whales based on PBDE concentrations in sediments and the water column throughout a lifetime of exposure. Calculated and observed PBDE concentrations exceeded the only toxicity reference value available for PBDEs in marine mammals (1500 μg/kg lipid) in southern resident killer whales but not in northern resident killer whales. Temporal trends (1993-2006) for PBDEs observed in southern resident killer whales showed a doubling time of ≈5 years. If current sediment quality guidelines available in Canada for polychlorinated biphenyls are applied to PBDEs, it can be expected that PBDE concentrations in killer whales will exceed available toxicity reference values by a large margin. Model calculations suggest that a PBDE concentration in sediments of approximately 1.0 μg/kg dw produces PBDE concentrations in resident killer whales that are below the current toxicity reference value for 95 % of the population, with this value serving as a precautionary benchmark for a management-based approach to reducing PBDE health risks to killer whales. The food web bioaccumulation model may be a useful risk management tool in support of regulatory protection for killer whales. PMID:26289814

  4. Food Web Bioaccumulation Model for Resident Killer Whales from the Northeastern Pacific Ocean as a Tool for the Derivation of PBDE-Sediment Quality Guidelines.

    PubMed

    Alava, Juan José; Ross, Peter S; Gobas, Frank A P C

    2016-01-01

    Resident killer whale populations in the NE Pacific Ocean are at risk due to the accumulation of pollutants, including polybrominated diphenyl ethers (PBDEs). To assess the impact of PBDEs in water and sediments in killer whale critical habitat, we developed a food web bioaccumulation model. The model was designed to estimate PBDE concentrations in killer whales based on PBDE concentrations in sediments and the water column throughout a lifetime of exposure. Calculated and observed PBDE concentrations exceeded the only toxicity reference value available for PBDEs in marine mammals (1500 μg/kg lipid) in southern resident killer whales but not in northern resident killer whales. Temporal trends (1993-2006) for PBDEs observed in southern resident killer whales showed a doubling time of ≈5 years. If current sediment quality guidelines available in Canada for polychlorinated biphenyls are applied to PBDEs, it can be expected that PBDE concentrations in killer whales will exceed available toxicity reference values by a large margin. Model calculations suggest that a PBDE concentration in sediments of approximately 1.0 μg/kg dw produces PBDE concentrations in resident killer whales that are below the current toxicity reference value for 95 % of the population, with this value serving as a precautionary benchmark for a management-based approach to reducing PBDE health risks to killer whales. The food web bioaccumulation model may be a useful risk management tool in support of regulatory protection for killer whales.

  5. Isolation and characterization of eight novel microsatellite loci in the double-crested cormorant (Phalacrocorax auritus)

    USGS Publications Warehouse

    Mercer, Dacey; Haig, Susan; Mullins, Thomas

    2010-01-01

    We describe the isolation and characterization of eight microsatellite loci from the double-crested cormorant (Phalacrocorax auritus). Genetic variability was assessed using 60 individuals from three populations. All loci were variable with the number of alleles ranging from two to 17 per locus, and observed heterozygosity varying from 0.05 to 0.89. No loci showed signs of linkage disequilibrium and all loci conformed to Hardy–Weinberg equilibrium frequencies. Further, all loci amplified and were polymorphic in two related Phalacrocorax species. These loci should prove useful for population genetic studies of the double-crested cormorant and other pelecaniform species.

  6. Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of Amoxicillin-Clavulanate–Induced Liver Injury in Spanish Patients

    PubMed Central

    Stephens, Camilla; Moreno-Casares, Antonia; López-Nevot, Miguel-Ángel; García-Cortés, Miren; Medina-Cáliz, Inmaculada; Hallal, Hacibe; Soriano, German; Roman, Eva; Ruiz-Cabello, Francisco; Romero-Gomez, Manuel; Lucena, M. Isabel; Andrade, Raúl J.

    2016-01-01

    Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI) is currently unknown. In this study, we examined KIR gene profiles and HLA class I polymorphisms in amoxicillin-clavulanate (AC) DILI patients in search for potential risk associations. One hundred and two AC DILI patients and 226 controls were genotyped for the presence or absence of 16 KIR loci, including the two pseudogenes 2DP1 and 3DP1. No significant differences were found in the distribution of individual KIRs between patients and controls, which were comparable to previously reported KIR data from ethnically similar cohorts. The 21.6 and 21.2% of the patients and controls, respectively, were homozygous haplotype A carriers, while 78.4 and 78.8%, respectively, contained at least one B haplotype (Bx). The genotypes translated into 27 (AC DILI) and 46 (controls) different gene profiles, with 19 being present in both groups. The most frequent Bx gene profile containing KIRs 2DS2, 2DL2, 2DL3, 2DP1, 2DL1, 3DL1, 2DS4, 3DL2, 3DL3, 2DL4, and 3PD1 was present in 16% of the DILI patients and 14% of the controls. The distribution of HLA class I epitopes did not differ significantly between AC DILI patients and controls. The most frequent receptor-ligand combinations in the DILI patients were 2DL3 + epitope C1 (67%) and 3DL1 + Bw4 motif (67%), while 2DL1 + epitope C2 (69%) and 3DL1 + Bw4 motif (69%) predominated in the controls. This is to our knowledge the first analysis of KIR receptor-HLA ligand

  7. Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of Amoxicillin-Clavulanate-Induced Liver Injury in Spanish Patients.

    PubMed

    Stephens, Camilla; Moreno-Casares, Antonia; López-Nevot, Miguel-Ángel; García-Cortés, Miren; Medina-Cáliz, Inmaculada; Hallal, Hacibe; Soriano, German; Roman, Eva; Ruiz-Cabello, Francisco; Romero-Gomez, Manuel; Lucena, M Isabel; Andrade, Raúl J

    2016-01-01

    Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI) is currently unknown. In this study, we examined KIR gene profiles and HLA class I polymorphisms in amoxicillin-clavulanate (AC) DILI patients in search for potential risk associations. One hundred and two AC DILI patients and 226 controls were genotyped for the presence or absence of 16 KIR loci, including the two pseudogenes 2DP1 and 3DP1. No significant differences were found in the distribution of individual KIRs between patients and controls, which were comparable to previously reported KIR data from ethnically similar cohorts. The 21.6 and 21.2% of the patients and controls, respectively, were homozygous haplotype A carriers, while 78.4 and 78.8%, respectively, contained at least one B haplotype (Bx). The genotypes translated into 27 (AC DILI) and 46 (controls) different gene profiles, with 19 being present in both groups. The most frequent Bx gene profile containing KIRs 2DS2, 2DL2, 2DL3, 2DP1, 2DL1, 3DL1, 2DS4, 3DL2, 3DL3, 2DL4, and 3PD1 was present in 16% of the DILI patients and 14% of the controls. The distribution of HLA class I epitopes did not differ significantly between AC DILI patients and controls. The most frequent receptor-ligand combinations in the DILI patients were 2DL3 + epitope C1 (67%) and 3DL1 + Bw4 motif (67%), while 2DL1 + epitope C2 (69%) and 3DL1 + Bw4 motif (69%) predominated in the controls. This is to our knowledge the first analysis of KIR receptor-HLA ligand

  8. Killer Immunoglobulin-Like Receptor Profiles Are not Associated with Risk of Amoxicillin-Clavulanate–Induced Liver Injury in Spanish Patients

    PubMed Central

    Stephens, Camilla; Moreno-Casares, Antonia; López-Nevot, Miguel-Ángel; García-Cortés, Miren; Medina-Cáliz, Inmaculada; Hallal, Hacibe; Soriano, German; Roman, Eva; Ruiz-Cabello, Francisco; Romero-Gomez, Manuel; Lucena, M. Isabel; Andrade, Raúl J.

    2016-01-01

    Natural killer cells are an integral part of the immune system and represent a large proportion of the lymphocyte population in the liver. The activity of these cells is regulated by various cell surface receptors, such as killer Ig-like receptors (KIR) that bind to human leukocyte antigen (HLA) class I ligands on the target cell. The composition of KIR receptors has been suggested to influence the development of specific diseases, in particularly autoimmune diseases, cancer and reproductive diseases. The role played in idiosyncratic drug-induced liver injury (DILI) is currently unknown. In this study, we examined KIR gene profiles and HLA class I polymorphisms in amoxicillin-clavulanate (AC) DILI patients in search for potential risk associations. One hundred and two AC DILI patients and 226 controls were genotyped for the presence or absence of 16 KIR loci, including the two pseudogenes 2DP1 and 3DP1. No significant differences were found in the distribution of individual KIRs between patients and controls, which were comparable to previously reported KIR data from ethnically similar cohorts. The 21.6 and 21.2% of the patients and controls, respectively, were homozygous haplotype A carriers, while 78.4 and 78.8%, respectively, contained at least one B haplotype (Bx). The genotypes translated into 27 (AC DILI) and 46 (controls) different gene profiles, with 19 being present in both groups. The most frequent Bx gene profile containing KIRs 2DS2, 2DL2, 2DL3, 2DP1, 2DL1, 3DL1, 2DS4, 3DL2, 3DL3, 2DL4, and 3PD1 was present in 16% of the DILI patients and 14% of the controls. The distribution of HLA class I epitopes did not differ significantly between AC DILI patients and controls. The most frequent receptor-ligand combinations in the DILI patients were 2DL3 + epitope C1 (67%) and 3DL1 + Bw4 motif (67%), while 2DL1 + epitope C2 (69%) and 3DL1 + Bw4 motif (69%) predominated in the controls. This is to our knowledge the first analysis of KIR receptor-HLA ligand

  9. Loss-of-function mutations in a glutathione S-transferase suppress the prune-Killer of prune lethal interaction.

    PubMed

    Provost, Elayne; Hersperger, Grafton; Timmons, Lisa; Ho, Wen Qi; Hersperger, Evelyn; Alcazar, Rosa; Shearn, Allen

    2006-01-01

    The prune gene of Drosophila melanogaster is predicted to encode a phosphodiesterase. Null alleles of prune are viable but cause an eye-color phenotype. The abnormal wing discs gene encodes a nucleoside diphosphate kinase. Killer of prune is a missense mutation in the abnormal wing discs gene. Although it has no phenotype by itself even when homozygous, Killer of prune when heterozygous causes lethality in the absence of prune gene function. A screen for suppressors of transgenic Killer of prune led to the recovery of three mutations, all of which are in the same gene. As heterozygotes these mutations are dominant suppressors of the prune-Killer of prune lethal interaction; as homozygotes these mutations cause early larval lethality and the absence of imaginal discs. These alleles are loss-of-function mutations in CG10065, a gene that is predicted to encode a protein with several zinc finger domains and glutathione S-transferase activity. PMID:16143620

  10. Quantitative trait loci for glucosinolate accumulation in Brassica rapa leaves.

    PubMed

    Lou, Ping; Zhao, Jianjun; He, Hongju; Hanhart, Corrie; Del Carpio, Dunia Pino; Verkerk, Ruud; Custers, Jan; Koornneef, Maarten; Bonnema, Guusje

    2008-01-01

    Glucosinolates and their breakdown products have been recognized for their effects on plant defense, human health, flavor and taste of cruciferous vegetables. Despite this importance, little is known about the regulation of the biosynthesis and degradation in Brassica rapa. Here, the identification of quantitative trait loci (QTL) for glucosinolate accumulation in B. rapa leaves in two novel segregating double haploid (DH) populations is reported: DH38, derived from a cross between yellow sarson R500 and pak choi variety HK Naibaicai; and DH30, from a cross between yellow sarson R500 and Kairyou Hakata, a Japanese vegetable turnip variety. An integrated map of 1068 cM with 10 linkage groups, assigned to the international agreed nomenclature, is developed based on the two individual DH maps with the common parent using amplified fragment length polymorphism (AFLP) and single sequence repeat (SSR) markers. Eight different glucosinolate compounds were detected in parents and F(1)s of the DH populations and found to segregate quantitatively in the DH populations. QTL analysis identified 16 loci controlling aliphatic glucosinolate accumulation, three loci controlling total indolic glucosinolate concentration and three loci regulating aromatic glucosinolate concentrations. Both comparative genomic analyses based on Arabidopsis-Brassica rapa synteny and mapping of candidate orthologous genes in B. rapa allowed the selection of genes involved in the glucosinolate biosynthesis pathway that may account for the identified QTL.

  11. Testing independence of fragment lengths within VNTR loci

    SciTech Connect

    Geisser, S. ); Johnson, W. )

    1993-11-01

    Methods that were devised to test independence of the bivariate fragment lengths obtained from VNTR loci are applied to several population databases. It is shown that for many of the probes independence (Hardy-Weinberg equilibrium) cannot be sustained. 3 refs., 3 tabs.

  12. The IQ Quantitative Trait Loci Project: A Critique.

    ERIC Educational Resources Information Center

    King, David

    1998-01-01

    Describes the IQ Quantitative Trait Loci (QTL) project, an attempt to identify genes underlying IQ score variations using maps from the Human Genome Project. The essay argues against funding the IQ QTL project because it will end the debates about the genetic basis of intelligence and may lead directly to eugenic programs of genetic testing. (SLD)

  13. STR data for the 13 CODIS loci in Singapore Malays.

    PubMed

    Ang, H C; Sornarajah, R; Lim, S E S; Syn, C K C; Tan-Siew, W F; Chow, S T; Budowle, Bruce

    2005-03-10

    Allele frequencies for the 13 CODIS (Combined DNA Index System, USA) STR loci included in the AmpFISTR Profiler Plus and AmpFISTR Cofiler kits (Applied Biosystems, Foster City, USA) were determined in a sample of 197 unrelated Malays in Singapore.

  14. Mapping of two suppressors of OVATE (sov) loci in tomato

    PubMed Central

    Rodríguez, G R; Kim, H J; van der Knaap, E

    2013-01-01

    Tomato fruit shape varies significantly in the cultivated germplasm. To a large extent, this variation can be explained by four genes including OVATE. While most varieties with the OVATE mutation bear elongated fruits, some accessions carry round fruit, suggesting the existence of suppressors of OVATE in the germplasm. We developed three intraspecific F2 populations with parents that carried the OVATE mutation but differed in fruit shape. We used a bulk segregant analysis approach and genotyped the extreme classes using a high-throughput genotyping platform, the SolCAP Infinium Assay. The analyses revealed segregation at two quantitative trait loci (QTLs), sov1 and sov2. These loci were confirmed by genotyping and QTL analyses of the entire population. More precise location of those loci using progeny testing confirmed that sov1 on chromosome 10 controlled obovoid and elongated shape, whereas sov2 on chromosome 11 controlled mainly elongated fruit shape. Both loci were located in intervals of <2.4 Mb on their respective chromosomes. PMID:23673388

  15. Chromosomal localization of microsatellite loci in Drosophila mediopunctata.

    PubMed

    Cavasini, Renato; Batista, Marcos Roberto Dias; Klaczko, Louis Bernard

    2015-03-01

    Drosophila mediopunctata has been used as a model organism for genetics and evolutionary studies in the last three decades. A linkage map with 48 microsatellite loci recently published for this species showed five syntenic groups, which had their homology determined to Drosophila melanogaster chromosomes. Then, by inference, each of the groups was associated with one of the five major chromosomes of D. mediopunctata. Our objective was to carry out a genetic (chromosomal) analysis to increase the number of available loci with known chromosomal location. We made a simultaneous analysis of visible mutant phenotypes and microsatellite genotypes in a backcross of a standard strain and a mutant strain, which had each major autosome marked. Hence, we could establish the chromosomal location of seventeen loci; including one from each of the five major linkage groups previously published, and twelve new loci. Our results were congruent with the previous location and they open new possibilities to future work integrating microsatellites, chromosomal inversions, and genetic determinants of physiological and morphological variation. PMID:25983625

  16. Novel loci and pathways significantly associated with longevity.

    PubMed

    Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; Xu, Hanshi; Wang, Mingbang; Ni, Ting; Li, Yang; Yan, Han; Zhang, Jin-Pei; Song, Chun; Chi, Li-Qing; Wang, Han-Ming; Dong, Jie; Zheng, Gu-Yan; Lin, Li; Qian, Feng; Qi, Yanwei; Liu, Xiao; Cao, Hongzhi; Wang, Yinghao; Zhang, Lijuan; Li, Zhaochun; Zhou, Yufeng; Wang, Yan; Lu, Jiehua; Li, Jianxin; Qi, Ming; Bolund, Lars; Yashin, Anatoliy; Land, Kenneth C; Gregory, Simon; Yang, Ze; Gottschalk, William; Tao, Wei; Wang, Jian; Wang, Jun; Xu, Xun; Bae, Harold; Nygaard, Marianne; Christiansen, Lene; Christensen, Kaare; Franceschi, Claudio; Lutz, Michael W; Gu, Jun; Tan, Qihua; Perls, Thomas; Sebastiani, Paola; Deelen, Joris; Slagboom, Eline; Hauser, Elizabeth; Xu, Huji; Tian, Xiao-Li; Yang, Huanming; Vaupel, James W

    2016-01-01

    Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity. PMID:26912274

  17. Overdominant quantitative trait loci for yield and fitness in tomato

    PubMed Central

    Semel, Yaniv; Nissenbaum, Jonathan; Menda, Naama; Zinder, Michael; Krieger, Uri; Issman, Noa; Pleban, Tzili; Lippman, Zachary; Gur, Amit; Zamir, Dani

    2006-01-01

    Heterosis, or hybrid vigor, is a major genetic force that contributes to world food production. The genetic basis of heterosis is not clear, and the importance of loci with overdominant (ODO) effects is debated. One problem has been the use of whole-genome segregating populations, where interactions often mask the effects of individual loci. To assess the contribution of ODO to heterosis in the absence of epistasis, we carried out quantitative genetic and phenotypic analyses on a population of tomato (Solanum lycopersicum) introgression lines (ILs), which carry single marker-defined chromosome segments from the distantly related wild species Solanum pennellii. The ILs revealed 841 quantitative trait loci (QTL) for 35 diverse traits measured in the field on homozygous and heterozygous plants. ILs showing greater reproductive fitness were characterized by the prevalence of ODO QTL, which were virtually absent for the nonreproductive traits. ODO can result from true ODO due to allelic interactions of a single gene or from pseudoODO that involves linked loci with dominant alleles in repulsion. The fact that we detected dominant and recessive QTL for all phenotypic categories but ODO only for the reproductive traits indicates that pseudoODO due to random linkage is unlikely to explain heterosis in the ILs. Thus, we favor the true ODO model involving a single functional Mendelian locus. We propose that the alliance of ODO QTL with higher reproductive fitness was selected for in evolution and was domesticated by man to improve yields of crop plants. PMID:16938842

  18. Overdominant quantitative trait loci for yield and fitness in tomato.

    PubMed

    Semel, Yaniv; Nissenbaum, Jonathan; Menda, Naama; Zinder, Michael; Krieger, Uri; Issman, Noa; Pleban, Tzili; Lippman, Zachary; Gur, Amit; Zamir, Dani

    2006-08-29

    Heterosis, or hybrid vigor, is a major genetic force that contributes to world food production. The genetic basis of heterosis is not clear, and the importance of loci with overdominant (ODO) effects is debated. One problem has been the use of whole-genome segregating populations, where interactions often mask the effects of individual loci. To assess the contribution of ODO to heterosis in the absence of epistasis, we carried out quantitative genetic and phenotypic analyses on a population of tomato (Solanum lycopersicum) introgression lines (ILs), which carry single marker-defined chromosome segments from the distantly related wild species Solanum pennellii. The ILs revealed 841 quantitative trait loci (QTL) for 35 diverse traits measured in the field on homozygous and heterozygous plants. ILs showing greater reproductive fitness were characterized by the prevalence of ODO QTL, which were virtually absent for the nonreproductive traits. ODO can result from true ODO due to allelic interactions of a single gene or from pseudoODO that involves linked loci with dominant alleles in repulsion. The fact that we detected dominant and recessive QTL for all phenotypic categories but ODO only for the reproductive traits indicates that pseudoODO due to random linkage is unlikely to explain heterosis in the ILs. Thus, we favor the true ODO model involving a single functional Mendelian locus. We propose that the alliance of ODO QTL with higher reproductive fitness was selected for in evolution and was domesticated by man to improve yields of crop plants.

  19. Educational Software for Mapping Quantitative Trait Loci (QTL)

    ERIC Educational Resources Information Center

    Helms, T. C.; Doetkott, C.

    2007-01-01

    This educational software was developed to aid teachers and students in their understanding of how the process of identifying the most likely quantitative trait loci (QTL) position is determined between two flanking DNA markers. The objective of the software that we developed was to: (1) show how a QTL is mapped to a position on a chromosome using…

  20. Novel loci and pathways significantly associated with longevity.

    PubMed

    Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; Xu, Hanshi; Wang, Mingbang; Ni, Ting; Li, Yang; Yan, Han; Zhang, Jin-Pei; Song, Chun; Chi, Li-Qing; Wang, Han-Ming; Dong, Jie; Zheng, Gu-Yan; Lin, Li; Qian, Feng; Qi, Yanwei; Liu, Xiao; Cao, Hongzhi; Wang, Yinghao; Zhang, Lijuan; Li, Zhaochun; Zhou, Yufeng; Wang, Yan; Lu, Jiehua; Li, Jianxin; Qi, Ming; Bolund, Lars; Yashin, Anatoliy; Land, Kenneth C; Gregory, Simon; Yang, Ze; Gottschalk, William; Tao, Wei; Wang, Jian; Wang, Jun; Xu, Xun; Bae, Harold; Nygaard, Marianne; Christiansen, Lene; Christensen, Kaare; Franceschi, Claudio; Lutz, Michael W; Gu, Jun; Tan, Qihua; Perls, Thomas; Sebastiani, Paola; Deelen, Joris; Slagboom, Eline; Hauser, Elizabeth; Xu, Huji; Tian, Xiao-Li; Yang, Huanming; Vaupel, James W

    2016-02-25

    Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10(-5)). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity.

  1. Homothetic Transformations and Geometric Loci: Properties of Triangles and Quadrilaterals

    ERIC Educational Resources Information Center

    Mammana, Maria Flavia

    2016-01-01

    In this paper, we use geometric transformations to find some interesting properties related with geometric loci. In particular, given a triangle or a cyclic quadrilateral, the locus generated by the centroid or by the orthocentre (for triangles) or by the anticentre (for cyclic quadrilaterals) when one vertex moves on the circumcircle of the…

  2. Novel loci and pathways significantly associated with longevity

    PubMed Central

    Zeng, Yi; Nie, Chao; Min, Junxia; Liu, Xiaomin; Li, Mengmeng; Chen, Huashuai; Xu, Hanshi; Wang, Mingbang; Ni, Ting; Li, Yang; Yan, Han; Zhang, Jin-Pei; Song, Chun; Chi, Li-Qing; Wang, Han-Ming; Dong, Jie; Zheng, Gu-Yan; Lin, Li; Qian, Feng; Qi, Yanwei; Liu, Xiao; Cao, Hongzhi; Wang, Yinghao; Zhang, Lijuan; Li, Zhaochun; Zhou, Yufeng; Wang, Yan; Lu, Jiehua; Li, Jianxin; Qi, Ming; Bolund, Lars; Yashin, Anatoliy; Land, Kenneth C.; Gregory, Simon; Yang, Ze; Gottschalk, William; Tao, Wei; Wang, Jian; Wang, Jun; Xu, Xun; Bae, Harold; Nygaard, Marianne; Christiansen, Lene; Christensen, Kaare; Franceschi, Claudio; Lutz, Michael W.; Gu, Jun; Tan, Qihua; Perls, Thomas; Sebastiani, Paola; Deelen, Joris; Slagboom, Eline; Hauser, Elizabeth; Xu, Huji; Tian, Xiao-Li; Yang, Huanming; Vaupel, James W.

    2016-01-01

    Only two genome-wide significant loci associated with longevity have been identified so far, probably because of insufficient sample sizes of centenarians, whose genomes may harbor genetic variants associated with health and longevity. Here we report a genome-wide association study (GWAS) of Han Chinese with a sample size 2.7 times the largest previously published GWAS on centenarians. We identified 11 independent loci associated with longevity replicated in Southern-Northern regions of China, including two novel loci (rs2069837-IL6; rs2440012-ANKRD20A9P) with genome-wide significance and the rest with suggestive significance (P < 3.65 × 10−5). Eight independent SNPs overlapped across Han Chinese, European and U.S. populations, and APOE and 5q33.3 were replicated as longevity loci. Integrated analysis indicates four pathways (starch, sucrose and xenobiotic metabolism; immune response and inflammation; MAPK; calcium signaling) highly associated with longevity (P ≤ 0.006) in Han Chinese. The association with longevity of three of these four pathways (MAPK; immunity; calcium signaling) is supported by findings in other human cohorts. Our novel finding on the association of starch, sucrose and xenobiotic metabolism pathway with longevity is consistent with the previous results from Drosophilia. This study suggests protective mechanisms including immunity and nutrient metabolism and their interactions with environmental stress play key roles in human longevity. PMID:26912274

  3. Microsatellite loci for the invasive colonial hydrozoan Cordylophora caspia

    EPA Science Inventory

    Cordylophora caspia, a colonial hydrozoan native to the Ponto-Caspian region, has become a common invader of both fresh and brackish water ecosystems of North America and Europe. Here we describe 11 polymorphic microsatellite loci for this species. Preliminary analyses indicate ...

  4. Prey items and predation behavior of killer whales (Orcinus orca) in Nunavut, Canada based on Inuit hunter interviews

    PubMed Central

    2012-01-01

    Background Killer whales (Orcinus orca) are the most widely distributed cetacean, occurring in all oceans worldwide, and within ocean regions different ecotypes are defined based on prey preferences. Prey items are largely unknown in the eastern Canadian Arctic and therefore we conducted a survey of Inuit Traditional Ecological Knowledge (TEK) to provide information on the feeding ecology of killer whales. We compiled Inuit observations on killer whales and their prey items via 105 semi-directed interviews conducted in 11 eastern Nunavut communities (Kivalliq and Qikiqtaaluk regions) from 2007-2010. Results Results detail local knowledge of killer whale prey items, hunting behaviour, prey responses, distribution of predation events, and prey capture techniques. Inuit TEK and published literature agree that killer whales at times eat only certain parts of prey, particularly of large whales, that attacks on large whales entail relatively small groups of killer whales, and that they hunt cooperatively. Inuit observations suggest that there is little prey specialization beyond marine mammals and there are no definitive observations of fish in the diet. Inuit hunters and elders also documented the use of sea ice and shallow water as prey refugia. Conclusions By combining TEK and scientific approaches we provide a more holistic view of killer whale predation in the eastern Canadian Arctic relevant to management and policy. Continuing the long-term relationship between scientists and hunters will provide for successful knowledge integration and has resulted in considerable improvement in understanding of killer whale ecology relevant to management of prey species. Combining scientists and Inuit knowledge will assist in northerners adapting to the restructuring of the Arctic marine ecosystem associated with warming and loss of sea ice. PMID:22520955

  5. Measurement of serum immunoglobulin concentration in killer whales and sea otters by radial immunodiffusion.

    PubMed

    Taylor, Bernadette C; Brotheridge, Rory M; Jessup, David A; Stott, Jeffrey L

    2002-10-28

    Killer whales and sea otters maintained in captivity are the subjects of routine health monitoring programs, and interest in immunologic studies in sea otters has been rising recently in response to potential impacts from infectious disease and environmental pollution on the threatened southern sea otter population. Development of species-specific reagents for immunologic studies in these two marine mammals is currently in its infancy. In this study, killer whale and sea otter immunoglobulin-specific polyclonal antibodies were generated, and used to develop tests for serum Ig concentration in the killer whale (Orcinus orca) and the southern (Enhydra lutris nereis) and northern sea otter (Enhydra lutris lutris). Killer whale serum IgG was purified using caprylic acid/ammonium sulfate precipitation. Sea otter plasma IgG was purified using protein-A-agarose. Polyclonal anti-Ig antisera were produced in rabbits, and specificity confirmed by immunoelectrophoresis. Radial immunodiffusion was used to measure Ig concentration in serum or plasma samples derived from 21 captive killer whales, 18 wild and 4 captive southern sea otters and 15 wild and 4 captive northern sea otters grouped by age. Mean killer whale serum Ig concentration (+/-95% confidence interval) ranged from 15.04 +/- 3.97 g/l for animals aged 0-5 years to 26.65 +/- 9.8 g/l for animals aged >10 years. Mean sea otter serum Ig concentration (+/-95% confidence interval) ranged from 28.39 +/- 11.00 g/l for southern sub-adults to 32.76 +/- 11.58 g/l for southern adults. No significant difference in serum Ig concentration was found between southern and northern sea otters. Serum Ig concentrations in two northern sea otter pups were low compared to those of adult sea otters. The two serum Ig quantitation assays produced were highly specific and reproducible and will be useful additions to the limited number of tests available for immune function in these marine mammal species. PMID:12383650

  6. Individual killer whale vocal variation during intra-group behavioral dynamics

    NASA Astrophysics Data System (ADS)

    Grebner, Dawn M.

