Acidic intracellular pH shift during Caenorhabditis elegans larval development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wadsworth, W.G.; Riddle, D.L.

1988-11-01

During recovery from the developmentally arrested, nonfeeding dauer stage of the nemotode Caenorhabditis elegans, metabolic activation is accompanied by a decrease in intracellular pH (pH{sub i}). Phosphorus-31 nuclear magnetic resonance ({sup 31}P NMR) analyses of perchloric acid extracts show that inorganic phosphate predominates in dauer larvae, whereas ATP and other high-energy metabolites are abundant within 6 hr after dauer larvae have been placed in food to initiate development. Although metabolic activation has been associated with an alkaline pH{sub i} shift in other organisms, in vivo {sup 31}P NMR analysis of recovering dauer larvae shows a pH{sub i} decrease from {approx}more » 7.3 to {approx} 6.3 within 3 hr after the animals encounter food. This shift occurs before feeding begins, and it coincides with, or soon follows, the developmental commitment to recover from the dauer stage, suggesting that control of pH{sub i} may be important in the regulation of larval development in nematodes.« less

Effects of a Caenorhabditis elegans dauer pheromone ascaroside on physiology and signal transduction pathways.

PubMed

Gallo, Marco; Riddle, Donald L

2009-02-01

Daumone is one of the three purified and artificially synthesized components of the Caenorhabditis elegans dauer pheromone. It affects the major signal transduction pathways known to discriminate between developmental arrest at the dauer stage and growth to the adult [the transforming growth factor beta (TGF-beta) and daf-2/IGF1R pathways], just as natural pheromone extracts do. Transcription of daf-7/TGF-beta is reduced in pre-dauer larvae, and nuclear localization of the DAF-16/FOXO transcription factor is increased in embryos and L1 larvae exposed to synthetic daumone. However, daumone does not require the cilia in the amphidial neurons to produce these effects nor does it require the Galpha protein GPA-3 to induce dauer entry, although GPA-3 is required for dauer induction by natural dauer pheromone extracts. Synthetic daumone has physiological effects that have not been observed with natural pheromone. It is toxic at the concentrations required for bioassay and is lethal to mutants with defective cuticles. The molecular and physiological effects of daumone and natural dauer pheromone are only partially overlapping.

Natural variation in Pristionchus pacificus dauer formation reveals cross-preference rather than self-preference of nematode dauer pheromones

PubMed Central

Mayer, Melanie G.; Sommer, Ralf J.

2011-01-01

Many free-living nematodes, including the laboratory model organisms Caenorhabditis elegans and Pristionchus pacificus, have a choice between direct and indirect development, representing an important case of phenotypic plasticity. Under harsh environmental conditions, these nematodes form dauer larvae, which arrest development, show high resistance to environmental stress and constitute a dispersal stage. Pristionchus pacificus occurs in a strong association with scarab beetles in the wild and remains in the dauer stage on the living beetle. Here, we explored the circumstances under which P. pacificus enters and exits the dauer stage by using a natural variation approach. The analysis of survival, recovery and fitness after dauer exit of eight P. pacificus strains revealed that dauer larvae can survive for up to 1 year under experimental conditions. In a second experiment, we isolated dauer pheromones from 16 P. pacificus strains, and tested for natural variation in pheromone production and sensitivity in cross-reactivity assays. Surprisingly, 13 of the 16 strains produce a pheromone that induces the highest dauer formation in individuals of other genotypes. These results argue against a simple adaptation model for natural variation in dauer formation and suggest that strains may have evolved to induce dauer formation precociously in other strains in order to reduce the fitness of these strains. We therefore discuss intraspecific competition among genotypes as a previously unconsidered aspect of dauer formation. PMID:21307052

Developmental and Cell Cycle Quiescence Is Mediated by the Nuclear Hormone Receptor Coregulator DIN-1S in the Caenorhabditis elegans Dauer Larva.

PubMed

Colella, Eileen; Li, Shaolin; Roy, Richard

2016-08-01

When faced with suboptimal growth conditions, Caenorhabditis elegans larvae can enter a diapause-like stage called "dauer" that is specialized for dispersal and survival. The decision to form a dauer larva is controlled by three parallel signaling pathways, whereby a compromise of TGFβ, cyclic guanosine monophosphate, or insulin/IGF-like signaling (ILS) results in dauer formation. Signals from these pathways converge on DAF-12, a nuclear hormone receptor that triggers the changes required to initiate dauer formation. DAF-12 is related to the vitamin D, liver-X, and androstane receptors, and like these human receptors, it responds to lipophilic hormone ligands. When bound to its ligand, DAF-12 acquires transcriptional activity that directs reproductive development, while unliganded DAF-12 forms a dauer-specifying complex with its interacting protein DIN-1S to regulate the transcription of genes required for dauer development. We report here that din-1S is required in parallel to par-4/LKB1 signaling within the gonad to establish cell cycle quiescence during the onset of the dauer stage. We show that din-1S is important for postdauer reproduction when ILS is impaired and is necessary for long-term dauer survival in response to reduced ILS. Our work uncovers several previously uncharacterized functions of DIN-1S in executing and maintaining many of the cellular and physiological processes required for appropriate dauer arrest, while also shedding light on the coordination of nuclear hormone signaling, the LKB1/AMPK signaling cascade, and ILS/TGFβ in the control of cell cycle quiescence and tissue growth: a key feature that is often misregulated in a number of hormone-dependent cancers. Copyright © 2016 by the Genetics Society of America.

Dauer larva quiescence alters the circuitry of microRNA pathways regulating cell fate progression in C. elegans.

PubMed

Karp, Xantha; Ambros, Victor

2012-06-01

In C. elegans larvae, the execution of stage-specific developmental events is controlled by heterochronic genes, which include those encoding a set of transcription factors and the microRNAs that regulate the timing of their expression. Under adverse environmental conditions, developing larvae enter a stress-resistant, quiescent stage called 'dauer'. Dauer larvae are characterized by the arrest of all progenitor cell lineages at a stage equivalent to the end of the second larval stage (L2). If dauer larvae encounter conditions favorable for resumption of reproductive growth, they recover and complete development normally, indicating that post-dauer larvae possess mechanisms to accommodate an indefinite period of interrupted development. For cells to progress to L3 cell fate, the transcription factor Hunchback-like-1 (HBL-1) must be downregulated. Here, we describe a quiescence-induced shift in the repertoire of microRNAs that regulate HBL-1. During continuous development, HBL-1 downregulation (and consequent cell fate progression) relies chiefly on three let-7 family microRNAs, whereas after quiescence, HBL-1 is downregulated primarily by the lin-4 microRNA in combination with an altered set of let-7 family microRNAs. We propose that this shift in microRNA regulation of HBL-1 expression involves an enhancement of the activity of lin-4 and let-7 microRNAs by miRISC modulatory proteins, including NHL-2 and LIN-46. These results illustrate how the employment of alternative genetic regulatory pathways can provide for the robust progression of progenitor cell fates in the face of temporary developmental quiescence.

Natural variation in Pristionchus pacificus dauer formation reveals cross-preference rather than self-preference of nematode dauer pheromones.

PubMed

Mayer, Melanie G; Sommer, Ralf J

2011-09-22

Many free-living nematodes, including the laboratory model organisms Caenorhabditis elegans and Pristionchus pacificus, have a choice between direct and indirect development, representing an important case of phenotypic plasticity. Under harsh environmental conditions, these nematodes form dauer larvae, which arrest development, show high resistance to environmental stress and constitute a dispersal stage. Pristionchus pacificus occurs in a strong association with scarab beetles in the wild and remains in the dauer stage on the living beetle. Here, we explored the circumstances under which P. pacificus enters and exits the dauer stage by using a natural variation approach. The analysis of survival, recovery and fitness after dauer exit of eight P. pacificus strains revealed that dauer larvae can survive for up to 1 year under experimental conditions. In a second experiment, we isolated dauer pheromones from 16 P. pacificus strains, and tested for natural variation in pheromone production and sensitivity in cross-reactivity assays. Surprisingly, 13 of the 16 strains produce a pheromone that induces the highest dauer formation in individuals of other genotypes. These results argue against a simple adaptation model for natural variation in dauer formation and suggest that strains may have evolved to induce dauer formation precociously in other strains in order to reduce the fitness of these strains. We therefore discuss intraspecific competition among genotypes as a previously unconsidered aspect of dauer formation. This journal is © 2011 The Royal Society

Sequestration of polyunsaturated fatty acids in membrane phospholipids of Caenorhabditis elegans dauer larva attenuates eicosanoid biosynthesis for prolonged survival.

PubMed

Lam, Sin Man; Wang, Zehua; Li, Jie; Huang, Xun; Shui, Guanghou

2017-08-01

Mechanistic basis governing the extreme longevity and developmental quiescence of dauer juvenile, a "non-ageing" developmental variant of Caenorhabditis elegans, has remained largely obscure. Using a lipidomic approach comprising multiple reaction monitoring transitions specific to distinct fatty acyl moieties, we demonstrated that in comparison to other developmental stages, the membrane phospholipids of dauer larva contain a unique enrichment of polyunsaturated fatty acids (PUFAs). Esterified PUFAs in phospholipids exhibited temporal accumulation throughout the course of dauer endurance, followed by sharp reductions prior to termination of diapause. Reductions in esterified PUFAs were accompanied by concomitant increases in unbound PUFAs, as well as their corresponding downstream oxidized derivatives (i.e. eicosanoids). Global phospholipidomics has unveiled that PUFA sequestration in membrane phospholipids denotes an essential aspect of dauer dormancy, principally via suppression of eicosanoid production; and a failure to upkeep membrane lipid homeostasis is associated with termination of dauer endurance. Copyright © 2017. Published by Elsevier B.V.

Integration of carbohydrate metabolism and redox state controls dauer larva formation in Caenorhabditis elegans.

PubMed

Penkov, Sider; Kaptan, Damla; Erkut, Cihan; Sarov, Mihail; Mende, Fanny; Kurzchalia, Teymuras V

2015-08-20

Under adverse conditions, Caenorhabditis elegans enters a diapause stage called the dauer larva. External cues signal the nuclear hormone receptor DAF-12, the activity of which is regulated by its ligands: dafachronic acids (DAs). DAs are synthesized from cholesterol, with the last synthesis step requiring NADPH, and their absence stimulates dauer formation. Here we show that NADPH levels determine dauer formation in a regulatory mechanism involving key carbohydrate and redox metabolic enzymes. Elevated trehalose biosynthesis diverts glucose-6-phosphate from the pentose phosphate pathway, which is the major source of cellular NADPH. This enhances dauer formation due to the decrease in the DA level. Moreover, DAF-12, in cooperation with DAF-16/FoxO, induces negative feedback of DA synthesis via activation of the trehalose-producing enzymes TPS-1/2 and inhibition of the NADPH-producing enzyme IDH-1. Thus, the dauer developmental decision is controlled by integration of the metabolic flux of carbohydrates and cellular redox potential.

Transgenic C. elegans dauer larvae expressing hookworm phospho null DAF-16/FoxO exit dauer.

PubMed

Gelmedin, Verena; Brodigan, Thomas; Gao, Xin; Krause, Michael; Wang, Zhu; Hawdon, John M

2011-01-01

Parasitic hookworms and the free-living model nematode Caenorhabtidis elegans share a developmental arrested stage, called the dauer stage in C. elegans and the infective third-stage larva (L3) in hookworms. One of the key transcription factors that regulate entrance to and exit from developmental arrest is the forkhead transcription factor DAF-16/FoxO. During the dauer stage, DAF-16 is activated and localized in the nucleus. DAF-16 is negatively regulated by phosphorylation by the upstream kinase AKT, which causes DAF-16 to localize out of the nucleus and the worm to exit from dauer. DAF-16 is conserved in hookworms, and hypothesized to control recovery from L3 arrest during infection. Lacking reverse genetic techniques for use in hookworms, we used C. elegans complementation assays to investigate the function of Ancylostoma caninum DAF-16 during entrance and exit from L3 developmental arrest. We performed dauer switching assays and observed the restoration of the dauer phenotype when Ac-DAF-16 was expressed in temperature-sensitive dauer defective C. elegans daf-2(e1370);daf-16(mu86) mutants. AKT phosphorylation site mutants of Ac-DAF-16 were also able to restore the dauer phenotype, but surprisingly allowed dauer exit when temperatures were lowered. We used fluorescence microscopy to localize DAF-16 during dauer and exit from dauer in C. elegans DAF-16 mutant worms expressing Ac-DAF-16, and found that Ac-DAF-16 exited the nucleus during dauer exit. Surprisingly, Ac-DAF-16 with mutated AKT phosphorylation sites also exited the nucleus during dauer exit. Our results suggest that another mechanism may be involved in the regulation DAF-16 nuclear localization during recovery from developmental arrest.

The Dauer Mutation of the Caenorhabditis Elegans, Simulated with the Penna and the Stauffer Models

NASA Astrophysics Data System (ADS)

Colonius, Kerstin

Two aging models were analyzed on whether they can confirm the dauer mutation of the nematode helps to preserve the species. As a result the Penna model shows that populations with dauer larvae survive bad environmental conditions, whereas populations without it die out. In the Stauffer model, the advantage of the dauer mutation for the survival is only given under certain conditions.

Molecular time-course and the metabolic basis of entry into dauer in Caenorhabditis elegans.

PubMed

Jeong, Pan-Young; Kwon, Min-Seok; Joo, Hyoe-Jin; Paik, Young-Ki

2009-01-01

When Caenorhabditis elegans senses dauer pheromone (daumone), signaling inadequate growth conditions, it enters the dauer state, which is capable of long-term survival. However, the molecular pathway of dauer entry in C. elegans has remained elusive. To systematically monitor changes in gene expression in dauer paths, we used a DNA microarray containing 22,625 gene probes corresponding to 22,150 unique genes from C. elegans. We employed two different paths: direct exposure to daumone (Path 1) and normal growth media plus liquid culture (Path 2). Our data reveal that entry into dauer is accomplished through the multi-step process, which appears to be compartmentalized in time and according to metabolic flux. That is, a time-course of dauer entry in Path 1 shows that dauer larvae formation begins at post-embryonic stage S4 (48 h) and is complete at S6 (72 h). Our results also suggest the presence of a unique adaptive metabolic control mechanism that requires both stage-specific expression of specific genes and tight regulation of different modes of fuel metabolite utilization to sustain the energy balance in the context of prolonged survival under adverse growth conditions. It is apparent that worms entering dauer stage may rely heavily on carbohydrate-based energy reserves, whereas dauer larvae utilize fat or glyoxylate cycle-based energy sources. We created a comprehensive web-based dauer metabolic database for C. elegans (www.DauerDB.org) that makes it possible to search any gene and compare its relative expression at a specific stage, or evaluate overall patterns of gene expression in both paths. This database can be accessed by the research community and could be widely applicable to other related nematodes as a molecular atlas.

Strongyloides stercoralis age-1: a potential regulator of infective larval development in a parasitic nematode.

PubMed

Stoltzfus, Jonathan D; Massey, Holman C; Nolan, Thomas J; Griffith, Sandra D; Lok, James B

2012-01-01

Infective third-stage larvae (L3i) of the human parasite Strongyloides stercoralis share many morphological, developmental, and behavioral attributes with Caenorhabditis elegans dauer larvae. The 'dauer hypothesis' predicts that the same molecular genetic mechanisms control both dauer larval development in C. elegans and L3i morphogenesis in S. stercoralis. In C. elegans, the phosphatidylinositol-3 (PI3) kinase catalytic subunit AGE-1 functions in the insulin/IGF-1 signaling (IIS) pathway to regulate formation of dauer larvae. Here we identify and characterize Ss-age-1, the S. stercoralis homolog of the gene encoding C. elegans AGE-1. Our analysis of the Ss-age-1 genomic region revealed three exons encoding a predicted protein of 1,209 amino acids, which clustered with C. elegans AGE-1 in phylogenetic analysis. We examined temporal patterns of expression in the S. stercoralis life cycle by reverse transcription quantitative PCR and observed low levels of Ss-age-1 transcripts in all stages. To compare anatomical patterns of expression between the two species, we used Ss-age-1 or Ce-age-1 promoter::enhanced green fluorescent protein reporter constructs expressed in transgenic animals for each species. We observed conservation of expression in amphidial neurons, which play a critical role in developmental regulation of both dauer larvae and L3i. Application of the PI3 kinase inhibitor LY294002 suppressed L3i in vitro activation in a dose-dependent fashion, with 100 µM resulting in a 90% decrease (odds ratio: 0.10, 95% confidence interval: 0.08-0.13) in the odds of resumption of feeding for treated L3i in comparison to the control. Together, these data support the hypothesis that Ss-age-1 regulates the development of S. stercoralis L3i via an IIS pathway in a manner similar to that observed in C. elegans dauer larvae. Understanding the mechanisms by which infective larvae are formed and activated may lead to novel control measures and treatments for strongyloidiasis and other soil-transmitted helminthiases.

Strongyloides stercoralis age-1: A Potential Regulator of Infective Larval Development in a Parasitic Nematode

PubMed Central

Stoltzfus, Jonathan D.; Massey, Holman C.; Nolan, Thomas J.; Griffith, Sandra D.; Lok, James B.

2012-01-01

Infective third-stage larvae (L3i) of the human parasite Strongyloides stercoralis share many morphological, developmental, and behavioral attributes with Caenorhabditis elegans dauer larvae. The ‘dauer hypothesis’ predicts that the same molecular genetic mechanisms control both dauer larval development in C. elegans and L3i morphogenesis in S. stercoralis. In C. elegans, the phosphatidylinositol-3 (PI3) kinase catalytic subunit AGE-1 functions in the insulin/IGF-1 signaling (IIS) pathway to regulate formation of dauer larvae. Here we identify and characterize Ss-age-1, the S. stercoralis homolog of the gene encoding C. elegans AGE-1. Our analysis of the Ss-age-1 genomic region revealed three exons encoding a predicted protein of 1,209 amino acids, which clustered with C. elegans AGE-1 in phylogenetic analysis. We examined temporal patterns of expression in the S. stercoralis life cycle by reverse transcription quantitative PCR and observed low levels of Ss-age-1 transcripts in all stages. To compare anatomical patterns of expression between the two species, we used Ss-age-1 or Ce-age-1 promoter::enhanced green fluorescent protein reporter constructs expressed in transgenic animals for each species. We observed conservation of expression in amphidial neurons, which play a critical role in developmental regulation of both dauer larvae and L3i. Application of the PI3 kinase inhibitor LY294002 suppressed L3i in vitro activation in a dose-dependent fashion, with 100 µM resulting in a 90% decrease (odds ratio: 0.10, 95% confidence interval: 0.08–0.13) in the odds of resumption of feeding for treated L3i in comparison to the control. Together, these data support the hypothesis that Ss-age-1 regulates the development of S. stercoralis L3i via an IIS pathway in a manner similar to that observed in C. elegans dauer larvae. Understanding the mechanisms by which infective larvae are formed and activated may lead to novel control measures and treatments for strongyloidiasis and other soil-transmitted helminthiases. PMID:22701676

Methylation of the sterol nucleus by STRM-1 regulates dauer larva formation in Caenorhabditis elegans.

PubMed

Hannich, J Thomas; Entchev, Eugeni V; Mende, Fanny; Boytchev, Hristio; Martin, René; Zagoriy, Vyacheslav; Theumer, Gabriele; Riezman, Isabelle; Riezman, Howard; Knölker, Hans-Joachim; Kurzchalia, Teymuras V

2009-06-01

In response to pheromone(s), Caenorhabditis elegans interrupts its reproductive life cycle and enters diapause as a stress-resistant dauer larva. This decision is governed by a complex system of neuronal and hormonal regulation. All the signals converge onto the nuclear hormone receptor DAF-12. A sterol-derived hormone, dafachronic acid (DA), supports reproductive development by binding to DAF-12 and inhibiting its dauer-promoting activity. Here, we identify a methyltransferase, STRM-1, that modulates DA levels and thus dauer formation. By modifying the substrates that are used for the synthesis of DA, STRM-1 can reduce the amount of hormone produced. Loss of STRM-1 function leads to elevated levels of DA and inefficient dauer formation. Sterol methylation was not previously recognized as a mechanism for regulating hormone activity. Moreover, the C-4 sterol nucleus methylation catalyzed by STRM-1 is unique to nematodes and thus could be a target for therapeutic strategies against parasitic nematode infections.

Genes that regulate both development and longevity in Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsen, P.L.; Albert, P.S.; Riddle, D.L.

1995-04-01

The nematode Caenorhabditis elegans responds to conditions of overcrowding and limited food by arresting development as a dauer larva. Genetic analysis of mutations that alter dauer larva formation (daf mutations) is presented along with an updated genetic pathway for dauer vs. nondauer development. Mutations in the daf-2 and daf-23 genes double adult life span, whereas mutations in four other dauer-constitutive genes positioned in a separate branch of this pathway (daf-1, daf-4, daf-7 and daf-8) do not. The increased life spans are suppressed completely by a daf-16 mutation and partially in a daf-2; daf-18 double mutant. A genetic pathway for determinationmore » of adult life span is presented based on the same strains and growth conditions used to characterize Daf phenotypes. Both dauer larva formation and adult life span are affected in daf-2; daf-12 double mutants in an allele-specific manner. Mutations in daf-12 do not extend adult life span, but certain combinations of daf-2 and daf-12 mutant alleles nearly quadruple it. This synergistic effect, which does not equivalently extend the fertile period, is the largest genetic extension of life span yet observed in a metazoan. 47 refs., 7 figs., 5 tabs.« less

A Method for Obtaining Large Populations of Synchronized Caenorhabditis elegans Dauer Larvae.

PubMed

Ow, Maria C; Hall, Sarah E

2015-01-01

The C. elegans dauer is an attractive model with which to investigate fundamental biological questions, such as how environmental cues are sensed and are translated into developmental decisions through a series of signaling cascades that ultimately result in a transformed animal. Here we describe a simple method of using egg white plates to obtain highly synchronized purified dauers that can be used in downstream applications requiring large quantities of dauers or postdauer animals.

RNAi screen of DAF-16/FOXO target genes in C. elegans links pathogenesis and dauer formation.