    The scientific goal of this dissertation was to carefully study the signal structure of killer whale communications and vocal complexity and link them to behavioral circumstances. The overall objective of this research sought to provide insight into killer whale call content and usage which may be conveying information to conspecifics in order to maintain group cohesion. Data were collected in the summers of 2006 and 2007 in Johnstone Strait, British Columbia. For both individuals and small groups, vocalizations were isolated using a triangular hydrophone array and the behavioral movement patterns were captured by a theodolite and video camera positioned on a cliff overlooking the hyrophone locations. This dissertation is divided into four analysis chapters. In Chapter 3, discriminant analysis was used to validate the four N04 call subtypes which were originally parsed due to variations in slope segments. The first two functions of the discriminant analysis explained 97% of the variability. Most of the variability for the N04 call was found in the front convex and the terminal portions of the call, while very little variability was found in the center region of the call. This research revealed that individual killer whales produced multiple subtypes of the N04 call. No correlations of behaviors to acoustic parameters obtained were found. The aim of the Chapter 4 was to determine if killer whale calling behavior varied prior to and after the animals had joined. Pulsed call rates were found to be greater pre- compared to post-joining events. Two-way vocal exchanges were more common occurring 74% of the time during pre-joining events. In Chapter 5, initiated and first response to calls varied between age/sex class groups when mothers were separated from an offspring. Solo mothers and calves initiated pulsed calls more often than they responded. Most of the no vocal responses were due to mothers who were foraging. Finally, observations of the frequency split in N04

  7. Does the evolutionary conservation of microsatellite loci imply function?

    SciTech Connect

    Shriver, M.D.; Deka, R.; Ferrell, R.E.

    1994-09-01

    Microsatellites are highly polymorphic tandem arrays of short (1-6 bp) sequence motifs which have been found widely distributed in the genomes of all eukaryotes. We have analyzed allele frequency data on 16 microsatellite loci typed in the great apes (human, chimp, orangutan, and gorilla). The majority of these loci (13) were isolated from human genomic libraries; three were cloned from chimpanzee genomic DNA. Most of these loci are not only present in all apes species, but are polymorphic with comparable levels of heterozygosity and have alleles which overlap in size. The extent of divergence of allele frequencies among these four species were studies using the stepwise-weighted genetic distance (Dsw), which was previously shown to conform to linearity with evolutionary time since divergence for loci where mutations exist in a stepwise fashion. The phylogenetic tree of the great apes constructed from this distance matrix was consistent with the expected topology, with a high bootstrap confidence (82%) for the human/chimp clade. However, the allele frequency distributions of these species are 10 times more similar to each other than expected when they were calibrated with a conservative estimate of the time since separation of humans and the apes. These results are in agreement with sequence-based surveys of microsatellites which have demonstrated that they are highly (90%) conserved over short periods of evolutionary time (< 10 million years) and moderately (30%) conserved over long periods of evolutionary time (> 60-80 million years). This evolutionary conservation has prompted some authors to speculate that there are functional constraints on microsatellite loci. In contrast, the presence of directional bias of mutations with constraints and/or selection against aberrant sized alleles can explain these results.

  8. Genomewide meta-analysis identifies novel multiple sclerosis susceptibility loci

    PubMed Central

    Patsopoulos, Nikolaos A.; de Bakker, Paul I.W.

    2011-01-01

    Objective To perform a one-stage meta-analysis of genome-wide association studies (GWAS) of multiple sclerosis (MS) susceptibility and explore functional consequences of new susceptibility loci. Methods We synthesized 7 MS GWAS. Each dataset was imputed using HapMap phase II and a per-SNP meta-analysis was performed across the 7 datasets. We explored RNA expression data using a quantitative trait analysis in peripheral blood mononuclear cells (PBMCs) of 228 subjects with demyelinating disease. Results We meta-analyzed 2,529,394 unique SNPs in 5,545 cases and 12,153 controls. We identified three novel susceptibility alleles: rs170934T at 3p24.1 (OR=1.17, P = 1.6 × 10−8) near EOMES, rs2150702G in the second intron of MLANA on chromosome 9p24.1 (OR = 1.16, P = 3.3 × 10−8), and rs6718520A in an intergenic region on chromosome 2p21, with THADA as the nearest flanking gene (OR = 1.17, P = 3.4 × 10−8). The three new loci do not have a strong “cis” effect on RNA expression in PBMCs. Ten other susceptibility loci had a suggestive P<1×10−6, some of which have evidence of association in other inflammatory diseases, i.e. IL12B, TAGAP, PLEK, and ZMIZ1. Interpretation We have performed a meta-analysis of GWAS in MS that more than doubles the size of previous gene discovery efforts and highlights three novel MS susceptibility loci. These and additional loci with suggestive evidence of association are excellent candidates for further investigations to refine and validate their role in the genetic architecture of MS. PMID:22190364

  9. A biodegradable killer microparticle to selectively deplete antigen-specific T cells in vitro and in vivo

    PubMed Central

    Wang, Wei; Fang, Kun; Li, Miao-Chen; Chang, Di; Shahzad, Khawar Ali; Xu, Tao; Zhang, Lei; Gu, Ning; Shen, Chuan-Lai

    2016-01-01

    The specific eradication of pathogenic T cells for the treatment of allograft rejections and autoimmune disorders without impairment of overall immune function is a fundamental goal. Here, cell-sized poly(lactic-co-glycolic acid) microparticles (PLGA MPs) were prepared as a scaffold to co-display the peptide/major histocompatibility complex (pMHC, target antigen) and anti-Fas monoclonal antibody (apoptosis-inducing molecule) for the generation of biodegradable killer MPs. Ovalbumin (OVA) antigen-targeted killer MPs significantly depleted OVA-specific CD8+ T cells in an antigen-specific manner, both in vitro and in OT-1 mice. After intravenous administration, the killer MPs predominantly accumulated in the liver, lungs, and gut of OT-1 mice with a retention time of up to 48 hours. The killing effects exerted by killer MPs persisted for 4 days after two injections. Moreover, the H-2Kb alloantigen-targeted killer MPs were able to eliminate low-frequency alloreactive T cells and prolong alloskin graft survival for 41.5 days in bm1 mice. Our data indicate that PLGA-based killer MPs are capable of specifically depleting pathogenic T cells, which highlights their therapeutic potential for treating allograft rejection and autoimmune disorders. PMID:26910923

  10. Hematological and serum biochemical analytes reflect physiological challenges during gestation and lactation in killer whales (Orcinus orca).

    PubMed

    Robeck, Todd R; Nollens, Hendrik H

    2013-01-01

    Gestation and lactation result in metabolic alterations of the dam because of varying demands of the fetus and offspring during the different stages of development. Despite killer whales (Orcinus orca) having one of the longest gestations and highest birth weights of all mammals in human care, these metabolic alterations, and their impact on the physiology of the dam have not been measured. The objectives of this analysis were to determine if physiologic demands on the killer whale during pregnancy and lactation have measurable effects on hematology and biochemical analytes and if detectable, to compare these changes to those which are observed in other mammalian species. Forty hematologic and biochemical analytes from seven female killer whales (22 pregnancies, 1,507 samples) were compared between the following stages: (1) non-pregnant or lactating (control); (2) gestation; and (3) the first 12 months of lactation. Decreased hematocrit, hemoglobin, and red blood cell counts were indicative of plasma volume expansion during mid and late gestation. The killer whales exhibited a progressively increasing physiologic inflammatory state leading up to parturition. Gestation and lactation caused significant shifts in the serum lipid profiles. Gestation and lactation cause significant physiologic changes in the killer whale dam. The last 12 months of gestation had greater physiological impact than lactation, but changes associated with and immediately following parturition were the most dramatic. During this period, killer whales may experience increased susceptibility to illness, and anthropogenic and environmental disturbances.

  11. Loss of Arctic sea ice causing punctuated change in sightings of killer whales (Orcinus orca) over the past century.

    PubMed

    Higdon, Jeff W; Ferguson, Steven H

    2009-07-01

    Killer whales (Orcinus orca) are major predators that may reshape marine ecosystems via top-down forcing. Climate change models predict major reductions in sea ice with the subsequent expectation for readjustments of species' distribution and abundance. Here, we measure changes in killer whale distribution in the Hudson Bay region with decreasing sea ice as an example of global readjustments occurring with climate change. We summarize records of killer whales in Hudson Bay, Hudson Strait, and Foxe Basin in the eastern Canadian Arctic and relate them to an historical sea ice data set while accounting for spatial and temporal autocorrelation in the data. We find evidence for "choke points," where sea ice inhibits killer whale movement, thereby creating restrictions to their Arctic distribution. We hypothesize that a threshold exists in seasonal sea ice concentration within these choke points that results in pulses in advancements in distribution of an ice-avoiding predator. Hudson Strait appears to have been a significant sea ice choke point that opened up .approximately 50 years ago allowing for an initial punctuated appearance of killer whales followed by a gradual advancing distribution within the entire Hudson Bay region. Killer whale sightings have increased exponentially and are now reported in the Hudson Bay region every summer. We predict that other choke points will soon open up with continued sea ice melt producing punctuated predator-prey trophic cascades across the Arctic.

  12. Call types of Bigg's killer whales (Orcinus orca) in western Alaska: Using vocal dialects to assess population structure

    NASA Astrophysics Data System (ADS)

    Sharpe, Deborah Lynn

    Apex predators are important indicators of ecosystem health, but little is known about the population structure of Bigg's killer whales ( Orcinus orca; i.e. 'transient' ecotype) in western Alaska. Currently, all Bigg's killer whales in western Alaska are ascribed to a single broad stock for management under the US Marine Mammal Protection Act. However, recent nuclear microsatellite and mitochondrial DNA analyses indicate that this stock is likely comprised of genetically distinct sub-populations. In accordance with what is known about killer whale vocal dialects in other locations, I sought to evaluate Bigg's killer whale population structure by examining the spatial distribution of group-specific call types in western Alaska. Digital audio recordings were collected from 33 encounters with Bigg's killer whales throughout the Aleutian and Pribilof Islands in the summers of 2001-2007 and 2009-2010. Recorded calls were perceptually classified into discrete types and then quantitatively described using 12 structural and time-frequency measures. Resulting call categories were objectively validated using a random forest approach. A total of 36 call types and subtypes were identified across the entire study area, and regional patterns of call type usage revealed three distinct dialects, each of which corresponding to proposed genetic delineations. I suggest that at least three acoustically and genetically distinct subpopulations are present in western Alaska, and put forth an initial catalog for this area describing the regional vocal repertoires of Bigg's killer whale call types.

  13. A biodegradable killer microparticle to selectively deplete antigen-specific T cells in vitro and in vivo.

    PubMed

    Wang, Wei; Fang, Kun; Li, Miao-Chen; Chang, Di; Shahzad, Khawar Ali; Xu, Tao; Zhang, Lei; Gu, Ning; Shen, Chuan-Lai

    2016-03-15

    The specific eradication of pathogenic T cells for the treatment of allograft rejections and autoimmune disorders without impairment of overall immune function is a fundamental goal. Here, cell-sized poly(lactic-co-glycolic acid) microparticles (PLGA MPs) were prepared as a scaffold to co-display the peptide/major histocompatibility complex (pMHC, target antigen) and anti-Fas monoclonal antibody (apoptosis-inducing molecule) for the generation of biodegradable killer MPs. Ovalbumin (OVA) antigen-targeted killer MPs significantly depleted OVA-specific CD8+ T cells in an antigen-specific manner, both in vitro and in OT-1 mice. After intravenous administration, the killer MPs predominantly accumulated in the liver, lungs, and gut of OT-1 mice with a retention time of up to 48 hours. The killing effects exerted by killer MPs persisted for 4 days after two injections. Moreover, the H-2Kb alloantigen-targeted killer MPs were able to eliminate low-frequency alloreactive T cells and prolong alloskin graft survival for 41.5 days in bm1 mice. Our data indicate that PLGA-based killer MPs are capable of specifically depleting pathogenic T cells, which highlights their therapeutic potential for treating allograft rejection and autoimmune disorders.

  14. Hematological and serum biochemical analytes reflect physiological challenges during gestation and lactation in killer whales (Orcinus orca).

    PubMed

    Robeck, Todd R; Nollens, Hendrik H

    2013-01-01

    Gestation and lactation result in metabolic alterations of the dam because of varying demands of the fetus and offspring during the different stages of development. Despite killer whales (Orcinus orca) having one of the longest gestations and highest birth weights of all mammals in human care, these metabolic alterations, and their impact on the physiology of the dam have not been measured. The objectives of this analysis were to determine if physiologic demands on the killer whale during pregnancy and lactation have measurable effects on hematology and biochemical analytes and if detectable, to compare these changes to those which are observed in other mammalian species. Forty hematologic and biochemical analytes from seven female killer whales (22 pregnancies, 1,507 samples) were compared between the following stages: (1) non-pregnant or lactating (control); (2) gestation; and (3) the first 12 months of lactation. Decreased hematocrit, hemoglobin, and red blood cell counts were indicative of plasma volume expansion during mid and late gestation. The killer whales exhibited a progressively increasing physiologic inflammatory state leading up to parturition. Gestation and lactation caused significant shifts in the serum lipid profiles. Gestation and lactation cause significant physiologic changes in the killer whale dam. The last 12 months of gestation had greater physiological impact than lactation, but changes associated with and immediately following parturition were the most dramatic. During this period, killer whales may experience increased susceptibility to illness, and anthropogenic and environmental disturbances. PMID:23813680

  15. Thousands of microsatellite loci from the venomous coralsnake (Micrurus fulvius) and variability of select loci across populations and related species

    PubMed Central

    Castoe, Todd A.; Streicher, Jeffrey W.; Meik, Jesse M.; Ingrasci, Matthew J.; Poole, Alexander W.; de Koning, A.P. Jason; Campbell, Jonathan A.; Parkinson, Christopher L.; Smith, Eric N.; Pollock, David D.

    2012-01-01

    Studies of population genetics increasingly use next-generation DNA sequencing to identify microsatellite loci in non-model organisms. There are, however, relatively few studies that validate the feasibility of transitioning from marker development to experimental application across populations and species. North American coralsnakes of the Micrurus fulvius species complex occur in the United States and Mexico, and little is known about their population structure and phylogenetic relationships. This absence of information and population genetics markers is particularly concerning because they are highly venomous and have important implications on human health. To alleviate this problem in coralsnakes, we investigated the feasibility of using 454 shotgun sequences for microsatellite marker development. First, a genomic shotgun library from a single individual was sequenced (~7.74 megabases; 26,831 reads) to identify potentially amplifiable microsatellite loci (PALs). We then hierarchically sampled 76 individuals from throughout the geographic distribution of the species complex and examined whether PALs were amplifiable and polymorphic. Approximately half of the loci tested were readily amplifiable from all individuals, and 80% of the loci tested for variation were variable and thus informative as population genetic markers. To evaluate the repetitive landscape characteristics across multiple snakes, we also compared microsatellite content between the coralsnake and two other previously sampled snakes, the venomous copperhead (Agkistrodon contortrix) and Burmese python (Python molurus). PMID:22938699

  16. Thousands of microsatellite loci from the venomous coralsnake Micrurus fulvius and variability of select loci across populations and related species.

    PubMed

    Castoe, Todd A; Streicher, Jeffrey W; Meik, Jesse M; Ingrasci, Matthew J; Poole, Alexander W; de Koning, A P Jason; Campbell, Jonathan A; Parkinson, Christopher L; Smith, Eric N; Pollock, David D

    2012-11-01

    Studies of population genetics increasingly use next-generation DNA sequencing to identify microsatellite loci in nonmodel organisms. There are, however, relatively few studies that validate the feasibility of transitioning from marker development to experimental application across populations and species. North American coralsnakes of the Micrurus fulvius species complex occur in the United States and Mexico, and little is known about their population structure and phylogenetic relationships. This absence of information and population genetics markers is particularly concerning because they are highly venomous and have important implications on human health. To alleviate this problem in coralsnakes, we investigated the feasibility of using 454 shotgun sequences for microsatellite marker development. First, a genomic shotgun library from a single individual was sequenced (approximately 7.74 megabases; 26,831 reads) to identify potentially amplifiable microsatellite loci (PALs). We then hierarchically sampled 76 individuals from throughout the geographic distribution of the species complex and examined whether PALs were amplifiable and polymorphic. Approximately half of the loci tested were readily amplifiable from all individuals, and 80% of the loci tested for variation were variable and thus informative as population genetic markers. To evaluate the repetitive landscape characteristics across multiple snakes, we also compared microsatellite content between the coralsnake and two other previously sampled snakes, the venomous copperhead (Agkistrodon contortrix) and Burmese python (Python molurus).

  17. Thousands of microsatellite loci from the venomous coralsnake Micrurus fulvius and variability of select loci across populations and related species.

    PubMed

    Castoe, Todd A; Streicher, Jeffrey W; Meik, Jesse M; Ingrasci, Matthew J; Poole, Alexander W; de Koning, A P Jason; Campbell, Jonathan A; Parkinson, Christopher L; Smith, Eric N; Pollock, David D

    2012-11-01

    Studies of population genetics increasingly use next-generation DNA sequencing to identify microsatellite loci in nonmodel organisms. There are, however, relatively few studies that validate the feasibility of transitioning from marker development to experimental application across populations and species. North American coralsnakes of the Micrurus fulvius species complex occur in the United States and Mexico, and little is known about their population structure and phylogenetic relationships. This absence of information and population genetics markers is particularly concerning because they are highly venomous and have important implications on human health. To alleviate this problem in coralsnakes, we investigated the feasibility of using 454 shotgun sequences for microsatellite marker development. First, a genomic shotgun library from a single individual was sequenced (approximately 7.74 megabases; 26,831 reads) to identify potentially amplifiable microsatellite loci (PALs). We then hierarchically sampled 76 individuals from throughout the geographic distribution of the species complex and examined whether PALs were amplifiable and polymorphic. Approximately half of the loci tested were readily amplifiable from all individuals, and 80% of the loci tested for variation were variable and thus informative as population genetic markers. To evaluate the repetitive landscape characteristics across multiple snakes, we also compared microsatellite content between the coralsnake and two other previously sampled snakes, the venomous copperhead (Agkistrodon contortrix) and Burmese python (Python molurus). PMID:22938699

  18. Severity of killer whale behavioral responses to ship noise: a dose-response study.

    PubMed

    Williams, Rob; Erbe, Christine; Ashe, Erin; Beerman, Amber; Smith, Jodi

    2014-02-15

    Critical habitats of at-risk populations of northeast Pacific "resident" killer whales can be heavily trafficked by large ships, with transits occurring on average once every hour in busy shipping lanes. We modeled behavioral responses of killer whales to ship transits during 35 "natural experiments" as a dose-response function of estimated received noise levels in both broadband and audiogram-weighted terms. Interpreting effects is contingent on a subjective and seemingly arbitrary decision about severity threshold indicating a response. Subtle responses were observed around broadband received levels of 130 dB re 1 μPa (rms); more severe responses are hypothesized to occur at received levels beyond 150 dB re 1 μPa, where our study lacked data. Avoidance responses are expected to carry minor energetic costs in terms of increased energy expenditure, but future research must assess the potential for reduced prey acquisition, and potential population consequences, under these noise levels. PMID:24373666

  19. In vitro induction of lymphokine-activated killer (LAK) activity in patients with neuroblastoma.

    PubMed

    Handgretinger, R; Bruchelt, G; Kimmig, A; Dopfer, R; Niethammer, D; Treuner, J

    1989-01-01

    Therapy of disseminated neuroblastoma remains an unsolved problem in pediatric oncology. Therefore, new therapeutic approaches have to be developed for this malignancy. In this paper, we investigated the possibility of the in vitro generation and expansion of lymphokine-activated killer (LAK) cells in patients with disseminated neuroblastoma. Although the patients had very low Natural Killer (NK) activity, it was possible to induce LAK activity in peripheral mononuclear lymphocytes (PMNC) by incubation with Interleukin-2 (IL-2). Moreover, the PMNCs could be expanded up to 50-fold in the presence of Interleukin-2 while maintaining or even increasing their LAK activity. The target cells were neuroblastoma cell lines and, in one case, autologous neuroblastoma cells. Additionally, it was possible to induce LAK cell activity against autologous neuroblastoma cells in bone marrow-derived mononuclear cells.

  20. The inpatient evaluation and treatment of a self-professed budding serial killer.

    PubMed

    Reisner, Andrew D; McGee, Mark; Noffsinger, Stephen G

    2003-02-01

    The authors present the case of a man who was hospitalized after claiming that he was about to become a serial killer. The patient presented with extensive written homicidal fantasies and homicidal intentions without evidence of actual homicidal acts. In addition to routine assessments, hospital staff members used case conferences, psychological testing, outside forensic consultation, and a forensic review process to make decisions regarding diagnosis, treatment planning, and discharge. The patient was discharged after 8 months of inpatient treatment and was apparently free of homicidal impulses or symptoms of severe mental illness. A 2-year court commitment allowed for the enactment and potential enforcement of a discharge plan that was endorsed by the patient, the hospital, and community care providers. The authors review diagnostic and risk management issues. Comparisons with known features of typical serial killers are made.

  1. High-frequency modulated signals of killer whales (Orcinus orca) in the North Pacific.

    PubMed

    Simonis, Anne E; Baumann-Pickering, Simone; Oleson, Erin; Melcón, Mariana L; Gassmann, Martin; Wiggins, Sean M; Hildebrand, John A

    2012-04-01

    Killer whales in the North Pacific, similar to Atlantic populations, produce high-frequency modulated signals, based on acoustic recordings from ship-based hydrophone arrays and autonomous recorders at multiple locations. The median peak frequency of these signals ranged from 19.6-36.1 kHz and median duration ranged from 50-163 ms. Source levels were 185-193 dB peak-to-peak re: 1 μPa at 1 m. These uniform, repetitive, down-swept signals are similar to bat echolocation signals and possibly could have echolocation functionality. A large geographic range of occurrence suggests that different killer whale ecotypes may utilize these signals.

  2. Interaction of SMKT, a killer toxin produced by Pichia farinosa, with the yeast cell membranes.

    PubMed

    Suzuki, C; Ando, Y; Machida, S

    2001-12-01

    SMKT (salt-mediated killer toxin), a killer toxin produced by the halotolerant yeast, Pichia farinosa, kills yeasts of several genera, including Saccharomyces cerevisiae. To elucidate the killing mechanism of SMKT, we examined the interaction of SMKT with membranes using liposomes. Leakage of calcein from calcein-entrapped liposomes was observed in the presence of SMKT. Destruction of liposomes was observed by dark-field microscopy. Comparison of intact S. cerevisiae cells with SMKT-treated cells by dark-field microscopy indicated that the spherical cell membrane is disrupted by SMKT. Using sodium carbonate extraction, we obtained direct evidence for the first time that SMKT is associated with the membrane of sensitive cells. Our results indicate that SMKT kills sensitive S. cerevisiae by interacting with the yeast cell membrane.

  3. The production and confinement of runaway electrons with impurity killer pellets in DIII-D

    SciTech Connect

    Evans, T.E.; Taylor, P.L.; Whyte, D.G.

    1998-12-01

    Prompt runaway electron bursts, generated by rapidly cooling DIII-D plasmas with argon killer pellets, are used to test a recent knock-on avalanche theory describing the growth of multi-MeV runaway electron currents during disruptions in tokamaks. Runaway current amplitudes, observed during some but not all DIII-D current quenches, are consistent with growth rates predicted by the theory assuming a pre-current quench runaway electron density of approximately 10{sup 15} m{sup {minus}3}. Argon killer pellet modeling yields runaway densities of between 10{sup 15}--10{sup 16} m{sup {minus}3} in these discharges. Although knock-on avalanching appears to agree rather well with the measurements, relatively small avalanche amplification factors combined with uncertainties in the spatial distribution of pellet mass and cooling rates make it difficult to unambiguously confirm the proposed theory with existing data.

  4. Effects of OK-432 on murine bone marrow and the production of natural killer cells

    SciTech Connect

    Pollack, S.B.; Rosse, C.

    1985-01-01

    The streptococcal preparation, OK-432, which augments anti-tumor responses in humans and mice, has been shown to be a potent immunomodulator. Among its effects is a pronounced augmentation of natural killer (NK) activity. The hypothesis that OK-432 alters the rates of production and maturation of NK cells in the bone marrow was tested. Studies to determine the kinetic parameters of NK cell production in normal C57BL/6J mice using tritiated thymidine, /sup 3/H-TdR, as a DNA marker are described. We are now extending those studies to determine the effect of OK-432 on the bone marrow and on the production of NK cells in the marrow. Initial observations are reported which indicate that OK-432 has profound effects on the cellularity and mitotic activity of the bone marrow, and in particular, on cells with the characteristics of natural killer cells within the marrow. 17 refs., 3 figs., 4 tabs.

  5. Killer-cell immunoglobulin-like receptor genes and ligands and their role in hematologic malignancies.

    PubMed

    Varbanova, Viktoria; Naumova, Elissaveta; Mihaylova, Anastasiya

    2016-04-01

    Natural killer (NK) cells are considered crucial for the elimination of emerging tumor cells. Effector NK-cell functions are controlled by interactions of inhibitory and activating killer-cell immunoglobulin-like receptors (KIRs) on NK cells with human leukocyte antigen (HLA) class I ligands on target cells. KIR and HLA are highly polymorphic genetic systems segregating independently, creating a great diversity in KIR/HLA gene profiles in different individuals. There is an increasing evidence supporting the relevance of KIR and HLA ligand gene background for the occurrence and outcome of certain cancers. However, the data are still controversial and the mechanisms of receptor-ligand mediated NK-cell action remain unclear. Here, the main characteristics and functions of KIRs and their HLA class I ligands are reviewed. In addition, we review the HLA and KIR correlations with different hematological malignancies and discuss our current understanding of the biological significance and mechanisms underlying these associations.

  6. The inpatient evaluation and treatment of a self-professed budding serial killer.

    PubMed

    Reisner, Andrew D; McGee, Mark; Noffsinger, Stephen G

    2003-02-01

    The authors present the case of a man who was hospitalized after claiming that he was about to become a serial killer. The patient presented with extensive written homicidal fantasies and homicidal intentions without evidence of actual homicidal acts. In addition to routine assessments, hospital staff members used case conferences, psychological testing, outside forensic consultation, and a forensic review process to make decisions regarding diagnosis, treatment planning, and discharge. The patient was discharged after 8 months of inpatient treatment and was apparently free of homicidal impulses or symptoms of severe mental illness. A 2-year court commitment allowed for the enactment and potential enforcement of a discharge plan that was endorsed by the patient, the hospital, and community care providers. The authors review diagnostic and risk management issues. Comparisons with known features of typical serial killers are made. PMID:12613432

  7. Severity of killer whale behavioral responses to ship noise: a dose-response study.

    PubMed

    Williams, Rob; Erbe, Christine; Ashe, Erin; Beerman, Amber; Smith, Jodi

    2014-02-15

    Critical habitats of at-risk populations of northeast Pacific "resident" killer whales can be heavily trafficked by large ships, with transits occurring on average once every hour in busy shipping lanes. We modeled behavioral responses of killer whales to ship transits during 35 "natural experiments" as a dose-response function of estimated received noise levels in both broadband and audiogram-weighted terms. Interpreting effects is contingent on a subjective and seemingly arbitrary decision about severity threshold indicating a response. Subtle responses were observed around broadband received levels of 130 dB re 1 μPa (rms); more severe responses are hypothesized to occur at received levels beyond 150 dB re 1 μPa, where our study lacked data. Avoidance responses are expected to carry minor energetic costs in terms of increased energy expenditure, but future research must assess the potential for reduced prey acquisition, and potential population consequences, under these noise levels.

  8. PCR primers for microsatellite loci in the desert tortoise (Gopherus agassizii, Testudinidae)

    USGS Publications Warehouse

    Edwards, T.; Goldberg, C.S.; Kaplan, M.E.; Schwalbe, C.R.; Swann, D.E.

    2003-01-01

    The desert tortoise, Gopherus agassizii, is a threatened species native to the North American desert southwest and is recognized as having distinct Mojave and Sonoran populations. We identified six polymorphic microsatellite loci in the desert tortoise. All six loci were polymorphic in Sonoran samples. Five of the loci were variable in Mojave samples with varying degrees of amplification success. Two of the loci exhibited low allelic variation (2-3 alleles) while four were highly variable (8-27 alleles).

  9. Regulation of natural killer activity of lymphocytes from normal subjects and patients with chronic lymphatic leukemia by interaction between T and non-T cells

    SciTech Connect

    Khonina, N.A.; Shubinskii, G.Z.; Lozovoi, V.P.

    1987-08-01

    The authors study the effect of culture of human cells on functional activity of natural killer cells and investigate the possible mechanisms of regulation of natural killer activity by acting on cytodifferentiation of lymphocytes in normal subjects and in patients with the B-cell variant of chromic lymphatic leukemia. To estimate natural killer cell function, a membranotoxic test was carried out, using cells of the transplantable line K-562, labeled with /sup 3/H-uridine as the targets.

  10. Ecological knowledge, leadership, and the evolution of menopause in killer whales.

    PubMed

    Brent, Lauren J N; Franks, Daniel W; Foster, Emma A; Balcomb, Kenneth C; Cant, Michael A; Croft, Darren P

    2015-03-16

    Classic life-history theory predicts that menopause should not occur because there should be no selection for survival after the cessation of reproduction [1]. Yet, human females routinely live 30 years after they have stopped reproducing [2]. Only two other species-killer whales (Orcinus orca) and short-finned pilot whales (Globicephala macrorhynchus) [3, 4]-have comparable postreproductive lifespans. In theory, menopause can evolve via inclusive fitness benefits [5, 6], but the mechanisms by which postreproductive females help their kin remain enigmatic. One hypothesis is that postreproductive females act as repositories of ecological knowledge and thereby buffer kin against environmental hardships [7, 8]. We provide the first test of this hypothesis using a unique long-term dataset on wild resident killer whales. We show three key results. First, postreproductively aged females lead groups during collective movement in salmon foraging grounds. Second, leadership by postreproductively aged females is especially prominent in difficult years when salmon abundance is low. This finding is critical because salmon abundance drives both mortality and reproductive success in resident killer whales [9, 10]. Third, females are more likely to lead their sons than they are to lead their daughters, supporting predictions of recent models [5] of the evolution of menopause based on kinship dynamics. Our results show that postreproductive females may boost the fitness of kin through the transfer of ecological knowledge. The value gained from the wisdom of elders can help explain why female resident killer whales and humans continue to live long after they have stopped reproducing. PMID:25754636

  11. An agent-based model of dialect evolution in killer whales.

    PubMed

    Filatova, Olga A; Miller, Patrick J O

    2015-05-21

    The killer whale is one of the few animal species with vocal dialects that arise from socially learned group-specific call repertoires. We describe a new agent-based model of killer whale populations and test a set of vocal-learning rules to assess which mechanisms may lead to the formation of dialect groupings observed in the wild. We tested a null model with genetic transmission and no learning, and ten models with learning rules that differ by template source (mother or matriline), variation type (random errors or innovations) and type of call change (no divergence from kin vs. divergence from kin). The null model without vocal learning did not produce the pattern of group-specific call repertoires we observe in nature. Learning from either mother alone or the entire matriline with calls changing by random errors produced a graded distribution of the call phenotype, without the discrete call types observed in nature. Introducing occasional innovation or random error proportional to matriline variance yielded more or less discrete and stable call types. A tendency to diverge from the calls of related matrilines provided fast divergence of loose call clusters. A pattern resembling the dialect diversity observed in the wild arose only when rules were applied in combinations and similar outputs could arise from different learning rules and their combinations. Our results emphasize the lack of information on quantitative features of wild killer whale dialects and reveal a set of testable questions that can draw insights into the cultural evolution of killer whale dialects. PMID:25817037

  12. Carbamate pesticide-induced apoptosis and necrosis in human natural killer cells.

    PubMed

    Li, Q; Kobayashi, M; Kawada, T

    2014-01-01

    We previously found that ziram, a carbamate fungicide, significantly induced apoptosis and necrosis in human NK-92MI, a natural killer cell line. To investigate whether other carbamate pesticides also induce apoptosis and necrosis in human natural killer cell, we conducted further experiments with NK-92CI, a human natural killer cell line using a more sensitive assay. NK-92CI cells were treated with ziram, thiram, maneb or carbaryl at 0.031-40 microM for 2-24 h in the present study. Apoptosis and necrosis were determined by FITC-Annexin-V/PI staining. To explore the mechanism of apoptosis, intracellular levels of active caspases 3 and mitochondrial cytochrome-c release were determined by flow cytometry. We found that ziram and thiram also induced apoptosis and necrosis in a time- and dose-dependent manner; however, maneb and carbaryl induced apoptosis and necrosis only at higher doses in NK-92CI cells. The strength of the apoptosis-inducing effect differed among the pesticides, and the order was as follows: thiram > ziram greater than maneb greater than carbaryl. NK-92CI was more sensitive to ziram than NK-92MI. Moreover, ziram and thiram significantly increased the intracellular level of active caspase 3 in NK-92CI and caspase inhibitor significantly inhibited the apoptosis. Ziram and thiram significantly caused mitochondrial cytochrome-c release in NK-92CI. These findings indicate that carbamate pesticides can induce apoptosis in natural killer cells, and the apoptosis is mediated by both the caspase-cascade and mitochondrial cytochrome-c pathways.

  13. Ecological knowledge, leadership, and the evolution of menopause in killer whales.

    PubMed

    Brent, Lauren J N; Franks, Daniel W; Foster, Emma A; Balcomb, Kenneth C; Cant, Michael A; Croft, Darren P

    2015-03-16

    Classic life-history theory predicts that menopause should not occur because there should be no selection for survival after the cessation of reproduction [1]. Yet, human females routinely live 30 years after they have stopped reproducing [2]. Only two other species-killer whales (Orcinus orca) and short-finned pilot whales (Globicephala macrorhynchus) [3, 4]-have comparable postreproductive lifespans. In theory, menopause can evolve via inclusive fitness benefits [5, 6], but the mechanisms by which postreproductive females help their kin remain enigmatic. One hypothesis is that postreproductive females act as repositories of ecological knowledge and thereby buffer kin against environmental hardships [7, 8]. We provide the first test of this hypothesis using a unique long-term dataset on wild resident killer whales. We show three key results. First, postreproductively aged females lead groups during collective movement in salmon foraging grounds. Second, leadership by postreproductively aged females is especially prominent in difficult years when salmon abundance is low. This finding is critical because salmon abundance drives both mortality and reproductive success in resident killer whales [9, 10]. Third, females are more likely to lead their sons than they are to lead their daughters, supporting predictions of recent models [5] of the evolution of menopause based on kinship dynamics. Our results show that postreproductive females may boost the fitness of kin through the transfer of ecological knowledge. The value gained from the wisdom of elders can help explain why female resident killer whales and humans continue to live long after they have stopped reproducing.

  14. Sadism linked to loneliness: psychodynamic dimensions of the sadistic serial killer Jeffrey Dahmer.

    PubMed

    Martens, Willem H J

    2011-08-01

    In this article the psychodynamic link between loneliness and sadism is examined on basis of a case report of the sadistic and cannibalistic serial killer Jeffery Dahmer. Envy, shame/rage mechanism, a disturbed oral-sadistic development, castration fear and severe feelings of inferiority, the conviction of being unlovable and unacceptable, need to diminish tension, powerful and sadistic fantasies as a consequence of inadequate and frustrated parenting, and reality distortion appear to be involved in sadistic etiology. PMID:21864144

  15. Natural killer T cell strategies to combat Epstein–Barr virus infection

    PubMed Central

    Priatel, John J; Chung, Brian K; Tsai, Kevin; Tan, Rusung

    2014-01-01

    Epstein–Barr virus (EBV) infection results in rapid loss of CD1d expression from the surface of infected B cells, thus enabling the virus to evade immune recognition by natural killer T (NKT) cells. Using pharmacologic means to boost CD1d expression, potent NKT cell effector functions can be elicited toward EBV-infected B cells, suggesting the promise of novel strategies to target EBV-associated diseases such as some B-cell malignancies. PMID:25050206

  16. Noninvasive Imaging of Natural Killer Cell-Mediated Apoptosis in a Mouse Tumor Model.

    PubMed

    Singh, Thoudam Debraj; Lee, Jaetae; Jeon, Yong Hyun

    2016-01-01

    Natural killer (NK) cells are cytotoxic lymphocytes that induce apoptosis in cancer cells infected with viruses and bacteria through a caspase-3-dependent pathway. Effective NK cell-based immunotherapy requires highly sensitive imaging tools for in vivo monitoring of the dynamic events involved in apoptosis. Here, we describe a noninvasive bioluminescence imaging approach to determine the antitumor effects of NK cell-based therapy by serial imaging of caspase-3-dependent apoptosis in a mouse model of human glioma. PMID:27177676

  17. Development of microsatellite loci for the endangered species Pityopsis ruthii (Asteraceae)1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Premise of the study: Microsatellite loci were developed for the endangered species Pityopsis ruthii and will permit genetic and conservation studies of the species. Methods and Results:A microsatellite enriched library was used to develop 12 polymorphic microsatellite loci for P. ruthii. The loci ...

  18. Isolation and characterization of microsatellite Loci for Cornus sanguniea (Cornaceae) 1

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Premise of the study: Microsatellite loci were developed for Cornus sanguinea and will permit genetic and conservation studies of the species. Methods and Results: A microsatellite-enriched library was used to develop 16 polymorphic microsatellite loci for C. sanguinea. The loci amplified 5-11 allel...

  19. Pilot Whales Attracted to Killer Whale Sounds: Acoustically-Mediated Interspecific Interactions in Cetaceans

    PubMed Central

    Curé, Charlotte; Antunes, Ricardo; Samarra, Filipa; Alves, Ana Catarina; Visser, Fleur; Kvadsheim, Petter H.; Miller, Patrick J. O.

    2012-01-01

    In cetaceans’ communities, interactions between individuals of different species are often observed in the wild. Yet, due to methodological and technical challenges very little is known about the mediation of these interactions and their effect on cetaceans’ behavior. Killer whales (Orcinus orca) are a highly vocal species and can be both food competitors and potential predators of many other cetaceans. Thus, the interception of their vocalizations by unintended cetacean receivers may be particularly important in mediating interspecific interactions. To address this hypothesis, we conducted playbacks of killer whale vocalizations recorded during herring-feeding activity to free-ranging long-finned pilot whales (Globicephala melas). Using a multi-sensor tag, we were able to track the whales and to monitor changes of their movements and social behavior in response to the playbacks. We demonstrated that the playback of killer whale sounds to pilot whales induced a clear increase in group size and a strong attraction of the animals towards the sound source. These findings provide the first experimental evidence that the interception of heterospecific vocalizations can mediate interactions between different cetacean species in previously unrecognized ways. PMID:23300613

  20. Effects of noise levels and call types on the source levels of killer whale calls.

    PubMed

    Holt, Marla M; Noren, Dawn P; Emmons, Candice K

    2011-11-01

    Accurate parameter estimates relevant to the vocal behavior of marine mammals are needed to assess potential effects of anthropogenic sound exposure including how masking noise reduces the active space of sounds used for communication. Information about how these animals modify their vocal behavior in response to noise exposure is also needed for such assessment. Prior studies have reported variations in the source levels of killer whale sounds, and a more recent study reported that killer whales compensate for vessel masking noise by increasing their call amplitude. The objectives of the current study were to investigate the source levels of a variety of call types in southern resident killer whales while also considering background noise level as a likely factor related to call source level variability. The source levels of 763 discrete calls along with corresponding background noise were measured over three summer field seasons in the waters surrounding the San Juan Islands, WA. Both noise level and call type were significant factors on call source levels (1-40 kHz band, range of 135.0-175.7 dB(rms) re 1 [micro sign]Pa at 1 m). These factors should be considered in models that predict how anthropogenic masking noise reduces vocal communication space in marine mammals.

  1. Pilot whales attracted to killer whale sounds: acoustically-mediated interspecific interactions in cetaceans.

    PubMed

    Curé, Charlotte; Antunes, Ricardo; Samarra, Filipa; Alves, Ana Catarina; Visser, Fleur; Kvadsheim, Petter H; Miller, Patrick J O

    2012-01-01

    In cetaceans' communities, interactions between individuals of different species are often observed in the wild. Yet, due to methodological and technical challenges very little is known about the mediation of these interactions and their effect on cetaceans' behavior. Killer whales (Orcinus orca) are a highly vocal species and can be both food competitors and potential predators of many other cetaceans. Thus, the interception of their vocalizations by unintended cetacean receivers may be particularly important in mediating interspecific interactions. To address this hypothesis, we conducted playbacks of killer whale vocalizations recorded during herring-feeding activity to free-ranging long-finned pilot whales (Globicephala melas). Using a multi-sensor tag, we were able to track the whales and to monitor changes of their movements and social behavior in response to the playbacks. We demonstrated that the playback of killer whale sounds to pilot whales induced a clear increase in group size and a strong attraction of the animals towards the sound source. These findings provide the first experimental evidence that the interception of heterospecific vocalizations can mediate interactions between different cetacean species in previously unrecognized ways.

  2. Effects of different analysis techniques and recording duty cycles on passive acoustic monitoring of killer whales.

    PubMed

    Riera, Amalis; Ford, John K; Ross Chapman, N

    2013-09-01

    Killer whales in British Columbia are at risk, and little is known about their winter distribution. Passive acoustic monitoring of their year-round habitat is a valuable supplemental method to traditional visual and photographic surveys. However, long-term acoustic studies of odontocetes have some limitations, including the generation of large amounts of data that require highly time-consuming processing. There is a need to develop tools and protocols to maximize the efficiency of such studies. Here, two types of analysis, real-time and long term spectral averages, were compared to assess their performance at detecting killer whale calls in long-term acoustic recordings. In addition, two different duty cycles, 1/3 and 2/3, were tested. Both the use of long term spectral averages and a lower duty cycle resulted in a decrease in call detection and positive pod identification, leading to underestimations of the amount of time the whales were present. The impact of these limitations should be considered in future killer whale acoustic surveys. A compromise between a lower resolution data processing method and a higher duty cycle is suggested for maximum methodological efficiency.

  3. Segmentation of Killer Whale Vocalizations Using the Hilbert-Huang Transform

    NASA Astrophysics Data System (ADS)

    Adam, Olivier

    2008-12-01

    The study of cetacean vocalizations is usually based on spectrogram analysis. The feature extraction is obtained from 2D methods like the edge detection algorithm. Difficulties appear when signal-to-noise ratios are weak or when more than one vocalization is simultaneously emitted. This is the case for acoustic observations in a natural environment and especially for the killer whales which swim in groups. To resolve this problem, we propose the use of the Hilbert-Huang transform. First, we illustrate how few modes (5) are satisfactory for the analysis of these calls. Then, we detail our approach which consists of combining the modes for extracting the time-varying frequencies of the vocalizations. This combination takes advantage of one of the empirical mode decomposition properties which is that the successive IMFs represent the original data broken down into frequency components from highest to lowest frequency. To evaluate the performance, our method is first applied on the simulated chirp signals. This approach allows us to link one chirp to one mode. Then we apply it on real signals emitted by killer whales. The results confirm that this method is a favorable alternative for the automatic extraction of killer whale vocalizations.

  4. A killer-rescue system for self-limiting gene drive of anti-pathogen constructs.

    PubMed

    Gould, Fred; Huang, Yunxin; Legros, Mathieu; Lloyd, Alun L

    2008-12-22

    A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2:1 release (engineered:wild) or after four 1:2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed.

  5. Interactive effects of Na and K in killing by natural killer cells

    SciTech Connect

    Schlichter, L.C.; MacCoubrey, I.C. )

    1989-09-01

    Contact-mediated lysis by human natural killer cells is inhibited by a number of drugs that block the predominant K channel. In this study the authors have further examined the role of the K channel and the interactions between passive K and Na transport in killing. Low external Na-inhibited killing and inhibition were not due to reduced inward current through the Na channels in the target cell. A role for the Na/H antiport is suggested since amiloride inhibited killing in a dose-dependent manner that was competitive with external Na. Depolarizing the killer cell with elevated external K did not inhibit killing. On the contrary, high K{sub 0} reduced the inhibition caused by low Na{sub 0} and by the K-channel blockers quinidine, verapamil, and retinoic acid. Hyperpolarizing the killer cell with low K{sub 0} or valinomycin inhibited killing. Hence, the primary role of the K channels during killing is not to maintain the negative membrane potential. On the contrary, depolarization may promote killing under conditions where killing is submaximal.

  6. Effects of different analysis techniques and recording duty cycles on passive acoustic monitoring of killer whales.

    PubMed

    Riera, Amalis; Ford, John K; Ross Chapman, N

    2013-09-01

    Killer whales in British Columbia are at risk, and little is known about their winter distribution. Passive acoustic monitoring of their year-round habitat is a valuable supplemental method to traditional visual and photographic surveys. However, long-term acoustic studies of odontocetes have some limitations, including the generation of large amounts of data that require highly time-consuming processing. There is a need to develop tools and protocols to maximize the efficiency of such studies. Here, two types of analysis, real-time and long term spectral averages, were compared to assess their performance at detecting killer whale calls in long-term acoustic recordings. In addition, two different duty cycles, 1/3 and 2/3, were tested. Both the use of long term spectral averages and a lower duty cycle resulted in a decrease in call detection and positive pod identification, leading to underestimations of the amount of time the whales were present. The impact of these limitations should be considered in future killer whale acoustic surveys. A compromise between a lower resolution data processing method and a higher duty cycle is suggested for maximum methodological efficiency. PMID:23968036

  7. Killer Whale (Orcinus orca) Deaths in Prince William Sound, Alaska, 1985–1990

    PubMed Central

    Fraker, Mark A.

    2013-01-01

    During 1985–1990, two groups of killer whales in Prince William Sound, Alaska, experienced unusually high rates of mortality, while seven others did not. Those affected were AB pod, part of the southern Alaska population of resident (fish-eating) killer whales, and the AT1 transient (marine mammal–eating) group, a very small, reproductively isolated population that last reproduced in 1984. In 1985–1986, several AB pod members were shot by fishermen defending their catch from depredation, which explains some of the deaths. Understanding the other deaths is complicated by the Exxon Valdez oil spill (March 1989) and uncertainties about the causes and times of the deaths. For AB pod, possible factors involved in the post-spill mortalities are delayed effects of bullet wounds, continued shooting, oil exposure, and consequences of being orphaned. For the AT1 group, possible factors are oil exposure, small population size, old age, and high-contaminant burdens. An analysis of possible effects of inhalation of volatile organic compounds, contact with the oil slick, and ingestion of oil with water or prey did not reveal route(s) of exposure that could explain the mortalities. The cause(s) of the killer whale deaths recorded following the oil spill remain uncertain. PMID:23335844

  8. Killer Whale (Orcinus orca) Deaths in Prince William Sound, Alaska, 1985-1990.

    PubMed

    Fraker, Mark A

    2013-01-01

    During 1985-1990, two groups of killer whales in Prince William Sound, Alaska, experienced unusually high rates of mortality, while seven others did not. Those affected were AB pod, part of the southern Alaska population of resident (fish-eating) killer whales, and the AT1 transient (marine mammal-eating) group, a very small, reproductively isolated population that last reproduced in 1984. In 1985-1986, several AB pod members were shot by fishermen defending their catch from depredation, which explains some of the deaths. Understanding the other deaths is complicated by the Exxon Valdez oil spill (March 1989) and uncertainties about the causes and times of the deaths. For AB pod, possible factors involved in the post-spill mortalities are delayed effects of bullet wounds, continued shooting, oil exposure, and consequences of being orphaned. For the AT1 group, possible factors are oil exposure, small population size, old age, and high-contaminant burdens. An analysis of possible effects of inhalation of volatile organic compounds, contact with the oil slick, and ingestion of oil with water or prey did not reveal route(s) of exposure that could explain the mortalities. The cause(s) of the killer whale deaths recorded following the oil spill remain uncertain. PMID:23335844

  9. CD94 expression and natural killer cell activity after acute exercise.

    PubMed

    Roberts, C; Pyne, D B; Horn, P L

    2004-06-01

    This study examined the effects of acute exercise on natural killer (NK) cell numbers, their expression of CD94 and cytotoxic capacity in triathletes over a 10-week training period. Nine highly trained male triathletes (age 25.9+/-4.1 yrs, VO2max 5.14+/-0.33 L.min(-1)) attended the laboratory on weeks 0, 2, 5 and 10 for incremental submaximal and maximal cycle ergometry. Peripheral blood was analysed for white blood cell counts, lymphocyte phenotype and cytolytic activity (51Cr release from K562 cells). Maximum oxygen consumption increased from week 2 (5.14+/-0.33 L.min(-1)) to week 10 (5.28+/-0.32 L.min(-1)). Resting NK cell numbers and their expression of CD94 were not altered over the 10-week study period. Natural killer cells expressing CD94+ were not differentially recruited into the circulation and cytolytic activity of exercise-recruited NKs did not differ from those present at rest. There was longitudinal stability (over the 10 weeks of the study) in CD94 expression on NK cells, exercise recruitment of CD94+ NK cells and cytolytic capacity of NK cells. The distribution and functional activity of NK cells are not markedly influenced by 10 weeks of training in competitive triathletes. Natural killer cytotoxic activity after exercise reflects numbers of NK cells and not a changed activation state of these cells per se.

  10. Killer Whale (Orcinus orca) Deaths in Prince William Sound, Alaska, 1985-1990.

    PubMed

    Fraker, Mark A

    2013-01-01

    During 1985-1990, two groups of killer whales in Prince William Sound, Alaska, experienced unusually high rates of mortality, while seven others did not. Those affected were AB pod, part of the southern Alaska population of resident (fish-eating) killer whales, and the AT1 transient (marine mammal-eating) group, a very small, reproductively isolated population that last reproduced in 1984. In 1985-1986, several AB pod members were shot by fishermen defending their catch from depredation, which explains some of the deaths. Understanding the other deaths is complicated by the Exxon Valdez oil spill (March 1989) and uncertainties about the causes and times of the deaths. For AB pod, possible factors involved in the post-spill mortalities are delayed effects of bullet wounds, continued shooting, oil exposure, and consequences of being orphaned. For the AT1 group, possible factors are oil exposure, small population size, old age, and high-contaminant burdens. An analysis of possible effects of inhalation of volatile organic compounds, contact with the oil slick, and ingestion of oil with water or prey did not reveal route(s) of exposure that could explain the mortalities. The cause(s) of the killer whale deaths recorded following the oil spill remain uncertain.

  11. Cross-cultural and cross-ecotype production of a killer whale `excitement' call suggests universality

    NASA Astrophysics Data System (ADS)

    Rehn, Nicola; Filatova, Olga A.; Durban, John W.; Foote, Andrew D.

    2011-01-01

    Facial and vocal expressions of emotion have been found in a number of social mammal species and are thought to have evolved to aid social communication. There has been much debate about whether such signals are culturally inherited or are truly biologically innate. Evidence for the innateness of such signals can come from cross-cultural studies. Previous studies have identified a vocalisation (the V4 or `excitement' call) associated with high arousal behaviours in a population of killer whales in British Columbia, Canada. In this study, we compared recordings from three different socially and reproductively isolated ecotypes of killer whales, including five vocal clans of one ecotype, each clan having discrete culturally transmitted vocal traditions. The V4 call was found in recordings of each ecotype and each vocal clan. Nine independent observers reproduced our classification of the V4 call from each population with high inter-observer agreement. Our results suggest the V4 call may be universal in Pacific killer whale populations and that transmission of this call is independent of cultural tradition or ecotype. We argue that such universality is more consistent with an innate vocalisation than one acquired through social learning and may be linked to its apparent function of motivational expression.

  12. Nitrogen availability of grape juice limits killer yeast growth and fermentation activity during mixed-culture fermentation with sensitive commercial yeast strains.

    PubMed Central

    Medina, K; Carrau, F M; Gioia, O; Bracesco, N

    1997-01-01

    The competition between selected or commercial killer strains of type K2 and sensitive commercial strains of Saccharomyces cerevisiae was studied under various conditions in sterile grape juice fermentations. The focus of this study was the effect of yeast inoculation levels and the role of assimilable nitrogen nutrition on killer activity. A study of the consumption of free amino nitrogen (FAN) by pure and mixed cultures of killer and sensitive cells showed no differences between the profiles of nitrogen assimilation in all cases, and FAN was practically depleted in the first 2 days of fermentation. The effect of the addition of assimilable nitrogen and the size of inoculum was examined in mixed killer and sensitive strain competitions. Stuck and sluggish wine fermentations were observed to depend on nitrogen availability when the ratio of killer to sensitive cells was low (1:10 to 1:100). A relationship between the initial assimilable nitrogen content of must and the proportion of killer cells during fermentation was shown. An indirect relationship was found between inoculum size and the percentage of killer cells: a smaller inoculum resulted in a higher proportion of killer cells in grape juice fermentations. In all cases, wines obtained with pure-culture fermentations were preferred to mixed-culture fermentations by sensory analysis. The reasons why killer cells do not finish fermentation under competitive conditions with sensitive cells are discussed. PMID:9212430

  13. Killer Cell Immunoglobulin-like Receptor Genotype and Haplotype Investigation of Natural Killer Cells from an Australian Population of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients.

    PubMed

    Huth, T K; Brenu, E W; Staines, D R; Marshall-Gradisnik, S M

    2016-01-01

    Killer cell immunoglobulin-like receptor (KIR) genes encode for activating and inhibitory surface receptors, which are correlated with the regulation of Natural Killer (NK) cell cytotoxic activity. Reduced NK cell cytotoxic activity has been consistently reported in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients, and KIR haplotypes and allelic polymorphism remain to be investigated. The aim of this article was to conduct a pilot study to examine KIR genotypes, haplotypes, and allelic polymorphism in CFS/ME patients and nonfatigued controls (NFCs). Comparison of KIR and allelic polymorphism frequencies revealed no significant differences between 20 CFS/ME patients and 20 NFCs. A lower frequency of the telomeric A/B motif (P < 0.05) was observed in CFS/ME patients compared with NFCs. This pilot study is the first to report the differences in the frequency of KIR on the telomeric A/B motif in CFS/ME patients. Further studies with a larger CFS/ME cohort are required to validate these results.

  14. Killer Cell Immunoglobulin-like Receptor Genotype and Haplotype Investigation of Natural Killer Cells from an Australian Population of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients

    PubMed Central

    Huth, T. K.; Brenu, E. W.; Staines, D. R.; Marshall-Gradisnik, S. M.

    2016-01-01

    Killer cell immunoglobulin-like receptor (KIR) genes encode for activating and inhibitory surface receptors, which are correlated with the regulation of Natural Killer (NK) cell cytotoxic activity. Reduced NK cell cytotoxic activity has been consistently reported in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients, and KIR haplotypes and allelic polymorphism remain to be investigated. The aim of this article was to conduct a pilot study to examine KIR genotypes, haplotypes, and allelic polymorphism in CFS/ME patients and nonfatigued controls (NFCs). Comparison of KIR and allelic polymorphism frequencies revealed no significant differences between 20 CFS/ME patients and 20 NFCs. A lower frequency of the telomeric A/B motif (P < 0.05) was observed in CFS/ME patients compared with NFCs. This pilot study is the first to report the differences in the frequency of KIR on the telomeric A/B motif in CFS/ME patients. Further studies with a larger CFS/ME cohort are required to validate these results. PMID:27346947

  15. Killer Cell Immunoglobulin-like Receptor Genotype and Haplotype Investigation of Natural Killer Cells from an Australian Population of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients.

    PubMed

    Huth, T K; Brenu, E W; Staines, D R; Marshall-Gradisnik, S M

    2016-01-01

    Killer cell immunoglobulin-like receptor (KIR) genes encode for activating and inhibitory surface receptors, which are correlated with the regulation of Natural Killer (NK) cell cytotoxic activity. Reduced NK cell cytotoxic activity has been consistently reported in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients, and KIR haplotypes and allelic polymorphism remain to be investigated. The aim of this article was to conduct a pilot study to examine KIR genotypes, haplotypes, and allelic polymorphism in CFS/ME patients and nonfatigued controls (NFCs). Comparison of KIR and allelic polymorphism frequencies revealed no significant differences between 20 CFS/ME patients and 20 NFCs. A lower frequency of the telomeric A/B motif (P < 0.05) was observed in CFS/ME patients compared with NFCs. This pilot study is the first to report the differences in the frequency of KIR on the telomeric A/B motif in CFS/ME patients. Further studies with a larger CFS/ME cohort are required to validate these results. PMID:27346947

  16. Seven newly identified loci for autoimmune thyroid disease.

    PubMed

    Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

    2012-12-01

    Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases. PMID:22922229

  17. CODIS STR loci data from 41 sample populations.

    PubMed

    Budowle, B; Shea, B; Niezgoda, S; Chakraborty, R

    2001-05-01

    Allele distributions for 12 or 13 CODIS core tetrameric short tandem repeat (STR) loci CSFIPO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, TPOX, and vWA were determined in 41 population data sets. The major population groups comprise African Americans, U.S. Caucasians, Hispanics, Far East Asians, and Native Americans. There was little evidence for departures from Hardy-Weinberg expectations (HWE) in any of the populations. The FST estimates over all thirteen STR loci are 0.0006 for African Americans, -0.0005 for Caucasians, 0.0021 for Hispanics, 0.0039 for Asians, and 0.0282 for Native Americans.

  18. Informativeness of the CODIS STR loci for admixture analysis.

    PubMed

    Barnholtz-Sloan, Jill S; Pfaff, Carrie L; Chakraborty, Ranajit; Long, Jeffrey C

    2005-11-01

    Population admixture (or ancestry) is used as an approach to gene discovery in complex diseases, particularly when the disease prevalence varies widely across geographic populations. Admixture analysis could be useful for forensics because an indication of a perpetrator's ancestry would narrow the pool of suspects for a particular crime. The purpose of this study was to use Fisher's information to identify informative sets of markers for admixture analysis. Using published founding population allele frequencies we test three marker sets for efficacy for estimating admixture: the FBI CODIS Core STR loci, the HGDP-CEPH Human Genome Diversity Cell Line Panel and the set of 39 ancestry informative SNPS from the Shriver lab at Pennsylvania State University. We conclude that the FBI CODIS Core STR set is valid for admixture analysis, but not the most precise. We recommend using a combination of the most informative markers from the HGDP-CEPH and Shriver loci sets.

  19. Seven newly identified loci for autoimmune thyroid disease.

    PubMed

    Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

    2012-12-01

    Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases.

  20. Esterase variation at three loci in meat ants.

    PubMed

    Halliday, R B

    1979-01-01

    The meat ant (Iridomyrmex purpureus) occurs in a number of color forms, with uncertain taxonomic status. Gel electrophresis of meat ant extracts, followed by nonspecific esterase staining, reveals several zones of activity. Allelic variation at three loci is proposed to account for variation in some of these zones. Two of the loci (Es-1, Es-2) appear to have recessive null alleles, whose frequencies have been estimated by the method of maximum likelihood. Geographic variation in allele frequency is attributed to behavioral and geographic subdivision of the population. Apparent disturbances in segregation ratios and deviations from Hardy-Weinberg equilibrium can be accounted for if it is argued that some nests contain more than one queen. Differences in gene frequency between sympatric populations of the red and blue forms of I. purpureus are observed, confirming their reproductive is isolation and sibling species status.

  1. Properties of multivariable root loci. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Yagle, A. E.

    1981-01-01

    Various properties of multivariable root loci are analyzed from a frequency domain point of view by using the technique of Newton polygons, and some generalizations of the SISO root locus rules to the multivariable case are pointed out. The behavior of the angles of arrival and departure is related to the Smith-MacMillan form of G(s) and explicit equations for these angles are obtained. After specializing to first order and a restricted class of higher order poles and zeros, some simple equations for these angles that are direct generalizations of the SISO equations are found. The unusual behavior of root loci on the real axis at branch points is studied. The SISO root locus rules for break-in and break-out points are shown to generalize directly to the multivariable case. Some methods for computing both types of points are presented.