PubMed

Jensen, Victor L; Simonsen, Karina T; Lee, Yu-Hui; Park, Donha; Riddle, Donald L

2010-12-31

The DAF-16/FOXO transcription factor is the major downstream output of the insulin/IGF1R signaling pathway controlling C. elegans dauer larva development and aging. To identify novel downstream genes affecting dauer formation, we used RNAi to screen candidate genes previously identified to be regulated by DAF-16. We used a sensitized genetic background [eri-1(mg366); sdf-9(m708)], which enhances both RNAi efficiency and constitutive dauer formation (Daf-c). Among 513 RNAi clones screened, 21 displayed a synthetic Daf-c (SynDaf) phenotype with sdf-9. One of these genes, srh-100, was previously identified to be SynDaf, but twenty have not previously been associated with dauer formation. Two of the latter genes, lys-1 and cpr-1, are known to participate in innate immunity and six more are predicted to do so, suggesting that the immune response may contribute to the dauer decision. Indeed, we show that two of these genes, lys-1 and clc-1, are required for normal resistance to Staphylococcus aureus. clc-1 is predicted to function in epithelial cohesion. Dauer formation exhibited by daf-8(m85), sdf-9(m708), and the wild-type N2 (at 27°C) were all enhanced by exposure to pathogenic bacteria, while not enhanced in a daf-22(m130) background. We conclude that knockdown of the genes required for proper pathogen resistance increases pathogenic infection, leading to increased dauer formation in our screen. We propose that dauer larva formation is a behavioral response to pathogens mediated by increased dauer pheromone production.

The thioredoxin TRX-1 modulates the function of the insulin-like neuropeptide DAF-28 during dauer formation in Caenorhabditis elegans.

PubMed

Fierro-González, Juan Carlos; Cornils, Astrid; Alcedo, Joy; Miranda-Vizuete, Antonio; Swoboda, Peter

2011-01-27

Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c) phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated), an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions.

The Thioredoxin TRX-1 Modulates the Function of the Insulin-Like Neuropeptide DAF-28 during Dauer Formation in Caenorhabditis elegans

PubMed Central

Fierro-González, Juan Carlos; Cornils, Astrid; Alcedo, Joy

2011-01-01

Thioredoxins comprise a conserved family of redox regulators involved in many biological processes, including stress resistance and aging. We report that the C. elegans thioredoxin TRX-1 acts in ASJ head sensory neurons as a novel modulator of the insulin-like neuropeptide DAF-28 during dauer formation. We show that increased formation of stress-resistant, long-lived dauer larvae in mutants for the gene encoding the insulin-like neuropeptide DAF-28 requires TRX-1 acting in ASJ neurons, upstream of the insulin-like receptor DAF-2. Genetic rescue experiments demonstrate that redox-independent functions of TRX-1 specifically in ASJ neurons are needed for the dauer formation constitutive (Daf-c) phenotype of daf-28 mutants. GFP reporters of trx-1 and daf-28 show opposing expression patterns in dauers (i.e. trx-1 is up-regulated and daf-28 is down-regulated), an effect that is not observed in growing L2/L3 larvae. In addition, functional TRX-1 is required for the down-regulation of a GFP reporter of daf-28 during dauer formation, a process that is likely subject to DAF-28-mediated feedback regulation. Our findings demonstrate that TRX-1 modulates DAF-28 signaling by contributing to the down-regulation of daf-28 expression during dauer formation. We propose that TRX-1 acts as a fluctuating neuronal signaling modulator within ASJ neurons to monitor the adjustment of neuropeptide expression, including insulin-like proteins, during dauer formation in response to adverse environmental conditions. PMID:21304598

Quantitative assessment of pheromone-induced Dauer formation in Caenorhabditis elegans.

PubMed

Neal, Scott J; Kim, Kyuhyung; Sengupta, Piali

2013-01-01

Environmental conditions experienced during early larval stages dictate the developmental trajectory of the nematode C. elegans. Favorable conditions such as low population density, abundant food, and lower temperatures allow reproductive growth, while stressful conditions promote entry of second-stage (L2) larvae into the alternate dauer developmental stage. Population density is signaled by the concentration and composition of a complex mixture of small molecules that is produced by all stages of animals, and is collectively referred to as dauer pheromone; pheromone concentration is a major trigger for dauer formation. Here, we describe a quantitative dauer formation assay that provides a measure of the potency of single or mixtures of pheromone components in regulating this critical developmental decision.

Is dauer pheromone of Caenorhabditis elegans really a pheromone?

NASA Astrophysics Data System (ADS)

Viney, M. E.; Franks, N. R.

Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called `dauer pheromone', produced by all worms. We suggest that the production of `dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that `dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.

Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans.

PubMed

Sinha, Amit; Sommer, Ralf J; Dieterich, Christoph

2012-06-19

An organism can respond to changing environmental conditions by adjusting gene regulation and by forming alternative phenotypes. In nematodes, these mechanisms are coupled because many species will form dauer larvae, a stress-resistant and non-aging developmental stage, when exposed to unfavorable environmental conditions, and execute gene expression programs that have been selected for the survival of the animal in the wild. These dauer larvae represent an environmentally induced, homologous developmental stage across many nematode species, sharing conserved morphological and physiological properties. Hence it can be expected that some core components of the associated transcriptional program would be conserved across species, while others might diverge over the course of evolution. However, transcriptional and metabolic analysis of dauer development has been largely restricted to Caenorhabditis elegans. Here, we use a transcriptomic approach to compare the dauer stage in the evolutionary model system Pristionchus pacificus with the dauer stage in C. elegans. We have employed Agilent microarrays, which represent 20,446 P. pacificus and 20,143 C. elegans genes to show an unexpected divergence in the expression profiles of these two nematodes in dauer and dauer exit samples. P. pacificus and C. elegans differ in the dynamics and function of genes that are differentially expressed. We find that only a small number of orthologous gene pairs show similar expression pattern in the dauers of the two species, while the non-orthologous fraction of genes is a major contributor to the active transcriptome in dauers. Interestingly, many of the genes acquired by horizontal gene transfer and orphan genes in P. pacificus, are differentially expressed suggesting that these genes are of evolutionary and functional importance. Our data set provides a catalog for future functional investigations and indicates novel insight into evolutionary mechanisms. We discuss the limited conservation of core developmental and transcriptional programs as a common aspect of animal evolution.

Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans

PubMed Central

2012-01-01

Background An organism can respond to changing environmental conditions by adjusting gene regulation and by forming alternative phenotypes. In nematodes, these mechanisms are coupled because many species will form dauer larvae, a stress-resistant and non-aging developmental stage, when exposed to unfavorable environmental conditions, and execute gene expression programs that have been selected for the survival of the animal in the wild. These dauer larvae represent an environmentally induced, homologous developmental stage across many nematode species, sharing conserved morphological and physiological properties. Hence it can be expected that some core components of the associated transcriptional program would be conserved across species, while others might diverge over the course of evolution. However, transcriptional and metabolic analysis of dauer development has been largely restricted to Caenorhabditis elegans. Here, we use a transcriptomic approach to compare the dauer stage in the evolutionary model system Pristionchus pacificus with the dauer stage in C. elegans. Results We have employed Agilent microarrays, which represent 20,446 P. pacificus and 20,143 C. elegans genes to show an unexpected divergence in the expression profiles of these two nematodes in dauer and dauer exit samples. P. pacificus and C. elegans differ in the dynamics and function of genes that are differentially expressed. We find that only a small number of orthologous gene pairs show similar expression pattern in the dauers of the two species, while the non-orthologous fraction of genes is a major contributor to the active transcriptome in dauers. Interestingly, many of the genes acquired by horizontal gene transfer and orphan genes in P. pacificus, are differentially expressed suggesting that these genes are of evolutionary and functional importance. Conclusion Our data set provides a catalog for future functional investigations and indicates novel insight into evolutionary mechanisms. We discuss the limited conservation of core developmental and transcriptional programs as a common aspect of animal evolution. PMID:22712530

A potent dauer pheromone component in Caenorhabditis elegans that acts synergistically with other components.

PubMed

Butcher, Rebecca A; Ragains, Justin R; Kim, Edward; Clardy, Jon

2008-09-23

In the model organism Caenorhabditis elegans, the dauer pheromone is the primary cue for entry into the developmentally arrested, dauer larval stage. The dauer is specialized for survival under harsh environmental conditions and is considered "nonaging" because larvae that exit dauer have a normal life span. C. elegans constitutively secretes the dauer pheromone into its environment, enabling it to sense its population density. Several components of the dauer pheromone have been identified as derivatives of the dideoxy sugar ascarylose, but additional unidentified components of the dauer pheromone contribute to its activity. Here, we show that an ascaroside with a 3-hydroxypropionate side chain is a highly potent component of the dauer pheromone that acts synergistically with previously identified components. Furthermore, we show that the active dauer pheromone components that are produced by C. elegans vary depending on cultivation conditions. Identifying the active components of the dauer pheromone, the conditions under which they are produced, and their mechanisms of action will greatly extend our understanding of how chemosensory cues from the environment can influence such fundamental processes as development, metabolism, and aging in nematodes and in higher organisms.

NAD+ Is a Food Component That Promotes Exit from Dauer Diapause in Caenorhabditis elegans.

PubMed

Mylenko, Mykola; Boland, Sebastian; Penkov, Sider; Sampaio, Julio L; Lombardot, Benoit; Vorkel, Daniela; Verbavatz, Jean-Marc; Kurzchalia, Teymuras V

2016-01-01

The free-living soil nematode Caenorhabditis elegans adapts its development to the availability of food. When food is scarce and population density is high, worms enter a developmentally arrested non-feeding diapause stage specialized for long-term survival called the dauer larva. When food becomes available, they exit from the dauer stage, resume growth and reproduction. It has been postulated that compound(s) present in food, referred to as the "food signal", promote exit from the dauer stage. In this study, we have identified NAD+ as a component of bacterial extract that promotes dauer exit. NAD+, when dissolved in alkaline medium, causes opening of the mouth and ingestion of food. We also show that to initiate exit from the dauer stage in response to NAD+ worms require production of serotonin. Thus, C. elegans can use redox cofactors produced by dietary organisms to sense food.

Biochemistry and molecular biology of the Caenorhabditis elegans dauer larva

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wadsworth, W.G.

1989-01-01

Biochemical and molecular techniques have been used to study the formation and recovery of the developmentally arrested, non-feeding dauer stage of the nematode Caenorhabditis elegans. While investigating developmental transitions in energy metabolism, a major metabolite isolated from perchloric acid extracts has been identified as a modified uridine nucleotide. The compound was isolated by gel filtration and ion-exchange chromatography and its structure was determined by {sup 1}H NMR and {sup 13}C NMR spectroscopy. This compound is the most abundant metabolite detected in {sup 31}PMR spectra of perchloric acid extracts from growing larvae. In the absence of phosphoarginine or phosphocreatine, this modifiedmore » nucleotide may have an important function in the nematode's energy metabolism, and it may also be found in several other invertebrates. During recovery from the dauer stage, metabolic activation is accompanied by a decrease in intracellular pH (pH{sub i}). Although metabolic activation has been associated with an alkaline pH{sub i} shift in other organisms, in vivo {sup 31}P NMR analysis of recovering dauer larvae shows a pH{sub i} decrease from {approximately}7.3 to {approximately}6.3 within 3 hr after the animals encounter food. This shift occurs before feeding begins, and coincides with, or soon follows, the development commitment to recover from the dauer stage, suggesting that control of pH{sub i} may be important in the regulation of larval development in nematodes. A library enriched for sequences expressed specifically during the L2d (predauer) stage was made by selecting plaques from a genomic lambda library that hybridized to subtracted L2d cDNA probes. Ultimately, three clones that were shown to hybridize only to L2d RNA were selected.« less

The dauer hypothesis and the evolution of parasitism: 20 years on and still going strong

PubMed Central

Crook, Matt

2013-01-01

How any complex trait has evolved is a fascinating question, yet the evolution of parasitism among the nematodes is arguably one of the most arresting. How did free-living nematodes cross that seemingly insurmountable evolutionary chasm between soil dwelling and survival inside another organism? Which of the many finely honed responses to the varied and harsh environments of free-living nematodes provided the material upon which natural selection could act? Although several complementary theories explain this phenomenon, I will focus on the dauer hypothesis. The dauer hypothesis posits that the arrested third-stage dauer larvae of free-living nematodes such as Caenorhabditis elegans are, due to their many physiological similarities with infective third-stage larvae of parasitic nematodes, a pre-adaptation to parasitism. If so, then a logical extension of this hypothesis is that the molecular pathways which control entry into and recovery from dauer formation by free-living nematodes in response to environmental cues have been co-opted to control the processes of infective larval arrest and activation in parasitic nematodes. The molecular machinery that controls dauer entry and exit is present in a wide range of parasitic nematodes. However, the developmental outputs of the different pathways are both conserved and divergent, not only between populations of C. elegans or between C. elegans and parasitic nematodes but also between different species of parasitic nematodes. Thus the picture that emerges is more nuanced than originally predicted and may provide insights into the evolution of such an interesting and complex trait. PMID:24095839

Contribution of the Peroxisomal acox Gene to the Dynamic Balance of Daumone Production in Caenorhabditis elegans*

PubMed Central

Joo, Hyoe-Jin; Kim, Kwang-Youl; Yim, Yong-Hyeon; Jin, You-Xun; Kim, Heekyeong; Kim, Mun-Young; Paik, Young-Ki

2010-01-01

Dauer pheromones or daumones, which are signaling molecules that interrupt development and reproduction (dauer larvae) during unfavorable growth conditions, are essential for cellular homeostasis in Caenorhabditis elegans. According to earlier studies, dauer larva formation in strain N2 is enhanced by a temperature increase, suggesting the involvement of a temperature-dependent component in dauer pheromone biosynthesis or sensing. Several naturally occurring daumone analogs (e.g. daumones 1–3) have been identified, and these molecules are predicted to be synthesized in different physiological settings in this nematode. To elucidate the molecular regulatory system that may influence the dynamic balance of specific daumone production in response to sudden temperature changes, we characterized the peroxisomal acox gene encoding acyl-CoA oxidase, which is predicted to catalyze the first reaction during biosynthesis of the fatty acid component of daumones. Using acox-1(ok2257) mutants and a new, robust analytical method, we quantified the three most abundant daumones in worm bodies and showed that acox likely contributes to the dynamic production of various quantities of three different daumones in response to temperature increase, changes that are critical in C. elegans for coping with the natural environmental changes it faces. PMID:20610393

The Orphan Gene dauerless Regulates Dauer Development and Intraspecific Competition in Nematodes by Copy Number Variation

PubMed Central

Mayer, Melanie G.; Rödelsperger, Christian; Witte, Hanh; Riebesell, Metta; Sommer, Ralf J.

2015-01-01

Many nematodes form dauer larvae when exposed to unfavorable conditions, representing an example of phenotypic plasticity and a major survival and dispersal strategy. In Caenorhabditis elegans, the regulation of dauer induction is a model for pheromone, insulin, and steroid-hormone signaling. Recent studies in Pristionchus pacificus revealed substantial natural variation in various aspects of dauer development, i.e. pheromone production and sensing and dauer longevity and fitness. One intriguing example is a strain from Ohio, having extremely long-lived dauers associated with very high fitness and often forming the most dauers in response to other strains´ pheromones, including the reference strain from California. While such examples have been suggested to represent intraspecific competition among strains, the molecular mechanisms underlying these dauer-associated patterns are currently unknown. We generated recombinant-inbred-lines between the Californian and Ohioan strains and used quantitative-trait-loci analysis to investigate the molecular mechanism determining natural variation in dauer development. Surprisingly, we discovered that the orphan gene dauerless controls dauer formation by copy number variation. The Ohioan strain has one dauerless copy causing high dauer formation, whereas the Californian strain has two copies, resulting in strongly reduced dauer formation. Transgenic animals expressing multiple copies do not form dauers. dauerless is exclusively expressed in CAN neurons, and both CAN ablation and dauerless mutations increase dauer formation. Strikingly, dauerless underwent several duplications and acts in parallel or downstream of steroid-hormone signaling but upstream of the nuclear-hormone-receptor daf-12. We identified the novel or fast-evolving gene dauerless as inhibitor of dauer development. Our findings reveal the importance of gene duplications and copy number variations for orphan gene function and suggest daf-12 as major target for dauer regulation. We discuss the consequences of the novel vs. fast-evolving nature of orphans for the evolution of developmental networks and their role in natural variation and intraspecific competition. PMID:26087034

The Orphan Gene dauerless Regulates Dauer Development and Intraspecific Competition in Nematodes by Copy Number Variation.

PubMed

Mayer, Melanie G; Rödelsperger, Christian; Witte, Hanh; Riebesell, Metta; Sommer, Ralf J

2015-06-01

Many nematodes form dauer larvae when exposed to unfavorable conditions, representing an example of phenotypic plasticity and a major survival and dispersal strategy. In Caenorhabditis elegans, the regulation of dauer induction is a model for pheromone, insulin, and steroid-hormone signaling. Recent studies in Pristionchus pacificus revealed substantial natural variation in various aspects of dauer development, i.e. pheromone production and sensing and dauer longevity and fitness. One intriguing example is a strain from Ohio, having extremely long-lived dauers associated with very high fitness and often forming the most dauers in response to other strains' pheromones, including the reference strain from California. While such examples have been suggested to represent intraspecific competition among strains, the molecular mechanisms underlying these dauer-associated patterns are currently unknown. We generated recombinant-inbred-lines between the Californian and Ohioan strains and used quantitative-trait-loci analysis to investigate the molecular mechanism determining natural variation in dauer development. Surprisingly, we discovered that the orphan gene dauerless controls dauer formation by copy number variation. The Ohioan strain has one dauerless copy causing high dauer formation, whereas the Californian strain has two copies, resulting in strongly reduced dauer formation. Transgenic animals expressing multiple copies do not form dauers. dauerless is exclusively expressed in CAN neurons, and both CAN ablation and dauerless mutations increase dauer formation. Strikingly, dauerless underwent several duplications and acts in parallel or downstream of steroid-hormone signaling but upstream of the nuclear-hormone-receptor daf-12. We identified the novel or fast-evolving gene dauerless as inhibitor of dauer development. Our findings reveal the importance of gene duplications and copy number variations for orphan gene function and suggest daf-12 as major target for dauer regulation. We discuss the consequences of the novel vs. fast-evolving nature of orphans for the evolution of developmental networks and their role in natural variation and intraspecific competition.

The dauer hypothesis and the evolution of parasitism: 20 years on and still going strong.

PubMed

Crook, Matt

2014-01-01

How any complex trait has evolved is a fascinating question, yet the evolution of parasitism among the nematodes is arguably one of the most arresting. How did free-living nematodes cross that seemingly insurmountable evolutionary chasm between soil dwelling and survival inside another organism? Which of the many finely honed responses to the varied and harsh environments of free-living nematodes provided the material upon which natural selection could act? Although several complementary theories explain this phenomenon, I will focus on the dauer hypothesis. The dauer hypothesis posits that the arrested third-stage dauer larvae of free-living nematodes such as Caenorhabditis elegans are, due to their many physiological similarities with infective third-stage larvae of parasitic nematodes, a pre-adaptation to parasitism. If so, then a logical extension of this hypothesis is that the molecular pathways which control entry into and recovery from dauer formation by free-living nematodes in response to environmental cues have been co-opted to control the processes of infective larval arrest and activation in parasitic nematodes. The molecular machinery that controls dauer entry and exit is present in a wide range of parasitic nematodes. However, the developmental outputs of the different pathways are both conserved and divergent, not only between populations of C. elegans or between C. elegans and parasitic nematodes but also between different species of parasitic nematodes. Thus the picture that emerges is more nuanced than originally predicted and may provide insights into the evolution of such an interesting and complex trait. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Population dynamics and habitat sharing of natural populations of Caenorhabditis elegans and C. briggsae

PubMed Central

2012-01-01

Background The nematode Caenorhabditis elegans is a major model organism in laboratory biology. Very little is known, however, about its ecology, including where it proliferates. In the past, C. elegans was mainly isolated from human-made compost heaps, where it was overwhelmingly found in the non-feeding dauer diapause stage. Results C. elegans and C. briggsae were found in large, proliferating populations in rotting plant material (fruits and stems) in several locations in mainland France. Both species were found to co-occur in samples isolated from a given plant species. Population counts spanned a range from one to more than 10,000 Caenorhabditis individuals on a single fruit or stem. Some populations with an intermediate census size (10 to 1,000) contained no dauer larvae at all, whereas larger populations always included some larvae in the pre-dauer or dauer stages. We report on associated micro-organisms, including pathogens. We systematically sampled a spatio-temporally structured set of rotting apples in an apple orchard in Orsay over four years. C. elegans and C. briggsae were abundantly found every year, but their temporal distributions did not coincide. C. briggsae was found alone in summer, whereas both species co-occurred in early fall and C. elegans was found alone in late fall. Competition experiments in the laboratory at different temperatures show that C. briggsae out-competes C. elegans at high temperatures, whereas C. elegans out-competes C. briggsae at lower temperatures. Conclusions C. elegans and C. briggsae proliferate in the same rotting vegetal substrates. In contrast to previous surveys of populations in compost heaps, we found fully proliferating populations with no dauer larvae. The temporal sharing of the habitat by the two species coincides with their temperature preference in the laboratory, with C. briggsae populations growing faster than C. elegans at higher temperatures, and vice at lower temperatures. PMID:22731941

C. elegans anaplastic lymphoma kinase ortholog SCD-2 controls dauer formation by modulating TGF-beta signaling.

PubMed

Reiner, David J; Ailion, Michael; Thomas, James H; Meyer, Barbara J

2008-08-05

Different environmental stimuli, including exposure to dauer pheromone, food deprivation, and high temperature, can induce C. elegans larvae to enter the dauer stage, a developmentally arrested diapause state. Although molecular and cellular pathways responsible for detecting dauer pheromone and temperature have been defined in part, other sensory inputs are poorly understood, as are the mechanisms by which these diverse sensory inputs are integrated to achieve a consistent developmental outcome. In this paper, we analyze a wild C. elegans strain isolated from a desert oasis. Unlike wild-type laboratory strains, the desert strain fails to respond to dauer pheromone at 25 degrees C, but it does respond at higher temperatures, suggesting a unique adaptation to the hot desert environment. We map this defect in dauer response to a mutation in the scd-2 gene, which, we show, encodes the nematode anaplastic lymphoma kinase (ALK) homolog, a proto-oncogene receptor tyrosine kinase. scd-2 acts in a genetic pathway shown here to include the HEN-1 ligand, the RTK adaptor SOC-1, and the MAP kinase SMA-5. The SCD-2 pathway modulates TGF-beta signaling, which mediates the response to dauer pheromone, but SCD-2 might mediate a nonpheromone sensory input, such as food. Our studies identify a new sensory pathway controlling dauer formation and shed light on ALK signaling, integration of signaling pathways, and adaptation to extreme environmental conditions.