  2. Evidence of selection at insulin receptor substrate-1 gene loci.

    PubMed

    Yoshiuchi, Issei

    2013-10-01

    Type 2 diabetes mellitus (T2DM) is a complex disease characterized by insulin resistance and defect of insulin secretion. The worldwide prevalence of T2DM is steadily increasing. T2DM is also significantly associated with obesity, coronary artery disease (CAD), and metabolic syndrome. There is a clear difference in the prevalence of T2DM among populations, and T2DM is highly heritable. Human adaptations to environmental changes in food supply, lifestyle, and geography may have pressured the selection of genes associated with the metabolism of glucose, lipids, carbohydrates, and energy. The insulin receptor substrate-1 (IRS1) gene is considered a major T2DM gene, and common genetic variations near the IRS1 gene were found to be associated with T2DM, insulin resistance, adiposity, and CAD. Here, we aimed to find evidence of selection at the IRS1 gene loci using the HapMap population data. We investigated a 3-step test procedure-Wright's F statistics (Fst), the long-range haplotype (LRH) test, and the integrated haplotype score (iHS) test-to detect selection at the IRS1 gene loci using the HapMap population data. We observed that 1 CAD-associated SNP (rs2943634) and 1 adiposity- and insulin resistance-associated SNP (rs2943650) exhibited high Fst values. We also found selection at the IRS1 gene loci by the LRH test and the iHS test. These findings suggest evidence of selection at the IRS1 gene loci and that further studies should examine the adaptive evolution of T2DM genes. PMID:22797928

  3. Mapping of quantitative trait loci for root hair length in wheat identifies loci that co-locate with loci for yield components

    PubMed Central

    Horn, R.; Wingen, L. U.; Snape, J. W.; Dolan, L.

    2016-01-01

    Root hairs are fast growing, ephemeral tubular extensions of the root epidermis. They arise in the unsuberized maturation zone of the root, effectively increasing the root surface area in the region over which nutrient and water uptake occur. Variation in root hair length (RHL) between varieties has been shown to be genetically determined, and could, therefore, have consequences for nutrient capture and yield potential in crops. We describe the development of a medium-to-high throughput screening method for assessing RHL in wheat at the seedling stage. This method was used to screen a number of wheat mapping population parental lines for variation in RHL. Parents of two populations derived from inter-varietal crosses differed for RHL: Spark vs Rialto and Charger vs Badger. We identified quantitative trait loci (QTLs) for RHL in the populations derived from these crosses. In Spark × Rialto, QTLs on chromosomes 1A, 2A and 6A were associated with variation in RHL, whilst in Charger × Badger, a QTL for RHL was identified on 2BL. The QTLs on 2A and 6A co-localized with previously described QTLs for yield components. Longer root hairs may confer an advantage by exploiting limiting mineral and water resources. This first QTL analysis of root hair length in wheat identifies loci that could usefully be further investigated for their role in tolerance to limiting conditions. PMID:27315832

  4. Mapping of quantitative trait loci for root hair length in wheat identifies loci that co-locate with loci for yield components.

    PubMed

    Horn, R; Wingen, L U; Snape, J W; Dolan, L

    2016-08-01

    Root hairs are fast growing, ephemeral tubular extensions of the root epidermis. They arise in the unsuberized maturation zone of the root, effectively increasing the root surface area in the region over which nutrient and water uptake occur. Variation in root hair length (RHL) between varieties has been shown to be genetically determined, and could, therefore, have consequences for nutrient capture and yield potential in crops. We describe the development of a medium-to-high throughput screening method for assessing RHL in wheat at the seedling stage. This method was used to screen a number of wheat mapping population parental lines for variation in RHL. Parents of two populations derived from inter-varietal crosses differed for RHL: Spark vs Rialto and Charger vs Badger. We identified quantitative trait loci (QTLs) for RHL in the populations derived from these crosses. In Spark × Rialto, QTLs on chromosomes 1A, 2A and 6A were associated with variation in RHL, whilst in Charger × Badger, a QTL for RHL was identified on 2BL. The QTLs on 2A and 6A co-localized with previously described QTLs for yield components. Longer root hairs may confer an advantage by exploiting limiting mineral and water resources. This first QTL analysis of root hair length in wheat identifies loci that could usefully be further investigated for their role in tolerance to limiting conditions. PMID:27315832

  5. Evolution of V genes from the TRV loci of mammals.

    PubMed

    Olivieri, David N; Gambón-Cerdá, Santiago; Gambón-Deza, Francisco

    2015-07-01

    Information concerning the evolution of T lymphocyte receptors (TCR) can be deciphered from that part of the molecule that recognizes antigen presented by major histocompatibility complex (MHC), namely the variable (V) regions. The genes that code for these variable regions are found within the TCR loci. Here, we describe a study of the evolutionary origin of V genes that code for the α and β chains of the TCR loci of mammals. In particular, we demonstrate that most of the 35 TRAV and 25 TRBV conserved genes found in Primates are also found in other Eutheria, while in Marsupials, Monotremes, and Reptiles, these genes diversified in a different manner. We also show that in mammals, all TRAV genes are derived from five ancestral genes, while all TRBV genes originate from four such genes. In Reptiles, the five TRAV and three out of the four TRBV ancestral genes exist, as well as other V genes not found in mammals. We also studied the TRGV and TRDV loci from all mammals, and we show a relationship of the TRDV to the TRAV locus throughout evolutionary time. PMID:26024913

  6. [Variability at 15 autosomal microsatellite DNA loci in Russian population].

    PubMed

    Maliarchuk, B a; Wozniak, M; Czarny, J; Derenko, M V; Grzybowski, T; Miscicka-Sliwka, D

    2007-01-01

    The paper presents allele frequencies at 15 STR loci (D3S1358, vWA, FGA, TH01, TPOX, CSFIPO, D5S818, D13S317, D7S820, D16S539, D2Sl338, D8S1179, D21S1l, D18S51, D19S433), used in forensic medicine, in Russian sample (n = 176) representing population of the European part of the Russian Federation. The combined power of discrimination (PD) and the combined power of exclusion (PE) for the 15 STR loci were 0.999 999 999 999 999 986 and 0.999 999 331 310 171 000, respectively. The data obtained for allele and genotype frequencies conformed to Hardy-Weinberg expectations. According to the presented data, loci D2S1338, D18S51, D21Sll and FGA are the most informative markers for Russians. The data obtained may be used as reference database for forensic medicine laboratories in Russian Federation.

  7. Quantitative trait loci influencing honeybee alarm pheromone levels.

    PubMed

    Hunt, G J; Collins, A M; Rivera, R; Page, R E; Guzmán-Novoa, E

    1999-01-01

    Quantitative trait loci (QTL) mapping procedures were used to identify loci that influence the levels of alarm pheromones found in the stinging apparatus of worker honeybees. An F1 queen was produced from a cross between a queen of European origin and a drone descended from an African subspecies. Haploid drones from the hybrid queen were individually backcrossed to European queens to produce 172 colonies. Samples of stings were taken from backcross workers of these colonies. Alarm pheromone levels were determined by gas chromatography. RAPD markers were scored from the haploid drone fathers of these colonies. The multiple-QTL model (MQM) of MapQTL was used to identify QTLs that influence the levels of four alarm pheromone components. Seven independent, potential QTLs were identified with LOD scores greater than two, and one at LOD 1.88. We identified one QTL for n-decyl acetate, three for n-octanol, four for isopentyl acetate, and one for hexyl acetate. One region of linkage group XI shows a strong influence on body size and the levels of three alarm pheromone components. This locus explained 40% of the variance for the amount of n-decyl acetate (LOD 6.57). In general, the QTLs influencing alarm pheromone levels were independent of previously identified loci that influenced the stinging behavior of these colonies. The only exception was a potential locus influencing levels of n-octanol, which was inversely correlated with stinging behavior. PMID:10544503

  8. Development of a Lac Operon Concept Inventory (LOCI)

    PubMed Central

    Stefanski, Katherine M.; Gardner, Grant E.; Seipelt-Thiemann, Rebecca L.

    2016-01-01

    Concept inventories (CIs) are valuable tools for educators that assess student achievement and identify misconceptions held by students. Results of student responses can be used to adjust or develop new instructional methods for a given topic. The regulation of gene expression in both prokaryotes and eukaryotes is an important concept in genetics and one that is particularly challenging for undergraduate students. As part of a larger study examining instructional methods related to gene regulation, the authors developed a 12-item CI assessing student knowledge of the lac operon. Using an established protocol, the authors wrote open-ended questions and conducted in-class testing with undergraduate microbiology and genetics students to discover common errors made by students about the lac operon and to determine aspects of item validity. Using these results, we constructed a 12-item multiple-choice lac operon CI called the Lac Operon Concept Inventory (LOCI), The LOCI was reviewed by two experts in the field for content validity. The LOCI underwent item analysis and was assessed for reliability with a sample of undergraduate genetics students (n = 115). The data obtained were found to be valid and reliable (coefficient alpha = 0.994) with adequate discriminatory power and item difficulty. PMID:27252300

  9. Seven New Loci Associated with Age-Related Macular Degeneration

    PubMed Central

    2013-01-01

    Age-related macular degeneration (AMD) is a common cause of blindness in older individuals. To accelerate understanding of AMD biology and help design new therapies, we executed a collaborative genomewide association study, examining >17,100 advanced AMD cases and >60,000 controls of European and Asian ancestry. We identified 19 genomic loci associated with AMD with p<5×10−8 and enriched for genes involved in regulation of complement activity, lipid metabolism, extracellular matrix remodeling and angiogenesis. Our results include 7 loci reaching p<5×10−8 for the first time, near the genes COL8A1/FILIP1L, IER3/DDR1, SLC16A8, TGFBR1, RAD51B, ADAMTS9/MIR548A2, and B3GALTL. A genetic risk score combining SNPs from all loci displayed similar good ability to distinguish cases and controls in all samples examined. Our findings provide new directions for biological, genetic and therapeutic studies of AMD. PMID:23455636

  10. Allele frequencies at microsatellite loci: The stepwise mutation model revisited

    SciTech Connect

    Valdes, A.M.; Slatkin, M. ); Freimer, N.B. )

    1993-03-01

    The authors summarize available data on the frequencies of alleles at microsatellite loci in human populations and compare observed distributions of allele frequencies to those generated by a simulation of the stepwise mutation model. They show that observed frequency distributions at 108 loci are consistent with the results of the model under the assumption that mutations cause an increase or decrease in repeat number by one and under the condition that the product Nu, where N is the effective population size and u is the mutation rate, is larger than one. It is also shown that the variance of the distribution of allele sizes is a useful estimator of Nu and performs much better than previously suggested estimators for the stepwise mutation model. In the data, there is no correlation between the mean and variance in allele size at a locus or between the number of alleles and mean allele size, which suggests that the mutation rate at these loci is independent of allele size. 39 refs., 6 figs., 4 tabs.

  11. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

    PubMed Central

    Andlauer, Till F. M.; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A.; Loleit, Verena; Luessi, Felix; Meuth, Sven G.; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H.; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K.; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O.; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B.; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M.; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M.; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-01-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis. PMID:27386562

  12. Genetic maps of polymorphic DNA loci on rat chromosome 1

    SciTech Connect

    Ding, Yan-Ping; Remmers, E.F.; Longman, R.E.

    1996-09-01

    Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes. Six markers for five genes, {gamma}-aminobutyric acid receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg, Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that the large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19. 38 refs., 1 fig., 3 tabs.

  13. Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis.

    PubMed

    Mayes, Maureen D; Bossini-Castillo, Lara; Gorlova, Olga; Martin, José Ezequiel; Zhou, Xiaodong; Chen, Wei V; Assassi, Shervin; Ying, Jun; Tan, Filemon K; Arnett, Frank C; Reveille, John D; Guerra, Sandra; Teruel, María; Carmona, Francisco David; Gregersen, Peter K; Lee, Annette T; López-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeón, Carmen Pilar; Castellví, Iván; González-Gay, Miguel Ángel; Zhernakova, Alexandra; Padyukov, Leonid; Alarcón-Riquelme, Marta; Wijmenga, Cisca; Brown, Matthew; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H W; Voskuyl, Alexandre E; Schuerwegh, Annemie J; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M; Hummers, Laura K; Varga, John; Hinchcliff, Monique E; Baron, Murray; Hudson, Marie; Pope, Janet E; Furst, Daniel E; Khanna, Dinesh; Phillips, Kristin; Schiopu, Elena; Segal, Barbara M; Molitor, Jerry A; Silver, Richard M; Steen, Virginia D; Simms, Robert W; Lafyatis, Robert A; Fessler, Barri J; Frech, Tracy M; Alkassab, Firas; Docherty, Peter; Kaminska, Elzbieta; Khalidi, Nader; Jones, Henry Niall; Markland, Janet; Robinson, David; Broen, Jasper; Radstake, Timothy R D J; Fonseca, Carmen; Koeleman, Bobby P; Martin, Javier

    2014-01-01

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.

  14. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

    PubMed

    Andlauer, Till F M; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A; Loleit, Verena; Luessi, Felix; Meuth, Sven G; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-06-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis. PMID:27386562

  15. Development of a Lac Operon Concept Inventory (LOCI).

    PubMed

    Stefanski, Katherine M; Gardner, Grant E; Seipelt-Thiemann, Rebecca L

    2016-01-01

    Concept inventories (CIs) are valuable tools for educators that assess student achievement and identify misconceptions held by students. Results of student responses can be used to adjust or develop new instructional methods for a given topic. The regulation of gene expression in both prokaryotes and eukaryotes is an important concept in genetics and one that is particularly challenging for undergraduate students. As part of a larger study examining instructional methods related to gene regulation, the authors developed a 12-item CI assessing student knowledge of the lac operon. Using an established protocol, the authors wrote open-ended questions and conducted in-class testing with undergraduate microbiology and genetics students to discover common errors made by students about the lac operon and to determine aspects of item validity. Using these results, we constructed a 12-item multiple-choice lac operon CI called the Lac Operon Concept Inventory (LOCI), The LOCI was reviewed by two experts in the field for content validity. The LOCI underwent item analysis and was assessed for reliability with a sample of undergraduate genetics students (n = 115). The data obtained were found to be valid and reliable (coefficient alpha = 0.994) with adequate discriminatory power and item difficulty. PMID:27252300

  16. Four loci explain 83% of size variation in the horse.

    PubMed

    Makvandi-Nejad, Shokouh; Hoffman, Gabriel E; Allen, Jeremy J; Chu, Erin; Gu, Esther; Chandler, Alyssa M; Loredo, Ariel I; Bellone, Rebecca R; Mezey, Jason G; Brooks, Samantha A; Sutter, Nathan B

    2012-01-01

    Horse body size varies greatly due to intense selection within each breed. American Miniatures are less than one meter tall at the withers while Shires and Percherons can exceed two meters. The genetic basis for this variation is not known. We hypothesize that the breed population structure of the horse should simplify efforts to identify genes controlling size. In support of this, here we show with genome-wide association scans (GWAS) that genetic variation at just four loci can explain the great majority of horse size variation. Unlike humans, which are naturally reproducing and possess many genetic variants with weak effects on size, we show that horses, like other domestic mammals, carry just a small number of size loci with alleles of large effect. Furthermore, three of our horse size loci contain the LCORL, HMGA2 and ZFAT genes that have previously been found to control human height. The LCORL/NCAPG locus is also implicated in cattle growth and HMGA2 is associated with dog size. Extreme size diversification is a hallmark of domestication. Our results in the horse, complemented by the prior work in cattle and dog, serve to pinpoint those very few genes that have played major roles in the rapid evolution of size during domestication.

  17. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis

    PubMed Central

    Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, José Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Teruel, María; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; López-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeón, Carmen Pilar; Castellví, Iván; González-Gay, Miguel Ángel; Ortego-Centeno, Norberto; Ríos, Raquel; Callejas, José Luis; Navarrete, Nuria; García Portales, Rosa; Camps, María Teresa; Fernández-Nebro, Antonio; González-Escribano, María F.; Sánchez-Román, Julio; García-Hernández, Francisco José; Castillo, María Jesús; Aguirre, María Ángeles; Gómez-Gracia, Inmaculada; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Vicente, Esther; Andreu, José Luis; Fernández de Castro, Mónica; García de la Peña, Paloma; López-Longo, Francisco Javier; Martínez, Lina; Fonollosa, Vicente; Espinosa, Gerard; Tolosa, Carlos; Pros, Anna; Rodríguez Carballeira, Mónica; Narváez, Francisco Javier; Rubio Rivas, Manel; Ortiz Santamaría, Vera; Díaz, Bernardino; Trapiella, Luis; Freire, María del Carmen; Sousa, Adrián; Egurbide, María Victoria; Fanlo Mateo, Patricia; Sáez-Comet, Luis; Díaz, Federico; Hernández, Vanesa; Beltrán, Emma; Román-Ivorra, José Andrés; Grau, Elena; Alegre Sancho, Juan José; Blanco García, Francisco J.; Oreiro, Natividad; Fernández Sueiro, Luis; Zhernakova, Alexandra; Padyukov, Leonid; Alarcón-Riquelme, Marta; Wijmenga, Cisca; Brown, Matthew; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H.W.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.; Furst, Daniel E.; Khanna, Dinesh; Phillips, Kristin; Schiopu, Elena; Segal, Barbara M.; Molitor, Jerry A.; Silver, Richard M.; Steen, Virginia D.; Simms, Robert W.; Lafyatis, Robert A.; Fessler, Barri J.; Frech, Tracy M.; AlKassab, Firas; Docherty, Peter; Kaminska, Elzbieta; Khalidi, Nader; Jones, Henry Niall; Markland, Janet; Robinson, David; Broen, Jasper; Radstake, Timothy R.D.J.; Fonseca, Carmen; Koeleman, Bobby P.; Martin, Javier

    2014-01-01

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci. PMID:24387989

  18. Evolution of V genes from the TRV loci of mammals.

    PubMed

    Olivieri, David N; Gambón-Cerdá, Santiago; Gambón-Deza, Francisco

    2015-07-01

    Information concerning the evolution of T lymphocyte receptors (TCR) can be deciphered from that part of the molecule that recognizes antigen presented by major histocompatibility complex (MHC), namely the variable (V) regions. The genes that code for these variable regions are found within the TCR loci. Here, we describe a study of the evolutionary origin of V genes that code for the α and β chains of the TCR loci of mammals. In particular, we demonstrate that most of the 35 TRAV and 25 TRBV conserved genes found in Primates are also found in other Eutheria, while in Marsupials, Monotremes, and Reptiles, these genes diversified in a different manner. We also show that in mammals, all TRAV genes are derived from five ancestral genes, while all TRBV genes originate from four such genes. In Reptiles, the five TRAV and three out of the four TRBV ancestral genes exist, as well as other V genes not found in mammals. We also studied the TRGV and TRDV loci from all mammals, and we show a relationship of the TRDV to the TRAV locus throughout evolutionary time.

  19. Quantitative trait loci influencing honeybee alarm pheromone levels.

    PubMed

    Hunt, G J; Collins, A M; Rivera, R; Page, R E; Guzmán-Novoa, E

    1999-01-01

    Quantitative trait loci (QTL) mapping procedures were used to identify loci that influence the levels of alarm pheromones found in the stinging apparatus of worker honeybees. An F1 queen was produced from a cross between a queen of European origin and a drone descended from an African subspecies. Haploid drones from the hybrid queen were individually backcrossed to European queens to produce 172 colonies. Samples of stings were taken from backcross workers of these colonies. Alarm pheromone levels were determined by gas chromatography. RAPD markers were scored from the haploid drone fathers of these colonies. The multiple-QTL model (MQM) of MapQTL was used to identify QTLs that influence the levels of four alarm pheromone components. Seven independent, potential QTLs were identified with LOD scores greater than two, and one at LOD 1.88. We identified one QTL for n-decyl acetate, three for n-octanol, four for isopentyl acetate, and one for hexyl acetate. One region of linkage group XI shows a strong influence on body size and the levels of three alarm pheromone components. This locus explained 40% of the variance for the amount of n-decyl acetate (LOD 6.57). In general, the QTLs influencing alarm pheromone levels were independent of previously identified loci that influenced the stinging behavior of these colonies. The only exception was a potential locus influencing levels of n-octanol, which was inversely correlated with stinging behavior.

  20. Multiple newly identified loci associated with prostate cancer susceptibility.

    PubMed

    Eeles, Rosalind A; Kote-Jarai, Zsofia; Giles, Graham G; Olama, Ali Amin Al; Guy, Michelle; Jugurnauth, Sarah K; Mulholland, Shani; Leongamornlert, Daniel A; Edwards, Stephen M; Morrison, Jonathan; Field, Helen I; Southey, Melissa C; Severi, Gianluca; Donovan, Jenny L; Hamdy, Freddie C; Dearnaley, David P; Muir, Kenneth R; Smith, Charmaine; Bagnato, Melisa; Ardern-Jones, Audrey T; Hall, Amanda L; O'Brien, Lynne T; Gehr-Swain, Beatrice N; Wilkinson, Rosemary A; Cox, Angie; Lewis, Sarah; Brown, Paul M; Jhavar, Sameer G; Tymrakiewicz, Malgorzata; Lophatananon, Artitaya; Bryant, Sarah L; Horwich, Alan; Huddart, Robert A; Khoo, Vincent S; Parker, Christopher C; Woodhouse, Christopher J; Thompson, Alan; Christmas, Tim; Ogden, Chris; Fisher, Cyril; Jamieson, Charles; Cooper, Colin S; English, Dallas R; Hopper, John L; Neal, David E; Easton, Douglas F

    2008-03-01

    Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at loci associated with prostate cancer on chromosomes 3, 6, 7, 10, 11, 19 and X (P = 2.7 x 10(-8) to P = 8.7 x 10(-29)). We confirmed previous reports of common loci associated with prostate cancer at 8q24 and 17q. Moreover, we found that three of the newly identified loci contain candidate susceptibility genes: MSMB, LMTK2 and KLK3.

  1. Homology of Melanoma-Inducing Loci in the Genus Xiphophorus

    PubMed Central

    Schartl, M.

    1990-01-01

    Several species of the genus Xiphophorus are polymorphic for specific pigment patterns. Some of these give rise to malignant melanoma following the appropriate crossings. For one of these pattern loci from the platyfish Xiphophorus maculatus the melanoma-inducing gene has been cloned and found to encode a novel receptor tyrosine kinase, designated Xmrk. Using molecular probes from this gene in Southern blot analyses on single fish DNA preparations from 600 specimens of different populations of various species of the genus Xiphophorus and their hybrids, either with or without melanoma-predisposing pattern, it was shown that all individuals contain the Xmrk gene as a proto-oncogene. It is located on the sex chromosome. All fish that carry a melanoma-predisposing locus which has been identified by Mendelian genetics contain an additional copy of Xmrk, closely linked to a specific melanophore pattern locus on the sex chromosome. The melanoma-inducing loci of the different species and populations are homologous. The additional copy of Xmrk obviously arose by a gene-duplication event, thereby acquiring the oncogenic potential. The homology of the melanoma-inducing loci points to a similar mechanism of tumor suppression in all feral fish populations of the different species of the genus Xiphophorus. PMID:1981761

  2. The Killer Fly Hunger Games: Target Size and Speed Predict Decision to Pursuit

    PubMed Central

    Wardill, Trevor J.; Knowles, Katie; Barlow, Laura; Tapia, Gervasio; Nordström, Karin; Olberg, Robert M.; Gonzalez-Bellido, Paloma T.

    2015-01-01

    Predatory animals have evolved to optimally detect their prey using exquisite sensory systems such as vision, olfaction and hearing. It may not be so surprising that vertebrates, with large central nervous systems, excel at predatory behaviors. More striking is the fact that many tiny insects, with their miniscule brains and scaled down nerve cords, are also ferocious, highly successful predators. For predation, it is important to determine whether a prey is suitable before initiating pursuit. This is paramount since pursuing a prey that is too large to capture, subdue or dispatch will generate a substantial metabolic cost (in the form of muscle output) without any chance of metabolic gain (in the form of food). In addition, during all pursuits, the predator breaks its potential camouflage and thus runs the risk of becoming prey itself. Many insects use their eyes to initially detect and subsequently pursue prey. Dragonflies, which are extremely efficient predators, therefore have huge eyes with relatively high spatial resolution that allow efficient prey size estimation before initiating pursuit. However, much smaller insects, such as killer flies, also visualize and successfully pursue prey. This is an impressive behavior since the small size of the killer fly naturally limits the neural capacity and also the spatial resolution provided by the compound eye. Despite this, we here show that killer flies efficiently pursue natural (Drosophila melanogaster) and artificial (beads) prey. The natural pursuits are initiated at a distance of 7.9 ± 2.9 cm, which we show is too far away to allow for distance estimation using binocular disparities. Moreover, we show that rather than estimating absolute prey size prior to launching the attack, as dragonflies do, killer flies attack with high probability when the ratio of the prey's subtended retinal velocity and retinal size is 0.37. We also show that killer flies will respond to a stimulus of an angular size that is smaller

  3. Isolation and characterization of 21 polymorphic microsatellite loci in the Japanese dace (Tribolodon hakonensis)

    USGS Publications Warehouse

    Koizumi, Noriyuki; Quinn, Thomas W.; Park, Myeongsoo; Fike, Jennifer A.; Nishida, Kazuya; Takemura, Takeshi; Watabe, Keiji; Mori, Atsushi

    2011-01-01

    Twenty one polymorphic microsatellite loci for the Japanese dace (Tribolodon hakonensis) were isolated and characterized. The number of observed alleles per locus in 32 individuals ranged from 3 to 30. The observed and expected heterozygosities ranged from 0.125 to 0.969 and from 0.175 to 0.973, respectively. All loci conformed to Hardy–Weinberg equilibrium, no linkage disequilibrium was observed between pairs of loci and no loci showed evidence of null alleles. These microsatellite loci will be useful for investigating the intraspecific genetic variation and population structure of this species.

  4. Characterization of 38 microsatellite loci in the European blackbird, Turdus merula (Turdidae, AVES).

    PubMed

    Simeoni, Michelle; Dawson, Deborah A; Gentle, Louise K; Coiffait, Lisette; Wolff, Kirsten; Evans, Karl L; Gaston, Kevin J; Hatchwell, Ben J

    2009-11-01

    We characterized 38 microsatellite loci in the European blackbird, Turdus merula. Thirty-seven loci were identified by testing 242 loci that had been originally isolated in other avian species. One additional locus was isolated from a European blackbird genomic library. All loci were characterized in 20-29 blackbirds from a population in the Czech Republic and displayed between two and 16 alleles, with observed heterozygosity ranging from 0.04 to 1.00. Thirty-seven loci could be assigned a chromosome location in the zebra finch (Taeniopygia guttata) genome based on sequence homology. PMID:21564948

  5. Evolutionary history of chloridoid grasses estimated from 122 nuclear loci.

    PubMed

    Fisher, Amanda E; Hasenstab, Kristen M; Bell, Hester L; Blaine, Ellen; Ingram, Amanda L; Columbus, J Travis

    2016-12-01

    Chloridoideae (chloridoid grasses) are a subfamily of ca. 1700 species with high diversity in arid habitats. Until now, their evolutionary relationships have primarily been studied with DNA sequences from the chloroplast, a maternally inherited organelle. Next-generation sequencing is able to efficiently recover large numbers of nuclear loci that can then be used to estimate the species phylogeny based upon bi-parentally inherited data. We sought to test our chloroplast-based hypotheses of relationships among chloridoid species with 122 nuclear loci generated through targeted-enrichment next-generation sequencing, sometimes referred to as hyb-seq. We targeted putative single-copy housekeeping genes, as well as genes that have been implicated in traits characteristic of, or particularly labile in, chloridoids: e.g., drought and salt tolerance. We recovered ca. 70% of the targeted loci (122 of 177 loci) in all 47 species sequenced using hyb-seq. We then analyzed the nuclear loci with Bayesian and coalescent methods and the resulting phylogeny resolves relationships between the four chloridoid tribes. Several novel findings with this data were: the sister lineage to Chloridoideae is unresolved; Centropodia+Ellisochloa are excluded from Chloridoideae in phylogenetic estimates using a coalescent model; Sporobolus subtilis is more closely related to Eragrostis than to other species of Sporobolus; and Tragus is more closely related to Chloris and relatives than to a lineage of mainly New World species. Relationships in Cynodonteae in the nuclear phylogeny are quite different from chloroplast estimates, but were not robust to changes in the method of phylogenetic analysis. We tested the data signal with several partition schemes, a concatenation analysis, and tests of alternative hypotheses to assess our confidence in this new, nuclear estimate of evolutionary relationships. Our work provides markers and a framework for additional phylogenetic studies that sample more

  6. STELLAR LOCI. I. METALLICITY DEPENDENCE AND INTRINSIC WIDTHS

    SciTech Connect

    Yuan, Haibo; Liu, Xiaowei; Xiang, Maosheng; Huang, Yang; Chen, Bingqiu E-mail: x.liu@pku.edu.cn

    2015-02-01

    Stellar loci are widely used for selection of interesting outliers, reddening determinations, and calibrations. However, until now, the dependence of stellar loci on metallicity has not been fully explored, and their intrinsic widths are unclear. In this paper, by combining the spectroscopic and recalibrated imaging data of the Sloan Digital Sky Survey (SDSS) Stripe 82, we have built a large, clean sample of dwarf stars with accurate colors and well-determined metallicities to investigate the metallicity dependence and intrinsic widths of the SDSS stellar loci. Typically, 1 dex decrease in metallicity causes 0.20 and 0.02 mag decrease in colors u – g and g – r and 0.02 and 0.02 mag increase in colors r – i and i – z, respectively. The variations are larger for metal-rich stars than for metal-poor ones, and larger for F/G/K stars than for A/M ones. Using the sample, we have performed two-dimensional polynomial fitting to the u – g, g – r, r – i, and i – z colors as a function of color g – i and metallicity [Fe/H]. The residuals, at the level of 0.029, 0.008, 0.008, and 0.011 mag for the u – g, g – r, r – i, and i – z colors, respectively, can be fully accounted for by the photometric errors and metallicity uncertainties, suggesting that the intrinsic widths of the loci are at maximum a few millimagnitudes. The residual distributions are asymmetric, revealing that a significant fraction of stars are binaries. In a companion paper, we will present an unbiased estimate of the binary fraction for field stars. Other potential applications of the metallicity-dependent stellar loci are briefly discussed.

  7. Evolutionary history of chloridoid grasses estimated from 122 nuclear loci.

    PubMed

    Fisher, Amanda E; Hasenstab, Kristen M; Bell, Hester L; Blaine, Ellen; Ingram, Amanda L; Columbus, J Travis

    2016-12-01

    Chloridoideae (chloridoid grasses) are a subfamily of ca. 1700 species with high diversity in arid habitats. Until now, their evolutionary relationships have primarily been studied with DNA sequences from the chloroplast, a maternally inherited organelle. Next-generation sequencing is able to efficiently recover large numbers of nuclear loci that can then be used to estimate the species phylogeny based upon bi-parentally inherited data. We sought to test our chloroplast-based hypotheses of relationships among chloridoid species with 122 nuclear loci generated through targeted-enrichment next-generation sequencing, sometimes referred to as hyb-seq. We targeted putative single-copy housekeeping genes, as well as genes that have been implicated in traits characteristic of, or particularly labile in, chloridoids: e.g., drought and salt tolerance. We recovered ca. 70% of the targeted loci (122 of 177 loci) in all 47 species sequenced using hyb-seq. We then analyzed the nuclear loci with Bayesian and coalescent methods and the resulting phylogeny resolves relationships between the four chloridoid tribes. Several novel findings with this data were: the sister lineage to Chloridoideae is unresolved; Centropodia+Ellisochloa are excluded from Chloridoideae in phylogenetic estimates using a coalescent model; Sporobolus subtilis is more closely related to Eragrostis than to other species of Sporobolus; and Tragus is more closely related to Chloris and relatives than to a lineage of mainly New World species. Relationships in Cynodonteae in the nuclear phylogeny are quite different from chloroplast estimates, but were not robust to changes in the method of phylogenetic analysis. We tested the data signal with several partition schemes, a concatenation analysis, and tests of alternative hypotheses to assess our confidence in this new, nuclear estimate of evolutionary relationships. Our work provides markers and a framework for additional phylogenetic studies that sample more

  8. Adaptation at Specific Loci. V. Metabolically Adjacent Enzyme Loci May Have Very Distinct Experiences of Selective Pressures

    PubMed Central

    Carter, P. A.; Watt, W. B.

    1988-01-01

    The polymorphic phosphoglucomutase (PGM) and glucose-6-phosphate dehydrogenase (G6PD) loci have been studied in parallel to experimental work on the phosphoglucose isomerase (PGI) polymorphism in Colias butterflies. PGI, PGM and G6PD are also autosomal in Colias. PGM and G6PD are loosely linked (and represent the first identified autosomal linkage group in Colias); they assort independently from PGI. Recombination occurs in both sexes. Neither PGM nor G6PD shows large, consistent differences in flight capacity through the day among its genotypes, as PGI does. PGM shows some change of allele frequencies, and match to Hardy-Weinberg expectation, with air temperature in middle and latter parts of the season, but not early in the season. G6PD may show some heterozygote excess over Hardy-Weinberg expectation early in the day, but more testing is needed. No evidence for differential survivorship was seen at PGM or G6PD, in contrast to PGI. At the PGM and G6PD loci, male heterozygotes are advantaged in mating with females, but without the evidence of female choice which occurs for PGI. These effects are not correlated among the three loci. There is no assortative mating at G6PD (nor at PGI). There is minor positive assortative mating of PGM heterozygotes, but it is too weak to account for the PGM-genotype-specific male mating advantage. No trends of multilocus genotype frequencies involving PGI are seen. Certain PGM-G6PD two-locus genotypes are over-represented, and others under-represented, in wild adult samples, particularly among males and uniformly among successfully mating males. Our results emphasize that enzyme loci sharing a substrate need not have common experience of the existence or strength of natural selection, and suggest initial food-resource processing and allocation as a possible context for fitness-related effects of the PGM and G6PD polymorphisms. PMID:2970419

  9. How many loci on the X-chromosome of Drosophila melanogaster can mutate to recessive lethals

    SciTech Connect

    Abrahamson, S.; Wuergler, F.E.; DeJongh, C.; Meyer, H.U.

    1980-01-01

    The sensitivity of the sex-linked recessive lethal test is due to the fact that a very large number of loci are included in the mutation study. From extensive studies on the spontaneous sex-linked recessive lethal frequency and spontaneous specific locus mutation rates, it is possible to derive an estimate of the number of loci included in the recessive lethal test. The average number derived from three estimates on male and female germ cells in 563 loci. A second independent approach derives from published data which analyzed short regions of the genome and the proportion of loci within these regions which mutate to lethality. This analysis suggests that 830 loci are potentially lethal mutables. We describe the reasons for concluding that 600 to 800 loci of the approximately 1000 loci on the X-chromosome are involved in the X-linked recessive lethal test.

  10. Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

    PubMed Central

    Cheng, Ching-Yu; Schache, Maria; Ikram, M. Kamran; Young, Terri L.; Guggenheim, Jeremy A.; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J.M.; Barathi, Veluchamy A.; Liao, Jiemin; Hysi, Pirro G.; Bailey-Wilson, Joan E.; St. Pourcain, Beate; Kemp, John P.; McMahon, George; Timpson, Nicholas J.; Evans, David M.; Montgomery, Grant W.; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F.; Amin, Najaf; van Leeuwen, Elisabeth M.; Wilson, James F.; Pennell, Craig E.; van Duijn, Cornelia M.; de Jong, Paulus T.V.M.; Vingerling, Johannes R.; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Rahi, Jugnoo S.; Hysi, Pirro G.; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Delcourt, Cécile; Maubaret, Cecilia; Williams, Cathy; Guggenheim, Jeremy A.; Northstone, Kate; Ring, Susan M.; Davey-Smith, George; Craig, Jamie E.; Burdon, Kathryn P.; Fogarty, Rhys D.; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Iyengar, Sudha K.; Igo, Robert P.; Chew, Emily; Janmahasathian, Sarayut; Stambolian, Dwight; Wilson, Joan E. Bailey; MacGregor, Stuart; Lu, Yi; Jonas, Jost B.; Xu, Liang; Saw, Seang-Mei; Baird, Paul N.; Rochtchina, Elena; Mitchell, Paul; Wang, Jie Jin; Jonas, Jost B.; Nangia, Vinay; Hayward, Caroline; Wright, Alan F.; Vitart, Veronique; Polasek, Ozren; Campbell, Harry; Vitart, Veronique; Rudan, Igor; Vatavuk, Zoran; Vitart, Veronique; Paterson, Andrew D.; Hosseini, S. Mohsen; Iyengar, Sudha K.; Igo, Robert P.; Fondran, Jeremy R.; Young, Terri L.; Feng, Sheng; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Metspalu, Andres; Haller, Toomas; Mihailov, Evelin; Pärssinen, Olavi; Wedenoja, Juho; Wilson, Joan E. Bailey; Wojciechowski, Robert; Baird, Paul N.; Schache, Maria; Pfeiffer, Norbert; Höhn, René; Pang, Chi Pui; Chen, Peng; Meitinger, Thomas; Oexle, Konrad; Wegner, Aharon; Yoshimura, Nagahisa; Yamashiro, Kenji; Miyake, Masahiro; Pärssinen, Olavi; Yip, Shea Ping; Ho, Daniel W.H.; Pirastu, Mario; Murgia, Federico; Portas, Laura; Biino, Genevra; Wilson, James F.; Fleck, Brian; Vitart, Veronique; Stambolian, Dwight; Wilson, Joan E. Bailey; Hewitt, Alex W.; Ang, Wei; Verhoeven, Virginie J.M.; Klaver, Caroline C.; van Duijn, Cornelia M.; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Wong, Tien-Yin; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Tai, E-Shyong; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Saw, Seang-Mei; Teo, Yik-Ying; Fan, Qiao; Cheng, Ching-Yu; Zhou, Xin; Ikram, M. Kamran; Mackey, David A.; MacGregor, Stuart; Hammond, Christopher J.; Hysi, Pirro G.; Deangelis, Margaret M.; Morrison, Margaux; Zhou, Xiangtian; Chen, Wei; Paterson, Andrew D.; Hosseini, S. Mohsen; Mizuki, Nobuhisa; Meguro, Akira; Lehtimäki, Terho; Mäkelä, Kari-Matti; Raitakari, Olli; Kähönen, Mika; Burdon, Kathryn P.; Craig, Jamie E.; Iyengar, Sudha K.; Igo, Robert P.; Lass, Jonathan H.; Reinhart, William; Belin, Michael W.; Schultze, Robert L.; Morason, Todd; Sugar, Alan; Mian, Shahzad; Soong, Hunson Kaz; Colby, Kathryn; Jurkunas, Ula; Yee, Richard; Vital, Mark; Alfonso, Eduardo; Karp, Carol; Lee, Yunhee; Yoo, Sonia; Hammersmith, Kristin; Cohen, Elisabeth; Laibson, Peter; Rapuano, Christopher; Ayres, Brandon; Croasdale, Christopher; Caudill, James; Patel, Sanjay; Baratz, Keith; Bourne, William; Maguire, Leo; Sugar, Joel; Tu, Elmer; Djalilian, Ali; Mootha, Vinod; McCulley, James; Bowman, Wayne; Cavanaugh, H. Dwight; Verity, Steven; Verdier, David; Renucci, Ann; Oliva, Matt; Rotkis, Walter; Hardten, David R.; Fahmy, Ahmad; Brown, Marlene; Reeves, Sherman; Davis, Elizabeth A.; Lindstrom, Richard; Hauswirth, Scott; Hamilton, Stephen; Lee, W. Barry; Price, Francis; Price, Marianne; Kelly, Kathleen; Peters, Faye; Shaughnessy, Michael; Steinemann, Thomas; Dupps, B.J.; Meisler, David M.; Mifflin, Mark; Olson, Randal; Aldave, Anthony; Holland, Gary; Mondino, Bartly J.; Rosenwasser, George; Gorovoy, Mark; Dunn, Steven P.; Heidemann, David G.; Terry, Mark; Shamie, Neda; Rosenfeld, Steven I.; Suedekum, Brandon; Hwang, David; Stone, Donald; Chodosh, James; Galentine, Paul G.; Bardenstein, David; Goddard, Katrina; Chin, Hemin; Mannis, Mark; Varma, Rohit; Borecki, Ingrid; Chew, Emily Y.; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L.; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J.; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Bramon, Elvira; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N.A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C.A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Donnelly, Peter; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Waller, Matthew; Weston, Paul; Widaa, Sara; Whittaker, Pamela; Barroso, Ines; Deloukas, Panos; Mathew, Christopher G.; Blackwell, Jenefer M.; Brown, Matthew A.; Corvin, Aiden; Spencer, Chris C.A.; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M.; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E.; Hosseini, S. Mohsen; Paterson, Andrew D.; Genuth, S.; Nathan, D.M.; Zinman, B.; Crofford, O.; Crandall, J.; Reid, M.; Brown-Friday, J.; Engel, S.; Sheindlin, J.; Martinez, H.; Shamoon, H.; Engel, H.; Phillips, M.; Gubitosi-Klug, R.; Mayer, L.; Pendegast, S.; Zegarra, H.; Miller, D.; Singerman, L.; Smith-Brewer, S.; Novak, M.; Quin, J.; Dahms, W.; Genuth, Saul; Palmert, M.; Brillon, D.; Lackaye, M.E.; Kiss, S.; Chan, R.; Reppucci, V.; Lee, T.; Heinemann, M.; Whitehouse, F.; Kruger, D.; Jones, J.K.; McLellan, M.; Carey, J.D.; Angus, E.; Thomas, A.; Galprin, A.; Bergenstal, R.; Johnson, M.; Spencer, M.; Morgan, K.; Etzwiler, D.; Kendall, D.; Aiello, Lloyd Paul; Golden, E.; Jacobson, A.; Beaser, R.; Ganda, O.; Hamdy, O.; Wolpert, H.; Sharuk, G.; Arrigg, P.; Schlossman, D.; Rosenzwieg, J.; Rand, L.; Nathan, D.M.; Larkin, M.; Ong, M.; Godine, J.; Cagliero, E.; Lou, P.; Folino, K.; Fritz, S.; Crowell, S.; Hansen, K.; Gauthier-Kelly, C.; Service, J.; Ziegler, G.; Luttrell, L.; Caulder, S.; Lopes-Virella, M.; Colwell, J.; Soule, J.; Fernandes, J.; Hermayer, K.; Kwon, S.; Brabham, M.; Blevins, A.; Parker, J.; Lee, D.; Patel, N.; Pittman, C.; Lindsey, P.; Bracey, M.; Lee, K.; Nutaitis, M.; Farr, A.; Elsing, S.; Thompson, T.; Selby, J.; Lyons, T.; Yacoub-Wasef, S.; Szpiech, M.; Wood, D.; Mayfield, R.; Molitch, M.; Schaefer, B.; Jampol, L.; Lyon, A.; Gill, M.; Strugula, Z.; Kaminski, L.; Mirza, R.; Simjanoski, E.; Ryan, D.; Kolterman, O.; Lorenzi, G.; Goldbaum, M.; Sivitz, W.; Bayless, M.; Counts, D.; Johnsonbaugh, S.; Hebdon, M.; Salemi, P.; Liss, R.; Donner, T.; Gordon, J.; Hemady, R.; Kowarski, A.; Ostrowski, D.; Steidl, S.; Jones, B.; Herman, W.H.; Martin, C.L.; Pop-Busui, R.; Sarma, A.; Albers, J.; Feldman, E.; Kim, K.; Elner, S.; Comer, G.; Gardner, T.; Hackel, R.; Prusak, R.; Goings, L.; Smith, A.; Gothrup, J.; Titus, P.; Lee, J.; Brandle, M.; Prosser, L.; Greene, D.A.; Stevens, M.J.; Vine, A.K.; Bantle, J.; Wimmergren, N.; Cochrane, A.; Olsen, T.; Steuer, E.; Rath, P.; Rogness, B.; Hainsworth, D.; Goldstein, D.; Hitt, S.; Giangiacomo, J.; Schade, D.S.; Canady, J.L.; Chapin, J.E.; Ketai, L.H.; Braunstein, C.S.; Bourne, P.A.; Schwartz, S.; Brucker, A.; Maschak-Carey, B.J.; Baker, L.; Orchard, T.; Silvers, N.; Ryan, C.; Songer, T.; Doft, B.; Olson, S.; Bergren, R.L.; Lobes, L.; Rath, P. Paczan; Becker, D.; Rubinstein, D.; Conrad, P.W.; Yalamanchi, S.; Drash, A.; Morrison, A.; Bernal, M.L.; Vaccaro-Kish, J.; Malone, J.; Pavan, P.R.; Grove, N.; Iyer, M.N.; Burrows, A.F.; Tanaka, E.A.; Gstalder, R.; Dagogo-Jack, S.; Wigley, C.; Ricks, H.; Kitabchi, A.; Murphy, M.B.; Moser, S.; Meyer, D.; Iannacone, A.; Chaum, E.; Yoser, S.; Bryer-Ash, M.; Schussler, S.; Lambeth, H.; Raskin, P.; Strowig, S.; Zinman, B.; Barnie, A.; Devenyi, R.; Mandelcorn, M.; Brent, M.; Rogers, S.; Gordon, A.; Palmer, J.; Catton, S.; Brunzell, J.; Wessells, H.; de Boer, I.H.; Hokanson, J.; Purnell, J.; Ginsberg, J.; Kinyoun, J.; Deeb, S.; Weiss, M.; Meekins, G.; Distad, J.; Van Ottingham, L.; Dupre, J.; Harth, J.; Nicolle, D.; Driscoll, M.; Mahon, J.; Canny, C.; May, M.; Lipps, J.; Agarwal, A.; Adkins, T.; Survant, L.; Pate, R.L.; Munn, G.E.; Lorenz, R.; Feman, S.; White, N.; Levandoski, L.; Boniuk, I.; Grand, G.; Thomas, M.; Joseph, D.D.; Blinder, K.; Shah, G.; Boniuk; Burgess; Santiago, J.; Tamborlane, W.; Gatcomb, P.; Stoessel, K.; Taylor, K.; Goldstein, J.; Novella, S.; Mojibian, H.; Cornfeld, D.; Lima, J.; Bluemke, D.; Turkbey, E.; van der Geest, R.J.; Liu, C.; Malayeri, A.; Jain, A.; Miao, C.; Chahal, H.; Jarboe, R.; Maynard, J.; Gubitosi-Klug, R.; Quin, J.; Gaston, P.; Palmert, M.; Trail, R.; Dahms, W.; Lachin, J.; Cleary, P.; Backlund, J.; Sun, W.; Braffett, B.; Klumpp, K.; Chan, K.; Diminick, L.; Rosenberg, D.; Petty, B.; Determan, A.; Kenny, D.; Rutledge, B.; Younes, Naji; Dews, L.; Hawkins, M.; Cowie, C.; Fradkin, J.; Siebert, C.; Eastman, R.; Danis, R.; Gangaputra, S.; Neill, S.; Davis, M.; Hubbard, L.; Wabers, H.; Burger, M.; Dingledine, J.; Gama, V.; Sussman, R.; Steffes, M.; Bucksa, J.; Nowicki, M.; Chavers, B.; O’Leary, D.; Polak, J.; Harrington, A.; Funk, L.; Crow, R.; Gloeb, B.; Thomas, S.; O’Donnell, C.; Soliman, E.; Zhang, Z.M.; Prineas, R.; Campbell, C.; Ryan, C.; Sandstrom, D.; Williams, T.; Geckle, M.; Cupelli, E.; Thoma, F.; Burzuk, B.; Woodfill, T.; Low, P.; Sommer, C.; Nickander, K.; Budoff, M.; Detrano, R.; Wong, N.; Fox, M.; Kim, L.; Oudiz, R.; Weir, G.; Espeland, M.; Manolio, T.; Rand, L.; Singer, D.; Stern, M.; Boulton, A.E.; Clark, C.; D’Agostino, R.; Lopes-Virella, M.; Garvey, W.T.; Lyons, T.J.; Jenkins, A.; Virella, G.; Jaffa, A.; Carter, Rickey; Lackland, D.; Brabham, M.; McGee, D.; Zheng, D.; Mayfield, R.K.; Boright, A.; Bull, S.; Sun, L.; Scherer, S.; Zinman, B.; Natarajan, R.; Miao, F.; Zhang, L.; Chen;, Z.; Nathan, D.M.; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K.H.; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J.; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G.; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W.; Williams, Cathy; Oostra, Ben A.; Teo, Yik-Ying; Hammond, Christopher J.; Stambolian, Dwight; Mackey, David A.; Klaver, Caroline C.W.; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N.

    2013-01-01

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways. PMID:24144296

  11. Nine loci for ocular axial length identified through genome-wide association studies, including shared loci with refractive error.

    PubMed

    Cheng, Ching-Yu; Schache, Maria; Ikram, M Kamran; Young, Terri L; Guggenheim, Jeremy A; Vitart, Veronique; MacGregor, Stuart; Verhoeven, Virginie J M; Barathi, Veluchamy A; Liao, Jiemin; Hysi, Pirro G; Bailey-Wilson, Joan E; St Pourcain, Beate; Kemp, John P; McMahon, George; Timpson, Nicholas J; Evans, David M; Montgomery, Grant W; Mishra, Aniket; Wang, Ya Xing; Wang, Jie Jin; Rochtchina, Elena; Polasek, Ozren; Wright, Alan F; Amin, Najaf; van Leeuwen, Elisabeth M; Wilson, James F; Pennell, Craig E; van Duijn, Cornelia M; de Jong, Paulus T V M; Vingerling, Johannes R; Zhou, Xin; Chen, Peng; Li, Ruoying; Tay, Wan-Ting; Zheng, Yingfeng; Chew, Merwyn; Burdon, Kathryn P; Craig, Jamie E; Iyengar, Sudha K; Igo, Robert P; Lass, Jonathan H; Chew, Emily Y; Haller, Toomas; Mihailov, Evelin; Metspalu, Andres; Wedenoja, Juho; Simpson, Claire L; Wojciechowski, Robert; Höhn, René; Mirshahi, Alireza; Zeller, Tanja; Pfeiffer, Norbert; Lackner, Karl J; Bettecken, Thomas; Meitinger, Thomas; Oexle, Konrad; Pirastu, Mario; Portas, Laura; Nag, Abhishek; Williams, Katie M; Yonova-Doing, Ekaterina; Klein, Ronald; Klein, Barbara E; Hosseini, S Mohsen; Paterson, Andrew D; Makela, Kari-Matti; Lehtimaki, Terho; Kahonen, Mika; Raitakari, Olli; Yoshimura, Nagahisa; Matsuda, Fumihiko; Chen, Li Jia; Pang, Chi Pui; Yip, Shea Ping; Yap, Maurice K H; Meguro, Akira; Mizuki, Nobuhisa; Inoko, Hidetoshi; Foster, Paul J; Zhao, Jing Hua; Vithana, Eranga; Tai, E-Shyong; Fan, Qiao; Xu, Liang; Campbell, Harry; Fleck, Brian; Rudan, Igor; Aung, Tin; Hofman, Albert; Uitterlinden, André G; Bencic, Goran; Khor, Chiea-Chuen; Forward, Hannah; Pärssinen, Olavi; Mitchell, Paul; Rivadeneira, Fernando; Hewitt, Alex W; Williams, Cathy; Oostra, Ben A; Teo, Yik-Ying; Hammond, Christopher J; Stambolian, Dwight; Mackey, David A; Klaver, Caroline C W; Wong, Tien-Yin; Saw, Seang-Mei; Baird, Paul N

    2013-08-01

    Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.

  12. Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine.

    PubMed

    Velázquez, Rocío; Zamora, Emiliano; Álvarez, Manuel; Álvarez, María L; Ramírez, Manuel

    2016-10-01

    The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. Saccharomyces cerevisiae killer yeasts were tested to increase cell death and autolysis during mixed-yeast-inoculated second fermentation and aging. These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. The effect was faster under high-pressure than under low-pressure conditions. Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine. PMID:27375256

  13. Characterization of novel killer toxins secreted by wine-related non-Saccharomyces yeasts and their action on Brettanomyces spp.

    PubMed

    Mehlomakulu, Ngwekazi N; Setati, Mathabatha E; Divol, Benoit

    2014-10-01

    Wine spoilage associated with Brettanomyces bruxellensis is a major concern for winemakers. An effective and reliable method to control the proliferation of this yeast is therefore of utmost importance. To achieve this purpose, sulphur dioxide (SO2) is commonly employed but the efficiency of this chemical compound is subject to wine composition and it can elicit allergic reactions in some consumers. Biological alternatives are therefore actively sought. The current study focused on identifying and characterizing killer toxins which are antimicrobial compounds that show potential in inhibiting B. bruxellensis in wine. Two killer toxins, CpKT1 and CpKT2, from the wine isolated yeast Candida pyralidae were identified and partially characterized. The two proteins had a molecular mass above 50kDa and exhibited killer activity against several B. bruxellensis strains especially in grape juice. They were active and stable at pH3.5-4.5, and temperatures between 15 and 25°C which are compatible with winemaking conditions. Furthermore, the activity of these killer toxins was not affected by the ethanol and sugar concentrations typically found in grape juice and wine. In addition, these killer toxins inhibited neither the Saccharomyces cerevisiae nor the lactic acid bacteria strains tested. These preliminary results indicated that the application of these toxins will have no effect on the main microbial agents that drive alcoholic and malolactic fermentations and further highlight the potential of using these toxins as agents to control the development of B. bruxellensis in grape juice or wine.

  14. Using mixed inocula of Saccharomyces cerevisiae killer strains to improve the quality of traditional sparkling-wine.

    PubMed

    Velázquez, Rocío; Zamora, Emiliano; Álvarez, Manuel; Álvarez, María L; Ramírez, Manuel

    2016-10-01

    The quality of traditional sparkling-wine depends on the aging process in the presence of dead yeast cells. These cells undergo a slow autolysis process thereby releasing some compounds, mostly colloidal polymers such as polysaccharides and mannoproteins, which influence the wine's foam properties and mouthfeel. Saccharomyces cerevisiae killer yeasts were tested to increase cell death and autolysis during mixed-yeast-inoculated second fermentation and aging. These yeasts killed sensitive strains in killer plate assays done under conditions of low pH and temperature similar to those used in sparkling-wine making, although some strains showed a different killer behaviour during the second fermentation. The fast killer effect improved the foam quality and mouthfeel of the mixed-inoculated wines, while the slow killer effect gave small improvements over single-inoculated wines. The effect was faster under high-pressure than under low-pressure conditions. Wine quality improvement did not correlate with the polysaccharide, protein, mannan, or aromatic compound concentrations, suggesting that the mouthfeel and foaming quality of sparkling wine are very complex properties influenced by other wine compounds and their interactions, as well as probably by the specific chemical composition of a given wine.

  15. Chromosomal localization of the human natural killer cell class I receptor family genes to 19q13.4 by fluorescence in situ hybridization

    SciTech Connect

    Suto, Yumiko; Maenaka, Katsumi; yabe, Toshio

    1996-07-01

    This report describes the localization of the human natural killer cell I receptor family genes to human chromosome 19q13.4 using fluorescence in situ hybridization. These genes mediate the inhibition of the cytotoxicity of subsets of natural killer cells. 8 refs., 1 fig.

  16. Combination chemo-immunotherapy: kinetics of in vivo and in vitro generation of natural killer cells and lymphokine-activated killer cells in the rat.

    PubMed Central

    Stewart, L S; Sewell, H F; Thomson, A W

    1990-01-01

    Rats received a single high dose of cyclophosphamide (Cy) (150 mg/kg), followed 48 h later (on day 0) by immunization with a T cell-dependent soluble antigen, ovalbumin in Freund's complete adjuvant (FCA). The effect of this treatment on lymphoid cell subpopulations in the spleen, natural killer (NK) cell and interleukin-2 (IL-2) induced lymphokine-activated killer (LAK) cell activity was examined. Cy (with and without ovalbumin) caused a large relative increase (by day 14) in splenic OX8+, OX19- cells with NK morphology. A marked relative increase in fresh NK cell activity was noted after Cy + ovalbumin, but not consistently after Cy alone. Elevated NK activity was Cy dose- and time-dependent, was evident within 7 days post Cy/ovalbumin and persisted for at least 28 days. Pooled splenic mononuclear cells (MNC), obtained 14 days after Cy/ovalbumin, lost all cytolytic activity against YAC-1 cells when cultured in the absence of human recombinant IL-2 (rIL-2). In contrast, similarly maintained cells from normal rats displayed NK activity higher than normal 'fresh' levels. Upon culture in medium containing 500 U/ml rIL-2, however, 'augmented' NK activity was equivalent, on a per-cell basis, in both normal and Cy/ovalbumin-pretreated groups. LAK activity generated in vitro (i.e. against NK-resistant target cells) was significantly lower in the latter group, and the overall yield of cells was reduced. By day 21 after Cy/ovalbumin, augmented NK activity was significantly greater than controls, on a per-cell and total culture yield basis. Moreover, LAK activity was now similar between groups. It is concluded that the chemotherapy/immunization protocol which we have used can greatly enhance NK activity in vivo and that these cells are responsive to induction of LAK activity by IL-2 in vitro. Images Fig. 1 PMID:2317946

  17. Peripheral Foxp3+ regulatory T cells and natural killer group 2, member D expression levels in natural killer cells of patients with colorectal cancer.

    PubMed

    Shen, Yajuan; Wang, Qian; Qi, Yuanying; Cui, Bin; Zhang, Zhifen; Su, Jingran; Liu, Xiaowen; Lu, Chao; Ye, Hui; Ju, Ying; Lu, Zhiming

    2014-08-01

    Foxp3+ regulatory T cells (Tregs) and natural killer group 2, member D (NKG2D)-positive natural killer (NK) cells are considered to be important in the immune escape of colorectal cancer (CRC). However, the association between these two variables remains obscure. Therefore, in the present study, the levels of peripheral Tregs and NKG2D expression in NK cells and the associations in CRC patients were investigated. A total of 35 CRC patients and 16 healthy controls were enrolled in this study. Flow cytometry was performed to assay Treg numbers and NKG2D expression levels in NK cells in peripheral blood samples. Serum carcino-embryonic antigen (CEA) protein was assayed by electrochemiluminescence. Peripheral Treg numbers were significantly increased (P<0.05), while NKG2D expression levels in NK cells were significantly reduced (P<0.01) in CRC patients compared with healthy controls. However, no significant differences were identified in Treg numbers between CRC patients with and without lymph node metastases and between CRC patients with different clinical stages of CRC. Similarly, no significant differences were detected in NKG2D expression levels in NK cells between the different patient groups. Statistical analysis revealed that increased Treg numbers were not correlated with reduced NKG2D expression levels in NK cells from CRC patients. In addition, no statistical correlation was observed between Treg numbers and serum CEA protein in CRC patients. In conclusion, the upregulation of Tregs was not significantly correlated with the downregulation of NKG2D expression in NK cells in peripheral blood from CRC patients.