A wax ester promotes collective host finding in the nematode Pristionchus pacificus.

PubMed

Penkov, Sider; Ogawa, Akira; Schmidt, Ulrike; Tate, Dhananjay; Zagoriy, Vyacheslav; Boland, Sebastian; Gruner, Margit; Vorkel, Daniela; Verbavatz, Jean-Marc; Sommer, Ralf J; Knölker, Hans-Joachim; Kurzchalia, Teymuras V

2014-04-01

Survival of nematode species depends on how successfully they disperse in the habitat and find a new host. As a new strategy for collective host finding in the nematode Pristionchus pacificus, dauer larvae synthesize an extremely long-chain polyunsaturated wax ester (nematoil) that covers the surface of the animal. The oily coat promotes congregation of up to one thousand individuals into stable 'dauer towers' that can reach a beetle host more easily.

Developmental plasticity and the evolution of parasitism in an unusual nematode, Parastrongyloides trichosuri.

PubMed

Stasiuk, Susan J; Scott, Maxwell J; Grant, Warwick N

2012-01-03

Parasitism is an important life history strategy in many metazoan taxa. This is particularly true of the Phylum Nematoda, in which parasitism has evolved independently at least nine times. The apparent ease with which parasitism has evolved amongst nematodes may, in part, be due to a feature of nematode development acting as a pre-adaptation for the transition from a free-living to a parasitic life history. One candidate pre-adaptive feature for evolution in terrestrial nematodes is the dauer larva, a developmentally arrested morph formed in response to environmental signals. We investigated the role of dauer development in the nematode, Parastrongyloides trichosuri, which has retained a complete free-living life cycle in addition to a life cycle as a mammalian gastrointestinal parasite. We show that the developmental switch between these life histories is sensitive to the same environmental cues as dauer arrest in free-living nematodes, including sensitivity to a chemical cue produced by the free-living stages. Furthermore, we show that genetic variation for the sensitivity of the cue(s) exists in natural populations of P. trichosuri, such that we derived inbred lines that were largely insensitive to the cue and other lines that were supersensitive to the cue. For this parasitic clade, and perhaps more widely in the phylum, the evolution of parasitism co-opted the dauer switch of a free-living ancestor. This lends direct support to the hypothesis that the switch to developmental arrest in the dauer larva acted as a pre-adaptation for the evolution of parasitism, and suggests that the sensory transduction machinery downstream of the cue may have been similarly co-opted and modified.

Developmental plasticity and the evolution of parasitism in an unusual nematode, Parastrongyloides trichosuri

PubMed Central

2012-01-01

Background Parasitism is an important life history strategy in many metazoan taxa. This is particularly true of the Phylum Nematoda, in which parasitism has evolved independently at least nine times. The apparent ease with which parasitism has evolved amongst nematodes may, in part, be due to a feature of nematode development acting as a pre-adaptation for the transition from a free-living to a parasitic life history. One candidate pre-adaptive feature for evolution in terrestrial nematodes is the dauer larva, a developmentally arrested morph formed in response to environmental signals. Results We investigated the role of dauer development in the nematode, Parastrongyloides trichosuri, which has retained a complete free-living life cycle in addition to a life cycle as a mammalian gastrointestinal parasite. We show that the developmental switch between these life histories is sensitive to the same environmental cues as dauer arrest in free-living nematodes, including sensitivity to a chemical cue produced by the free-living stages. Furthermore, we show that genetic variation for the sensitivity of the cue(s) exists in natural populations of P. trichosuri, such that we derived inbred lines that were largely insensitive to the cue and other lines that were supersensitive to the cue. Conclusions For this parasitic clade, and perhaps more widely in the phylum, the evolution of parasitism co-opted the dauer switch of a free-living ancestor. This lends direct support to the hypothesis that the switch to developmental arrest in the dauer larva acted as a pre-adaptation for the evolution of parasitism, and suggests that the sensory transduction machinery downstream of the cue may have been similarly co-opted and modified. PMID:22214222

Quantitative assessment of the nematode fauna present on Geotrupes dung beetles reveals species-rich communities with a heterogeneous distribution.

PubMed

Weller, Andreas M; Mayer, Werner E; Rae, Robbie; Sommer, Ralf J

2010-06-01

Pristionchus spp. nematodes exhibit several traits that might serve as pre-adaptations to parasitism. Under harsh environmental conditions, these nematodes can arrest development and form dauer larvae. In addition, they have been shown to live in necromenic association with a range of beetles, including dung beetles ( Geotrupes stercorosus ) on which, for example, Pristionchus entomophagus is commonly found. It has been argued that the formation of dauer larvae and the association with invertebrates represent intermediate steps towards parasitism. To better understand necromenic associations, and to gain information on Pristionchus spp. abundance and the general species composition on dung beetles, we extracted all the nematode fauna present on 114 individuals of G. stercorosus. By direct sequencing using the 18S SSU, we provide a barcode for all nematodes isolated from the beetle samples. In total, 5,002 dauer-stage nematodes were sequenced, which included Pristionchus spp., Koerneria spp. (Diplogastridae), Pelodera spp. (Rhabditidae), and Strongyloidea as well as Spirurida. Intensities of infection varied from over 1,000 nematodes isolated from a single G. stercorosus to none, with Pelodera spp. being the most abundant group isolated. This study presents the first quantitative data on the Pristionchus spp. infection of beetles.

Dauer-specific dendrite arborization in C. elegans is regulated by KPC-1/Furin.

PubMed

Schroeder, Nathan E; Androwski, Rebecca J; Rashid, Alina; Lee, Harksun; Lee, Junho; Barr, Maureen M

2013-08-19

Dendrites often display remarkably complex and diverse morphologies that are influenced by developmental and environmental cues. Neuroplasticity in response to adverse environmental conditions entails both hypertrophy and resorption of dendrites. How dendrites rapidly alter morphology in response to unfavorable environmental conditions is unclear. The nematode Caenorhabditis elegans enters into a stress-resistant dauer larval stage in response to an adverse environment. Here we show that the IL2 bipolar sensory neurons undergo dendrite arborization and axon remodeling during dauer development. When dauer larvae are returned to favorable environmental conditions, animals resume reproductive development and IL2 dendritic branches retract, leaving behind remnant branches in postdauer L4 and adult animals. The C. elegans furin homolog KPC-1 is required for dauer IL2 dendritic arborization and dauer-specific nictation behavior. KPC-1 is also necessary for dendritic arborization of PVD and FLP sensory neurons. In mammals, furin is essential, ubiquitously expressed, and associated with numerous pathologies, including neurodegenerative diseases. While broadly expressed in C. elegans neurons and epithelia, KPC-1 acts cell autonomously in IL2 neurons to regulate dauer-specific dendritic arborization and nictation. Neuroplasticity of the C. elegans IL2 sensory neurons provides a paradigm to study stress-induced and reversible dendritic branching, and the role of environmental and developmental cues in this process. The newly discovered role of KPC-1 in dendrite morphogenesis provides insight into the function of proprotein convertases in nervous system development. Copyright © 2013 Elsevier Ltd. All rights reserved.

A C. elegans mutant that lives twice as long as wild type.

PubMed

Kenyon, C; Chang, J; Gensch, E; Rudner, A; Tabtiang, R

1993-12-02

We have found that mutations in the gene daf-2 can cause fertile, active, adult Caenorhabditis elegans hermaphrodites to live more than twice as long as wild type. This lifespan extension, the largest yet reported in any organism, requires the activity of a second gene, daf-16. Both genes also regulate formation of the dauer larva, a developmentally arrested larval form that is induced by crowding and starvation and is very long-lived. Our findings raise the possibility that the longevity of the dauer is not simply a consequence of its arrested growth, but instead results from a regulated lifespan extension mechanism that can be uncoupled from other aspects of dauer formation. daf-2 and daf-16 provide entry points into understanding how lifespan can be extended.

Regulation of a hitchhiking behavior by neuronal insulin and TGF-β signaling in the nematode Caenorhabditis elegans.

PubMed

Lee, Daehan; Lee, Harksun; Kim, Nari; Lim, Daisy S; Lee, Junho

2017-03-04

Free-living nematode Caenorhabditis elegans exhibits various behaviors to adapt to the fluctuating environment. When early larvae of C. elegans experience the harsh environmental condition, they develop to an alternative developmental stage called dauer, which shows nictation, a stage-specific waving behavior. Nictation enables dauers to attach to more mobile animals, which helps them disperse to other habitats beyond physical barriers. However, underlying molecular mechanisms that regulate nictation behavior are largely unknown. In this study, we show that insulin signaling and transforming growth beta (TGF-β) signaling, the two major parallel signaling pathways that mediate dauer development, are involved in the regulation of dauer-specific nictation behavior. Genetic analysis revealed that downregulation of insulin signaling enhanced nictation behavior. Heat-shock induced rescue experiments showed that the action period of the insulin signaling is before dauer formation. Surprisingly, lowering of TGF-β signaling inhibited the normal performance of nictation, suggesting that TGF-β signaling acts in an opposite way from that for dauer formation. Cell-specific rescue experiments revealed that two signaling pathways act in the nervous system and an epistasis experiment showed that TGF-β signaling is epistatic to insulin signaling. Taken together, we propose that the neuroendocrinal insulin signaling and TGF-β signaling regulate nictation behavior during development in response to environmental conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

The unfolded protein response in a pair of sensory neurons promotes entry of C. elegans into dauer diapause.

PubMed

Kulalert, Warakorn; Kim, Dennis H

2013-12-16

In response to unfavorable environmental conditions such as starvation, crowding, and elevated temperature, Caenorhabditis elegans larvae enter an alternative developmental stage known as dauer, which is characterized by adaptive changes in stress resistance and metabolism. The genetic dissection of the molecular mechanisms of the C. elegans dauer developmental decision has defined evolutionarily conserved signaling pathways of organismal neuroendocrine physiology. Here, we have identified a mechanism by which a dominant mutation in a neuronal insulin gene, daf-28(sa191), causes constitutive entry into dauer diapause. We demonstrate that expression of the mutant DAF-28 insulin peptide results in endoplasmic reticulum (ER) stress in the ASI pair of chemosensory neurons. The neuronal ER stress does not compromise cellular survival but activates PEK-1, the C. elegans ortholog of the mammalian eIF2α kinase PERK, which in turn phosphorylates Ser49 of eIF2α, specifically in the ASI neuron pair, to promote entry into dauer diapause. Our data establish a novel role for ER stress and the unfolded protein response (UPR) in promoting entry into dauer diapause and suggest that, in addition to cell-autonomous activities in the maintenance of ER homeostasis, the UPR may act in a non-cell-autonomous manner to promote organismal adaptation to stress during larval development. Copyright © 2013 Elsevier Ltd. All rights reserved.

The C. elegans dauer larva as a paradigm to study metabolic suppression and desiccation tolerance.

PubMed

Erkut, Cihan; Kurzchalia, Teymuras V

2015-08-01

The hypometabolic, stress-resistant dauer larva of Caenorhabditis elegans serves as an excellent model to study the molecular mechanisms of desiccation tolerance, such as maintenance of membrane organization, protein folding, xenobiotic and ROS detoxification in the dry state. Many organisms from diverse taxa of life have the remarkable ability to survive extreme desiccation in the nature by entering an ametabolic state known as anhydrobiosis (life without water). The hallmark of the anhydrobiotic state is the achievement and maintenance of an exceedingly low metabolic rate, as well as preservation of the structural integrity of the cell. Although described more than three centuries ago, the biochemical and biophysical mechanisms underlying this phenomenon are still not fully comprehended. This is mainly due to the fact that anhydrobiosis in animals was studied using non-model organisms, which are very difficult, if not impossible, to manipulate at the molecular level. Recently, we introduced the roundworm (nematode) Caenorhabditis elegans as a model for anhydrobiosis. Taking advantage of powerful genetic, biochemical and biophysical tools, we investigated several aspects of anhydrobiosis in a particular developmental stage (the dauer larva) of this organism. First, our studies allowed confirming the previously suggested role of the disaccharide trehalose in the preservation of lipid membranes. Moreover, in addition to known pathways such as reactive oxygen species defense, heat-shock and intrinsically disordered protein expression, evidence for some novel strategies of anhydrobiosis has been obtained. These are increased glyoxalase activity, polyamine and polyunsaturated fatty acid biosynthesis. All these pathways may constitute a generic toolbox of anhydrobiosis, which is possibly conserved between animals and plants.

Interspecific nematode signals regulate dispersal behavior

USDA-ARS?s Scientific Manuscript database

Dispersal is an important nematode behavior. Upon crowding or food depletion, the free living bacteriovorus nematode Caenorhabditis elegans produces stress resistant dispersal larvae, called dauer, which are analogous to second stage juveniles (J2) of plant parasitic Meloidogyne spp. and infective ...

Divergent evolution of arrested development in the dauer stage of Caenorhabditis elegans and the infective stage of Heterodera glycines

PubMed Central

Elling, Axel A; Mitreva, Makedonka; Recknor, Justin; Gai, Xiaowu; Martin, John; Maier, Thomas R; McDermott, Jeffrey P; Hewezi, Tarek; McK Bird, David; Davis, Eric L; Hussey, Richard S; Nettleton, Dan; McCarter, James P; Baum, Thomas J

2007-01-01

Background The soybean cyst nematode Heterodera glycines is the most important parasite in soybean production worldwide. A comprehensive analysis of large-scale gene expression changes throughout the development of plant-parasitic nematodes has been lacking to date. Results We report an extensive genomic analysis of H. glycines, beginning with the generation of 20,100 expressed sequence tags (ESTs). In-depth analysis of these ESTs plus approximately 1,900 previously published sequences predicted 6,860 unique H. glycines genes and allowed a classification by function using InterProScan. Expression profiling of all 6,860 genes throughout the H. glycines life cycle was undertaken using the Affymetrix Soybean Genome Array GeneChip. Our data sets and results represent a comprehensive resource for molecular studies of H. glycines. Demonstrating the power of this resource, we were able to address whether arrested development in the Caenorhabditis elegans dauer larva and the H. glycines infective second-stage juvenile (J2) exhibits shared gene expression profiles. We determined that the gene expression profiles associated with the C. elegans dauer pathway are not uniformly conserved in H. glycines and that the expression profiles of genes for metabolic enzymes of C. elegans dauer larvae and H. glycines infective J2 are dissimilar. Conclusion Our results indicate that hallmark gene expression patterns and metabolism features are not shared in the developmentally arrested life stages of C. elegans and H. glycines, suggesting that developmental arrest in these two nematode species has undergone more divergent evolution than previously thought and pointing to the need for detailed genomic analyses of individual parasite species. PMID:17919324

The glyoxylate shunt is essential for desiccation tolerance in C. elegans and budding yeast

PubMed Central

Erkut, Cihan; Gade, Vamshidhar R; Laxman, Sunil; Kurzchalia, Teymuras V

2016-01-01

Many organisms, including species from all kingdoms of life, can survive desiccation by entering a state with no detectable metabolism. To survive, C. elegans dauer larvae and stationary phase S. cerevisiae require elevated amounts of the disaccharide trehalose. We found that dauer larvae and stationary phase yeast switched into a gluconeogenic mode in which metabolism was reoriented toward production of sugars from non-carbohydrate sources. This mode depended on full activity of the glyoxylate shunt (GS), which enables synthesis of trehalose from acetate. The GS was especially critical during preparation of worms for harsh desiccation (preconditioning) and during the entry of yeast into stationary phase. Loss of the GS dramatically decreased desiccation tolerance in both organisms. Our results reveal a novel physiological role for the GS and elucidate a conserved metabolic rewiring that confers desiccation tolerance on organisms as diverse as worm and yeast. DOI: http://dx.doi.org/10.7554/eLife.13614.001 PMID:27090086

Single and compound effects of radiation and microgravity responses in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Wang, Wei; Sun, Yeqing; Xu, Dan; Yang, Jun; Luo, Yajing

2016-07-01

Space radiation and microgravity are main factors of spaceflight which could cause effects on organism. However, studies on the combined effects of microgravity and radiation have had conflicting results. For further elucidate the single factor effects of radiation or microgravity and the compound factor effects of them, the wild-type strain (Bristol N2) and muscle repair defective strain (dys-1) of Caenorhabditis elegansin dauer larvae were treated by ground simulated radiation in different doses (0.2Gy,2Gy) and/or 16.5-day simulated microgravity. The locomotory capacity assay and proteomic analysis were processed after the recovery of dauer larvae to adult. Locomotory capacity assay showed that the N2 nematodes were susceptible to simulated microgravity while dys-1 nematodes were susceptible to simulation radiation especially in high dose radiation (2Gy). The compound factor of microgravity and radiation has different influences to different strains. Proteomic results indicated that a wide range but different biological processes were involved in responding to radiation and/or microgravity.

Density-based regulation of ascr#2 and ascr#4 expression in Caenorhabditis elegans

USDA-ARS?s Scientific Manuscript database

The ascarosides are a family of nematode small molecules, many of which induce formation of long-lived and highly stress resistant dauer larvae. More recent studies have shown that ascarosides serve additional functions as social signals and mating pheromones. For example, the male attracting pherom...

Synthetic Ligands of Cannabinoid Receptors Affect Dauer Formation in the Nematode Caenorhabditis elegans.

PubMed

Reis Rodrigues, Pedro; Kaul, Tiffany K; Ho, Jo-Hao; Lucanic, Mark; Burkewitz, Kristopher; Mair, William B; Held, Jason M; Bohn, Laura M; Gill, Matthew S

2016-06-01

Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound. Similarly, loss of function mutations in the energy-sensing AMP-activated kinase subunit, aak-2, enhanced the dauer-suppressing effects of AM251, while constitutive activation of aak-2 in neurons was sufficient to inhibit AM251 activity. Chemical epistasis experiments indicated that AM251 acts via G-protein signaling and requires the TGF-β ligand DAF-7, the insulin peptides DAF-28 and INS-6, and a functional ASI neuron to promote reproductive growth. AM251 also required the presence of the SER-5 serotonin receptor, but in vitro experiments suggest that this may not be via a direct interaction. Interestingly, we found that other antagonists of mammalian CB receptors also suppress dauer entry, while the nonselective CB receptor agonist, O-2545, not only inhibited the activity of AM251, but also was able to promote dauer entry when administered alone. Since worms do not have obvious orthologs of CB receptors, the effects of synthetic CBs on neuroendocrine signaling in C. elegans are likely to be mediated via another, as yet unknown, receptor mechanism. However, we cannot exclude the existence of a noncanonical CB receptor in C. elegans. Copyright © 2016 Rodrigues et al.

Angiostrongylus cantonensis daf-2 regulates dauer, longevity and stress in Caenorhabditis elegans.

PubMed

Yan, Baolong; Sun, Weiwei; Shi, Xiaomeng; Huang, Liyang; Chen, Lingzi; Wang, Suhua; Yan, Lanzhu; Liang, Shaohui; Huang, Huicong

2017-06-15

The insulin-like signaling (IIS) pathway is considered to be significant in regulating fat metabolism, dauer formation, stress response and longevity in Caenorhabditis elegans. "Dauer hypothesis" indicates that similar IIS transduction mechanism regulates dauer development in free-living nematode C. elegans and the development of infective third-stage larvae (iL3) in parasitic nematodes, and this is bolstered by a few researches on structures and functions of the homologous genes in the IIS pathway cloned from several parasitic nematodes. In this study, we identified the insulin-like receptor encoding gene, Acan-daf-2, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. The sequence of Acan-DAF-2, consisting of 1413 amino acids, contained all of the characteristic domains of insulin-like receptors from other taxa. The expression patterns of Acan-daf-2 in the C. elegans surrogate system showed that pAcan-daf-2:gfp was only expressed in intestine, compared with the orthologue in C. elegans, Ce-daf-2 in both intestine and neurons. In addition to the similar genomic organization to Ce-daf-2, Acan-DAF-2 could also negatively regulate Ce-DAF-16A through nuclear/cytosolic translocation and partially restore the C. elegans daf-2(e1370) mutation in longevity, dauer formation and stress resistance. These findings provided further evidence of the functional conservation of DAF-2 between parasitic nematodes and the free-living nematode C. elegans, and might be significant in understanding the developmental biology of nematode parasites, particularly in the infective process and the host-specificity. Copyright © 2017. Published by Elsevier B.V.

Synthetic Ligands of Cannabinoid Receptors Affect Dauer Formation in the Nematode Caenorhabditis elegans

PubMed Central

Reis Rodrigues, Pedro; Kaul, Tiffany K.; Ho, Jo-Hao; Lucanic, Mark; Burkewitz, Kristopher; Mair, William B.; Held, Jason M.; Bohn, Laura M.; Gill, Matthew S.

2016-01-01

Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound. Similarly, loss of function mutations in the energy-sensing AMP-activated kinase subunit, aak-2, enhanced the dauer-suppressing effects of AM251, while constitutive activation of aak-2 in neurons was sufficient to inhibit AM251 activity. Chemical epistasis experiments indicated that AM251 acts via G-protein signaling and requires the TGF-β ligand DAF-7, the insulin peptides DAF-28 and INS-6, and a functional ASI neuron to promote reproductive growth. AM251 also required the presence of the SER-5 serotonin receptor, but in vitro experiments suggest that this may not be via a direct interaction. Interestingly, we found that other antagonists of mammalian CB receptors also suppress dauer entry, while the nonselective CB receptor agonist, O-2545, not only inhibited the activity of AM251, but also was able to promote dauer entry when administered alone. Since worms do not have obvious orthologs of CB receptors, the effects of synthetic CBs on neuroendocrine signaling in C. elegans are likely to be mediated via another, as yet unknown, receptor mechanism. However, we cannot exclude the existence of a noncanonical CB receptor in C. elegans. PMID:27172180

Nematode orphan genes are adopted by conserved regulatory networks and find a home in ecology.