  18. Blood Pressure Loci Identified with a Gene-Centric Array

    PubMed Central

    Johnson, Toby; Gaunt, Tom R.; Newhouse, Stephen J.; Padmanabhan, Sandosh; Tomaszewski, Maciej; Kumari, Meena; Morris, Richard W.; Tzoulaki, Ioanna; O'Brien, Eoin T.; Poulter, Neil R.; Sever, Peter; Shields, Denis C.; Thom, Simon; Wannamethee, Sasiwarang G.; Whincup, Peter H.; Brown, Morris J.; Connell, John M.; Dobson, Richard J.; Howard, Philip J.; Mein, Charles A.; Onipinla, Abiodun; Shaw-Hawkins, Sue; Zhang, Yun; Smith, George Davey; Day, Ian N.M.; Lawlor, Debbie A.; Goodall, Alison H.; Fowkes, F. Gerald; Abecasis, Gonçalo R.; Elliott, Paul; Gateva, Vesela; Braund, Peter S.; Burton, Paul R.; Nelson, Christopher P.; Tobin, Martin D.; van der Harst, Pim; Glorioso, Nicola; Neuvrith, Hani; Salvi, Erika; Staessen, Jan A.; Stucchi, Andrea; Devos, Nabila; Jeunemaitre, Xavier; Plouin, Pierre-François; Tichet, Jean; Juhanson, Peeter; Org, Elin; Putku, Margus; Sõber, Siim; Veldre, Gudrun; Viigimaa, Margus; Levinsson, Anna; Rosengren, Annika; Thelle, Dag S.; Hastie, Claire E.; Hedner, Thomas; Lee, Wai K.; Melander, Olle; Wahlstrand, Björn; Hardy, Rebecca; Wong, Andrew; Cooper, Jackie A.; Palmen, Jutta; Chen, Li; Stewart, Alexandre F.R.; Wells, George A.; Westra, Harm-Jan; Wolfs, Marcel G.M.; Clarke, Robert; Franzosi, Maria Grazia; Goel, Anuj; Hamsten, Anders; Lathrop, Mark; Peden, John F.; Seedorf, Udo; Watkins, Hugh; Ouwehand, Willem H.; Sambrook, Jennifer; Stephens, Jonathan; Casas, Juan-Pablo; Drenos, Fotios; Holmes, Michael V.; Kivimaki, Mika; Shah, Sonia; Shah, Tina; Talmud, Philippa J.; Whittaker, John; Wallace, Chris; Delles, Christian; Laan, Maris; Kuh, Diana; Humphries, Steve E.; Nyberg, Fredrik; Cusi, Daniele; Roberts, Robert; Newton-Cheh, Christopher; Franke, Lude; Stanton, Alice V.; Dominiczak, Anna F.; Farrall, Martin; Hingorani, Aroon D.; Samani, Nilesh J.; Caulfield, Mark J.; Munroe, Patricia B.

    2011-01-01

    Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10−7 study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r2 = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10−7 at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies. PMID:22100073

  19. Positive Selection on Loci Associated with Drug and Alcohol Dependence

    PubMed Central

    Sadler, Brooke; Haller, Gabe; Edenberg, Howard; Tischfield, Jay; Brooks, Andy; Kramer, John; Schuckit, Marc; Nurnberger, John; Goate, Alison

    2015-01-01

    Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs) on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans) to examine whether natural selection has occurred at these loci. We used Tajima’s D and the integrated haplotype score (iHS) to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA) to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS) Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies. PMID:26270548

  20. Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus

    PubMed Central

    Sanchez, Elena; Nadig, Ajay; Richardson, Bruce C; Freedman, Barry I; Kaufman, Kenneth M; Kelly, Jennifer A; Niewold, Timothy B; Kamen, Diane L; Gilkeson, Gary S; Ziegler, Julie T; Langefeld, Carl D; Alarcón, Graciela S; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Brown, Elizabeth E; Kimberly, Robert P; Reveille, John D; Vilá, Luis M; Merrill, Joan T; Anaya, Juan-Manuel; James, Judith A; Pons-Estel, Bernardo A; Martin, Javier; Park, So-Yeon; Bang, So-Young; Bae, Sang-Cheol; Moser, Kathy L; Vyse, Timothy J; Criswell, Lindsey A; Gaffney, Patrick M; Tsao, Betty P; Jacob, Chaim O; Harley, John B; Alarcón-Riquelme, Marta E; Sawalha, Amr H

    2011-01-01

    Objective Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods 4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0×10−6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of <0.05 and pass the significance threshold using Bonferroni correction for multiple testing. Conclusion Significant associations were found between lupus clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future. PMID:21719445

  1. Quantitative trait loci affecting reproductive phenology in peach

    PubMed Central

    2014-01-01

    Background The reproductive phenology of perennial plants in temperate climates is largely conditioned by the duration of bud dormancy, and fruit developmental processes. Bud dormancy release and bud break depends on the perception of cumulative chilling and heat during the bud development. The objective of this work was to identify new quantitative trait loci (QTLs) associated to temperature requirements for bud dormancy release and flowering and to fruit harvest date, in a segregating population of peach. Results We have identified QTLs for nine traits related to bud dormancy, flowering and fruit harvest in an intraspecific hybrid population of peach in two locations differing in chilling time accumulation. QTLs were located in a genetic linkage map of peach based on single nucleotide polymorphism (SNP) markers for eight linkage groups (LGs) of the peach genome sequence. QTLs for chilling requirements for dormancy release and blooming clustered in seven different genomic regions that partially coincided with loci identified in previous works. The most significant QTL for chilling requirements mapped to LG1, close to the evergrowing locus. QTLs for heat requirement related traits were distributed in nine genomic regions, four of them co-localizing with QTLs for chilling requirement trait. Two major loci in LG4 and LG6 determined fruit harvest time. Conclusions We identified QTLs associated to nine traits related to the reproductive phenology in peach. A search of candidate genes for these QTLs rendered different genes related to flowering regulation, chromatin modification and hormone signalling. A better understanding of the genetic factors affecting crop phenology might help scientists and breeders to predict changes in genotype performance in a context of global climate change. PMID:24559033

  2. Making the giant leap with augmented cognition technologies : what will be the first %22killer app?%22.

    SciTech Connect

    Forsythe, James Chris

    2007-02-01

    This paper highlights key topic areas to be discussed the authors in a panel format during the Augmented Cognition thematic area paper session: 'Augmented Cognition Lessons Learned and Future Directions for Enabling 'Anyone, Anytime, Anywhere' Applications'. The term 'killer app' has been part of the vernacular in the commercial computer software and electronic devices industry to refer to breakthrough technologies [2]. A 'killer app' generally emerges with the development of related technologies that extends over some time and involves numerous variations on a basic concept. Hypotheses may be offered with respect to the conditions that will be needed to enable a similar situation with augmented cognition technologies. This paper and resulting panel session will address the numerous concepts that have emerged from the augmented cognition field to date and postulate how and when this field's first 'killer app' may emerge (e.g., 5, 10, 15, or more years from now).

  3. [Experimental study on the optimal treatment schedule for combination of BRM (immunostimulators, cultured killer cells or interleukin-2) and chemotherapy].

    PubMed

    Kan, N; Okino, T; Satoh, K; Mise, K; Teramura, Y; Yamasaki, S; Harada, T; Ohgaki, K; Tobe, T

    1990-08-01

    In the present study we tried to reevaluate the optimal combination timing in the experimental treatment with BRM and chemotherapeutic agents. BALB/c mice with advanced malignant ascites tumor (MOPC 104 E) were treated with cyclophosphamide (CPA, 2 mg/kg) and BRM such as immunostimulator (OK-432, Lentinan or Bestatin), interleukin-2 (IL 2) or cultured killer cells. The survival of mice was prolonged when immunostimulators were given before CPA. However, no combined effect was seen when immunostimulators were administered after CPA. Treatment with cultured killer cells and in vivo IL 2 after immunochemotherapy (immunostimulator followed by CPA) was the most effective protocol in which immunostimulator, chemotherapy, killer cells and IL 2 respectively seemed to induce, regulate, supplement and amplify anti-tumor effector cells.

  4. DNA polymorphism at the casein loci in sheep.

    PubMed

    Di Gregorio, P; Rando, A; Pieragostini, E; Masina, P

    1991-01-01

    By using seven endonucleases and four bovine cDNA probes specific for alpha S1-, alpha S2-, beta-, and kappa-casein genes, nine restriction fragment length polymorphisms (RFLPs) have been found in the sheep orthologous DNA regions. In contrast to the low level of variation observed at the protein level, these DNA polymorphisms determine a high level of heterozygosity and, therefore, represent useful tools for genetic analyses since they can also be obtained without the need for gene expression. In fact, informative matings suggest that in sheep, as in cattle, the four loci are linked.

  5. Nine microsatellite loci developed from the octocoral, Paragorgia arborea

    USGS Publications Warehouse

    Coykendall, Dolly K.; Morrison, Cheryl L.

    2015-01-01

    Paragorgia arborea, or bubblegum coral, occurs in continental slope habitats worldwide, which are increasingly threatened by human activities such as energy development and fisheries practices. From 101 putative loci screened, nine microsatellite markers were developed from samples taken from Baltimore canyon in the western North Atlantic Ocean. The number of alleles ranged from two to thirteen per locus and each displayed equilibrium. These nuclear resources will help further research on population connectivity in threatened coral species where mitochondrial markers are known to lack fine-scale genetic diversity.

  6. Mapping autism risk loci using genetic linkage and chromosomal rearrangements

    PubMed Central

    Szatmari, Peter; Paterson, Andrew; Zwaigenbaum, Lonnie; Roberts, Wendy; Brian, Jessica; Liu, Xiao-Qing; Vincent, John; Skaug, Jennifer; Thompson, Ann; Senman, Lili; Feuk, Lars; Qian, Cheng; Bryson, Susan; Jones, Marshall; Marshall, Christian; Scherer, Stephen; Vieland, Veronica; Bartlett, Christopher; Mangin, La Vonne; Goedken, Rhinda; Segre, Alberto; Pericak-Vance, Margaret; Cuccaro, Michael; Gilbert, John; Wright, Harry; Abramson, Ruth; Betancur, Catalina; Bourgeron, Thomas; Gillberg, Christopher; Leboyer, Marion; Buxbaum, Joseph; Davis, Kenneth; Hollander, Eric; Silverman, Jeremy; Hallmayer, Joachim; Lotspeich, Linda; Sutcliffe, James; Haines, Jonathan; Folstein, Susan; Piven, Joseph; Wassink, Thomas; Sheffield, Val; Geschwind, Daniel; Bucan, Maja; Brown, Ted; Cantor, Rita; Constantino, John; Gilliam, Conrad; Herbert, Martha; Lajonchere, Clara; Ledbetter, David; Lese-Martin, Christa; Miller, Janet; Nelson, Stan; Samango-Sprouse, Carol; Spence, Sarah; State, Matthew; Tanzi, Rudolph; Coon, Hilary; Dawson, Geraldine; Devlin, Bernie; Estes, Annette; Flodman, Pamela; Klei, Lambertus; Mcmahon, William; Minshew, Nancy; Munson, Jeff; Korvatska, Elena; Rodier, Patricia; Schellenberg, Gerard; Smith, Moyra; Spence, Anne; Stodgell, Chris; Tepper, Ping Guo; Wijsman, Ellen; Yu, Chang-En; Rogé, Bernadette; Mantoulan, Carine; Wittemeyer, Kerstin; Poustka, Annemarie; Felder, Bärbel; Klauck, Sabine; Schuster, Claudia; Poustka, Fritz; Bölte, Sven; Feineis-Matthews, Sabine; Herbrecht, Evelyn; Schmötzer, Gabi; Tsiantis, John; Papanikolaou, Katerina; Maestrini, Elena; Bacchelli, Elena; Blasi, Francesca; Carone, Simona; Toma, Claudio; Van Engeland, Herman; De Jonge, Maretha; Kemner, Chantal; Koop, Frederieke; Langemeijer, Marjolein; Hijmans, Channa; Staal, Wouter; Baird, Gillian; Bolton, Patrick; Rutter, Michael; Weisblatt, Emma; Green, Jonathan; Aldred, Catherine; Wilkinson, Julie-Anne; Pickles, Andrew; Le Couteur, Ann; Berney, Tom; Mcconachie, Helen; Bailey, Anthony; Francis, Kostas; Honeyman, Gemma; Hutchinson, Aislinn; Parr, Jeremy; Wallace, Simon; Monaco, Anthony; Barnby, Gabrielle; Kobayashi, Kazuhiro; Lamb, Janine; Sousa, Ines; Sykes, Nuala; Cook, Edwin; Guter, Stephen; Leventhal, Bennett; Salt, Jeff; Lord, Catherine; Corsello, Christina; Hus, Vanessa; Weeks, Daniel; Volkmar, Fred; Tauber, Maïté; Fombonne, Eric; Shih, Andy; Meyer, Kacie

    2007-01-01

    Autism spectrum disorders (ASD) are common, heritable neurodevelopmental conditions. The genetic architecture of ASD is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASD by using Affymetrix 10K single nucleotide polymorphism (SNP) arrays and 1168 families with ≥ 2 affected individuals to perform the largest linkage scan to date, while also analyzing copy number variation (CNV) in these families. Linkage and CNV analyses implicate chromosome 11p12-p13 and neurexins, respectively, amongst other candidate loci. Neurexins team with previously-implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for ASD. PMID:17322880

  7. M by Fritz Lang (Germany, 1931) Phenomenology of Evil: a serial killer and his social group.

    PubMed

    Secchi, Cesare

    2015-10-01

    In 1931 an unknown murderer of little girls (Peter Lorre) is terrorizing the city of Berlin. We see him entice a new victim, the little Elsie Beckmann, who is coming home from school: whistling a tune by Grieg, he buys her a balloon from a blind beggar. When her corpse is discovered, the police undertake a major mobilization aimed at seeking the serial killer in the criminal underworld; meanwhile, the ever more terrified population starts to see the dangerous murderer in everyone. Since the roundups and incursions into the seediest parts of town disturb the gangsters' activities, the leaders of organized crime, headed by Schränker (Gustav Gründgens), take it upon themselves also to hunt down the solitary child-killer, engaging the community of beggars. Every corner of the city is catalogued and sifted by the dual activity of the police and the gangsters. The 'monster', a former psychiatric patient, mild and harmless in manner, is finally tracked down via two parallel routes: the clue of a cigarette packet enables Inspector Lohmann (Otto Wernicke) to track down the serial killer's address, while the blind beggar recognizes the whistled tune. The murderer is identified by a 'slap' from a young criminal which leaves an M marked in chalk on a shoulder of the man's overcoat. Thus he is caught and undergoes a kind of trial at the hands of the gangsters who tie him up in order to lynch him, but they are interrupted by the arrival of the forces of law and order. PMID:26463110

  8. Natural killer cell receptor genes in the family Equidae: not only Ly49.

    PubMed

    Futas, Jan; Horin, Petr

    2013-01-01

    Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of

  9. Natural Killer Cell Receptor Genes in the Family Equidae: Not only Ly49

    PubMed Central

    Futas, Jan; Horin, Petr

    2013-01-01

    Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of

  10. Skin TLR7 triggering promotes accumulation of respiratory dendritic cells and natural killer cells.

    PubMed

    Hackstein, Holger; Hagel, Nicole; Knoche, Angela; Kranz, Sabine; Lohmeyer, Jürgen; von Wulffen, Werner; Kershaw, Olivia; Gruber, Achim D; Bein, Gregor; Baal, Nelli

    2012-01-01

    The TLR7 agonist imiquimod has been used successfully as adjuvant for skin treatment of virus-associated warts and basal cell carcinoma. The effects of skin TLR7 triggering on respiratory leukocyte populations are unknown. In a placebo-controlled experimental animal study we have used multicolour flow cytometry to systematically analyze the modulation of respiratory leukocyte subsets after skin administration of imiquimod. Compared to placebo, skin administration of imiquimod significantly increased respiratory dendritic cells (DC) and natural killer cells, whereas total respiratory leukocyte, alveolar macrophages, classical CD4+ T helper and CD8+ T killer cell numbers were not or only moderately affected. DC subpopulation analyses revealed that elevation of respiratory DC was caused by an increase of respiratory monocytic DC and CD11b(hi) DC subsets. Lymphocyte subpopulation analyses indicated a marked elevation of respiratory natural killer cells and a significant reduction of B lymphocytes. Analysis of cytokine responses of respiratory leukocytes after stimulation with Klebsiella pneumonia indicated reduced IFN-γ and TNF-α expression and increased IL-10 and IL-12p70 production after 7 day low dose skin TLR7 triggering. Additionally, respiratory NK cytotoxic activity was increased after 7d skin TLR7 triggering. In contrast, lung histology and bronchoalveolar cell counts were not affected suggesting that skin TLR7 stimulation modulated respiratory leukocyte composition without inducing overt pulmonary inflammation. These data suggest the possibility to modulate respiratory leukocyte composition and respiratory cytokine responses against pathogens like Klebsiella pneumonia through skin administration of a clinically approved TLR7 ligand. Skin administration of synthetic TLR7 ligands may represent a novel, noninvasive means to modulate respiratory immunity. PMID:22927956

  11. Skin TLR7 Triggering Promotes Accumulation of Respiratory Dendritic Cells and Natural Killer Cells

    PubMed Central

    Hackstein, Holger; Hagel, Nicole; Knoche, Angela; Kranz, Sabine; Lohmeyer, Jürgen; von Wulffen, Werner; Kershaw, Olivia; Gruber, Achim D.; Bein, Gregor; Baal, Nelli

    2012-01-01

    The TLR7 agonist imiquimod has been used successfully as adjuvant for skin treatment of virus-associated warts and basal cell carcinoma. The effects of skin TLR7 triggering on respiratory leukocyte populations are unknown. In a placebo-controlled experimental animal study we have used multicolour flow cytometry to systematically analyze the modulation of respiratory leukocyte subsets after skin administration of imiquimod. Compared to placebo, skin administration of imiquimod significantly increased respiratory dendritic cells (DC) and natural killer cells, whereas total respiratory leukocyte, alveolar macrophages, classical CD4+ T helper and CD8+ T killer cell numbers were not or only moderately affected. DC subpopulation analyses revealed that elevation of respiratory DC was caused by an increase of respiratory monocytic DC and CD11bhi DC subsets. Lymphocyte subpopulation analyses indicated a marked elevation of respiratory natural killer cells and a significant reduction of B lymphocytes. Analysis of cytokine responses of respiratory leukocytes after stimulation with Klebsiella pneumonia indicated reduced IFN-γ and TNF-α expression and increased IL-10 and IL-12p70 production after 7 day low dose skin TLR7 triggering. Additionally, respiratory NK cytotoxic activity was increased after 7d skin TLR7 triggering. In contrast, lung histology and bronchoalveolar cell counts were not affected suggesting that skin TLR7 stimulation modulated respiratory leukocyte composition without inducing overt pulmonary inflammation. These data suggest the possibility to modulate respiratory leukocyte composition and respiratory cytokine responses against pathogens like Klebsiella pneumonia through skin administration of a clinically approved TLR7 ligand. Skin administration of synthetic TLR7 ligands may represent a novel, noninvasive means to modulate respiratory immunity. PMID:22927956

  12. Association of polymorphisms in natural killer cell-related genes with preterm birth.

    PubMed

    Harmon, Quaker E; Engel, Stephanie M; Olshan, Andrew F; Moran, Thomas; Stuebe, Alison M; Luo, Jingchun; Wu, Michael C; Avery, Christy L

    2013-10-15

    Inflammation is implicated in preterm birth, but genetic studies of inflammatory genes have yielded inconsistent results. Maternal DNA from 1,646 participants in the Pregnancy, Infection, and Nutrition Cohort, enrolled in Orange and Wake counties, North Carolina (1995-2005), were genotyped for 432 tag single-nucleotide polymorphisms (SNPs) in 30 candidate genes. Gene-level and SNP associations were modeled within strata of genetic ancestry. Six genes were associated with preterm birth among European Americans: interleukin 12A (IL12A); colony-stimulating factor 2 (CSF2); interferon γ receptor 2 (IFNGR2); killer cell immunoglobulin-like receptor, three domain, long cytoplasmic tail, 2 (KIR3DL2); interleukin 4 (IL4); and interleukin 13 (IL13). Of these, relatively strong single-SNP associations were seen in IFNGR2 and KIR3DL2. Among the 4 genes related to natural killer cell function, 2 (IL12A and CSF2) were consistently associated with reduced risk of prematurity for both European and African Americans. SNPs tagging a locus control region for IL4 and IL13 were associated with an increased risk of spontaneous preterm birth for European Americans (rs3091307; risk ratio = 1.9; 95% confidence interval: 1.4, 2.5). Although gene-level associations were detected only in European Americans, single-SNP associations among European and African Americans were often similar in direction, though estimated with less precision among African Americans. In conclusion, we identified novel associations between variants in the natural killer cell immune pathway and prematurity in this biracial US population.

  13. M by Fritz Lang (Germany, 1931) Phenomenology of Evil: a serial killer and his social group.

    PubMed

    Secchi, Cesare

    2015-10-01

    In 1931 an unknown murderer of little girls (Peter Lorre) is terrorizing the city of Berlin. We see him entice a new victim, the little Elsie Beckmann, who is coming home from school: whistling a tune by Grieg, he buys her a balloon from a blind beggar. When her corpse is discovered, the police undertake a major mobilization aimed at seeking the serial killer in the criminal underworld; meanwhile, the ever more terrified population starts to see the dangerous murderer in everyone. Since the roundups and incursions into the seediest parts of town disturb the gangsters' activities, the leaders of organized crime, headed by Schränker (Gustav Gründgens), take it upon themselves also to hunt down the solitary child-killer, engaging the community of beggars. Every corner of the city is catalogued and sifted by the dual activity of the police and the gangsters. The 'monster', a former psychiatric patient, mild and harmless in manner, is finally tracked down via two parallel routes: the clue of a cigarette packet enables Inspector Lohmann (Otto Wernicke) to track down the serial killer's address, while the blind beggar recognizes the whistled tune. The murderer is identified by a 'slap' from a young criminal which leaves an M marked in chalk on a shoulder of the man's overcoat. Thus he is caught and undergoes a kind of trial at the hands of the gangsters who tie him up in order to lynch him, but they are interrupted by the arrival of the forces of law and order.

  14. Natural killer cell receptor genes in the family Equidae: not only Ly49.

    PubMed

    Futas, Jan; Horin, Petr

    2013-01-01

    Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of

  15. Identification of the ancestral killer immunoglobulin-like receptor gene in primates

    PubMed Central

    Sambrook, Jennifer G; Bashirova, Arman; Andersen, Hanne; Piatak, Mike; Vernikos, George S; Coggill, Penny; Lifson, Jeff D; Carrington, Mary; Beck, Stephan

    2006-01-01

    Background Killer Immunoglobulin-like Receptors (KIR) are essential immuno-surveillance molecules. They are expressed on natural killer and T cells, and interact with human leukocyte antigens. KIR genes are highly polymorphic and contribute vital variability to our immune system. Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving. Since few KIR remain orthologous between species, with only one of them, KIR2DL4, shown to be common to human, apes and monkeys, the evolution of the KIR gene family in primates remains unclear. Results Using comparative analyses, we have identified the ancestral KIR lineage (provisionally named KIR3DL0) in primates. We show KIR3DL0 to be highly conserved with the identification of orthologues in human (Homo sapiens), common chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), rhesus monkey (Macaca mulatta) and common marmoset (Callithrix jacchus). We predict KIR3DL0 to encode a functional molecule in all primates by demonstrating expression in human, chimpanzee and rhesus monkey. Using the rhesus monkey as a model, we further show the expression profile to be typical of KIR by quantitative measurement of KIR3DL0 from an enriched population of natural killer cells. Conclusion One reason why KIR3DL0 may have escaped discovery for so long is that, in human, it maps in between two related leukocyte immunoglobulin-like receptor clusters outside the known KIR gene cluster on Chromosome 19. Based on genomic, cDNA, expression and phylogenetic data, we report a novel lineage of immunoglobulin receptors belonging to the KIR family, which is highly conserved throughout 50 million years of primate evolution. PMID:16911775

  16. Comparison of amikacin pharmacokinetics in a killer whale (Orcinus orca) and a beluga whale (Delphinapterus leucas).

    PubMed

    KuKanich, Butch; Papich, Mark; Huff, David; Stoskopf, Michael

    2004-06-01

    Amikacin, an aminoglycoside antimicrobial, was administered to a killer whale (Orcinus orca) and a beluga whale (Delphinapterus leucas) for the treatment of clinical signs consistent with gram-negative aerobic bacterial infections. Dosage regimens were designed to target a maximal plasma concentration 8-10 times the minimum inhibitory concentrations of the pathogen and to reduce the risk of aminoglycoside toxicity. Allometric analysis of published pharmacokinetic parameters in mature animals yielded a relationship for amikacin's volume of distribution, in milliliters, given by the equation Vd = 151.058(BW)1.043. An initial dose for amikacin was estimated by calculating the volume of distribution and targeted maximal concentration. With this information, dosage regimens for i.m. administration were designed for a killer whale and a beluga whale. Therapeutic drug monitoring was performed on each whale to assess the individual pharmacokinetic parameters. The elimination half-life (5.99 hr), volume of distribution per bioavailability (319 ml/kg). and clearance per bioavailability (0.61 ml/min/kg) were calculated for the killer whale. The elimination half-life (5.03 hr), volume of distribution per bioavailability (229 ml/kg). and clearance per bioavailability (0.53 ml/min/kg) were calculated for the beluga whale. The volume of distribution predicted from the allometric equation for both whales was similar to the calculated pharmacokinetic parameter. Both whales exhibited a prolonged elimination half-life and decreased clearance when compared with other animal species despite normal renal parameters on biochemistry panels. Allometric principles and therapeutic drug monitoring were used to accurately determine the doses in these cases and to avoid toxicity.

  17. Isolation and characterization of linear deoxyribonucleic acid plasmids from Kluyveromyces lactis and the plasmid-associated killer character.

    PubMed Central

    Gunge, N; Tamaru, A; Ozawa, F; Sakaguchi, K

    1981-01-01

    Two linear deoxyribonucleic acid plasmids, designated pGK11 and pGK12, were isolated from the yeast Kluyveromyces lactis IFO 1267. pGK11 and pGK12 had molecular weights of 5.4 X 10(6) and 8.4 X 10(6), respectively. Both plasmids possessed the same density of 1.687 g/cm3, lighter than the densities of mitochondrial (1.692 g/cm3) and nuclear (1.699 g/cm3) deoxyribonucleic acids. A restriction map of pGK11 was constructed from digestions by EcoRI, HindIII, PstI, and BamHI. pGK12 was cleaved by EcoRI into seven fragments and by BamHI into two fragments K. lactis IFO 1267 killed Saccharomyces cerevisiae sensitive and killer strains and certain strains of Saccharomyces italicus, K. lactis, Kluyveromyces thermotolerans, and K. vanudenii. All K. lactis strains lacking the pGK1 plasmids were nonkillers. A hybrid was constructed between K. lactis IFO 1267 and a nonkiller K. lactis strain lacking the plasmids and subjected to tetrad analysis after sporulation. The killer character was extrachromosomally transmitted in all tetrads in association with the pGK1 plasmids. The double-stranded ribonucleic acid killer plasmid could not be detected in any K. lactis killer strains. It is thus highly probable that the killer character is mediated by the linear deoxyribonucleic acid plasmids. A single chromosomal gene was found which was responsible for the resistance to the K. lactis killer. Images PMID:6257636

  18. Killer whales (Orcinus orca) feeding on schooling herring (Clupea harengus) using underwater tail-slaps: kinematic analyses of field observations.

    PubMed

    Domenici, P; Batty, R S; Similä, T; Ogam, E

    2000-01-01

    Killer whales (Orcinus orca) feeding on herring (Clupea harengus) in a fjord in northern Norway were observed using underwater video. The whales cooperatively herded herring into tight schools close to the surface. During herding and feeding, killer whales swam around and under a school of herring, periodically lunging at it and stunning the herring by slapping them with the underside of their flukes while completely submerged. The kinematics of tail-slapping were analysed in detail. Tail-slaps were made up of a biphasic behaviour consisting of two phases with opposite angles of attack, a preparatory phase (negative angles of attack) and a slap phase (positive angles of attack). During the slap phase, the mean maximum angle of attack of the flukes was 47 degrees. The maximum speed of the flukes, measured at the notch, increased with whale length (L(w)) and was 2.2 L(w )s(-)(1), while the maximum acceleration of the flukes was size-independent and was 48 m s(-)(2). When killer whales slapped the herring successfully, disoriented herring appeared on the video at approximately the time of maximum fluke velocity, in synchrony with a loud noise. This noise was not heard when the tail-slaps 'missed' the target, suggesting that the herring were stunned by physical contact. Killer whales then ate the stunned herring one by one. Of the tail-slaps observed, 61 % were preceded by lunges into the school. We suggest that lunging was aimed at directing the school rather than at capturing the herring, since it occurred at a relatively low speed and there were no observations of the killer whales attempting to capture the herring during lunging behaviour. Given the high performance of the tail-slaps in terms of speed and acceleration, we suggest that tail-slapping by killer whales is a more efficient strategy of prey capture than whole-body attacks, since acceleration and manoeuvrability are likely to be poor in such large vertebrates.

  19. Ustilago maydis killer toxin as a new tool for the biocontrol of the wine spoilage yeast Brettanomyces bruxellensis.

    PubMed

    Santos, Antonio; Navascués, Eva; Bravo, Enrique; Marquina, Domingo

    2011-01-31

    Brettanomyces bruxellensis is one of the most damaging species for wine quality, and tools for controlling its growth are limited. In this study, thirty-nine strains belonging to Saccharomyces cerevisiae and B. bruxellensis have been isolated from wineries, identified and then tested against a panel of thirty-nine killer yeasts. Here, for the first time, the killer activity of Ustilago maydis is proven to be effective against B. bruxellensis. Mixed cultures in winemaking conditions show that U. maydis CYC 1410 has the ability to inhibit B. bruxellensis, while S. cerevisiae is fully resistant to its killer activity, indicating that it could be used in wine fermentation to avoid the development of B. bruxellensis without undesirable effects on the fermentative yeast. The characterization of the dsRNAs isolated and purified from U. maydis CYC 1410 indicated that this strain produces a KP6-related toxin. Killer toxin extracts were active against B. bruxellensis at pH values between 3.0 and 4.5 and temperatures comprised between 15 °C and 25 °C, confirming their biocontrol activity in winemaking and wine aging conditions. Furthermore, small amounts (100 AU/ml) of killer toxin extracts from U. maydis significantly reduced the amount of 4-ethylphenol produced by B. bruxellensis, indicating that in addition to the growth inhibition observed for high killer toxin concentrations (ranging from 400 to 2000 AU/ml), small amounts of the toxin are able to reduce the production of volatile phenols responsible for the aroma defects in wines caused by B. bruxellensis.

  20. Disproportionate emission of bubble streams with killer whale biphonic calls: perspectives on production and function.

    PubMed

    Bowles, Ann E; Grebner, Dawn M; Musser, Whitney B; Nash, Juliette S; Crance, Jessica L

    2015-02-01

    Stereotyped pulsed calls were attributed to 11 killer whales (Orcinus orca) with and without synchronous bubble streams in three datasets collected from two facilities from 1993 to 2012. Calls with and without synchronous bubble streams and divergent overlapping high frequency components ("biphonic" vs "monophonic") were compared. Subjects produced bubbles significantly more often when calls had divergent high frequency components. However, acoustic features in one biphonic call shared by five subjects provided little evidence for an acoustic effect of synchronous bubble flow. Disproportionate bubbling supported other evidence that biphonic calls form a distinct category, but suggested a function in short-range communication. PMID:25698045

  1. Disproportionate emission of bubble streams with killer whale biphonic calls: perspectives on production and function.

    PubMed

    Bowles, Ann E; Grebner, Dawn M; Musser, Whitney B; Nash, Juliette S; Crance, Jessica L

    2015-02-01

    Stereotyped pulsed calls were attributed to 11 killer whales (Orcinus orca) with and without synchronous bubble streams in three datasets collected from two facilities from 1993 to 2012. Calls with and without synchronous bubble streams and divergent overlapping high frequency components ("biphonic" vs "monophonic") were compared. Subjects produced bubbles significantly more often when calls had divergent high frequency components. However, acoustic features in one biphonic call shared by five subjects provided little evidence for an acoustic effect of synchronous bubble flow. Disproportionate bubbling supported other evidence that biphonic calls form a distinct category, but suggested a function in short-range communication.

  2. [Killer toxin and enzyme production by Candida albicans isolated from buccal mucosa in patients with cancer].

    PubMed

    de Oliveira, E E; Silva, S C; Soares, A J; Attux, C; Cruvinel, B; Silva, M do R

    1998-01-01

    Opportunistic infections of the oral cavity are primarily caused by Candida and frequently occur in patients with cancer who are undergoing chemotherapy and antibiotic treatment. Of the specimens received from the oral mucosa of 44 patients with cancer, 25 (56.8%) yielded Candida on culture in Sabouraud agar. Twenty four of these isolates were identified as C. albicans (96%) and 1 as C. krusei (4%). The phenotypic characteristics of these isolates showed that all of them were strongly proteolytic, had a high ability to produce phospholipase, and presented the byotypes characterized as 811 (95.8%) and 511 (4.2%) in terms of susceptibility to killer toxins. PMID:9859695

  3. Maternal uterine natural killer cells nurture fetal growth: in medio stat virtus.

    PubMed

    Colucci, Francesco; Kieckbusch, Jens

    2015-02-01

    Much research in reproductive immunology is preoccupied with maternal tolerance of the semi-allogeneic fetus. This inevitably leads to the assumption that the maternal immune system should be suppressed, similarly to the immunosuppression needed to avoid rejection of an allograft. However, the parallels with transplantation immunology are misleading, and we discuss how interactions between variable immune system genes expressed on maternal natural killer (NK) cells and on the fetal trophoblast modulate fetal growth. Exaggerated suppression or activation of maternal NK cells associates with both extremes of birth weight.

  4. Enough! Stop the arguments and get on with the science of natural killer cell testing.

    PubMed

    Sacks, Gavin

    2015-07-01

    Natural killer cell testing is currently practised widely, and there are studies indicating potential benefit in terms of targeting women with repeated reproductive failure for immune therapy. This may be a better approach than empirical immune therapy without any investigation. More and better studies are needed before such an approach can be fully endorsed. There is still uncertainty over the precise pathophysiological basis for all immune investigation and therapy, but this should not be a barrier for clinical observation and empirical care. On the contrary, clinicians and researchers should work more closely together to provide the best care for our patients.

  5. Natural Killer Cell Diversity in Viral Infection: Why and How Much?

    PubMed Central

    Blish, Catherine A.

    2016-01-01

    Natural killer cells are a diverse group of innate lymphocytes that are specialized to rapidly respond to cancerous or virus-infected cells. NK cell function is controlled by the integration of signals from activating and inhibitory receptors expressed at the cell surface. Variegated expression patterns of these activating and inhibitory receptors at the single cell level leads to a highly diverse NK cell repertoire. Here I review the factors that influence NK cell repertoire diversity and its functional consequences for our ability to fight viruses. PMID:27635417

  6. Natural killer lymphoma/leukemia: an uncommon pediatric case with indolent course.

    PubMed

    Di Cataldo, Andrea; Bertuna, Gregoria; Mirabile, Elena; Munda, Silvana; Tettoni, Katia; Notarangelo, Luigi D; Facchetti, Fabio; Lo Nigro, Luca

    2004-08-01

    Natural killer (NK) cell lymphomas are rare in the USA and Europe but more common in Asia and Central America although very rare among children. We report a case of Epstein-Barr virus-positive NK lymphoma/leukemia, that showed peculiar features represented by a very long clinical course with a significant interval between the first clinical signs and the diagnosis, detection of neoplastic cells in the peripheral blood but not in the bone marrow, and good response to treatment and clinical outcome.

  7. Male-killer dynamics in the tropical butterfly, Acraea encedana (Lepidoptera: Nymphalidae).

    PubMed

    Hassan, Sami Saeed M; Idris, Eihab; Majerus, Michael E N

    2013-12-01

    Sex ratio distortion in the tropical butterfly Acraea encedana is caused by infection with a male-killing bacterium of the genus Wolbachia. Previous research on this species has reported extreme female bias, high bacterial prevalences, and full sex role reversal. In this paper, we provide an assessment for the dynamics of the male-killer, based on a survey for sex ratios and Wolbachia prevalences among wild populations of A. encedana in Uganda. The study reveals that Wolbachia infection showed considerable variation over both spatial and temporal scales.

  8. Developing criteria and data to determine best options for expanding the core CODIS loci

    PubMed Central

    2012-01-01

    Background Recently, the Combined DNA Index System (CODIS) Core Loci Working Group established by the US Federal Bureau of Investigation (FBI) reviewed and recommended changes to the CODIS core loci. The Working Group identified 20 short tandem repeat (STR) loci (composed of the original CODIS core set loci (minus TPOX), four European recommended loci, PentaE, and DYS391) plus the Amelogenin marker as the new core set. Before selecting and finalizing the core loci, some evaluations are needed to provide guidance for the best options of core selection. Method The performance of current and newly proposed CODIS core loci sets were evaluated with simplified analyses for adventitious hit rates in reasonably large datasets under single-source profile comparisons, mixture comparisons and kinship searches, and for international data sharing. Informativeness (for example, match probability, average kinship index (AKI)) and mutation rates of each locus were some of the criteria to consider for loci selection. However, the primary factor was performance with challenged forensic samples. Results The current battery of loci provided in already validated commercial kits meet the needs for single-source profile comparisons and international data sharing, even with relatively large databases. However, the 13 CODIS core loci are not sufficiently powerful for kinship analyses and searching potential contributors of mixtures in larger databases; 19 or more autosomal STR loci perform better. Y-chromosome STR (Y-STR) loci are very useful to trace paternal lineage, deconvolve female and male mixtures, and resolve inconsistencies with Amelogenin typing. The DYS391 locus is of little theoretical or practical use. Combining five or six Y-chromosome STR loci with existing autosomal STR loci can produce better performance than the same number of autosomal loci for kinship analysis and still yield a sufficiently low match probability for single-source profile comparisons. Conclusion A more

  9. High-throughput identification of informative nuclear loci for shallow-scale phylogenetics and phylogeography.

    PubMed

    Lemmon, Alan R; Lemmon, Emily Moriarty

    2012-10-01

    One of the major challenges for researchers studying phylogeography and shallow-scale phylogenetics is the identification of highly variable and informative nuclear loci for the question of interest. Previous approaches to locus identification have generally required extensive testing of anonymous nuclear loci developed from genomic libraries of the target taxon, testing of loci of unknown utility from other systems, or identification of loci from the nearest model organism with genomic resources. Here, we present a fast and economical approach to generating thousands of variable, single-copy nuclear loci for any system using next-generation sequencing. We performed Illumina paired-end sequencing of three reduced-representation libraries (RRLs) in chorus frogs (Pseudacris) to identify orthologous, single-copy loci across libraries and to estimate sequence divergence at multiple taxonomic levels. We also conducted PCR testing of these loci across the genus Pseudacris and outgroups to determine whether loci developed for phylogeography can be extended to deeper phylogenetic levels. Prior to sequencing, we conducted in silico digestion of the most closely related reference genome (Xenopus tropicalis) to generate expectations for the number of loci and degree of coverage for a particular experimental design. Using the RRL approach, we: (i) identified more than 100,000 single-copy nuclear loci, 6339 of which were obtained for divergent conspecifics and 904 of which were obtained for heterospecifics; (ii) estimated average nuclear sequence divergence at 0.1% between alleles within an individual, 1.1% between conspecific individuals that represent two different clades, and 1.8% between species; and (iii) determined from PCR testing that 53% of the loci successfully amplify within-species and also many amplify to the genus-level and deeper in the phylogeny (16%). Our study effectively identified nuclear loci present in the genome that have levels of sequence divergence on

  10. The skin test antigen stimulated killer (STAK) cell mediating NK like CMC is OKM1 positive and OKT3 negative.

    PubMed Central

    Tartof, D; Curran, J J; Levitt, D; Loken, M R

    1983-01-01

    Recently we demonstrated that candida antigen stimulated natural killer cell like cell-mediated cytolysis (NK like CMC) in peripheral blood mononuclear cells (PBMNC) isolated from normal individuals (Tartof et al., 1980). Utilizing monoclonal antibodies directed against human mononuclear cell subpopulations in conjunction with a fluorescence activated cell sorter (FACS) we determined that, similar to the previously described NK cell, the skin test antigen stimulated killer (STAK) cell is a larger OKM1 positive, OKT3 negative cell. We obtained similar results using two different skin test antigens. Thus, stimulation of NK like CMC in PBMNC by skin test antigens probably represents activation of NK or NK like cells. PMID:6360439

  11. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

    PubMed

    Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I; Monda, Keri L; Thorleifsson, Gudmar; Jackson, Anne U; Lango Allen, Hana; Lindgren, Cecilia M; Luan, Jian'an; Mägi, Reedik; Randall, Joshua C; Vedantam, Sailaja; Winkler, Thomas W; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M; Steinthorsdottir, Valgerdur; Stringham, Heather M; Weedon, Michael N; Wheeler, Eleanor; Wood, Andrew R; Ferreira, Teresa; Weyant, Robert J; Segrè, Ayellet V; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpeläinen, Tuomas O; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tõnu; Feitosa, Mary F; Kutalik, Zoltán; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K; Absher, Devin M; Amin, Najaf; Dixon, Anna L; Fisher, Eva; Glazer, Nicole L; Goddard, Michael E; Heard-Costa, Nancy L; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F; Myers, Richard H; Narisu, Narisu; Perry, John R B; Peters, Marjolein J; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J; Timpson, Nicholas J; Tyrer, Jonathan P; van Wingerden, Sophie; Watanabe, Richard M; White, Charles C; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I; Cooper, Matthew N; Jansson, John-Olov; Lawrence, Robert W; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T S; Almgren, Peter; Arnold, Alice M; Aspelund, Thor; Atwood, Larry D; Balkau, Beverley; Balmforth, Anthony J; Bennett, Amanda J; Ben-Shlomo, Yoav; Bergman, Richard N; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I F; Boes, Tanja; Bonnycastle, Lori L; Bornstein, Stefan R; Brown, Morris J; Buchanan, Thomas A; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P; Cavalcanti-Proença, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N M; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R; Eriksson, Johan G; Facheris, Maurizio F; Felix, Stephan B; Fischer-Posovszky, Pamela; Folsom, Aaron R; Friedrich, Nele; Freimer, Nelson B; Fu, Mao; Gaget, Stefan; Gejman, Pablo V; Geus, Eco J C; Gieger, Christian; Gjesing, Anette P; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Grässler, Jürgen; Greenawalt, Danielle M; Groves, Christopher J; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S; Havulinna, Aki S; Hayward, Caroline; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W; Kolcic, Ivana; König, Inke R; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaløy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J; Lecoeur, Cecile; Lehtimäki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G; McArdle, Wendy L; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W; Morken, Mario A; Morris, Andrew P; Mulic, Rosanda; Ngwa, Julius S; Nelis, Mari; Neville, Matt J; Nyholt, Dale R; O'Donnell, Christopher J; O'Rahilly, Stephen; Ong, Ken K; Oostra, Ben; Paré, Guillaume; Parker, Alex N; Perola, Markus; Pichler, Irene; Pietiläinen, Kirsi H; Platou, Carl G P; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W; Ridderstråle, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R; Sandhu, Manjinder S; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S; Smit, Jan H; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M; Thompson, John R; Thomson, Brian; Tönjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B J; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I G; Voight, Benjamin F; Waite, Lindsay L; Wallaschofski, Henri; Walters, G Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H; Willemsen, Gonneke; Witte, Daniel R; Witteman, Jacqueline C; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P; Farooqi, I Sadaf; Hebebrand, Johannes; Huikuri, Heikki V; James, Alan L; Kähönen, Mika; Levinson, Douglas F; Macciardi, Fabio; Nieminen, Markku S; Ohlsson, Claes; Palmer, Lyle J; Ridker, Paul M; Stumvoll, Michael; Beckmann, Jacques S; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I; Caulfield, Mark J; Chanock, Stephen J; Collins, Francis S; Cupples, L Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Grönberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B; Hattersley, Andrew T; Hayes, Richard B; Heinrich, Joachim; Hu, Frank B; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A; Metspalu, Andres; Munroe, Patricia B; Ouwehand, Willem H; Pedersen, Oluf; Penninx, Brenda W; Peters, Annette; Pramstaller, Peter P; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J; Schwarz, Peter E H; Shuldiner, Alan R; Spector, Timothy D; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, André; Valle, Timo T; Wabitsch, Martin; Waeber, Gérard; Wareham, Nicholas J; Watkins, Hugh; Wilson, James F; Wright, Alan F; Zillikens, M Carola; Chatterjee, Nilanjan; McCarroll, Steven A; Purcell, Shaun; Schadt, Eric E; Visscher, Peter M; Assimes, Themistocles L; Borecki, Ingrid B; Deloukas, Panos; Fox, Caroline S; Groop, Leif C; Haritunians, Talin; Hunter, David J; Kaplan, Robert C; Mohlke, Karen L; O'Connell, Jeffrey R; Peltonen, Leena; Schlessinger, David; Strachan, David P; van Duijn, Cornelia M; Wichmann, H-Erich; Frayling, Timothy M; Thorsteinsdottir, Unnur; Abecasis, Gonçalo R; Barroso, Inês; Boehnke, Michael; Stefansson, Kari; North, Kari E; McCarthy, Mark I; Hirschhorn, Joel N; Ingelsson, Erik; Loos, Ruth J F

    2010-11-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

  12. Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures.

    PubMed

    Wang, Xinchen; Tucker, Nathan R; Rizki, Gizem; Mills, Robert; Krijger, Peter Hl; de Wit, Elzo; Subramanian, Vidya; Bartell, Eric; Nguyen, Xinh-Xinh; Ye, Jiangchuan; Leyton-Mange, Jordan; Dolmatova, Elena V; van der Harst, Pim; de Laat, Wouter; Ellinor, Patrick T; Newton-Cheh, Christopher; Milan, David J; Kellis, Manolis; Boyer, Laurie A

    2016-01-01

    Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information from association studies with epigenomic maps to demonstrate that enhancers significantly overlap known loci associated with the cardiac QT interval and QRS duration. We apply functional criteria to identify loci associated with QT interval that do not meet genome-wide significance and are missed by existing studies. We demonstrate that these 'sub-threshold' signals represent novel loci, and that epigenomic maps are effective at discriminating true biological signals from noise. We experimentally validate the molecular, gene-regulatory, cellular and organismal phenotypes of these sub-threshold loci, demonstrating that most sub-threshold loci have regulatory consequences and that genetic perturbation of nearby genes causes cardiac phenotypes in mouse. Our work provides a general approach for improving the detection of novel loci associated with complex human traits. PMID:27162171

  13. Developing microsatellites when they are rare: trinucleotide repeat loci in the northern mockingbird Mimus polyglottos.

    PubMed

    Hughes, C R; Deloach, D M

    1997-11-01

    The great value of microsatellite loci to population studies spurs their development. However, finding loci is difficult when microsatellites are uncommon in the genome. Because trinucleotide-repeat loci are rare in northern mockingbirds Mimus polyglottos, we sought a new method for developing a suite of loci. Here we show that a bacterio-phage cloning vector, Lambda Zap Express (Stratagene, La Jolla, CA, USA) has several features which make it suitable for this purpose. Using this vector, we made a library of 150,000 size-selected clones and screened with an AAT10 probe; 97 positives were identified. From these, 12 pairs of PCR primers were developed, nine of which amplify polymorphic loci. Certain combinations of these primer pairs enable simultaneous amplification of up to three loci.

  14. Characterization of 19 microsatellite loci in the clonal monkshood Aconitum kusnezoffii (Ranunculaceae)1

    PubMed Central

    Ge, Xing-Yue; Tian, Hao; Liao, Wan-Jin

    2016-01-01

    Premise of the study: Microsatellite loci were isolated and characterized from Aconitum kusnezoffii (Ranunculaceae) to estimate male and female reproductive success and evaluate the effects of clonal growth on sexual reproduction. Methods and Results: A genomic enrichment approach was used to develop microsatellite markers. In three investigated A. kusnezoffii populations, a total of 19 microsatellite loci were successfully amplified, and 13 of these loci were polymorphic. Most of the primer pairs designed for the identified loci also amplified corresponding microsatellite loci in A. barbatum var. puberulum and A. alboviolaceum. Conclusions: The identified microsatellite loci will be useful for quantifying male and female fitness in A. kusnezoffii and evaluating the effects of clonal growth on sexual reproduction. PMID:27347450

  15. Development of microsatellite loci in Artocarpus altilis (Moraceae) and cross-amplification in congeneric species1

    PubMed Central

    Witherup, Colby; Ragone, Diane; Wiesner-Hanks, Tyr; Irish, Brian; Scheffler, Brian; Simpson, Sheron; Zee, Francis; Zuberi, M. Iqbal; Zerega, Nyree J. C.

    2013-01-01

    • Premise of the study: Microsatellite loci were isolated and characterized from enriched genomic libraries of Artocarpus altilis (breadfruit) and tested in four Artocarpus species and one hybrid. The microsatellite markers provide new tools for further studies in Artocarpus. • Methods and Results: A total of 25 microsatellite loci were evaluated across four Artocarpus species and one hybrid. Twenty-one microsatellite loci were evaluated on A. altilis (241), A. camansi (34), A. mariannensis (15), and A. altilis × mariannensis (64) samples. Nine of those loci plus four additional loci were evaluated on A. heterophyllus (jackfruit, 426) samples. All loci are polymorphic for at least one species. The average number of alleles ranges from two to nine within taxa. • Conclusions: These microsatellite primers will facilitate further studies on the genetic structure and evolutionary and domestication history of Artocarpus species. They will aid in cultivar identification and establishing germplasm conservation strategies for breadfruit and jackfruit. PMID:25202565

  16. An analysis of microsatellite loci in Arabidopsis thaliana: mutational dynamics and application.

    PubMed Central

    Symonds, V Vaughan; Lloyd, Alan M

    2003-01-01

    Microsatellite loci are among the most commonly used molecular markers. These loci typically exhibit variation for allele frequency distribution within a species. However, the factors contributing to this variation are not well understood. To expand on the current knowledge of microsatellite evolution, 20 microsatellite loci were examined for 126 accessions of the flowering plant, Arabidopsis thaliana. Substantial variability in mutation pattern among loci was found, most of which cannot be explained by the assumptions of the traditional stepwise mutation model or infinite alleles model. Here it is shown that the degree of locus diversity is strongly correlated with the number of contiguous repeats, more so than with the total number of repeats. These findings support a strong role for repeat disruptions in stabilizing microsatellite loci by reducing the substrate for polymerase slippage and recombination. Results of cluster analyses are also presented, demonstrating the potential of microsatellite loci for resolving relationships among accessions of A. thaliana. PMID:14668396

  17. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.

    PubMed

    Speliotes, Elizabeth K; Willer, Cristen J; Berndt, Sonja I; Monda, Keri L; Thorleifsson, Gudmar; Jackson, Anne U; Lango Allen, Hana; Lindgren, Cecilia M; Luan, Jian'an; Mägi, Reedik; Randall, Joshua C; Vedantam, Sailaja; Winkler, Thomas W; Qi, Lu; Workalemahu, Tsegaselassie; Heid, Iris M; Steinthorsdottir, Valgerdur; Stringham, Heather M; Weedon, Michael N; Wheeler, Eleanor; Wood, Andrew R; Ferreira, Teresa; Weyant, Robert J; Segrè, Ayellet V; Estrada, Karol; Liang, Liming; Nemesh, James; Park, Ju-Hyun; Gustafsson, Stefan; Kilpeläinen, Tuomas O; Yang, Jian; Bouatia-Naji, Nabila; Esko, Tõnu; Feitosa, Mary F; Kutalik, Zoltán; Mangino, Massimo; Raychaudhuri, Soumya; Scherag, Andre; Smith, Albert Vernon; Welch, Ryan; Zhao, Jing Hua; Aben, Katja K; Absher, Devin M; Amin, Najaf; Dixon, Anna L; Fisher, Eva; Glazer, Nicole L; Goddard, Michael E; Heard-Costa, Nancy L; Hoesel, Volker; Hottenga, Jouke-Jan; Johansson, Asa; Johnson, Toby; Ketkar, Shamika; Lamina, Claudia; Li, Shengxu; Moffatt, Miriam F; Myers, Richard H; Narisu, Narisu; Perry, John R B; Peters, Marjolein J; Preuss, Michael; Ripatti, Samuli; Rivadeneira, Fernando; Sandholt, Camilla; Scott, Laura J; Timpson, Nicholas J; Tyrer, Jonathan P; van Wingerden, Sophie; Watanabe, Richard M; White, Charles C; Wiklund, Fredrik; Barlassina, Christina; Chasman, Daniel I; Cooper, Matthew N; Jansson, John-Olov; Lawrence, Robert W; Pellikka, Niina; Prokopenko, Inga; Shi, Jianxin; Thiering, Elisabeth; Alavere, Helene; Alibrandi, Maria T S; Almgren, Peter; Arnold, Alice M; Aspelund, Thor; Atwood, Larry D; Balkau, Beverley; Balmforth, Anthony J; Bennett, Amanda J; Ben-Shlomo, Yoav; Bergman, Richard N; Bergmann, Sven; Biebermann, Heike; Blakemore, Alexandra I F; Boes, Tanja; Bonnycastle, Lori L; Bornstein, Stefan R; Brown, Morris J; Buchanan, Thomas A; Busonero, Fabio; Campbell, Harry; Cappuccio, Francesco P; Cavalcanti-Proença, Christine; Chen, Yii-Der Ida; Chen, Chih-Mei; Chines, Peter S; Clarke, Robert; Coin, Lachlan; Connell, John; Day, Ian N M; den Heijer, Martin; Duan, Jubao; Ebrahim, Shah; Elliott, Paul; Elosua, Roberto; Eiriksdottir, Gudny; Erdos, Michael R; Eriksson, Johan G; Facheris, Maurizio F; Felix, Stephan B; Fischer-Posovszky, Pamela; Folsom, Aaron R; Friedrich, Nele; Freimer, Nelson B; Fu, Mao; Gaget, Stefan; Gejman, Pablo V; Geus, Eco J C; Gieger, Christian; Gjesing, Anette P; Goel, Anuj; Goyette, Philippe; Grallert, Harald; Grässler, Jürgen; Greenawalt, Danielle M; Groves, Christopher J; Gudnason, Vilmundur; Guiducci, Candace; Hartikainen, Anna-Liisa; Hassanali, Neelam; Hall, Alistair S; Havulinna, Aki S; Hayward, Caroline; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hinney, Anke; Hofman, Albert; Homuth, Georg; Hui, Jennie; Igl, Wilmar; Iribarren, Carlos; Isomaa, Bo; Jacobs, Kevin B; Jarick, Ivonne; Jewell, Elizabeth; John, Ulrich; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Kaakinen, Marika; Kajantie, Eero; Kaplan, Lee M; Kathiresan, Sekar; Kettunen, Johannes; Kinnunen, Leena; Knowles, Joshua W; Kolcic, Ivana; König, Inke R; Koskinen, Seppo; Kovacs, Peter; Kuusisto, Johanna; Kraft, Peter; Kvaløy, Kirsti; Laitinen, Jaana; Lantieri, Olivier; Lanzani, Chiara; Launer, Lenore J; Lecoeur, Cecile; Lehtimäki, Terho; Lettre, Guillaume; Liu, Jianjun; Lokki, Marja-Liisa; Lorentzon, Mattias; Luben, Robert N; Ludwig, Barbara; Manunta, Paolo; Marek, Diana; Marre, Michel; Martin, Nicholas G; McArdle, Wendy L; McCarthy, Anne; McKnight, Barbara; Meitinger, Thomas; Melander, Olle; Meyre, David; Midthjell, Kristian; Montgomery, Grant W; Morken, Mario A; Morris, Andrew P; Mulic, Rosanda; Ngwa, Julius S; Nelis, Mari; Neville, Matt J; Nyholt, Dale R; O'Donnell, Christopher J; O'Rahilly, Stephen; Ong, Ken K; Oostra, Ben; Paré, Guillaume; Parker, Alex N; Perola, Markus; Pichler, Irene; Pietiläinen, Kirsi H; Platou, Carl G P; Polasek, Ozren; Pouta, Anneli; Rafelt, Suzanne; Raitakari, Olli; Rayner, Nigel W; Ridderstråle, Martin; Rief, Winfried; Ruokonen, Aimo; Robertson, Neil R; Rzehak, Peter; Salomaa, Veikko; Sanders, Alan R; Sandhu, Manjinder S; Sanna, Serena; Saramies, Jouko; Savolainen, Markku J; Scherag, Susann; Schipf, Sabine; Schreiber, Stefan; Schunkert, Heribert; Silander, Kaisa; Sinisalo, Juha; Siscovick, David S; Smit, Jan H; Soranzo, Nicole; Sovio, Ulla; Stephens, Jonathan; Surakka, Ida; Swift, Amy J; Tammesoo, Mari-Liis; Tardif, Jean-Claude; Teder-Laving, Maris; Teslovich, Tanya M; Thompson, John R; Thomson, Brian; Tönjes, Anke; Tuomi, Tiinamaija; van Meurs, Joyce B J; van Ommen, Gert-Jan; Vatin, Vincent; Viikari, Jorma; Visvikis-Siest, Sophie; Vitart, Veronique; Vogel, Carla I G; Voight, Benjamin F; Waite, Lindsay L; Wallaschofski, Henri; Walters, G Bragi; Widen, Elisabeth; Wiegand, Susanna; Wild, Sarah H; Willemsen, Gonneke; Witte, Daniel R; Witteman, Jacqueline C; Xu, Jianfeng; Zhang, Qunyuan; Zgaga, Lina; Ziegler, Andreas; Zitting, Paavo; Beilby, John P; Farooqi, I Sadaf; Hebebrand, Johannes; Huikuri, Heikki V; James, Alan L; Kähönen, Mika; Levinson, Douglas F; Macciardi, Fabio; Nieminen, Markku S; Ohlsson, Claes; Palmer, Lyle J; Ridker, Paul M; Stumvoll, Michael; Beckmann, Jacques S; Boeing, Heiner; Boerwinkle, Eric; Boomsma, Dorret I; Caulfield, Mark J; Chanock, Stephen J; Collins, Francis S; Cupples, L Adrienne; Smith, George Davey; Erdmann, Jeanette; Froguel, Philippe; Grönberg, Henrik; Gyllensten, Ulf; Hall, Per; Hansen, Torben; Harris, Tamara B; Hattersley, Andrew T; Hayes, Richard B; Heinrich, Joachim; Hu, Frank B; Hveem, Kristian; Illig, Thomas; Jarvelin, Marjo-Riitta; Kaprio, Jaakko; Karpe, Fredrik; Khaw, Kay-Tee; Kiemeney, Lambertus A; Krude, Heiko; Laakso, Markku; Lawlor, Debbie A; Metspalu, Andres; Munroe, Patricia B; Ouwehand, Willem H; Pedersen, Oluf; Penninx, Brenda W; Peters, Annette; Pramstaller, Peter P; Quertermous, Thomas; Reinehr, Thomas; Rissanen, Aila; Rudan, Igor; Samani, Nilesh J; Schwarz, Peter E H; Shuldiner, Alan R; Spector, Timothy D; Tuomilehto, Jaakko; Uda, Manuela; Uitterlinden, André; Valle, Timo T; Wabitsch, Martin; Waeber, Gérard; Wareham, Nicholas J; Watkins, Hugh; Wilson, James F; Wright, Alan F; Zillikens, M Carola; Chatterjee, Nilanjan; McCarroll, Steven A; Purcell, Shaun; Schadt, Eric E; Visscher, Peter M; Assimes, Themistocles L; Borecki, Ingrid B; Deloukas, Panos; Fox, Caroline S; Groop, Leif C; Haritunians, Talin; Hunter, David J; Kaplan, Robert C; Mohlke, Karen L; O'Connell, Jeffrey R; Peltonen, Leena; Schlessinger, David; Strachan, David P; van Duijn, Cornelia M; Wichmann, H-Erich; Frayling, Timothy M; Thorsteinsdottir, Unnur; Abecasis, Gonçalo R; Barroso, Inês; Boehnke, Michael; Stefansson, Kari; North, Kari E; McCarthy, Mark I; Hirschhorn, Joel N; Ingelsson, Erik; Loos, Ruth J F

    2010-11-01

    Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. PMID:20935630

  18. Mapping loci controlling flowering time in Brassica oleracea.

    PubMed

    Camargo, L E; Osborn, T C

    1996-04-01

    The timing of the transition from vegetative to reproductive phase is a major determinant of the morphology and value of Brassica oleracea crops. Quantitative trait loci (QTLs) controlling flowering time in B. oleracea were mapped using restriction fragment length polymorphism (RFLP) loci and flowering data of F3 families derived from a cabbage by broccoli cross. Plants were grown in the field, and a total of 15 surveys were made throughout the experiment at 5-15 day intervals, in which plants were inspected for the presence of flower buds or open flowers. The flowering traits used for data analysis were the proportion of annual plants (PF) within each F3 family at the end of the experiment, and a flowering-time index (FT) that combined both qualitative (annual/biennial) and quantitative (days to flowering) information. Two QTLs on different linkage groups were found associated with both PF and FT and one additional QTL was found associated only with FT. When combined in a multi-locus model, all three QTLs explained 54.1% of the phenotypic variation in FT. Epistasis was found between two genomic regions associated with FT. Comparisons of map positions of QTLs in B. oleracea with those in B. napus and B. rapa provided no evidence for conservation of genomic regions associated with flowering time between these species.