PubMed

Mayer, Melanie G; Sommer, Ralf J

2015-01-01

Nematode dauer formation represents an essential survival and dispersal strategy and is one of a few ecologically relevant traits that can be studied in laboratory approaches. Under harsh environmental conditions, the nematode model organisms Caenorhabditis elegans and Pristionchus pacificus arrest their development and induce the formation of stress-resistant dauer larvae in response to dauer pheromones, representing a key example of phenotypic plasticity. Previous studies have indicated that in P. pacificus, many wild isolates show cross-preference of dauer pheromones and compete for access to a limited food source. When investigating the genetic mechanisms underlying this intraspecific competition, we recently discovered that the orphan gene dauerless (dau-1) controls dauer formation by copy number variation. Our results show that dau-1 acts in parallel to or downstream of steroid hormone signaling but upstream of the nuclear hormone receptor daf-12, suggesting that DAU-1 represents a novel inhibitor of DAF-12. Phylogenetic analysis reveals that the observed copy number variation is part of a complex series of gene duplication events that occurred over short evolutionary time scales. Here, we comment on the incorporation of novel or fast-evolving genes into conserved genetic networks as a common principle for the evolution of phenotypic plasticity and intraspecific competition. We discuss the possibility that orphan genes might often function in the regulation and execution of ecologically relevant traits. Given that only few ecological processes can be studied in model organisms, the function of such genes might often go unnoticed, explaining the large number of uncharacterized genes in model system genomes.

Quantitative Profiling Identifies Potential Regulatory Proteins Involved in Development from Dauer Stage to L4 Stage in Caenorhabditis elegans.

PubMed

Kim, Sunhee; Lee, Hyoung-Joo; Hahm, Jeong-Hoon; Jeong, Seul-Ki; Park, Don-Ha; Hancock, William S; Paik, Young-Ki

2016-02-05

When Caenorhabditis elegans encounters unfavorable growth conditions, it enters the dauer stage, an alternative L3 developmental period. A dauer larva resumes larval development to the normal L4 stage by uncharacterized postdauer reprogramming (PDR) when growth conditions become more favorable. During this transition period, certain heterochronic genes involved in controlling the proper sequence of developmental events are known to act, with their mutations suppressing the Muv (multivulva) phenotype in C. elegans. To identify the specific proteins in which the Muv phenotype is highly suppressed, quantitative proteomic analysis with iTRAQ labeling of samples obtained from worms at L1 + 30 h (for continuous development [CD]) and dauer recovery +3 h (for postdauer development [PD]) was carried out to detect changes in protein abundance in the CD and PD states of both N2 and lin-28(n719). Of the 1661 unique proteins identified with a < 1% false discovery rate at the peptide level, we selected 58 proteins exhibiting ≥2-fold up-regulation or ≥2-fold down-regulation in the PD state and analyzed the Gene Ontology terms. RNAi assays against 15 selected up-regulated genes showed that seven genes were predicted to be involved in higher Muv phenotype (p < 0.05) in lin-28(n791), which is not seen in N2. Specifically, two genes, K08H10.1 and W05H9.1, displayed not only the highest rate (%) of Muv phenotype in the RNAi assay but also the dauer-specific mRNA expression, indicating that these genes may be required for PDR, leading to the very early onset of dauer recovery. Thus, our proteomic approach identifies and quantitates the regulatory proteins potentially involved in PDR in C. elegans, which safeguards the overall lifecycle in response to environmental changes.

Functional Conservation and Divergence of daf-22 Paralogs in Pristionchus pacificus Dauer Development.

PubMed

Markov, Gabriel V; Meyer, Jan M; Panda, Oishika; Artyukhin, Alexander B; Claaßen, Marc; Witte, Hanh; Schroeder, Frank C; Sommer, Ralf J

2016-10-01

Small-molecule signaling in nematode dauer formation has emerged as a major model to study chemical communication in development and evolution. Developmental arrest as nonfeeding and stress-resistant dauer larvae represents the major survival and dispersal strategy. Detailed studies in Caenorhabditis elegans and Pristionchus pacificus revealed that small-molecule communication changes rapidly in evolution resulting in extreme structural diversity of small-molecule compounds. In C. elegans, a blend of ascarosides constitutes the dauer pheromone, whereas the P. pacificus dauer pheromone includes additional paratosides and integrates building blocks from diverse primary metabolic pathways. Despite this complexity of small-molecule structures and functions, little is known about the biosynthesis of small molecules in nematodes outside C. elegans Here, we show that the genes encoding enzymes of the peroxisomal β-oxidation pathway involved in small-molecule biosynthesis evolve rapidly, including gene duplications and domain switching. The thiolase daf-22, the most downstream factor in C. elegans peroxisomal β-oxidation, has duplicated in P. pacificus, resulting in Ppa-daf-22.1, which still contains the sterol-carrier-protein (SCP) domain that was lost in C. elegans daf-22, and Ppa-daf-22.2. Using the CRISPR/Cas9 system, we induced mutations in both P. pacificus daf-22 genes and identified an unexpected complexity of functional conservation and divergence. Under well-fed conditions, ascaroside biosynthesis proceeds exclusively via Ppa-daf-22.1 In contrast, starvation conditions induce Ppa-daf-22.2 activity, resulting in the production of a specific subset of ascarosides. Gene expression studies indicate a reciprocal up-regulation of both Ppa-daf-22 genes, which is, however, independent of starvation. Thus, our study reveals an unexpected functional complexity of dauer development and evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Molecular strategies of the Caenorhabditis elegans dauer larva to survive extreme desiccation.

PubMed

Erkut, Cihan; Vasilj, Andrej; Boland, Sebastian; Habermann, Bianca; Shevchenko, Andrej; Kurzchalia, Teymuras V

2013-01-01

Massive water loss is a serious challenge for terrestrial animals, which usually has fatal consequences. However, some organisms have developed means to survive this stress by entering an ametabolic state called anhydrobiosis. The molecular and cellular mechanisms underlying this phenomenon are poorly understood. We recently showed that Caenorhabditis elegans dauer larva, an arrested stage specialized for survival in adverse conditions, is resistant to severe desiccation. However, this requires a preconditioning step at a mild desiccative environment to prepare the organism for harsher desiccation conditions. A systems approach was used to identify factors that are activated during this preconditioning. Using microarray analysis, proteomics, and bioinformatics, genes, proteins, and biochemical pathways that are upregulated during this process were identified. These pathways were validated via reverse genetics by testing the desiccation tolerances of mutants. These data show that the desiccation response is activated by hygrosensation (sensing the desiccative environment) via head neurons. This leads to elimination of reactive oxygen species and xenobiotics, expression of heat shock and intrinsically disordered proteins, polyamine utilization, and induction of fatty acid desaturation pathway. Remarkably, this response is specific and involves a small number of functional pathways, which represent the generic toolkit for anhydrobiosis in plants and animals.

Molecular Strategies of the Caenorhabditis elegans Dauer Larva to Survive Extreme Desiccation

PubMed Central

Erkut, Cihan; Vasilj, Andrej; Boland, Sebastian; Habermann, Bianca; Shevchenko, Andrej; Kurzchalia, Teymuras V.

2013-01-01

Massive water loss is a serious challenge for terrestrial animals, which usually has fatal consequences. However, some organisms have developed means to survive this stress by entering an ametabolic state called anhydrobiosis. The molecular and cellular mechanisms underlying this phenomenon are poorly understood. We recently showed that Caenorhabditis elegans dauer larva, an arrested stage specialized for survival in adverse conditions, is resistant to severe desiccation. However, this requires a preconditioning step at a mild desiccative environment to prepare the organism for harsher desiccation conditions. A systems approach was used to identify factors that are activated during this preconditioning. Using microarray analysis, proteomics, and bioinformatics, genes, proteins, and biochemical pathways that are upregulated during this process were identified. These pathways were validated via reverse genetics by testing the desiccation tolerances of mutants. These data show that the desiccation response is activated by hygrosensation (sensing the desiccative environment) via head neurons. This leads to elimination of reactive oxygen species and xenobiotics, expression of heat shock and intrinsically disordered proteins, polyamine utilization, and induction of fatty acid desaturation pathway. Remarkably, this response is specific and involves a small number of functional pathways, which represent the generic toolkit for anhydrobiosis in plants and animals. PMID:24324795

Interspecific nematode signals regulate dispersal behavior.

PubMed

Kaplan, Fatma; Alborn, Hans T; von Reuss, Stephan H; Ajredini, Ramadan; Ali, Jared G; Akyazi, Faruk; Stelinski, Lukasz L; Edison, Arthur S; Schroeder, Frank C; Teal, Peter E

2012-01-01

Dispersal is an important nematode behavior. Upon crowding or food depletion, the free living bacteriovorus nematode Caenorhabditis elegans produces stress resistant dispersal larvae, called dauer, which are analogous to second stage juveniles (J2) of plant parasitic Meloidogyne spp. and infective juveniles (IJ)s of entomopathogenic nematodes (EPN), e.g., Steinernema feltiae. Regulation of dispersal behavior has not been thoroughly investigated for C. elegans or any other nematode species. Based on the fact that ascarosides regulate entry in dauer stage as well as multiple behaviors in C. elegans adults including mating, avoidance and aggregation, we hypothesized that ascarosides might also be involved in regulation of dispersal behavior in C. elegans and for other nematodes such as IJ of phylogenetically related EPNs. Liquid chromatography-mass spectrometry analysis of C. elegans dauer conditioned media, which shows strong dispersing activity, revealed four known ascarosides (ascr#2, ascr#3, ascr#8, icas#9). A synthetic blend of these ascarosides at physiologically relevant concentrations dispersed C. elegans dauer in the presence of food and also caused dispersion of IJs of S. feltiae and J2s of plant parasitic Meloidogyne spp. Assay guided fractionation revealed structural analogs as major active components of the S. feltiae (ascr#9) and C. elegans (ascr#2) dispersal blends. Further analysis revealed ascr#9 in all Steinernema spp. and Heterorhabditis spp. infected insect host cadavers. Ascaroside blends represent evolutionarily conserved, fundamentally important communication systems for nematodes from diverse habitats, and thus may provide sustainable means for control of parasitic nematodes.

Effects of associated bacteria on the pathogenicity and reproduction of the insect-parasitic nematode Rhabditis blumi (Nematoda: Rhabditida).

PubMed

Park, Hae Woong; Kim, Yong Ook; Ha, Jae-Seok; Youn, Sung Hun; Kim, Hyeong Hwan; Bilgrami, Anwar L; Shin, Chul Soo

2011-09-01

Three bacteria, Alcaligenes faecalis , Flavobacterium sp., and Providencia vermicola , were isolated from dauer juveniles of Rhabditis blumi . The pathogenic effects of the bacteria against 4th instar larvae of Galleria mellonella were investigated. Providencia vermicola and Flavobacterium sp. showed 100% mortality at 48 h after haemocoelic injection, whereas A. faecalis showed less than 30% mortality. Dauer juveniles showed 100% mortality against G. mellonella larvae, whereas axenic juveniles, which do not harbor associated bacteria, exhibited little mortality. All of the associated bacteria were used as a food source for nematode growth, and nematode yield differed with bacterial species. Among the bacterial species, P. vermicola was most valued for nematode yield, showing the highest yield of 5.2 × 10(4) nematodes/mL in the plate. In bacterial cocultures using two of the three associated bacteria, one kind stimulated the other. The highest total bacterial yield of 12.6 g/L was obtained when the inoculum ratio of P. vermicola to A. faecalis was 10:1. In air-lift bioreactors, the nematode growth rate increased with an increasing level of dissolved oxygen. The maximum nematode yield of 1.75 × 10(5) nematodes/mL was obtained at 192 h with an aeration rate of 6 vvm.

AMP-Activated Kinase Regulates Lipid Droplet Localization and Stability of Adipose Triglyceride Lipase in C. elegans Dauer Larvae.

PubMed

Xie, Meng; Roy, Richard

2015-01-01

Animals have developed diverse mechanisms to adapt to their changing environment. Like many organisms the free-living nematode C. elegans can alternate between a reproductive mode or a diapause-like "dauer" stage during larval development to circumvent harsh environmental conditions. The master metabolic regulator AMP-activated protein kinase (AMPK) is critical for survival during the dauer stage, where it phosphorylates adipose triglyceride lipase (ATGL-1) at multiple sites to block lipid hydrolysis and ultimately protect the cellular triglyceride-based energy depot from rapid depletion. However, how the AMPK-mediated phosphorylation affects the function of ATGL-1 has not been characterised at the molecular level. Here we show that AMPK phosphorylation leads to the generation of 14-3-3 binding sites on ATGL-1, which are recognized by the C. elegans 14-3-3 protein orthologue PAR-5. Physical interaction of ATGL-1 with PAR-5 results in sequestration of ATGL-1 away from the lipid droplets and eventual proteasome-mediated degradation. In addition, we also show that the major AMPK phosphorylation site on ATGL-1, Ser 303, is required for both modification of its lipid droplet localization and its degradation. Our data provide mechanistic insight as to how AMPK functions to enhance survival through its ability to protect the accumulated triglyceride deposits from rapid hydrolysis to preserve the energy stores during periods of extended environmental duress.

In vitro development of cyathostomin larvae from the third stage larvae to the fourth stage: morphologic characterization, effects of refrigeration, and species-specific patterns.

PubMed

Brianti, Emanuele; Giannetto, Salvatore; Traversa, Donato; Chirgwin, Sharon R; Shakya, Krishna; Klei, Thomas R

2009-08-26

A mixed population of equine cyathostomin (Nematoda, Strongyloidea) infective third stage larvae (L3) was cultured in vitro using a cell-free medium. Some L3 were cultured immediately after Baermann collection from fecal cultures, while others were kept in water at 4 degrees C for 7 days before initiating the in vitro cultures. Cultures were examined daily for viability. At days 2, 7, 14 and 21 larvae were collected for identification of developmental stage and morphological changes, using both light and scanning electron microscopy. Larvae were classified as early L3 (EL3), developing L3 (DL3), late L3 (LL3) and fourth stage larvae (L4) on the basis of morphological features. Viability remained high throughout the entire study period in cultures of both non-refrigerated (84.7%) and refrigerated (77.4%) larvae. However, viability of the non-refrigerated was significantly greater from 7 through 21 days of culture. Significant differences were also observed in the percentage of DL3 between the non-refrigerated and refrigerated larval cultures by day 7. The highest percentage of DL3 larvae (22.5%) was reached at the end of study in those larvae that were not previously refrigerated. The data suggests that prior refrigeration decreases viability and slows L3 development. At day 21 LL3 larvae were only a small percentage of the DL3: 6.9 and 5% in non-refrigerated and refrigerated cultures, respectively. Few of these larvae freed themselves from the L3 cuticle and moulted to L4 stage. Characteristics of individual species in vitro developmental patterns were determined by the molecular identification of individual larvae in pools of larvae randomly collected at days 0 and 21. Seven species (Coronocyclus coronatus, Cylicostephanus goldi, Cylicostephanus longibursatus, Cyathostomum catinatum, Cylicocyclus nassatus, Cylicocyclus ashworthi, Petrovinema poculatum) were identified in the day 0 pool. The greatest tendency to develop in vitro was shown by the genus Cylicostephanus with the species C. goldi and C. longibursatus that developed to the LL3-L4 stages. C. nassatus, C. ashworthi and C. coronatus did not progress in their development beyond the EL3 stage, while no apparent signs of development were registered for C. catinatum.

Exposure to the metabolic inhibitor sodium azide induces stress protein expression and thermotolerance in the nematode Caenorhabditis elegans

PubMed Central

Massie, Michelle R.; Lapoczka, Elizabeth M.; Boggs, Kristy D.; Stine, Karen E.; White, Glenn E.

2003-01-01

Historically, sodium azide has been used to anesthetize the nematode Caenorhabditis elegans; however, the mechanism by which it survives this exposure is not understood. In this study, we report that exposure of wild-type C elegans to 10 mM sodium azide for up to 90 minutes confers thermotolerance (defined as significantly increased survival probability [SP] at 37°C) on the animal. In addition, sodium dodecyl sulfate–polyacrylamide gel electrophoresis revealed enhanced Hsp70 expression, whereas Western blot analysis revealed the induction of Hsp16. We also tested the only known C elegans Hsp mutant daf-21 (codes for Hsp90), which constitutively enters the stress-resistant state known as the dauer larvae. Daf-21 mutants also acquire sodium azide–induced thermotolerance, whereas 3 non-Hsp, constitutive dauer-forming mutants exhibited a variable response to azide exposure. We conclude that the ability of C elegans to survive exposure to azide is associated with the induction of at least 2 stress proteins. PMID:12820649

Positive selection of Caenorhabditis elegans mutants with increased stress resistance and longevity.

PubMed Central

Muñoz, Manuel J; Riddle, Donald L

2003-01-01

We developed selective conditions for long-lived mutants of the nematode Caenorhabditis elegans by subjecting the first larval stage (L1) to thermal stress at 30 degrees for 7 days. The surviving larvae developed to fertile adults after the temperature was shifted to 15 degrees. A total of one million F(2) progeny and a half million F(3) progeny of ethyl-methanesulfonate-mutagenized animals were treated in three separate experiments. Among the 81 putative mutants that recovered and matured to the reproductive adult, 63 retested as thermotolerant and 49 (80%) exhibited a >15% increase in mean life span. All the known classes of dauer formation (Daf) mutant that affect longevity were found, including six new alleles of daf-2, and a unique temperature-sensitive, dauer-constitutive allele of age-1. Alleles of dyf-2 and unc-13 were isolated, and mutants of unc-18, a gene that interacts with unc-13, were also found to be long lived. Thirteen additional mutations define at least four new genes. PMID:12586705

RNAseq Analysis of the Parasitic Nematode Strongyloides stercoralis Reveals Divergent Regulation of Canonical Dauer Pathways

PubMed Central

Stoltzfus, Jonathan D.; Minot, Samuel; Berriman, Matthew; Nolan, Thomas J.; Lok, James B.

2012-01-01

The infectious form of many parasitic nematodes, which afflict over one billion people globally, is a developmentally arrested third-stage larva (L3i). The parasitic nematode Strongyloides stercoralis differs from other nematode species that infect humans, in that its life cycle includes both parasitic and free-living forms, which can be leveraged to investigate the mechanisms of L3i arrest and activation. The free-living nematode Caenorhabditis elegans has a similar developmentally arrested larval form, the dauer, whose formation is controlled by four pathways: cyclic GMP (cGMP) signaling, insulin/IGF-1-like signaling (IIS), transforming growth factor β (TGFβ) signaling, and biosynthesis of dafachronic acid (DA) ligands that regulate a nuclear hormone receptor. We hypothesized that homologous pathways are present in S. stercoralis, have similar developmental regulation, and are involved in L3i arrest and activation. To test this, we undertook a deep-sequencing study of the polyadenylated transcriptome, generating over 2.3 billion paired-end reads from seven developmental stages. We constructed developmental expression profiles for S. stercoralis homologs of C. elegans dauer genes identified by BLAST searches of the S. stercoralis genome as well as de novo assembled transcripts. Intriguingly, genes encoding cGMP pathway components were coordinately up-regulated in L3i. In comparison to C. elegans, S. stercoralis has a paucity of genes encoding IIS ligands, several of which have abundance profiles suggesting involvement in L3i development. We also identified seven S. stercoralis genes encoding homologs of the single C. elegans dauer regulatory TGFβ ligand, three of which are only expressed in L3i. Putative DA biosynthetic genes did not appear to be coordinately regulated in L3i development. Our data suggest that while dauer pathway genes are present in S. stercoralis and may play a role in L3i development, there are significant differences between the two species. Understanding the mechanisms governing L3i development may lead to novel treatment and control strategies. PMID:23145190

RNAseq analysis of the parasitic nematode Strongyloides stercoralis reveals divergent regulation of canonical dauer pathways.

PubMed

Stoltzfus, Jonathan D; Minot, Samuel; Berriman, Matthew; Nolan, Thomas J; Lok, James B

2012-01-01

The infectious form of many parasitic nematodes, which afflict over one billion people globally, is a developmentally arrested third-stage larva (L3i). The parasitic nematode Strongyloides stercoralis differs from other nematode species that infect humans, in that its life cycle includes both parasitic and free-living forms, which can be leveraged to investigate the mechanisms of L3i arrest and activation. The free-living nematode Caenorhabditis elegans has a similar developmentally arrested larval form, the dauer, whose formation is controlled by four pathways: cyclic GMP (cGMP) signaling, insulin/IGF-1-like signaling (IIS), transforming growth factor β (TGFβ) signaling, and biosynthesis of dafachronic acid (DA) ligands that regulate a nuclear hormone receptor. We hypothesized that homologous pathways are present in S. stercoralis, have similar developmental regulation, and are involved in L3i arrest and activation. To test this, we undertook a deep-sequencing study of the polyadenylated transcriptome, generating over 2.3 billion paired-end reads from seven developmental stages. We constructed developmental expression profiles for S. stercoralis homologs of C. elegans dauer genes identified by BLAST searches of the S. stercoralis genome as well as de novo assembled transcripts. Intriguingly, genes encoding cGMP pathway components were coordinately up-regulated in L3i. In comparison to C. elegans, S. stercoralis has a paucity of genes encoding IIS ligands, several of which have abundance profiles suggesting involvement in L3i development. We also identified seven S. stercoralis genes encoding homologs of the single C. elegans dauer regulatory TGFβ ligand, three of which are only expressed in L3i. Putative DA biosynthetic genes did not appear to be coordinately regulated in L3i development. Our data suggest that while dauer pathway genes are present in S. stercoralis and may play a role in L3i development, there are significant differences between the two species. Understanding the mechanisms governing L3i development may lead to novel treatment and control strategies.

C. elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity

PubMed Central

Zhang, Yanmei; Xu, Jinling; Puscau, Cristina; Kim, Yongsoon; Wang, Xi; Alam, Hena; Hu, Patrick J.

2008-01-01

SUMMARY Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The dauer arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals. PMID:18241854

Phenotypic plasticity and remodeling in the stress-induced Caenorhabditis elegans dauer.