  19. Protein Interaction Networks Link Schizophrenia Risk Loci to Synaptic Function

    PubMed Central

    Schwarz, Emanuel; Izmailov, Rauf; Liò, Pietro; Meyer-Lindenberg, Andreas

    2016-01-01

    Schizophrenia is a severe and highly heritable psychiatric disorder affecting approximately 1% of the population. Genome-wide association studies have identified 108 independent genetic loci with genome-wide significance but their functional importance has yet to be elucidated. Here, we develop a novel strategy based on network analysis of protein–protein interactions (PPI) to infer biological function associated with variants most strongly linked to illness risk. We show that the schizophrenia loci are strongly linked to synaptic transmission (P FWE < .001) and ion transmembrane transport (P FWE = .03), but not to ontological categories previously found to be shared across psychiatric illnesses. We demonstrate that brain expression of risk-linked genes within the identified processes is strongly modulated during birth and identify a set of synaptic genes consistently changed across multiple brain regions of adult schizophrenia patients. These results suggest synaptic function as a developmentally determined schizophrenia process supported by the illness’s most associated genetic variants and their PPI networks. The implicated genes may be valuable targets for mechanistic experiments and future drug development approaches. PMID:27056717

  20. High polymorphism at microsatellite loci in the Chinese donkey.

    PubMed

    Zhang, R F; Xie, W M; Zhang, T; Lei, C Z

    2016-01-01

    To reveal the genetic diversity and phylogenetic relationships between Chinese donkey breeds, 415 individuals representing ten breeds were investigated using ten microsatellite markers. The observed number of alleles, mean effective number of alleles (NE), mean expected heterozygosity (HE), and polymorphic information content (PIC) of each breed and polymorphic locus were analyzed. The results showed that seven (HTG7, HTG10, AHT4, HTG6, HMS6, HMS3, and HMS7) of ten microsatellite loci were polymorphic. The mean PIC, HE, and NE of seven polymorphic loci for the ten donkey breeds were 0.7679, 0.8072, and 6.0275, respectively. These results suggest that domestic Chinese donkey breeds possess higher levels of genetic diversity and heterozygosity than foreign donkeys. A neighbor-joining tree based on Nei's standard genetic distance showed that there was close genetic distance among Xinjiang, Qingyang, Xiji, and Guanzhong donkey breeds. In addition, Mongolia and Dezhou donkey breeds were placed in the same category. The phylogenetic tree revealed that the genetic relationships between Chinese donkey breeds are consistent with their geographic distribution and breeding history. PMID:27420967

  1. Two Susceptibility Loci Identified for Prostate Cancer Aggressiveness

    PubMed Central

    Berndt, Sonja I.; Wang, Zhaoming; Yeager, Meredith; Alavanja, Michael C.; Albanes, Demetrius; Amundadottir, Laufey; Andriole, Gerald; Freeman, Laura Beane; Campa, Daniele; Cancel-Tassin, Geraldine; Canzian, Federico; Cornu, Jean-Nicolas; Cussenot, Olivier; Diver, W. Ryan; Gapstur, Susan M.; Grönberg, Henrik; Haiman, Christopher A.; Henderson, Brian; Hutchinson, Amy; Hunter, David J.; Key, Timothy J.; Kolb, Suzanne; Koutros, Stella; Kraft, Peter; Le Marchand, Loic; Lindström, Sara; Machiela, Mitchell J.; Ostrander, Elaine A.; Riboli, Elio; Schumacher, Fred; Siddiq, Afshan; Stanford, Janet L.; Stevens, Victoria L.; Travis, Ruth C.; Tsilidis, Konstantinos K.; Virtamo, Jarmo; Weinstein, Stephanie; Wilkund, Fredrik; Xu, Jianfeng; Zheng, S. Lilly; Yu, Kai; Wheeler, William; Zhang, Han; Sampson, Joshua; Black, Amanda; Jacobs, Kevin; Hoover, Robert N; Tucker, Margaret; Chanock, Stephen J.

    2015-01-01

    Most men diagnosed with prostate cancer will experience indolent disease; hence discovering genetic variants that distinguish aggressive from non-aggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49×10-9) and rs78943174 at 3q26.31 (NAALADL2, P=4.18×10-8). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85×10-5) with no association for non-aggressive prostate cancer compared to controls (P=0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation. PMID:25939597

  2. Independent Replication and Meta-Analysis for Endometriosis Risk Loci.

    PubMed

    Sapkota, Yadav; Fassbender, Amelie; Bowdler, Lisa; Fung, Jenny N; Peterse, Daniëlle; O, Dorien; Montgomery, Grant W; Nyholt, Dale R; D'Hooghe, Thomas M

    2015-10-01

    Endometriosis is a complex disease that affects 6-10% of women in their reproductive years and 20-50% of women with infertility. Genome-wide and candidate-gene association studies for endometriosis have identified 10 independent risk loci, and of these, nine (rs7521902, rs13394619, rs4141819, rs6542095, rs1519761, rs7739264, rs12700667, rs1537377, and rs10859871) are polymorphic in European populations. Here we investigate the replication of nine SNP loci in 998 laparoscopically and histologically confirmed endometriosis cases and 783 disease-free controls from Belgium. SNPs rs7521902, rs13394619, and rs6542095 show nominally significant (p < .05) associations with endometriosis, while the directions of effect for seven SNPs are consistent with the original reports. Association of rs6542095 at the IL1A locus with 'All' (p = .066) and 'Grade_B' (p = .01) endometriosis is noteworthy because this is the first successful replication in an independent population. Meta-analysis with the published results yields genome-wide significant evidence for rs7521902, rs13394619, rs6542095, rs12700667, rs7739264, and rs1537377. Notably, three coding variants in GREB1 (near rs13394619) and CDKN2B-AS1 (near rs1537377) also showed nominally significant associations with endometriosis. Overall, this study provides important replication in a uniquely characterized independent population, and indicates that the majority of the original genome-wide association findings are not due to chance alone.

  3. Physical Characterization of Genetic Rearrangements at the Mouse Renin Loci

    PubMed Central

    Abel, K. J.; Gross, K. W.

    1990-01-01

    Many inbred strains of mice have a single locus encoding renin, Ren-1, whereas other inbred strains have two tandemly linked loci, Ren-1 and Ren-2. Each of these renin genes in inbred mice exhibits a unique pattern of tissue-specific expression. As a prerequisite to understanding the structural basis for the expression differences, we have physically characterized the sequence organization of this chromosomal region in both types of strains. Pulsed field gel electrophoresis was initially used to compare the long-range structure of this region in C57BL/6 (Ren-1) and DBA/2 (Ren-1+Ren-2) mice. The structure in both inbred strains is extremely similar, except for an additional 30 kb containing Ren-2 in DBA/2 mice. The boundaries of the extra 30-kb segment were sequenced and compared to homologous sequences flanking the Ren-1 alleles. This analysis identified the precise recombination site, and also the presence of a large insertion, between the renin loci in DBA/2. The renin gene duplication apparently resulted from recombination between sequences sharing little homology, suggesting that nonhomologous chromosomal breakage and rejoining may have been involved mechanistically in the event. PMID:2157628

  4. [Genetic diversity of microsatellite loci in captive Amur tigers].

    PubMed

    Zhang, Yu-Gaung; Li, Di-Qiang; Xiao, Qi-Ming; Rao, Li-Qun; Zhang, Xue-Wen

    2004-09-01

    The tiger is one of the most threatened wildlife species since the abundance and distribution of tiger have decreased dramatically in the last century. The wild Amur tiger (Panthera tigris altaica) only distributed in northeast China, the far east area of Russia and the north Korea and its size of wild population is about 450 in the world and 20 in China. Several hundred captive populations of Amur tigers are the main source to protect gene library of tiger and the source of recovering the wild populations. The Breeding Center for Felidae at Hengdaohezi and Haoerbin Tiger Park in Heilongjiang Province is the biggest captive breeding base in China. How to make clear the genetic pedigree and establish reasonable breeding system is the urgent issues. So we use the microsatellite DNA markers and non-invasive technology to research on the genetic diversity of captive Amur tiger in this study. Ten microsatellite loci (Fca005, Fca075, Fca094, Fca152, Fca161, Fca294, Pti002, Pti003, Pti007 and Pti010), highly variable nuclear markers, were studied their genetic diversity in 113 captive Amur tigers. The PCR amplified products of microsatellite loci were detected by non-denatured polyacrylamide gel electrophoresis. Allele numbers, allelic frequency, gene heterozygosity(H(e)), polymorphism information content(PIC) and effective number of allele(N(e)) were calculated. 41 alleles were found and their size were ranged from 110bp to 250bp in ten microsatellite loci, Fca152 had 6 alleles, Fca075, Fca094 and Fca294 had 5 alleles, Fca005 and Pti002 had 4 alleles and the others had 3 alleles in all tiger samples, respectively. The allelic frequencies were from 0.009 to 0.767; The He ranged from 0.385 to 0.707, and Fca294 and Pti010 locus had the highest and lowest value; the PIC were from 0.353 to 0.658, Fca294 and Pti010 locus had the highest and lowest value; and N(e) were from 1.626 to 3.409, Fca294 and Pti010 locus had the highest and lowest value, which showed the ten

  5. Isolation and characterization of microsatellite loci in the purpleback flying squid (Sthenoteuthis oualaniensi).

    PubMed

    Lin, L; Li, P; Chen, Z Z; Xiao, Y Y; Xu, S N; Liu, Y; Li, C H

    2015-07-13

    The purpleback flying squid (Sthenoteuthis oualaniensis) is a pelagic squid with tremendous potential for commercial exploitation. We isolated and characterized 21 polymorphic microsatellite loci for S. oualaniensis using a (GT)13-enriched genomic library. The number of alleles per locus varied from 6 to 32. The observed and expected heterozygosities ranged from 0.188 to 0.890, and 0.537 to 0.968, respectively. No significant linkage disequilibrium was detected at these loci. Five loci significantly deviated from the Hardy-Weinberg equilibrium, and four loci may have exhibited null alleles. These microsatellite markers will facilitate further studies in population genetics and the sustainable utilization of S. oualaniensis.

  6. Alzheimer disease (AD) specific transcription, DNA methylation and splicing in twenty AD associated loci.

    PubMed

    Humphries, Crystal; Kohli, Martin A; Whitehead, Patrice; Mash, Deborah C; Pericak-Vance, Margaret A; Gilbert, John

    2015-07-01

    Genome-wide association studies have identified twenty loci associated with late-onset Alzheimer disease (LOAD). We examined each of the twenty loci, specifically the ±50kb region surrounding the most strongly associated variant, for changes in gene(s) transcription specific to LOAD. Post-mortem human brain samples were examined for expression, methylation, and splicing differences. LOAD specific differences were detected by comparing LOAD to normal and "disease" controls. Eight loci, prominently ABCA7, contain LOAD specific differences. Significant changes in the CELF1 and ZCWPW1 loci occurred in genes not located nearest the associated variant, suggesting that these genes should be investigated further as LOAD candidates.

  7. Characterization of ten microsatellite loci in midget faded rattlesnake (Crotalus oreganus concolor)

    USGS Publications Warehouse

    Oyler-McCance, Sara J.; Parker, Joshua M.

    2010-01-01

    Primers for 10 microsatellite loci were developed for midget faded rattlesnake (Crotalus oreganus concolor), a small bodied subspecies of the Western Rattlesnake, which is found in the Colorado Plateau of eastern Utah, western Colorado and southwestern Wyoming. In a screen of 23 individuals from the most northern portion of the subspecies range in southwestern Wyoming, the 10 loci were found to have levels of variability ranging from 4 to 11 alleles. No loci were found to be linked, although one locus revealed significant departures from Hardy–Weinberg equilibrium. These microsatellite loci will be applicable for population genetic analyses, which will ultimately aid in management efforts for this rare subspecies of rattlesnake.

  8. Isolation and characterization of microsatellite loci from the Arctic cisco (Coregonus autumnalis)

    USGS Publications Warehouse

    Ramey, A.; Graziano, S.L.; Nielsen, J.L.

    2008-01-01

    Eight polymorphic microsatellite loci were isolated and characterized for the Arctic cisco, Coregonus autumnalis. Loci were evaluated in 21 samples from the Colville River subsistence fishery. The number of alleles per locus ranged from two to 18. Observed heterozygosity of loci varied from 0.10 to 1.00, and expected heterozygosity ranged from 0.09 to 0.92. All eight microsatellite markers were in Hardy-Weinberg equilibrium. The loci presented here will be useful in describing population structure and exploring populations of origin for Arctic cisco. ?? 2007 Blackwell Publishing Ltd.

  9. Isolation and characterization of dinucleotide microsatellite loci in the Asian elephant (Elephas maximus).

    PubMed

    Kongrit, C; Siripunkaw, C; Brockelman, W Y; Akkarapatumwong, V; Wright, T F; Eggert, L S

    2008-01-01

    The endangered Asian elephant is found today primarily in protected areas. We characterized 18 dinucleotide microsatellite loci in this species. Allelic diversity ranged from three to eight per locus, and observed heterozygosity ranged from 0.200 to 0.842 in a wild population. All loci were in Hardy-Weinberg equilibrium, but linkage disequilibrium was detected between two loci in the wild, but not in the zoo elephants. These loci will be useful for the population-level studies of this species.

  10. Polymorphic microsatellite loci isolated from the yellowbelly threadfin bream, Nemipterus bathybius.

    PubMed

    Kong, X L; Chen, Z Z; Lin, L; Li, C H; Xu, S N; Liu, Y

    2014-01-01

    Twenty-two polymorphic microsatellite loci were isolated and characterized from a (GT)13-enriched Nemipterus bathybius genomic library. The number of alleles per locus ranged from 4 to 13, with an average of 7.86. The observed and expected heterozygosity was 0.167-0.889 and 0.278-0.904, respectively, with averages of 0.590 and 0.690. Three loci deviated from Hardy-Weinberg proportions, and 2 loci showed evidence of null alleles. No significant linkage disequilibrium was detected in the pairwise comparisons among the 22 loci. These markers are expected to be useful for the population genetic analysis of N. bathybius.

  11. Support for the beam focusing hypothesis in the false killer whale.

    PubMed

    Kloepper, Laura N; Buck, John R; Smith, Adam B; Supin, Alexander Ya; Gaudette, Jason E; Nachtigall, Paul E

    2015-08-01

    The odontocete sound production system is complex and composed of tissues, air sacs and a fatty melon. Previous studies suggested that the emitted sonar beam might be actively focused, narrowing depending on target distance. In this study, we further tested this beam focusing hypothesis in a false killer whale. Using three linear arrays of hydrophones, we recorded the same emitted click at 2, 4 and 7 m distance and calculated the beamwidth, intensity, center frequency and bandwidth as recorded on each array at every distance. If the whale did not focus her beam, acoustics predicts the intensity would decay with range as a function of spherical spreading and the angular beamwidth would remain constant. On the contrary, our results show that as the distance from the whale to the array increases, the beamwidth is narrower and the received click intensity is higher than that predicted by a spherical spreading function. Each of these measurements is consistent with the animal focusing her beam on a target at a given range. These results support the hypothesis that the false killer whale is 'focusing' its sonar beam, producing a narrower and more intense signal than that predicted by spherical spreading. PMID:26056247

  12. Variations in killer whale food-associated calls produced during different prey behavioural contexts.

    PubMed

    Samarra, Filipa I P

    2015-07-01

    Killer whales produce herding calls to increase herring school density but previous studies suggested that these calls were made only when feeding upon spawning herring. Herring schools less densely when spawning compared to overwintering; therefore, producing herding calls may be advantageous only when feeding upon less dense spawning schools. To investigate if herding calls were produced across different prey behavioural contexts and whether structural variants occurred and correlated with prey behaviour, this study recorded killer whales when feeding upon spawning and overwintering herring. Herding calls were produced by whales feeding on both spawning and overwintering herring, however, calls recorded during overwintering had significantly different duration and peak frequency to those recorded during spawning. Calls recorded in herring overwintering grounds were more variable and sometimes included nonlinear phenomena. Thus, herding calls were not produced exclusively when feeding upon spawning herring, likely because the call increases feeding efficiency regardless of herring school density or behaviour. Variations in herding call structure were observed between prey behavioural contexts and did not appear to be adapted to prey characteristics. Herding call structural variants may be more likely a result of individual or group variation rather than a reflection of properties of the food source. PMID:25934134

  13. Evolution of population structure in a highly social top predator, the killer whale.

    PubMed

    Hoelzel, A Rus; Hey, Jody; Dahlheim, Marilyn E; Nicholson, Colin; Burkanov, Vladimir; Black, Nancy

    2007-06-01

    Intraspecific resource partitioning and social affiliations both have the potential to structure populations, though it is rarely possible to directly assess the impact of these mechanisms on genetic diversity and population divergence. Here, we address this for killer whales (Orcinus orca), which specialize on prey species and hunting strategy and have long-term social affiliations involving both males and females. We used genetic markers to assess the structure and demographic history of regional populations and test the hypothesis that known foraging specializations and matrifocal sociality contributed significantly to the evolution of population structure. We find genetic structure in sympatry between populations of foraging specialists (ecotypes) and evidence for isolation by distance within an ecotype. Fitting of an isolation with migration model suggested ongoing, low-level migration between regional populations (within and between ecotypes) and small effective sizes for extant local populations. The founding of local populations by matrifocal social groups was indicated by the pattern of fixed mtDNA haplotypes in regional populations. Simulations indicate that this occurred within the last 20,000 years (after the last glacial maximum). Our data indicate a key role for social and foraging behavior in the evolution of genetic structure among conspecific populations of the killer whale. PMID:17400573

  14. Arthroscopic All-Inside Posterior Cruciate Ligament Reconstruction: Overcoming the "Killer Turn".

    PubMed

    Vasdev, Attique; Rajgopal, Ashok; Gupta, Himanshu; Dahiya, Vivek; Tyagi, Vipin Chand

    2016-06-01

    One of the most challenging arthroscopic surgical procedures is posterior cruciate ligament (PCL) reconstruction. PCL injuries account for 20% of all knee ligament-related injuries. These may be isolated or occur as part of poly-ligament injuries. With the possibility of PCL reconstruction with the all-inside technique, there has been a surge in interest in treating PCL injuries. With the PCL being one of the strongest ligaments in the body and a primary restraint to posterior translation of the tibia, the need for PCL reconstruction is being more and more recognized. Surgeons often find it difficult to negotiate the so-called killer turn while attempting arthroscopic PCL reconstruction. We describe the use of the GraftLink graft construct through the posteromedial portal in 7 patients (6 male and 1 female patient) with isolated PCL injuries, which we believe not only allows us to perform the all-inside PCL reconstruction but also does away with the difficulty of the killer turn encountered while performing the arthroscopic PCL reconstruction.

  15. Yeast killer plasmid mutations affecting toxin secretion and activity and toxin immunity function

    SciTech Connect

    Bussey, H.; Sacks, W.; Galley, D.; Saville, D.

    1982-04-01

    M double-stranded RNA (MdsRNA) plasmid mutants were obtained by mutagenesis and screening of a diploid killer culture partially heat cured of the plasmid, so that a high proportion of the cells could be expected to have only one M plasmid. Mutants with neutral (K/sup -/), immune (R/sup +/) or suicide (killer (K/sup +/), sensitive (R/sup -/)) phenotypes were examined. All mutants became K/sup -/ R/sup -/ sensitives on heat curing of the MdsRNA plasmid, and showed cytoplasmic inheritance by random spore analysis. In some cases, M plasmid mutations were indicated by altered mobility of the MdsRNA by agarose gel electrophoresis or by altered size of in vitro translation products from denatured dsRNA. Neutral mutants were of two types: nonsecretors of the toxin protein or secretors of an inactive toxin. Of three neutral nonsecretors examined, one (NLP-1), probably a nonsense mutation, made a smaller protoxin precursor in vitro and in vivo, and two made full-size protoxin molecules. The in vivo protoxin of 43,000 molecular weight was unstable in the wild type and kinetically showed a precursor product relationship to the processed, secreted 11,000-molecular-weight toxin. In one nonsecretor (N1), the protoxin appeared more stable in a pulse-chase experiment, and could be altered in a recognition site required for protein processing.

  16. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia.

    PubMed

    Romee, Rizwan; Rosario, Maximillian; Berrien-Elliott, Melissa M; Wagner, Julia A; Jewell, Brea A; Schappe, Timothy; Leong, Jeffrey W; Abdel-Latif, Sara; Schneider, Stephanie E; Willey, Sarah; Neal, Carly C; Yu, Liyang; Oh, Stephen T; Lee, Yi-Shan; Mulder, Arend; Claas, Frans; Cooper, Megan A; Fehniger, Todd A

    2016-09-21

    Natural killer (NK) cells are an emerging cellular immunotherapy for patients with acute myeloid leukemia (AML); however, the best approach to maximize NK cell antileukemia potential is unclear. Cytokine-induced memory-like NK cells differentiate after a brief preactivation with interleukin-12 (IL-12), IL-15, and IL-18 and exhibit enhanced responses to cytokine or activating receptor restimulation for weeks to months after preactivation. We hypothesized that memory-like NK cells exhibit enhanced antileukemia functionality. We demonstrated that human memory-like NK cells have enhanced interferon-γ production and cytotoxicity against leukemia cell lines or primary human AML blasts in vitro. Using mass cytometry, we found that memory-like NK cell functional responses were triggered against primary AML blasts, regardless of killer cell immunoglobulin-like receptor (KIR) to KIR-ligand interactions. In addition, multidimensional analyses identified distinct phenotypes of control and memory-like NK cells from the same individuals. Human memory-like NK cells xenografted into mice substantially reduced AML burden in vivo and improved overall survival. In the context of a first-in-human phase 1 clinical trial, adoptively transferred memory-like NK cells proliferated and expanded in AML patients and demonstrated robust responses against leukemia targets. Clinical responses were observed in five of nine evaluable patients, including four complete remissions. Thus, harnessing cytokine-induced memory-like NK cell responses represents a promising translational immunotherapy approach for patients with AML.

  17. Expression of killer inhibitory receptors on cytotoxic cells from HIV-1-infected individuals

    PubMed Central

    Galiani, M D; Aguado, E; Tarazona, R; Romero, P; Molina, I; Santamaria, M; Solana, R; PeñA, J

    1999-01-01

    Dysfunction of cytotoxic activity of T and natural killer (NK) lymphocytes is a main immunological feature in patients with AIDS, but its basis are not well understood. It has been recently described that T and NK cell-mediated cytotoxicity can be regulated by HLA killer inhibitory receptors (KIR). In this work, we have determined on cytotoxic T cells and NK cells from HIV-1-infected individuals the expression of the following KIR molecules: p58, p70, and ILT2 (immunoglobulin-like family KIR) as well as CD94 and NKG2A (C-lectin-type family KIR). With some exceptions, no significant changes were found on the expression of immunoglobulin-like KIR in either CD8+ or CD56+ cells. Interestingly, the percentages of CD8+ and CD56+ cells expressing CD94 were significantly increased in these individuals. We also show that, in vitro, IL-10 up-regulates CD94 expression on CD8+ and CD56+ cells obtained from normal individuals, suggesting that the augmented expression observed in HIV-infected individuals could be related to the high levels of IL-10 previously described in HIV-1-infected individuals. PMID:10193420

  18. Diversity in sound pressure levels and estimated active space of resident killer whale vocalizations.

    PubMed

    Miller, Patrick J O

    2006-05-01

    Signal source intensity and detection range, which integrates source intensity with propagation loss, background noise and receiver hearing abilities, are important characteristics of communication signals. Apparent source levels were calculated for 819 pulsed calls and 24 whistles produced by free-ranging resident killer whales by triangulating the angles-of-arrival of sounds on two beamforming arrays towed in series. Levels in the 1-20 kHz band ranged from 131 to 168 dB re 1 microPa at 1 m, with differences in the means of different sound classes (whistles: 140.2+/-4.1 dB; variable calls: 146.6+/-6.6 dB; stereotyped calls: 152.6+/-5.9 dB), and among stereotyped call types. Repertoire diversity carried through to estimates of active space, with "long-range" stereotyped calls all containing overlapping, independently-modulated high-frequency components (mean estimated active space of 10-16 km in sea state zero) and "short-range" sounds (5-9 km) included all stereotyped calls without a high-frequency component, whistles, and variable calls. Short-range sounds are reported to be more common during social and resting behaviors, while long-range stereotyped calls predominate in dispersed travel and foraging behaviors. These results suggest that variability in sound pressure levels may reflect diverse social and ecological functions of the acoustic repertoire of killer whales.

  19. Classification of human natural killer cells based on migration behavior and cytotoxic response.

    PubMed

    Vanherberghen, Bruno; Olofsson, Per E; Forslund, Elin; Sternberg-Simon, Michal; Khorshidi, Mohammad Ali; Pacouret, Simon; Guldevall, Karolin; Enqvist, Monika; Malmberg, Karl-Johan; Mehr, Ramit; Önfelt, Björn

    2013-02-21

    Despite intense scrutiny of the molecular interactions between natural killer (NK) and target cells, few studies have been devoted to dissection of the basic functional heterogeneity in individual NK cell behavior. Using a microchip-based, time-lapse imaging approach allowing the entire contact history of each NK cell to be recorded, in the present study, we were able to quantify how the cytotoxic response varied between individual NK cells. Strikingly, approximately half of the NK cells did not kill any target cells at all, whereas a minority of NK cells was responsible for a majority of the target cell deaths. These dynamic cytotoxicity data allowed categorization of NK cells into 5 distinct classes. A small but particularly active subclass of NK cells killed several target cells in a consecutive fashion. These "serial killers" delivered their lytic hits faster and induced faster target cell death than other NK cells. Fast, necrotic target cell death was correlated with the amount of perforin released by the NK cells. Our data are consistent with a model in which a small fraction of NK cells drives tumor elimination and inflammation.

  20. Ocular anatomy, ganglion cell distribution and retinal resolution of a killer whale (Orcinus orca).

    PubMed

    Mass, Alla M; Supin, Alexander Y; Abramov, Andrey V; Mukhametov, Lev M; Rozanova, Elena I

    2013-01-01

    Retinal topography, cell density and sizes of ganglion cells in the killer whale (Orcinus orca) were analyzed in retinal whole mounts stained with cresyl violet. A distinctive feature of the killer whale's retina is the large size of ganglion cells and low cell density compared to terrestrial mammals. The ganglion cell diameter ranged from 8 to 100 µm, with the majority of cells within a range of 20-40 µm. The topographic distribution of ganglion cells displayed two spots of high cell density located in the temporal and nasal quadrants, 20 mm from the optic disk. The high-density areas were connected by a horizontal belt-like area passing below the optic disk of the retina. Peak cell densities in these areas were evaluated. Mean peak cell densities were 334 and 288 cells/mm(2) in the temporal and nasal high-density areas, respectively. With a posterior nodal distance of 19.5 mm, these high-density data predict a retinal resolution of 9.6' (3.1 cycles/deg.) and 12.6' (2.4 cycles/deg.) in the temporal and nasal areas, respectively, in water. PMID:23018493