PubMed

Androwski, Rebecca J; Flatt, Kristen M; Schroeder, Nathan E

2017-09-01

Organisms are often capable of modifying their development to better suit their environment. Under adverse conditions, the nematode Caenorhabditis elegans develops into a stress-resistant alternative larval stage called dauer. The dauer stage is the primary survival stage for C. elegans in nature. Large-scale tissue remodeling during dauer conveys resistance to harsh environments. The environmental and genetic regulation of the decision to enter dauer has been extensively studied. However, less is known about the mechanisms regulating tissue remodeling. Changes to the cuticle and suppression of feeding in dauers lead to an increased resistance to external stressors. Meanwhile reproductive development arrests during dauer while preserving the ability to reproduce once favorable environmental conditions return. Dramatic remodeling of neurons, glia, and muscles during dauer likely facilitate dauer-specific behaviors. Dauer-specific pulsation of the excretory duct likely mediates a response to osmotic stress. The power of C. elegans genetics has uncovered some of the molecular pathways regulating dauer tissue remodeling. In addition to genes that regulate single remodeling events, several mutants result in pleiotropic defects in dauer remodeling. This review details the individual aspects of morphological changes that occur during dauer formation and discusses molecular mechanisms regulating these processes. The dauer stage provides us with an excellent model for understanding phenotypic plasticity and remodeling from the individual cell to an entire animal. WIREs Dev Biol 2017, 6:e278. doi: 10.1002/wdev.278 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

In vivo imaging of Dauer-specific neuronal remodeling in C. elegans.

PubMed

Schroeder, Nathan E; Flatt, Kristen M

2014-09-04

The mechanisms controlling stress-induced phenotypic plasticity in animals are frequently complex and difficult to study in vivo. A classic example of stress-induced plasticity is the dauer stage of C. elegans. Dauers are an alternative developmental larval stage formed under conditions of low concentrations of bacterial food and high concentrations of a dauer pheromone. Dauers display extensive developmental and behavioral plasticity. For example, a set of four inner-labial quadrant (IL2Q) neurons undergo extensive reversible remodeling during dauer formation. Utilizing the well-known environmental pathways regulating dauer entry, a previously established method for the production of crude dauer pheromone from large-scale liquid nematode cultures is demonstrated. With this method, a concentration of 50,000 - 75,000 nematodes/ml of liquid culture is sufficient to produce a highly potent crude dauer pheromone. The crude pheromone potency is determined by a dose-response bioassay. Finally, the methods used for in vivo time-lapse imaging of the IL2Qs during dauer formation are described.

Methods for evaluating the Caenorhabditis elegans dauer state: standard dauer-formation assay using synthetic daumones and proteomic analysis of O-GlcNAc modifications.

PubMed

Lee, Jeeyong; Kim, Kwang-Youl; Joo, Hyoe-Jin; Kim, Heekyeong; Jeong, Pan-Young; Paik, Young-Ki

2011-01-01

The dauer state is a non-feeding, alternative L3 state characterized by a number of distinctive metabolic and morphological changes. There are many naturally occurring dauer-inducing pheromones, termed daumones, that have been suggested by some to exhibit differences in dauer-inducing activity. Here, we have established a standard dauer-formation assay that uses synthetic daumones 1, 2, and 3, the three major daumones. To analyze the proteome of Caenorhabditis elegans in the dauer state, we focused on O-GlcNAc modification, a cytosolic modification of proteins that is known to interact either competitively or synergistically with protein phosphorylation. Protein O-GlcNAc modification is an important biological process in cells that can ensure the timely response to extracellular stimuli, such as daumone, and maintain cellular homeostasis. Establishing a standard method for assaying dauer formation using different synthetic daumones, and using differences in O-GlcNAcylated proteins during the dauer state to analyze the dauer proteome will lead to a better understanding of dauer biology of C. elegans in the context of animal longevity and adaptation under harsh environments. Copyright © 2011 Elsevier Inc. All rights reserved.

Genes that act downstream of sensory neurons to influence longevity, dauer formation, and pathogen responses in Caenorhabditis elegans.

PubMed

Gaglia, Marta M; Jeong, Dae-Eun; Ryu, Eun-A; Lee, Dongyeop; Kenyon, Cynthia; Lee, Seung-Jae

2012-01-01

The sensory systems of multicellular organisms are designed to provide information about the environment and thus elicit appropriate changes in physiology and behavior. In the nematode Caenorhabditis elegans, sensory neurons affect the decision to arrest during development in a diapause state, the dauer larva, and modulate the lifespan of the animals in adulthood. However, the mechanisms underlying these effects are incompletely understood. Using whole-genome microarray analysis, we identified transcripts whose levels are altered by mutations in the intraflagellar transport protein daf-10, which result in impaired development and function of many sensory neurons in C. elegans. In agreement with existing genetic data, the expression of genes regulated by the transcription factor DAF-16/FOXO was affected by daf-10 mutations. In addition, we found altered expression of transcriptional targets of the DAF-12/nuclear hormone receptor in the daf-10 mutants and showed that this pathway influences specifically the dauer formation phenotype of these animals. Unexpectedly, pathogen-responsive genes were repressed in daf-10 mutant animals, and these sensory mutants exhibited altered susceptibility to and behavioral avoidance of bacterial pathogens. Moreover, we found that a solute transporter gene mct-1/2, which was induced by daf-10 mutations, was necessary and sufficient for longevity. Thus, sensory input seems to influence an extensive transcriptional network that modulates basic biological processes in C. elegans. This situation is reminiscent of the complex regulation of physiology by the mammalian hypothalamus, which also receives innervations from sensory systems, most notably the visual and olfactory systems.

A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans.

PubMed

Neal, Scott J; Park, JiSoo; DiTirro, Danielle; Yoon, Jason; Shibuya, Mayumi; Choi, Woochan; Schroeder, Frank C; Butcher, Rebecca A; Kim, Kyuhyung; Sengupta, Piali

2016-05-03

Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation. Copyright © 2016 Neal et al.

Small-molecule pheromones that control dauer development in Caenorhabditis elegans.

PubMed

Butcher, Rebecca A; Fujita, Masaki; Schroeder, Frank C; Clardy, Jon

2007-07-01

In response to high population density or low food supply, the nematode Caenorhabditis elegans enters an alternative larval stage, known as the dauer, that can withstand adverse conditions for prolonged periods. C. elegans senses its population density through a small-molecule signal, traditionally called the dauer pheromone, that it secretes into its surroundings. Here we show that the dauer pheromone consists of several structurally related ascarosides-derivatives of the dideoxysugar ascarylose-and that two of these ascarosides (1 and 2) are roughly two orders of magnitude more potent at inducing dauer formation than a previously reported dauer pheromone component (3) and constitute a physiologically relevant signal. The identification of dauer pheromone components 1 and 2 will facilitate the identification of target receptors and downstream signaling proteins.

FMRFamide-like peptides expand the behavioral repertoire of a densely connected nervous system

PubMed Central

Schaedel, Oren N.; Rogers, Alicia K.

2017-01-01

Animals, including humans, can adapt to environmental stress through phenotypic plasticity. The free-living nematode Caenorhabditis elegans can adapt to harsh environments by undergoing a whole-animal change, involving exiting reproductive development and entering the stress-resistant dauer larval stage. The dauer is a dispersal stage with dauer-specific behaviors for finding and stowing onto carrier animals, but how dauers acquire these behaviors, despite having a physically limited nervous system of 302 neurons, is poorly understood. We compared dauer and reproductive development using whole-animal RNA sequencing at fine time points and at sufficient depth to measure transcriptional changes within single cells. We detected 8,042 genes differentially expressed during dauer and reproductive development and observed striking up-regulation of neuropeptide genes during dauer entry. We knocked down neuropeptide processing using sbt-1 mutants and demonstrate that neuropeptide signaling promotes the decision to enter dauer rather than reproductive development. We also demonstrate that during dauer neuropeptides modulate the dauer-specific nictation behavior (carrier animal-hitchhiking) and are necessary for switching from repulsion to CO2 (a carrier animal cue) in nondauers to CO2 attraction in dauers. We tested individual neuropeptides using CRISPR knockouts and existing strains and demonstrate that the combined effects of flp-10 and flp-17 mimic the effects of sbt-1 on nictation and CO2 attraction. Through meta-analysis, we discovered similar up-regulation of neuropeptides in the dauer-like infective juveniles of diverse parasitic nematodes, suggesting the antiparasitic target potential of SBT-1. Our findings reveal that, under stress, increased neuropeptide signaling in C. elegans enhances their decision-making accuracy and expands their behavioral repertoire. PMID:29167374

Biosynthesis of the Caenorhabditis elegans dauer pheromone.

PubMed

Butcher, Rebecca A; Ragains, Justin R; Li, Weiqing; Ruvkun, Gary; Clardy, Jon; Mak, Ho Yi

2009-02-10

To sense its population density and to trigger entry into the stress-resistant dauer larval stage, Caenorhabditis elegans uses the dauer pheromone, which consists of ascaroside derivatives with short, fatty acid-like side chains. Although the dauer pheromone has been studied for 25 years, its biosynthesis is completely uncharacterized. The daf-22 mutant is the only known mutant defective in dauer pheromone production. Here, we show that daf-22 encodes a homolog of human sterol carrier protein SCPx, which catalyzes the final step in peroxisomal fatty acid beta-oxidation. We also show that dhs-28, which encodes a homolog of the human d-bifunctional protein that acts just upstream of SCPx, is also required for pheromone production. Long-term daf-22 and dhs-28 cultures develop dauer-inducing activity by accumulating less active, long-chain fatty acid ascaroside derivatives. Thus, daf-22 and dhs-28 are required for the biosynthesis of the short-chain fatty acid-derived side chains of the dauer pheromone and link dauer pheromone production to metabolic state.

Two chemoreceptors mediate developmental effects of dauer pheromone in C. elegans.

PubMed

Kim, Kyuhyung; Sato, Koji; Shibuya, Mayumi; Zeiger, Danna M; Butcher, Rebecca A; Ragains, Justin R; Clardy, Jon; Touhara, Kazushige; Sengupta, Piali

2009-11-13

Intraspecific chemical communication is mediated by signals called pheromones. Caenorhabditis elegans secretes a mixture of small molecules (collectively termed dauer pheromone) that regulates entry into the alternate dauer larval stage and also modulates adult behavior via as yet unknown receptors. Here, we identify two heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) that mediate dauer formation in response to a subset of dauer pheromone components. The SRBC-64 and SRBC-66 GPCRs are members of the large Caenorhabditis-specific SRBC subfamily and are expressed in the ASK chemosensory neurons, which are required for pheromone-induced dauer formation. Expression of both, but not each receptor alone, confers pheromone-mediated effects on heterologous cells. Identification of dauer pheromone receptors will allow a better understanding of the signaling cascades that transduce the context-dependent effects of ecologically important chemical signals.

HSF-1 is involved in regulation of ascaroside pheromone biosynthesis by heat stress in Caenorhabditis elegans.

PubMed

Joo, Hyoe-Jin; Park, Saeram; Kim, Kwang-Youl; Kim, Mun-Young; Kim, Heekyeong; Park, Donha; Paik, Young-Ki

2016-03-15

The nematode worm Caenorhabditis elegans survives by adapting to environmental stresses such as temperature extremes by increasing the concentrations of ascaroside pheromones, termed ascarosides or daumones, which signal early C. elegans larvae to enter a non-aging dauer state for long-term survival. It is well known that production of ascarosides is stimulated by heat stress, resulting in enhanced dauer formation by which worms can adapt to environmental insults. However, the molecular mechanism by which ascaroside pheromone biosynthesis is stimulated by heat stress remains largely unknown. In the present study, we show that the heat-shock transcription factor HSF-1 can mediate enhanced ascaroside pheromone biosynthesis in response to heat stress by activating the peroxisomal fatty acid β-oxidation genes in C. elegans. To explore the potential molecular mechanisms, we examined the four major genes involved in the ascaroside biosynthesis pathway and then quantified the changes in both the expression of these genes and ascaroside production under heat-stress conditions. The transcriptional activation of ascaroside pheromone biosynthesis genes by HSF-1 was quite notable, which is not only supported by chromatin immunoprecipitation assays, but also accompanied by the enhanced production of chemically detectable major ascarosides (e.g. daumones 1 and 3). Consequently, the dauer formation rate was significantly increased by the ascaroside pheromone extracts from N2 wild-type but not from hsf-1(sy441) mutant animals grown under heat-stress conditions. Hence heat-stress-enhanced ascaroside production appears to be mediated at least in part by HSF-1, which seems to be important in adaptation strategies for coping with heat stress in this nematode. © 2016 Authors; published by Portland Press Limited.

Natural variation in dauer pheromone production and sensing supports intraspecific competition in nematodes.

PubMed

Bose, Neelanjan; Meyer, Jan M; Yim, Joshua J; Mayer, Melanie G; Markov, Gabriel V; Ogawa, Akira; Schroeder, Frank C; Sommer, Ralf J

2014-07-07

Dauer formation, a major nematode survival strategy, represents a model for small-molecule regulation of metazoan development [1-10]. Free-living nematodes excrete dauer-inducing pheromones that have been assumed to target conspecifics of the same genotype [9, 11]. However, recent studies in Pristionchus pacificus revealed that the dauer pheromone of some strains affects conspecifics of other genotypes more strongly than individuals of the same genotype [12]. To elucidate the mechanistic basis for this intriguing cross-preference, we compared six P. pacificus wild isolates to determine the chemical composition of their dauer-inducing metabolomes and responses to individual pheromone components. We found that these isolates produce dauer pheromone blends of different composition and respond differently to individual pheromone components. Strikingly, there is no correlation between production of and dauer response to a specific compound in individual strains. Specifically, pheromone components that are abundantly produced by one genotype induce dauer formation in other genotypes, but not necessarily in the abundant producer. Furthermore, some genotypes respond to pheromone components they do not produce themselves. These results support a model of intraspecific competition in nematode dauer formation. Indeed, we observed intraspecific competition among sympatric strains in a novel experimental assay, suggesting a new role of small molecules in nematode ecology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Signaling in Parasitic Nematodes: Physicochemical Communication Between Host and Parasite and Endogenous Molecular Transduction Pathways Governing Worm Development and Survival.

PubMed

Lok, James B

2016-12-01

Signaling or communication between host and parasite may occur over relatively long ranges to enable host finding and acquisition by infective parasitic nematode larvae. Innate behaviors in infective larvae transmitted from the soil that enhance the likelihood of host contact, such as negative geotaxis and hypermotility, are likely mediated by mechanoreception and neuromuscular signaling. Host cues such as vibration of the substratum, elevated temperature, exhaled CO 2 , and other volatile odorants are perceived by mechanosensory and chemosensory neurons of the amphidial complex. Beyond this, the molecular systems that transduce these external cues within the worm are unknown at this time. Overall, the signal transduction mechanisms that regulate switching between dauer and continuous reproductive development in Caenorhabditis elegans , and doubtless other free-living nematodes, have provided a useful framework for testing hypotheses about how the morphogenesis and development of infective parasitic nematode larvae and the lifespan of adult parasites are regulated. In C. elegans , four major signal transduction pathways, G protein-coupled receptor signaling, insulin/insulin-like growth factor signaling, TGFβ-like signaling and steroid-nuclear hormone receptor signaling govern the switch between dauer and continuous development and regulate adult lifespan. Parasitic nematodes appear to have conserved the functions of G-protein-coupled signaling, insulin-like signaling and steroid-nuclear hormone receptor signaling to regulate larval development before and during the infective process. By contrast, TGFβ-like signaling appears to have been adapted for some other function, perhaps modulation of the host immune response. Of the three signal transduction pathways that appear to regulate development in parasitic nematodes, steroid-nuclear hormone signaling is the most straightforward to manipulate with administered small molecules and may form the basis of new chemotherapeutic strategies. Signaling between parasites and their hosts' immune systems also occurs and serves to modulate these responses to allow chronic infection and down regulate acute inflammatory responses. Knowledge of the precise nature of this signaling may form the basis of immunological interventions to protect against parasitism or related lesions and to alleviate inflammatory diseases of various etiologies.

A host beetle pheromone regulates development and behavior in the nematode Pristionchus pacificus.

PubMed

Cinkornpumin, Jessica K; Wisidagama, Dona R; Rapoport, Veronika; Go, James L; Dieterich, Christoph; Wang, Xiaoyue; Sommer, Ralf J; Hong, Ray L

2014-10-15

Nematodes and insects are the two most speciose animal phyla and nematode-insect associations encompass widespread biological interactions. To dissect the chemical signals and the genes mediating this association, we investigated the effect of an oriental beetle sex pheromone on the development and behavior of the nematode Pristionchus pacificus. We found that while the beetle pheromone is attractive to P. pacificus adults, the pheromone arrests embryo development, paralyzes J2 larva, and inhibits exit of dauer larvae. To uncover the mechanism that regulates insect pheromone sensitivity, a newly identified mutant, Ppa-obi-1, is used to reveal the molecular links between altered attraction towards the beetle pheromone, as well as hypersensitivity to its paralyzing effects. Ppa-obi-1 encodes lipid-binding domains and reaches its highest expression in various cell types, including the amphid neuron sheath and excretory cells. Our data suggest that the beetle host pheromone may be a species-specific volatile synomone that co-evolved with necromeny.

Hc-daf-2 encodes an insulin-like receptor kinase in the barber's pole worm, Haemonchus contortus, and restores partial dauer regulation.

PubMed

Li, Facai; Lok, James B; Gasser, Robin B; Korhonen, Pasi K; Sandeman, Mark R; Shi, Deshi; Zhou, Rui; Li, Xiangrui; Zhou, Yanqin; Zhao, Junlong; Hu, Min

2014-06-01

Infective L3s (iL3s) of parasitic nematodes share common behavioural, morphological and developmental characteristics with the developmentally arrested (dauer) larvae of the free-living nematode Caenorhabditis elegans. It is proposed that similar molecular mechanisms regulate entry into or exit from the dauer stage in C. elegans, and the transition from free-living to parasitic forms of parasitic nematodes. In C. elegans, one of the key factors regulating the dauer transition is the insulin-like receptor (designated Ce-DAF-2) encoded by the gene Ce-daf-2. However, nothing is known about DAF-2 homologues in most parasitic nematodes. Here, using a PCR-based approach, we identified and characterised a gene (Hc-daf-2) and its inferred product (Hc-DAF-2) in Haemonchus contortus (a socioeconomically important parasitic nematode of ruminants). The sequence of Hc-DAF-2 displays significant sequence homology to insulin receptors (IR) in both vertebrates and invertebrates, and contains conserved structural domains. A sequence encoding an important proteolytic motif (RKRR) identified in the predicted peptide sequence of Hc-DAF-2 is consistent with that of the human IR, suggesting that it is involved in the formation of the IR complex. The Hc-daf-2 gene was transcribed in all life stages of H. contortus, with a significant up-regulation in the iL3 compared with other stages. To compare patterns of expression between Hc-daf-2 and Ce-daf-2, reporter constructs fusing the Ce-daf-2 or Hc-daf-2 promoter to sequence encoding GFP were microinjected into the N2 strain of C. elegans, and transgenic lines were established and examined. Both genes showed similar patterns of expression in amphidial (head) neurons, which relate to sensation and signal transduction. Further study by heterologous genetic complementation in a daf-2-deficient strain of C. elegans (CB1370) showed partial rescue of function by Hc-daf-2. Taken together, these findings provide a first insight into the roles of Hc-daf-2/Hc-DAF-2 in the biology and development of H. contortus, particularly in the transition to parasitism. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

RNAi pathways contribute to developmental history-dependent phenotypic plasticity in C. elegans

PubMed Central

Hall, Sarah E.; Chirn, Gung-Wei; Lau, Nelson C.; Sengupta, Piali

2013-01-01

Early environmental experiences profoundly influence adult phenotypes through complex mechanisms that are poorly understood. We previously showed that adult Caenorhabditis elegans that transiently passed through the stress-induced dauer larval stage (post-dauer adults) exhibit significant changes in gene expression profiles, chromatin states, and life history traits when compared with adults that bypassed the dauer stage (control adults). These wild-type, isogenic animals of equivalent developmental stages exhibit different signatures of molecular marks that reflect their distinct developmental trajectories. To gain insight into the mechanisms that contribute to these developmental history-dependent phenotypes, we profiled small RNAs from post-dauer and control adults by deep sequencing. RNA interference (RNAi) pathways are known to regulate genome-wide gene expression both at the chromatin and post-transcriptional level. By quantifying changes in endogenous small interfering RNA (endo-siRNA) levels in post-dauer as compared with control animals, our analyses identified a subset of genes that are likely targets of developmental history-dependent reprogramming through a complex RNAi-mediated mechanism. Mutations in specific endo-siRNA pathways affect expected gene expression and chromatin state changes for a subset of genes in post-dauer animals, as well as disrupt their increased brood size phenotype. We also find that both chromatin state and endo-siRNA distribution in dauers are unique, and suggest that remodeling in dauers provides a template for the subsequent establishment of adult post-dauer profiles. Our results indicate a role for endo-siRNA pathways as a contributing mechanism to early experience-dependent phenotypic plasticity in adults, and describe how developmental history can program adult physiology and behavior via epigenetic mechanisms. PMID:23329696

Regulation of Dauer formation by O-GlcNAcylation in Caenorhabditis elegans.

PubMed

Lee, Jeeyong; Kim, Kwang-Youl; Lee, Jihyun; Paik, Young-Ki

2010-01-29

Modification of proteins at serine or threonine residues with N-acetylglucosamine, termed O-GlcNAcylation, plays an important role in most eukaryotic cells. To understand the molecular mechanism by which O-GlcNAcylation regulates the entry of Caenorhabditis elegans into the non-aging dauer state, we performed proteomic studies using two mutant strains: the O-GlcNAc transferase-deficient ogt-1(ok430) strain and the O-GlcNAcase-defective oga-1(ok1207) strain. In the presence of the dauer pheromone daumone, ogt-1 showed suppression of dauer formation, whereas oga-1 exhibited enhancement of dauer formation. Consistent with these findings, treatment of wild-type N2 worms with low concentrations of daumone and the O-GlcNAcase inhibitor O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) enhanced dauer formation, which was dependent on intact O-GlcNAcylation metabolism. We also found that the treatment of daumone enhanced O-GlcNAcylation in vivo. Seven proteins, identified by coupled two-dimensional electrophoresis/liquid chromatography-mass spectroscopy (LC-MS) analysis, were differentially expressed in oga-1(ok1207) worms compared with wild-type N2 worms. The identities of these proteins suggest that O- GlcNAcylation influences stress resistance, protein folding, and mitochondrial function. Using O-GlcNAc labeling with fluorescent dye combined with two-dimensional electrophoresis/LC-MS analysis, we also identified five proteins that were differentially O-GlcNAcylated during dauer formation. Analysis of these candidate O-GlcNAcylated proteins suggests that O-GlcNAcylation may regulate cytoskeleton modifications and protein turnover during dauer formation.

Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity.

PubMed

Ewald, Collin Y; Landis, Jess N; Porter Abate, Jess; Murphy, Coleen T; Blackwell, T Keith

2015-03-05

Interventions that delay ageing mobilize mechanisms that protect and repair cellular components, but it is unknown how these interventions might slow the functional decline of extracellular matrices, which are also damaged during ageing. Reduced insulin/IGF-1 signalling (rIIS) extends lifespan across the evolutionary spectrum, and in juvenile Caenorhabditis elegans also allows the transcription factor DAF-16/FOXO to induce development into dauer, a diapause that withstands harsh conditions. It has been suggested that rIIS delays C. elegans ageing through activation of dauer-related processes during adulthood, but some rIIS conditions confer robust lifespan extension unaccompanied by any dauer-like traits. Here we show that rIIS can promote C. elegans longevity through a program that is genetically distinct from the dauer pathway, and requires the Nrf (NF-E2-related factor) orthologue SKN-1 acting in parallel to DAF-16. SKN-1 is inhibited by IIS and has been broadly implicated in longevity, but is rendered dispensable for rIIS lifespan extension by even mild activity of dauer-related processes. When IIS is decreased under conditions that do not induce dauer traits, SKN-1 most prominently increases expression of collagens and other extracellular matrix genes. Diverse genetic, nutritional, and pharmacological pro-longevity interventions delay an age-related decline in collagen expression. These collagens mediate adulthood extracellular matrix remodelling, and are needed for ageing to be delayed by interventions that do not involve dauer traits. By genetically delineating a dauer-independent rIIS ageing pathway, our results show that IIS controls a broad set of protective mechanisms during C. elegans adulthood, and may facilitate elucidation of processes of general importance for longevity. The importance of collagen production in diverse anti-ageing interventions implies that extracellular matrix remodelling is a generally essential signature of longevity assurance, and that agents promoting extracellular matrix youthfulness may have systemic benefit.

Co-option of the hormone-signalling module dafachronic acid-DAF-12 in nematode evolution.

PubMed

Bento, Gilberto; Ogawa, Akira; Sommer, Ralf J

2010-07-22

Morphological novelties are lineage-specific traits that serve new functions. Developmental polyphenisms have been proposed to be facilitators of phenotypic evolution, but little is known about the interplay between the associated genetic and environmental factors. Here, we study two alternative morphologies in the mouth of the nematode Pristionchus pacificus and the formation of teeth-like structures that are associated with bacteriovorous feeding and predatory behaviour on fungi and other worms. These teeth-like denticles represent an evolutionary novelty, which is restricted to some members of the nematode family Diplogastridae but is absent from Caenorhabditis elegans and related nematodes. We show that the mouth dimorphism is a polyphenism that is controlled by starvation and the co-option of an endocrine switch mechanism. Mutations in the nuclear hormone receptor DAF-12 and application of its ligand, the sterol hormone dafachronic acid, strongly influence this switch mechanism. The dafachronic acid-DAF-12 module has been shown to control the formation of arrested dauer larvae in both C. elegans and P. pacificus, as well as related life-history decisions in distantly related nematodes. The comparison of dauer formation and mouth morphology switch reveals that different thresholds of dafachronic acid signalling provide specificity. This study shows how hormonal signalling acts by coupling environmental change and genetic regulation and identifies dafachronic acid as a key hormone in nematode evolution.

Caenorhabditis elegans utilizes dauer pheromone biosynthesis to dispose of toxic peroxisomal fatty acids for cellular homoeostasis

USDA-ARS?s Scientific Manuscript database

Caenorhabditis elegans secretes a dauer pheromone or daumone composed of ascarylose and a fatty acid side chain, perception of which enables worms to gauge depletion of food or a high worm population density. As a result, worms enter the dauer state, a specific developmental stage capable of surviv...

The Caenorhabditis Elegans Unc-31 Gene Affects Multiple Nervous System-Controlled Functions

PubMed Central

Avery, L.; Bargmann, C. I.; Horvitz, H. R.

1993-01-01

We have devised a method for selecting Caenorhabditis elegans mutants that execute feeding motions in the absence of food. One mutation isolated in this way is an allele of the gene unc-31, first discovered by S. Brenner in 1974, because of its effects on locomotion. We find that strong unc-31 mutations cause defects in four functions controlled by the nervous system. Mutant worms are lethargic, feed constitutively, are defective in egg-laying and produce dauer larvae that fail to recover. We discuss two extreme models to explain this pleiotropy: either unc-31 affects one or a few neurons that coordinately control several different functions, or it affects many neurons that independently control different functions. PMID:8325482

Analysis and functional classification of transcripts from the nematode Meloidogyne incognita

PubMed Central

McCarter, James P; Dautova Mitreva, Makedonka; Martin, John; Dante, Mike; Wylie, Todd; Rao, Uma; Pape, Deana; Bowers, Yvette; Theising, Brenda; Murphy, Claire V; Kloek, Andrew P; Chiapelli, Brandi J; Clifton, Sandra W; Bird, David Mck; Waterston, Robert H

2003-01-01

Background Plant parasitic nematodes are major pathogens of most crops. Molecular characterization of these species as well as the development of new techniques for control can benefit from genomic approaches. As an entrée to characterizing plant parasitic nematode genomes, we analyzed 5,700 expressed sequence tags (ESTs) from second-stage larvae (L2) of the root-knot nematode Meloidogyne incognita. Results From these, 1,625 EST clusters were formed and classified by function using the Gene Ontology (GO) hierarchy and the Kyoto KEGG database. L2 larvae, which represent the infective stage of the life cycle before plant invasion, express a diverse array of ligand-binding proteins and abundant cytoskeletal proteins. L2 are structurally similar to Caenorhabditis elegans dauer larva and the presence of transcripts encoding glyoxylate pathway enzymes in the M. incognita clusters suggests that root-knot nematode larvae metabolize lipid stores while in search of a host. Homology to other species was observed in 79% of translated cluster sequences, with the C. elegans genome providing more information than any other source. In addition to identifying putative nematode-specific and Tylenchida-specific genes, sequencing revealed previously uncharacterized horizontal gene transfer candidates in Meloidogyne with high identity to rhizobacterial genes including homologs of nodL acetyltransferase and novel cellulases. Conclusions With sequencing from plant parasitic nematodes accelerating, the approaches to transcript characterization described here can be applied to more extensive datasets and also provide a foundation for more complex genome analyses. PMID:12702207

A genome-wide screen of bacterial mutants that enhance dauer formation in C. elegans.

PubMed

Khanna, Amit; Kumar, Jitendra; Vargas, Misha A; Barrett, LaKisha; Katewa, Subhash; Li, Patrick; McCloskey, Tom; Sharma, Amit; Naudé, Nicole; Nelson, Christopher; Brem, Rachel; Killilea, David W; Mooney, Sean D; Gill, Matthew; Kapahi, Pankaj

2016-12-13

Molecular pathways involved in dauer formation, an alternate larval stage that allows Caenorhabditis elegans to survive adverse environmental conditions during development, also modulate longevity and metabolism. The decision to proceed with reproductive development or undergo diapause depends on food abundance, population density, and temperature. In recent years, the chemical identities of pheromone signals that modulate dauer entry have been characterized. However, signals derived from bacteria, the major source of nutrients for C. elegans, remain poorly characterized. To systematically identify bacterial components that influence dauer formation and aging in C. elegans, we utilized the individual gene deletion mutants in E. coli (K12). We identified 56 diverse E. coli deletion mutants that enhance dauer formation in an insulin-like receptor mutant (daf-2) background. We describe the mechanism of action of a bacterial mutant cyaA, that is defective in the production of cyclic AMP, which extends lifespan and enhances dauer formation through the modulation of TGF-β (daf-7) signaling in C. elegans. Our results demonstrate the importance of bacterial components in influencing developmental decisions and lifespan in C. elegans. Furthermore, we demonstrate that C. elegans is a useful model to study bacterial-host interactions.

Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans.

PubMed

Luciani, Genna M; Magomedova, Lilia; Puckrin, Rachel; Urbanus, Malene L; Wallace, Iain M; Giaever, Guri; Nislow, Corey; Cummins, Carolyn L; Roy, Peter J

2011-11-06

The DAF-9 cytochrome P450 is a key regulator of dauer formation, developmental timing and longevity in the nematode Caenorhabditis elegans. Here we describe the first identified chemical inhibitor of DAF-9 and the first reported small-molecule tool that robustly induces dauer formation in typical culture conditions. This molecule (called dafadine) also inhibits the mammalian ortholog of DAF-9(CYP27A1), suggesting that dafadine can be used to interrogate developmental control and longevity in other animals.

Endogenous RNAi Pathways Are Required in Neurons for Dauer Formation in Caenorhabditis elegans.

PubMed

Bharadwaj, Pallavi S; Hall, Sarah E

2017-04-01

Animals can adapt to unfavorable environments through changes in physiology or behavior. In the nematode, Caenorhabditis elegans , environmental conditions perceived early in development determine whether the animal enters either the reproductive cycle, or enters into an alternative diapause stage named dauer. Here, we show that endogenous RNAi pathways play a role in dauer formation in crowding (high pheromone), starvation, and high temperature conditions. Disruption of the Mutator proteins or the nuclear Argonaute CSR-1 result in differential dauer-deficient phenotypes that are dependent upon the experienced environmental stress. We provide evidence that the RNAi pathways function in chemosensory neurons for dauer formation, upstream of the TGF-β and insulin signaling pathways. In addition, we show that Mutator MUT-16 expression in a subset of individual pheromone-sensing neurons is sufficient for dauer formation in high pheromone conditions, but not in starvation or high temperature conditions. Furthermore, we also show that MUT-16 and CSR-1 are required for expression of a subset of G proteins with functions in the detection of pheromone components. Together, our data suggest a model where Mutator -amplified siRNAs that associate with the CSR-1 pathway promote expression of genes required for the detection and signaling of environmental conditions to regulate development and behavior in C. elegans This study highlights a mechanism whereby RNAi pathways mediate the link between environmental stress and adaptive phenotypic plasticity in animals. Copyright © 2017 by the Genetics Society of America.

Heat shock factor-1 intertwines insulin/IGF-1, TGF-β and cGMP signaling to control development and aging.

PubMed

Barna, János; Princz, Andrea; Kosztelnik, Mónika; Hargitai, Balázs; Takács-Vellai, Krisztina; Vellai, Tibor

2012-11-01

Temperature affects virtually all cellular processes. A quick increase in temperature challenges the cells to undergo a heat shock response to maintain cellular homeostasis. Heat shock factor-1 (HSF-1) functions as a major player in this response as it activates the transcription of genes coding for molecular chaperones (also called heat shock proteins) that maintain structural integrity of proteins. However, the mechanisms by which HSF-1 adjusts fundamental cellular processes such as growth, proliferation, differentiation and aging to the ambient temperature remain largely unknown. We demonstrate here that in Caenorhabditis elegans HSF-1 represses the expression of daf-7 encoding a TGF-β (transforming growth factor-beta) ligand, to induce young larvae to enter the dauer stage, a developmentally arrested, non-feeding, highly stress-resistant, long-lived larval form triggered by crowding and starvation. Under favorable conditions, HSF-1 is inhibited by crowding pheromone-sensitive guanylate cyclase/cGMP (cyclic guanosine monophosphate) and systemic nutrient-sensing insulin/IGF-1 (insulin-like growth factor-1) signaling; loss of HSF-1 activity allows DAF-7 to promote reproductive growth. Thus, HSF-1 interconnects the insulin/IGF-1, TGF-β and cGMP neuroendocrine systems to control development and longevity in response to diverse environmental stimuli. Furthermore, HSF-1 upregulates another TGF-β pathway-interacting gene, daf-9/cytochrome P450, thereby fine-tuning the decision between normal growth and dauer formation. Together, these results provide mechanistic insight into how temperature, nutrient availability and population density coordinately influence development, lifespan, behavior and stress response through HSF-1.

pkc-1 regulates daf-2 insulin/IGF signalling-dependent control of dauer formation in Caenorhabditis elegans.

PubMed

Monje, José M; Brokate-Llanos, Ana M; Pérez-Jiménez, Mercedes M; Fidalgo, Manuel A; Muñoz, Manuel J

2011-12-01

In Caenorhabditis elegans, the insulin/IGF pathway participates in the decision to initiate dauer development. Dauer is a diapause stage that is triggered by environmental stresses, such as a lack of nutrients. Insulin/IGF receptor mutants arrest constitutively in dauer, an effect that can be suppressed by mutations in other elements of the insulin/IGF pathway or by a reduction in the activity of the nuclear hormone receptor daf-12. We have isolated a pkc-1 mutant that acts as a novel suppressor of the dauer phenotypes caused by insulin/IGF receptor mutations. Interactions between insulin/IGF mutants and the pkc-1 suppressor mutant are similar to those described for daf-12 or the DAF-12 coregulator din-1. Moreover, we show that the expression of the DAF-12 target daf-9, which is normally elevated upon a reduction in insulin/IGF receptor activity, is suppressed in a pkc-1 mutant background, suggesting that pkc-1 could link the daf-12 and insulin/IGF pathways. pkc-1 has been implicated in the regulation of peptide neurosecretion in C. elegans. Although we demonstrate that pkc-1 expression in the nervous system regulates dauer formation, our results suggest that the requirement for pkc-1 in neurosecretion is independent of its role in modulating insulin/IGF signalling. pkc-1 belongs to the novel protein kinase C (nPKC) family, members of which have been implicated in insulin resistance and diabetes in mammals, suggesting a conserved role for pkc-1 in the regulation of the insulin/IGF pathway. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Unexpected role for dosage compensation in the control of dauer arrest, insulin-like signaling, and FoxO transcription factor activity in Caenorhabditis elegans.

PubMed

Dumas, Kathleen J; Delaney, Colin E; Flibotte, Stephane; Moerman, Donald G; Csankovszki, Gyorgyi; Hu, Patrick J

2013-07-01

During embryogenesis, an essential process known as dosage compensation is initiated to equalize gene expression from sex chromosomes. Although much is known about how dosage compensation is established, the consequences of modulating the stability of dosage compensation postembryonically are not known. Here we define a role for the Caenorhabditis elegans dosage compensation complex (DCC) in the regulation of DAF-2 insulin-like signaling. In a screen for dauer regulatory genes that control the activity of the FoxO transcription factor DAF-16, we isolated three mutant alleles of dpy-21, which encodes a conserved DCC component. Knockdown of multiple DCC components in hermaphrodite and male animals indicates that the dauer suppression phenotype of dpy-21 mutants is due to a defect in dosage compensation per se. In dpy-21 mutants, expression of several X-linked genes that promote dauer bypass is elevated, including four genes encoding components of the DAF-2 insulin-like pathway that antagonize DAF-16/FoxO activity. Accordingly, dpy-21 mutation reduced the expression of DAF-16/FoxO target genes by promoting the exclusion of DAF-16/FoxO from nuclei. Thus, dosage compensation enhances dauer arrest by repressing X-linked genes that promote reproductive development through the inhibition of DAF-16/FoxO nuclear translocation. This work is the first to establish a specific postembryonic function for dosage compensation in any organism. The influence of dosage compensation on dauer arrest, a larval developmental fate governed by the integration of multiple environmental inputs and signaling outputs, suggests that the dosage compensation machinery may respond to external cues by modulating signaling pathways through chromosome-wide regulation of gene expression.

No Significant Increase in the Δ4- and Δ7-Dafachronic Acid Concentration in the Long-Lived glp-1 Mutant, nor in the Mutants Defective in Dauer Formation.

PubMed

Li, Tie-Mei; Liu, Weilong; Lu, Shan; Zhang, Yan-Ping; Jia, Le-Mei; Chen, Jie; Li, Xiangke; Lei, Xiaoguang; Dong, Meng-Qiu

2015-05-12

The steroid hormone dafachronic acid (DA) regulates dauer formation and lifespan in Caenorhabditis elegans by binding to the nuclear receptor DAF-12. However, little is known about how DA concentrations change under various physiologic conditions and about how DA/DAF-12 signaling interacts with other signaling pathways that also regulate dauer formation and lifespan. Using a sensitive bioanalytical method, we quantified the endogenous DA concentrations in a long-lived germline-less glp-1 mutant and in the Dauer formation-defective (Daf-d) mutants daf-12, daf-16, daf-5, and daf-3. We found that the DA concentration in the glp-1 mutant was similar to that in the wild type (WT). This result is contrary to the long-held belief that germline loss-induced longevity involves increased DA production and suggests instead that this type of longevity involves an enhanced response to DA. We also found evidence suggesting that increased DA sensitivity underlies lifespan extension triggered by exogenous DA. At the L2/L3 stage, the DA concentration in a daf-12 null mutant decreased to 22% of the WT level. This finding is consistent with the previously proposed positive feedback regulation between DAF-12 and DA production. Surprisingly, the DA concentrations in the daf-16, daf-5, and daf-3 mutants were only 19-34% of the WT level at the L2/L3 stage, slightly greater than those in the Dauer formation-constitutive (Daf-c) mutants at the pre-dauer stage (4-15% of the WT L2 control). Our experimental evidence suggested that the positive feedback between DA and DAF-12 was partially induced in the three Daf-d mutants. Copyright © 2015 Li et al.

Insulin/Insulin-like growth factor signaling controls non-Dauer developmental speed in the nematode Caenorhabditis elegans.

PubMed

Ruaud, Anne-Françoise; Katic, Iskra; Bessereau, Jean-Louis

2011-01-01

Identified as a major pathway controlling entry in the facultative dauer diapause stage, the DAF-2/Insulin receptor (InsR) signaling acts in multiple developmental and physiological regulation events in Caenorhabditis elegans. Here we identified a role of the insulin-like pathway in controlling developmental speed during the C. elegans second larval stage. This role relies on the canonical DAF-16/FOXO-dependent branch of the insulin-like signaling and is largely independent of dauer formation. Our studies provide further evidence for broad conservation of insulin/insulin-like growth factor (IGF) functions in developmental speed control.

Ascaroside expression in Caenorhabditis elegans is strongly dependent on diet and developmental stage

USDA-ARS?s Scientific Manuscript database

A group of small signaling molecules called ascarosides, associated with dauer formation, male attraction and social behavior in the nematode Caenorhabditis elegans, are shown to be regulated by developmental stage and environmental factors. The concentration of dauer-inducing ascaroside, ascr#2, i...

Concentration dependent differential activity of signalling molecules in Caenorhabditis elegans

USDA-ARS?s Scientific Manuscript database

Caenorhabditis elegans employs specific glycosides of the dideoxysugar ascarylose (the ‘ascarosides’) for monitoring population density/ dauer formation and finding mates. A synergistic blend of three ascarosides, called ascr#2, ascr#3 and ascr#4 acts as a dauer pheromone at a high concentration na...

Transmission of the Diachasmimorpha longicaudata rhabdovirus (DlRhV) to wasp offspring: an ultrastructural analysis.

PubMed

Lawrence, Pauline O; Matos, Luis F

2005-02-01

During oviposition, the parasitic wasp Diachasmimorpha longicaudata introduces an entomopoxvirus (DlEPV) and a rhabdovirus (DlRhV) into larvae of its tephritid fruit fly host Anastrepha suspensa. DlEPV and DlRhV replicate, respectively, in host hemocytes and epidermal cells. Both viruses, like many beneficial viruses of parasitic wasps, are retained in all wasp generations but their avenue(s) of transmission are unknown. This study tests the hypothesis that DlRhV is transmitted transovarially or through larval feeding on infected host hemolymph. Transmission electron microscopy (TEM) revealed no virions in pre-vitellogenic or vitellogenic ova, or in the lateral oviduct of D. longicaudata females. However, numerous virions occurred in subchorionic regions of 33-36-h-old oviposited eggs. This suggests that DlRhV is introduced into the egg either as (a) intact virions after chorionogenesis but prior to oviposition and/or as (b) unencapsidated RNA molecules, undetectable by TEM in pre-vitellogenic ova, that subsequently replicate and assemble into mature virions. DlRhV particles also occurred in the midgut lumen of 20-24-h-old wasp first instars, suggesting that they were ingested. These virions may have been released from the egg into the hemolymph during hatching or may have come from virions introduced by the female wasp directly into the host, separate from the egg. DlRhV particles were also evident in the intracellular vesicles and intercellular spaces of the larval midgut. Taken together, these data support the hypothesis that DlRhV is transovarially transmitted as virions and/or as unencapsidated RNA. Further studies are needed to determine whether the DlRhV that ultimately resides within the female wasp's accessory gland filaments is the progeny of the virus from the egg and/or larval midgut cells.

TATN-1 Mutations Reveal a Novel Role for Tyrosine as a Metabolic Signal That Influences Developmental Decisions and Longevity in Caenorhabditis elegans

PubMed Central

Ferguson, Annabel A.; Dumas, Kathleen J.; Ritov, Vladimir B.; Matern, Dietrich; Hu, Patrick J.; Fisher, Alfred L.

2013-01-01

Recent work has identified changes in the metabolism of the aromatic amino acid tyrosine as a risk factor for diabetes and a contributor to the development of liver cancer. While these findings could suggest a role for tyrosine as a direct regulator of the behavior of cells and tissues, evidence for this model is currently lacking. Through the use of RNAi and genetic mutants, we identify tatn-1, which is the worm ortholog of tyrosine aminotransferase and catalyzes the first step of the conserved tyrosine degradation pathway, as a novel regulator of the dauer decision and modulator of the daf-2 insulin/IGF-1-like (IGFR) signaling pathway in Caenorhabditis elegans. Mutations affecting tatn-1 elevate tyrosine levels in the animal, and enhance the effects of mutations in genes that lie within the daf-2/insulin signaling pathway or are otherwise upstream of daf-16/FOXO on both dauer formation and worm longevity. These effects are mediated by elevated tyrosine levels as supplemental dietary tyrosine mimics the phenotypes produced by a tatn-1 mutation, and the effects still occur when the enzymes needed to convert tyrosine into catecholamine neurotransmitters are missing. The effects on dauer formation and lifespan require the aak-2/AMPK gene, and tatn-1 mutations increase phospho-AAK-2 levels. In contrast, the daf-16/FOXO transcription factor is only partially required for the effects on dauer formation and not required for increased longevity. We also find that the controlled metabolism of tyrosine by tatn-1 may function normally in dauer formation because the expression of the TATN-1 protein is regulated both by daf-2/IGFR signaling and also by the same dietary and environmental cues which influence dauer formation. Our findings point to a novel role for tyrosine as a developmental regulator and modulator of longevity, and support a model where elevated tyrosine levels play a causal role in the development of diabetes and cancer in people. PMID:24385923

Functional analysis of neuronal microRNAs in Caenorhabditis elegans dauer formation by combinational genetics and Neuronal miRISC immunoprecipitation.

PubMed

Than, Minh T; Kudlow, Brian A; Han, Min

2013-06-01

Identifying the physiological functions of microRNAs (miRNAs) is often challenging because miRNAs commonly impact gene expression under specific physiological conditions through complex miRNA::mRNA interaction networks and in coordination with other means of gene regulation, such as transcriptional regulation and protein degradation. Such complexity creates difficulties in dissecting miRNA functions through traditional genetic methods using individual miRNA mutations. To investigate the physiological functions of miRNAs in neurons, we combined a genetic "enhancer" approach complemented by biochemical analysis of neuronal miRNA-induced silencing complexes (miRISCs) in C. elegans. Total miRNA function can be compromised by mutating one of the two GW182 proteins (AIN-1), an important component of miRISC. We found that combining an ain-1 mutation with a mutation in unc-3, a neuronal transcription factor, resulted in an inappropriate entrance into the stress-induced, alternative larval stage known as dauer, indicating a role of miRNAs in preventing aberrant dauer formation. Analysis of this genetic interaction suggests that neuronal miRNAs perform such a role partly by regulating endogenous cyclic guanosine monophosphate (cGMP) signaling, potentially influencing two other dauer-regulating pathways. Through tissue-specific immunoprecipitations of miRISC, we identified miRNAs and their likely target mRNAs within neuronal tissue. We verified the biological relevance of several of these miRNAs and found that many miRNAs likely regulate dauer formation through multiple dauer-related targets. Further analysis of target mRNAs suggests potential miRNA involvement in various neuronal processes, but the importance of these miRNA::mRNA interactions remains unclear. Finally, we found that neuronal genes may be more highly regulated by miRNAs than intestinal genes. Overall, our study identifies miRNAs and their targets, and a physiological function of these miRNAs in neurons. It also suggests that compromising other aspects of gene expression, along with miRISC, can be an effective approach to reveal miRNA functions in specific tissues under specific physiological conditions.

Effect of Beach Nourishment and Borrowing on Marine Organisms.

DTIC Science & Technology

1982-12-01

turbellarians (flat- wormsN, nematode (roundworms), gastrotrichs, and harpacticoid copepods (crustacean6). The vertical distribution of many of these organisms in...were washed inshore increasing species diversity along the beach. Simon and Dauer (1977) studied faunal damage caused by red tide at Tampa Bay, Florida...and Ecology, Vol. 46, 1980, pp. 59-71. 56. SIMON, J.L., and DAUER , D.M., "Reestablishment of a Benthic Community Following Natural Defaunation

C. elegans dauer formation and the molecular basis of plasticity

PubMed Central

Fielenbach, Nicole; Antebi, Adam

2008-01-01

Because life is often unpredictable, dynamic, and complex, all animals have evolved remarkable abilities to cope with changes in their external environment and internal physiology. This regulatory plasticity leads to shifts in behavior and metabolism, as well as to changes in development, growth, and reproduction, which is thought to improve the chances of survival and reproductive success. In favorable environments, the nematode Caenorhabditis elegans develops rapidly to reproductive maturity, but in adverse environments, animals arrest at the dauer diapause, a long-lived stress resistant stage. A molecular and genetic analysis of dauer formation has revealed key insights into how sensory and dietary cues are coupled to conserved endocrine pathways, including insulin/IGF, TGF-β, serotonergic, and steroid hormone signal transduction, which govern the choice between reproduction and survival. These and other pathways reveal a molecular basis for metazoan plasticity in response to extrinsic and intrinsic signals. PMID:18708575

Untangling Longevity, Dauer, and Healthspan in Caenorhabditis elegans Insulin/IGF-1-Signalling.

PubMed

Ewald, Collin Yvès; Castillo-Quan, Jorge Iván; Blackwell, T Keith

2018-01-01

The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode Caenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor gene daf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. In C. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enables C. elegans to endure harsh environments through morphological adaptation, improved cellular repair, and slowed metabolism. Considerable progress has been made uncovering mechanisms that are affected by C. elegans rIIS. However, from the beginning it has remained unclear to what extent rIIS extends C. elegans lifespan by mobilizing dauer-associated mechanisms in adults. As we discuss, recent work has shed light on this question by determining that rIIS can extend C. elegans lifespan comparably through downstream processes that are either dauer-related or -independent. Importantly, these two lifespan extension programs can be distinguished genetically. It will now be critical to tease apart these programs, because each may involve different longevity-promoting mechanisms that may be relevant to higher organisms. A recent analysis of organismal "healthspan" has questioned the value of C. elegans rIIS as a paradigm for understanding healthy aging, as opposed to simply extending life. We discuss other work that argues strongly that C. elegans rIIS is indeed an invaluable model and consider the likely possibility that dauer-related processes affect parameters associated with health under rIIS conditions. Together, these studies indicate that C. elegans and analyses of rIIS in this organism will continue to provide unexpected and exciting results, and new paradigms that will be valuable for understanding healthy aging in humans. © 2017 S. Karger AG, Basel.

Lifespan extending activity of substances secreted by the nematode Caenorhabditis elegans that include the dauer-inducing pheromone.

PubMed

Kawano, Tsuyoshi; Kataoka, Naoya; Abe, Sunao; Ohtani, Mari; Honda, Yoko; Honda, Shuji; Kimura, Yasuo

2005-12-01

The nematode Caenorhabditis elegans yields a substance(s) inducing the larval diapause, called dauer-inducing pheromone. We discovered that the crude pheromone extract extends the adult lifespan in the animal. This extension does not occur in the mutant animal, in which expansion of the lifespan caused by other mutations reducing insulin signaling is suppressed. This is the first description concerning the relevancy of the pheromone to the longevity in the animal.

Dredging Operations Technical Support Program. A Framework for Assessing the Need for Seasonal Restrictions on Dredging and Disposal Operations

DTIC Science & Technology

1991-07-01

size will influence whether burial will occur. Although meiofaunal or- ganisms such as nematodes and harpacticoid copepods are relatively mobile, they...Saloman and Naughton 1977, Simon and Dauer 1977). Meiobenthic assemblages, on the other hand, have been reported to have very low rates (years) of...pp 541-558. Shulenberger, E. 1970. Responses of Gemma gemma to a Catastrophic Burial," Veliger, Vol 13, pp 163-170. Simon, J. L., and Dauer , D. M. 1977

Alloionema californicum n. sp. (Nematoda: Alloionematidae): a new alloionematid from USA.

PubMed

Nermuť, Jiří; Půža, Vladimír; Mráček, Zdeněk; Lewis, Edwin

2016-11-07

A new species of the family Alloionematidae was isolated from a rotten winged gourd at White Crane Garden, San Francisco, USA, sampled by Christopher Nelson in November 2010, and a live culture is deposited in Félix Lab Strain Database (http://www.justbio.com/worms/index.php), IBENS, Paris, France. Specimens from the culture have been examined. Both morphologically and molecularly, the nematode described herein as Alloionema californicum n. sp. differs from the other alloionematid species, A. appendiculatum and Neoalloionema tricaudatum. It is characterised by having a narrow stoma, 2.5-3.5 or 4 times longer than broad in adults or dauer juveniles respectively. Lateral fields are not present in adults but occur as one prominent ridge in dauers. Males have no bursa, six pairs of genital papillae and one single papilla. Dauers have large apparent phasmids in the middle of the tail. The ecology of the newly described species is unknown but probably it is a saprobic bacteriophagous nematode preferring rotting organic material.

Hormone signaling and phenotypic plasticity in nematode development and evolution.

PubMed

Sommer, Ralf J; Ogawa, Akira

2011-09-27

Phenotypic plasticity refers to the ability of an organism to adopt different phenotypes depending on environmental conditions. In animals and plants, the progression of juvenile development and the formation of dormant stages are often associated with phenotypic plasticity, indicating the importance of phenotypic plasticity for life-history theory. Phenotypic plasticity has long been emphasized as a crucial principle in ecology and as facilitator of phenotypic evolution. In nematodes, several examples of phenotypic plasticity have been studied at the genetic and developmental level. In addition, the influence of different environmental factors has been investigated under laboratory conditions. These studies have provided detailed insight into the molecular basis of phenotypic plasticity and its ecological and evolutionary implications. Here, we review recent studies on the formation of dauer larvae in Caenorhabditis elegans, the evolution of nematode parasitism and the generation of a novel feeding trait in Pristionchus pacificus. These examples reveal a conserved and co-opted role of an endocrine signaling module involving the steroid hormone dafachronic acid. We will discuss how hormone signaling might facilitate life-history and morphological evolution. Copyright © 2011 Elsevier Ltd. All rights reserved.

A conserved neuronal DAF-16/FoxO plays an important role in conveying pheromone signals to elicit repulsion behavior in Caenorhabditis elegans.

PubMed

Park, Donha; Hahm, Jeong-Hoon; Park, Saeram; Ha, Go; Chang, Gyeong-Eon; Jeong, Haelim; Kim, Heekyeong; Kim, Sunhee; Cheong, Eunji; Paik, Young-Ki

2017-08-03

Animals use pheromones as a conspecific chemical language to respond appropriately to environmental changes. The soil nematode Caenorhabditis elegans secretes ascaroside pheromones throughout the lifecycle, which influences entry into dauer phase in early larvae, in addition to sexual attraction and aggregation. In adult hermaphrodites, pheromone sensory signals perceived by worms usually elicit repulsion as an initial behavioral signature. However, the molecular mechanisms underlying neuronal pheromone sensory process from perception to repulsion in adult hermaphrodites remain poorly understood. Here, we show that pheromone signals perceived by GPA-3 is conveyed through glutamatergic neurotransmission in which neuronal DAF-16/FoxO plays an important modulatory role by controlling glutaminase gene expression. We further provide evidence that this modulatory role for DAF-16/FoxO seems to be conserved evolutionarily by electro-physiological study in mouse primary hippocampal neurons that are responsible for glutamatergic neurotransmission. These findings provide the basis for understanding the nematode pheromone signaling, which seems crucial for adaptation of adult hermaphrodites to changes in environmental condition for survival.

Developmental programming modulates olfactory behavior in C. elegans via endogenous RNAi pathways

PubMed Central

Sims, Jennie R; Ow, Maria C; Nishiguchi, Mailyn A; Kim, Kyuhyung; Sengupta, Piali; Hall, Sarah E

2016-01-01

Environmental stress during early development can impact adult phenotypes via programmed changes in gene expression. C. elegans larvae respond to environmental stress by entering the stress-resistant dauer diapause pathway and resume development once conditions improve (postdauers). Here we show that the osm-9 TRPV channel gene is a target of developmental programming and is down-regulated specifically in the ADL chemosensory neurons of postdauer adults, resulting in a corresponding altered olfactory behavior that is mediated by ADL in an OSM-9-dependent manner. We identify a cis-acting motif bound by the DAF-3 SMAD and ZFP-1 (AF10) proteins that is necessary for the differential regulation of osm-9, and demonstrate that both chromatin remodeling and endo-siRNA pathways are major contributors to the transcriptional silencing of the osm-9 locus. This work describes an elegant mechanism by which developmental experience influences adult phenotypes by establishing and maintaining transcriptional changes via RNAi and chromatin remodeling pathways. DOI: http://dx.doi.org/10.7554/eLife.11642.001 PMID:27351255

H3K4 demethylase activities repress proliferative and postmitotic aging

PubMed Central

Alvares, Stacy M; Mayberry, Gaea A; Joyner, Ebony Y; Lakowski, Bernard; Ahmed, Shawn

2014-01-01

Homeostasis of postmitotic and proliferating cells is maintained by pathways that repress stress. We found that the Caenorhabditis elegans histone 3 lysine 4 (H3K4) demethylases RBR-2 and SPR-5 promoted postmitotic longevity of stress-resistant daf-2 adults, altered pools of methylated H3K4, and promoted silencing of some daf-2 target genes. In addition, RBR-2 and SPR-5 were required for germ cell immortality at a high temperature. Transgenerational proliferative aging was enhanced for spr-5; rbr-2 double mutants, suggesting that these histone demethylases may function sequentially to promote germ cell immortality by targeting distinct H3K4 methyl marks. RBR-2 did not play a comparable role in the maintenance of quiescent germ cells in dauer larvae, implying that it represses stress that occurs as a consequence of germ cell proliferation, rather than stress that accumulates in nondividing cells. We propose that H3K4 demethylase activities promote the maintenance of chromatin states during stressful growth conditions, thereby repressing postmitotic aging of somatic cells as well as proliferative aging of germ cells. PMID:24134677

Strongyloides stercoralis and relatives: recent advances in general and molecular biology.

PubMed

Lok, James B

2014-12-01

Human strongyloidiasis is a threat to global health, presenting significant challenges in diagnosis and clinical management. The imperative to incorporate strongyoidiasis more fully into control programs for soil-transmitted helminths is increasingly recognized. The unique life cycles of S. stercoralis and congeneric species contain both free-living and parasitic generations, and transcriptomic methods have recently identified genes of potential importance to parasitism in these parasites. Proteomics recently revealed stage-specific secreted proteins that appear crucial to the host-parasite interaction. A comprehensive genome sequencing project for Strongyloides spp. is now nearing completion. Recent technical advances in transgenesis for S. stercoralis and S. ratti , including the first establishment of stable transgenic lines, promise to advance functional evaluations of genes expressed in conjunction with crucial life cycle events. Studies employing these methods recently bolstered the hypothesis that S. stercoralis uses cellular signaling pathways homologous to three that regulate dauer larval development in Caenorhabditis elegans to regulate morphogenesis and development of its infective third-stage larva. The free-living generation of Strongyloides makes classical genetics formally possible. Recent advances, such as a genetic map of S. ratti and a molecular genetic and karyotypic analysis of sex determination in S. papillosus , will greatly facilitate this approach. Advanced methods for study of chemosensation in C. elegans were recently applied to discover numerous host attractant molecules that mediate host finding and contact by infective third-stage larvae of Strongyloides spp. Finally, nucleic acid-based diagnostic methods have recently come to the fore as alternatives to parasitological and immunodiagnostic techniques.

Expanding the view on the evolution of the nematode dauer signalling pathways: refinement through gene gain and pathway co-option.

PubMed

Gilabert, Aude; Curran, David M; Harvey, Simon C; Wasmuth, James D

2016-06-27

Signalling pathways underlie development, behaviour and pathology. To understand patterns in the evolution of signalling pathways, we undertook a comprehensive investigation of the pathways that control the switch between growth and developmentally quiescent dauer in 24 species of nematodes spanning the phylum. Our analysis of 47 genes across these species indicates that the pathways and their interactions are not conserved throughout the Nematoda. For example, the TGF-β pathway was co-opted into dauer control relatively late in a lineage that led to the model species Caenorhabditis elegans. We show molecular adaptations described in C. elegans that are restricted to its genus or even just to the species. Similarly, our analyses both identify species where particular genes have been lost and situations where apparently incorrect orthologues have been identified. Our analysis also highlights the difficulties of working with genome sequences from non-model species as reliance on the published gene models would have significantly restricted our understanding of how signalling pathways evolve. Our approach therefore offers a robust standard operating procedure for genomic comparisons.

Venereal worms: sexually transmitted nematodes in the decorated cricket.

PubMed

Luong, L T; Platzer, E G; Zuk, M; Giblin-Davis, R M

2000-06-01

The nematode, Mehdinema alii, occurs in the alimentary canal of the decorated cricket Gryllodes sigillatus. Adult nematodes occur primarily in the hindgut of mature male crickets, whereas juvenile nematodes are found in the genital chambers of mature male and female crickets. Here, we present experimental evidence for the venereal transmission of M. alii in G. sigillatus. Infectivity experiments were conducted to test for transmission via oral-fecal contamination, same-sex contact, and copulation. The infective dauers of the nematode are transferred from male to female crickets during copulation. Adult female crickets harboring infective dauers subsequently transfer the nematode to their next mates. Thus, M. alii is transmitted sexually during copulation.

WormSizer: high-throughput analysis of nematode size and shape.

PubMed

Moore, Brad T; Jordan, James M; Baugh, L Ryan

2013-01-01

The fundamental phenotypes of growth rate, size and morphology are the result of complex interactions between genotype and environment. We developed a high-throughput software application, WormSizer, which computes size and shape of nematodes from brightfield images. Existing methods for estimating volume either coarsely model the nematode as a cylinder or assume the worm shape or opacity is invariant. Our estimate is more robust to changes in morphology or optical density as it only assumes radial symmetry. This open source software is written as a plugin for the well-known image-processing framework Fiji/ImageJ. It may therefore be extended easily. We evaluated the technical performance of this framework, and we used it to analyze growth and shape of several canonical Caenorhabditis elegans mutants in a developmental time series. We confirm quantitatively that a Dumpy (Dpy) mutant is short and fat and that a Long (Lon) mutant is long and thin. We show that daf-2 insulin-like receptor mutants are larger than wild-type upon hatching but grow slow, and WormSizer can distinguish dauer larvae from normal larvae. We also show that a Small (Sma) mutant is actually smaller than wild-type at all stages of larval development. WormSizer works with Uncoordinated (Unc) and Roller (Rol) mutants as well, indicating that it can be used with mutants despite behavioral phenotypes. We used our complete data set to perform a power analysis, giving users a sense of how many images are needed to detect different effect sizes. Our analysis confirms and extends on existing phenotypic characterization of well-characterized mutants, demonstrating the utility and robustness of WormSizer.

An improved kit for culturing clean nematode, larvae from faeces.

PubMed

Ndalahwa, J B; Lwambo, N J

1989-03-01

A kit for rapid recovery of clean hookworm and Strongyloides stercoralis larvae from faeces was devised. It consists of a 2.0dl perspex cup shaped container 35 x 30 x 24mm in size. A horse shoe stirrup aluminium sheet 54mm long and 20mm wide is inserted into the container so that the free ends stand at the bottom of the apparatus. The back of the stirrup carries a plastic disc 30mm in diameter through which two adjacent crescent shaped openings are cut. A strip of filter paper 40 x 20mm in size passes through the crescent openings astride the stirrup and its loose ends are bound together by means of a stapler. When the kit is assembled, the disk fits firmly in the middle of the container dividing it into lower and upper chambers. The staples free ends of the filter paper hang immersed into water in the lower chamber of the apparatus. A faecal sample is smeared on the upper part of the filter paper. Nematode larvae, if present, crawl from the faeces down the damp filter paper into the water at the bottom of the container.

Structural and functional characterisation of FOXO/Acan-DAF-16 from the parasitic nematode Angiostrongylus cantonensis.

PubMed

Yan, Baolong; Sun, Weiwei; Yan, Lanzhu; Zhang, Liangliang; Zheng, Yuan; Zeng, Yuzhen; Huang, Huicong; Liang, Shaohui

2016-12-01

Fork head box transcription factors subfamily O (FoxO) is regarded to be significant in cell-cycle control, cell differentiation, ageing, stress response, apoptosis, tumour formation and DNA damage repair. In the free-living nematode Caenorhabditis elegans, the FoxO transcription factor is encoded by Ce-daf-16, which is negatively regulated by insulin-like signaling (IIS) and involved in promoting dauer formation through bringing about its hundreds of downstream genes expression. In nematode parasites, orthologues of daf-16 from several species have been identified, with functions in rescue of dauer phenotypes determined in a surrogate system C. elegans. In this study, we identified the FoxO encoding gene, Acan-daf-16, from the parasitic nematode Angiostrongylus cantonensis, and determined the genomic structures, transcripts and functions far more thorough in longevity, stress resistance and dauer formation. Acan-daf-16 encodes two proteins, Acan-DAF-16A and Acan-DAF-16B, consisting of 555 and 491 amino acids, respectively. Both isoforms possess the highly conserved fork head domains. Acan-daf-16A and Acan-daf-16B are expressed from distinct promoters. The expression patterns of Acan-daf-16 isoforms in the C. elegans surrogate system showed that p Acan-daf-16a:gfp was expressed in all cells of C. elegans, including the pharynx, and the expression of p Acan-daf-16b:gfp was restricted to the pharynx. In addition to the same genomic organization to the orthologue in C. elegans, Ce-daf-16, both Acan-DAF-16 isoforms could restore the C. elegans daf-16(mg54) mutation in longevity, dauer formation and stress resistance, in spite of the partial complementation of Acan-DAF-16B isoform in longevity. These findings provide further evidence of the functional conservation of DAF-16s between parasitic nematodes and the free-living nematode C. elegans. Copyright © 2016. Published by Elsevier B.V.

Activated AKT/PKB signaling in C. elegans uncouples temporally distinct outputs of DAF-2/insulin-like signaling

PubMed Central

Gami, Minaxi S; Iser, Wendy B; Hanselman, Keaton B; Wolkow, Catherine A

2006-01-01

Background In the nematode, Caenorhabditis elegans, a conserved insulin-like signaling pathway controls larval development, stress resistance and adult lifespan. AGE-1, a homolog of the p110 catalytic subunit of phosphoinositide 3-kinases (PI3K) comprises the major known effector pathway downstream of the insulin receptor, DAF-2. Phospholipid products of AGE-1/PI3K activate AKT/PKB kinase signaling via PDK-1. AKT/PKB signaling antagonizes nuclear translocation of the DAF-16/FOXO transcription factor. Reduced AGE-1/PI3K signaling permits DAF-16 to direct dauer larval arrest and promote long lifespan in adult animals. In order to study the downstream effectors of AGE-1/PI3K signaling in C. elegans, we conducted a genetic screen for mutations that suppress the constitutive dauer arrest phenotype of age-1(mg109) animals. Results This report describes mutations recovered in a screen for suppressors of the constitutive dauer arrest (daf-C) phenotype of age-1(mg109). Two mutations corresponded to alleles of daf-16. Two mutations were gain-of-function alleles in the genes, akt-1 and pdk-1, encoding phosphoinositide-dependent serine/threonine kinases. A fifth mutation, mg227, located on chromosome X, did not correspond to any known dauer genes, suggesting that mg227 may represent a new component of the insulin pathway. Genetic epistasis analysis by RNAi showed that reproductive development in age-1(mg109);akt-1(mg247) animals was dependent on the presence of pdk-1. Similarly, reproductive development in age-1(mg109);pdk-1(mg261) animals was dependent on akt-1. However, reproductive development in age-1(mg109); mg227 animals required only akt-1, and pdk-1 activity was dispensable in this background. Interestingly, while mg227 suppressed dauer arrest in age-1(mg109) animals, it enhanced the long lifespan phenotype. In contrast, akt-1(mg247) and pdk-1(mg261) did not affect lifespan or stress resistance, while both daf-16 alleles fully suppressed these phenotypes. Conclusion A screen for suppressors of PI3K mutant phenotypes identified activating mutations in two known pathway components, providing insights into their regulation. In particular, the interdependence of akt-1 and pdk-1, even in activated forms, supports the existence of AGE-1-independent pathways for these phospholipid-dependent kinases. Phenotypic analysis of these alleles shows that the larval and adult outputs of AGE-1/PI3K are fully separable in these mutants. PMID:17020605

Caenorhabditis elegans Pheromones Regulate Multiple Complex Behaviors

PubMed Central

Edison, Arthur S.

2009-01-01

Summary of recent advances A family of small molecules called ascarosides act as pheromones to control multiple behaviors in the nematode Caenorhabditis elegans. At picomolar concentrations, a synergistic mixture of at least three ascarosides produced by hermaphrodites causes male-specific attraction. At higher concentrations, the same ascarosides, perhaps in a different mixture, induce the developmentally arrested stage known as dauer. The production of ascarosides is strongly dependent on environmental conditions, although relatively little is known about the major variables and mechanisms of their regulation. Thus, male mating and dauer formation are linked through a common set of small molecules whose expression is sensitive to a given microenvironment, suggesting a model by which ascarosides regulate the overall life cycle of C. elegans. PMID:19665885

Succession and dynamics of Pristionchus nematodes and their microbiome during decomposition of Oryctes borbonicus on La Réunion Island.

PubMed

Meyer, Jan M; Baskaran, Praveen; Quast, Christian; Susoy, Vladislav; Rödelsperger, Christian; Glöckner, Frank O; Sommer, Ralf J

2017-04-01

Insects and nematodes represent the most species-rich animal taxa and they occur together in a variety of associations. Necromenic nematodes of the genus Pristionchus are found on scarab beetles with more than 30 species known from worldwide samplings. However, little is known about the dynamics and succession of nematodes and bacteria during the decomposition of beetle carcasses. Here, we study nematode and bacterial succession of the decomposing rhinoceros beetle Oryctes borbonicus on La Réunion Island. We show that Pristionchus pacificus exits the arrested dauer stage seven days after the beetles´ deaths. Surprisingly, new dauers are seen after 11 days, suggesting that some worms return to the dauer stage after one reproductive cycle. We used high-throughput sequencing of the 16S rRNA genes of decaying beetles, beetle guts and nematodes to study bacterial communities in comparison to soil. We find that soil environments have the most diverse bacterial communities. The bacterial community of living and decaying beetles are more stable but one single bacterial family dominates the microbiome of decaying beetles. In contrast, the microbiome of nematodes is relatively similar even across different families. This study represents the first characterization of the dynamics of nematode-bacterial interactions during the decomposition of insects. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Methionine as a safe and effective novel biorational mosquito larvicide.

PubMed

Weeks, Emma N I; Baniszewski, Julie; Gezan, Salvador A; Allan, Sandra A; Cuda, James P; Stevens, Bruce R

2018-06-11

Mosquito larvicides provide a source-reduction strategy to diminish adult females that bite and potentially spread pathogens. Demands are mounting for new and innovative effective biorational larvicides, due to the development of resistance to some currently utilized mosquito larvicides, undesirable non-target effects, and U.S. Environmental Protection Agency (EPA) restrictions. Methionine is a human nutrient essential amino acid that unexpectedly has been shown to be a valuable safe pest management tool against select insect pests that possess alkaline gut physiology. The present study evaluated larvicidal toxicity of methionine in several pestiferous mosquito (Diptera: Culicidae) genera. Concentration-dependent DL-methionine kinetics assays of survival and pupation were conducted in larvae of Aedes albopictus Skuse, Anopheles quadrimaculatus Say, and Culex tarsalis Coquillett in glass jars. Higher concentrations of DL-methionine yielded 100% mortality for all test species and prevented pupation at a rate equivalent to Bacillus thuringiensis israelensis (Bti) treatments. Concentration kinetics indicated that An. quadrimaculatus was 10-fold more sensitive to DL-methionine than Ae. albopictus and Cx. tarsalis. EPA regulations currently exempt methionine in pesticide formulations applied to agricultural crops. This study demonstrates that methionine is a highly effective mosquito larvicide that can provide a beneficial new biorational, environmentally sustainable tool to control pestiferous mosquitoes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Titres of biogenic amines and ecdysteroids: effect of octopamine on the production of ecdysteroids in the silkworm Bombyx mori.

PubMed

Hirashima, A; Hirokado, S; Ohta, H; Suetsugu, E; Sakaguchi, M; Kuwano, E; Taniguchi, E; Eto, M

1999-09-01

At day two, a sharp peak of octopamine (OA) was observed in last instar female Bombyx mori larvae. This peak also appeared in male larvae a day later than in females at day three. An OA peak was also observed before the 3rd ecdysis. However, no OA peaks were observed in 4th instar larvae. At day eight and nine of the 5th instar, another OA peak was observed for male and female, respectively. A peak of tyramine (TA) was found at day one followed by a peak of OA at day two in 3rd instar larvae. At day two, a day before OA peak, a peak of TA was observed for male insects and before the 2nd peak of OA, TA titre was also high in 5th instar larvae. Immediately after 3rd ecdysis, a high titre of DL-beta-(3,4-dihydroxyphenyl)alanine (DOPA) was observed, followed by a peak of dopamine (DA) at day five. A peak of DOPA was found at day one followed by a peak of DA at day two in 3rd instar larvae. Similarly, a small peak of DOPA was observed at day two, followed by an increase of DA at days eight and nine after the 4th ecdysis. Ecdysteroid peaks were observed just before the 3rd and 4th ecdysis and an ecdysteroid titre increased after the start of spinning. The effects of OA and JH on production of ecdysteroids by prothoracic glands (PGs) were examined in order to identify neuromediators responsible for triggering pupation in B. mori larvae. Exogeneous OA (10-100 mM) reduced and 10 &mgr;M OA stimulated the production of ecdysteroids in the presence and absence of brain extracts by PGs in the final instar (day five) of B. mori in vitro. Meanwhile, exogeneous JHI (10 &mgr;g/ml) stimulated and at 5 &mgr;g/ml it reduced production of ecdysteroids in the presence of brain extracts. Gramine, an OA antagonist, delayed pupation when applied in the diet. Thus, OA may produce some biological effects on the programming of larval-pupal development.

Drosophila larvae synthesize the putative oncometabolite L-2-hydroxyglutarate during normal developmental growth

PubMed Central

Li, Hongde; Chawla, Geetanjali; Hurlburt, Alexander J.; Sterrett, Maria C.; Zaslaver, Olga; Cox, James; Karty, Jonathan A.; Rosebrock, Adam P.; Caudy, Amy A.

2017-01-01

L-2-hydroxyglutarate (L-2HG) has emerged as a putative oncometabolite that is capable of inhibiting enzymes involved in metabolism, chromatin modification, and cell differentiation. However, despite the ability of L-2HG to interfere with a broad range of cellular processes, this molecule is often characterized as a metabolic waste product. Here, we demonstrate that Drosophila larvae use the metabolic conditions established by aerobic glycolysis to both synthesize and accumulate high concentrations of L-2HG during normal developmental growth. A majority of the larval L-2HG pool is derived from glucose and dependent on the Drosophila estrogen-related receptor (dERR), which promotes L-2HG synthesis by up-regulating expression of the Drosophila homolog of lactate dehydrogenase (dLdh). We also show that dLDH is both necessary and sufficient for directly synthesizing L-2HG and the Drosophila homolog of L-2-hydroxyglutarate dehydrogenase (dL2HGDH), which encodes the enzyme that breaks down L-2HG, is required for stage-specific degradation of the L-2HG pool. In addition, dLDH also indirectly promotes L-2HG accumulation via synthesis of lactate, which activates a metabolic feed-forward mechanism that inhibits dL2HGDH activity and stabilizes L-2HG levels. Finally, we use a genetic approach to demonstrate that dLDH and L-2HG influence position effect variegation and DNA methylation, suggesting that this compound serves to coordinate glycolytic flux with epigenetic modifications. Overall, our studies demonstrate that growing animal tissues synthesize L-2HG in a controlled manner, reveal a mechanism that coordinates glucose catabolism with L-2HG synthesis, and establish the fly as a unique model system for studying the endogenous functions of L-2HG during cell growth and proliferation. PMID:28115720

Drosophila larvae synthesize the putative oncometabolite L-2-hydroxyglutarate during normal developmental growth.

PubMed

Li, Hongde; Chawla, Geetanjali; Hurlburt, Alexander J; Sterrett, Maria C; Zaslaver, Olga; Cox, James; Karty, Jonathan A; Rosebrock, Adam P; Caudy, Amy A; Tennessen, Jason M

2017-02-07

L-2-hydroxyglutarate (L-2HG) has emerged as a putative oncometabolite that is capable of inhibiting enzymes involved in metabolism, chromatin modification, and cell differentiation. However, despite the ability of L-2HG to interfere with a broad range of cellular processes, this molecule is often characterized as a metabolic waste product. Here, we demonstrate that Drosophila larvae use the metabolic conditions established by aerobic glycolysis to both synthesize and accumulate high concentrations of L-2HG during normal developmental growth. A majority of the larval L-2HG pool is derived from glucose and dependent on the Drosophila estrogen-related receptor (dERR), which promotes L-2HG synthesis by up-regulating expression of the Drosophila homolog of lactate dehydrogenase (dLdh). We also show that dLDH is both necessary and sufficient for directly synthesizing L-2HG and the Drosophila homolog of L-2-hydroxyglutarate dehydrogenase (dL2HGDH), which encodes the enzyme that breaks down L-2HG, is required for stage-specific degradation of the L-2HG pool. In addition, dLDH also indirectly promotes L-2HG accumulation via synthesis of lactate, which activates a metabolic feed-forward mechanism that inhibits dL2HGDH activity and stabilizes L-2HG levels. Finally, we use a genetic approach to demonstrate that dLDH and L-2HG influence position effect variegation and DNA methylation, suggesting that this compound serves to coordinate glycolytic flux with epigenetic modifications. Overall, our studies demonstrate that growing animal tissues synthesize L-2HG in a controlled manner, reveal a mechanism that coordinates glucose catabolism with L-2HG synthesis, and establish the fly as a unique model system for studying the endogenous functions of L-2HG during cell growth and proliferation.

An entomoparasitic adult form in Bursaphelenchus doui (Nematoda: Tylenchomorpha) associated with Acalolepta fraudatrix.

PubMed

Kanzaki, Natsumi; Maehara, Noritoshi; Aikawa, Takuya; Nakamura, Katsunori

2013-10-01

The nematode family Aphelenchoididae (Rhabditida: Tylenchomorpha) includes species with various feeding habitats. Bursaphelenchus, a member of the family, has for a long time been considered as a home for plant parasitic or mycophagous species (or both). However, recent intensive biological studies on the family revealed that the genus contains several insect parasitic species. Dauer juveniles of Bursaphelenchus doui were isolated from Acalolepta fraudatrix during a field study of longhorn beetle-Bursaphelenchus nematode associations. Two different insect-associated forms, an "entomoparasitic adult form" and a regular dauer juvenile, were isolated from a single individual beetle in a subsequent laboratory investigation of the B. doui-A. fraudatrix relationship. Thus these 2 distinct, insect-associated forms were confirmed to occur simultaneously. The entomoparasitic form is morphologically similar to that of Bursaphelenchus luxuriosae, with a dome-shaped head and vacuole-like spots assumed to be an internal structure of sensory organ, a stylet, a metacorpus (median bulb), and a moderately-developed and seemingly fully functional reproductive system. It is distinguishable from B. luxuriosae based on male spicule morphology and female tail morphology. A degenerate ingestive-digestive system distinguishes the entomoparasitic form from the propagative form and, unlike dauer juveniles, it has a moderately-developed reproductive system. The presence of this characteristic parasitic adult form is known only in these 2 Bursaphelenchus species. However, these 2 species did not form a clear monophyletic clade within the Bursaphelenchus xylophilus group and, thus, this characteristic parasitic form may occur independently in each species.

The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans.

PubMed

Dorman, J B; Albinder, B; Shroyer, T; Kenyon, C

1995-12-01

Recessive mutations in two genes, daf-2 and age-1, extend the lifespan of Caenorhabditis elegans significantly. The daf-2 gene also regulates formation of an alternative developmental state called the dauer. Here we asked whether these two genes function in the same or different lifespan pathways. We found that the longevity of both age-1 and daf-2 mutants requires the activities of the same two genes, daf-16 and daf-18. In addition, the daf-2(e1370); age-1(hx546) double mutant did not live significantly longer than the daf-2 single mutant. We also found that, like daf-2 mutations, the age-1(hx546) mutation affects certain aspects of dauer formation. These findings suggest that age-1 and daf-2 mutations do act in the same lifespan pathway and extend lifespan by triggering similar if not identical processes.

The Age-1 and Daf-2 Genes Function in a Common Pathway to Control the Lifespan of Caenorhabditis Elegans

PubMed Central

Dorman, J. B.; Albinder, B.; Shroyer, T.; Kenyon, C.

1995-01-01

Recessive mutations in two genes, daf-2 and age-1, extend the lifespan of Caenorhabditis elegans significantly. The daf-2 gene also regulates formation of an alternative developmental state called the dauer. Here we asked whether these two genes function in the same or different lifespan pathways. We found that the longevity of both age-1 and daf-2 mutants requires the activities of the same two genes, daf-16 and daf-18. In addition, the daf-2(e1370); age-1(hx546) double mutant did not live significantly longer than the daf-2 single mutant. We also found that, like daf-2 mutations, the age-1(hx546) mutation affects certain aspects of dauer formation. These findings suggest that age-1 and daf-2 mutations do act in the same lifespan pathway and extend lifespan by triggering similar if not identical processes. PMID:8601482

Influence of developmental stage, salts and food presence on various end points using Caenorhabditis elegans for aquatic toxicity testing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donkin, S.G.; Williams, P.L.

1995-12-01

This study used a randomized block design to investigate the importance of several variables in using the free-living soil nematode, Caenorhabditis elegans, for aquatic toxicity testing. Concentration-response data were obtained on nematodes of various developmental stages exposed to four metals (Cd, Pb, Cu, and Hg) and a water-soluble organic toxicant, sodium pentachlorophenate (PCP), under conditions of varied solvent medium (with or without salts and with or without a bacterial food source). The end points measured were 24- and 96-h mortality LC50 value, as well as development of larval stages to adulthood and evidence of reproduction. The results suggest that nematodesmore » of various ages respond similarity to a given toxicant for all end points measured, although adults cultured from eggs appeared more sensitive than adults cultured from dauer larvae. The most important environmental variable in determining toxicity was the medium in which the tests were conducted. The presence of potassium and sodium salts in the medium significantly (p < 0.05) reduced the toxicity of many test samples. The presence of bacteria had little effect on 24-h tests with salts, but was important in 96-h survival and development. Based on sensitivity and ease of handling, adults cultured from eggs are recommended in both 24h and 96-h tests.« less

Minimal resin embedding of multicellular specimens for targeted FIB-SEM imaging.

PubMed

Schieber, Nicole L; Machado, Pedro; Markert, Sebastian M; Stigloher, Christian; Schwab, Yannick; Steyer, Anna M

2017-01-01

Correlative light and electron microscopy (CLEM) is a powerful tool to perform ultrastructural analysis of targeted tissues or cells. The large field of view of the light microscope (LM) enables quick and efficient surveys of the whole specimen. It is also compatible with live imaging, giving access to functional assays. CLEM protocols take advantage of the features to efficiently retrace the position of targeted sites when switching from one modality to the other. They more often rely on anatomical cues that are visible both by light and electron microscopy. We present here a simple workflow where multicellular specimens are embedded in minimal amounts of resin, exposing their surface topology that can be imaged by scanning electron microscopy (SEM). LM and SEM both benefit from a large field of view that can cover whole model organisms. As a result, targeting specific anatomic locations by focused ion beam-SEM (FIB-SEM) tomography becomes straightforward. We illustrate this application on three different model organisms, used in our laboratory: the zebrafish embryo Danio rerio, the marine worm Platynereis dumerilii, and the dauer larva of the nematode Caenorhabditis elegans. Here we focus on the experimental steps to reduce the amount of resin covering the samples and to image the specimens inside an FIB-SEM. We expect this approach to have widespread applications for volume electron microscopy on multiple model organisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Liquid culture mass production of biocontrol nematodes, Heterorhabditis bacteriophora (Nematoda: Rhabditida): improved timing of dauer juvenile inoculation.

PubMed

Johnigk, S-A; Ecke, F; Poehling, M; Ehlers, R-U

2004-06-01

Heterorhabditis bacteriophora is used in biological control of soil-borne insect pests in horticulture and turf. Mass production is carried out in monoxenic liquid cultures pre-incubated with the symbiont of the nematodes, the bacterium Photorhabdus luminescens, before nematode dauer juveniles (DJ) are inoculated. As a response to bacterial food signals, the DJ recover from the developmentally arrested dauer stage, grow to adults and produce DJ offspring. Variable DJ recovery after inoculation into cultures of P. luminescens often causes process failure due to low numbers of adult nematodes in the medium. In order to enhance DJ recovery, improve nematode population management and increase yields, the optimal timing for DJ inoculation was sought. The process parameter pH and respiration quotient (RQ) were recorded in order to test whether changes can be used to identify the best moment for DJ inoculation. When DJ were inoculated during the lag and early logarithmic growth phases of P. luminescens cultures, DJ recovery was low and almost no nematode reproduction was obtained. High populations of P. luminescens phase variants were recorded. Recovery and yields increased when DJ were inoculated during the latter log phase during which the RQ dropped to values <0.8 and the pH reached a maximum. The highest DJ recovery and yields were observed in cultures that were inoculated during the late stationary growth phase. This period started with the increase of the pH after its distinct minimum at pH <8.0. Thus optimal timing for DJ inoculation can be defined through monitoring of the pH in the P. luminescens culture.

Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans

PubMed Central

Ow, Maria C.; Nichitean, Alexandra M.; Dorus, Steve; Hall, Sarah E.

2018-01-01

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite (“seesaw”) transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome. PMID:29447162

Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans.

PubMed

Motola, Daniel L; Cummins, Carolyn L; Rottiers, Veerle; Sharma, Kamalesh K; Li, Tingting; Li, Yong; Suino-Powell, Kelly; Xu, H Eric; Auchus, Richard J; Antebi, Adam; Mangelsdorf, David J

2006-03-24

In response to environmental and dietary cues, the C. elegans orphan nuclear receptor, DAF-12, regulates dauer diapause, reproductive development, fat metabolism, and life span. Despite strong evidence for hormonal control, the identification of the DAF-12 ligand has remained elusive. In this work, we identified two distinct 3-keto-cholestenoic acid metabolites of DAF-9, a cytochrome P450 involved in hormone production, that function as ligands for DAF-12. At nanomolar concentrations, these steroidal ligands (called dafachronic acids) bind and transactivate DAF-12 and rescue the hormone deficiency of daf-9 mutants. Interestingly, DAF-9 has a biochemical activity similar to mammalian CYP27A1 catalyzing addition of a terminal acid to the side chain of sterol metabolites. Together, these results define the first steroid hormones in nematodes as ligands for an invertebrate orphan nuclear receptor and demonstrate that steroidal regulation of reproduction, from biology to molecular mechanism, is conserved from worms to humans.

Assessing the Developmental Neurotoxicity of 27 ...

EPA Pesticide Factsheets

Assessing the Developmental Neurotoxicity of 27 Organophosphorus Pesticides Using a Zebrafish Behavioral Assay, Waalkes, M., Hunter, D.L., Jarema, K., Mundy, W., and S. Padilla. The U.S. Environmental Protection Agency is evaluating methods to screen and prioritize organophosphorus pesticides for developmental neurotoxicity. As such, we are exploring a behavioral testing paradigm that can assess the effects of sublethal and subteratogenic concentrations of developmental neurotoxicants on zebrafish (Danio rerio). This in vivo assay quantifies the locomotor response to light stimuli under tandem light and dark conditions in a 96-well plate using a video tracking system on 6 day post fertilization zebrafish larvae. Each of twenty-seven organophosphorus pesticides was tested for their developmental neurotoxic potential by exposing zebrafish embryos/larvae to the pesticide at several concentrations (≤ 100 μM nominal concentration) during the first five days of development, followed by 24 hours of depuration and then behavioral testing. Approximately 22% of the chemicals (Acephate, Dichlorvos, Diazoxon, Bensulide,Tribufos, Tebupirimfos) did not produce any behavioral changes after developmental exposure, while many (Malaoxon Fosthiazate, Dimethoate, Dicrotophos, Ethoprop, Malathion, Naled, Diazinon, Methamidophos, Terbufos, Trichlorfon, Phorate, Pirimiphos-methyl, Profenofos, Z-Tetrachlorvinphos, Chlorpyrifos, Coumaphos, Phosmet, Omethoate) produced changes in swi

Effects of developmental stage, salts, and food presence on aquatic toxicological endpoints using Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donkin, S.G.; Williams, P.L.

1995-12-31

The objective of this study was to standardize the testing protocol for aquatic toxicity tests with the nematode Caenorhabditis elegans. Several variables which may be important in determining the test outcome were investigated in a randomized block design. Concentration-response data were obtained on nematodes of various developmental stages exposed to four metals (Cd, Pb, Cu, and Hg) and a water-soluble organic toxicant, sodium Pentachlorophenate (PCP), under conditions of varied solvent medium (with or without salts and with or without a bacterial food source). The endpoints measured were 24 and 96-h mortality, as well as development of larval stages to adulthoodmore » and evidence of reproduction. The results suggest that nematodes of various ages respond similarly to a given toxicant for all endpoints measured, although adults cultured from eggs appeared more sensitive than adults cultured from dauer larvae. The most important environmental variable in determining toxicity was the medium in which the tests were conducted. The presence of potassium and sodium salts in the medium significantly (p<0.05) reduced the toxicity of many test samples. The presence of bacteria had little effect on 24-h tests with salts, but was important in 96-h survival and development. Based on sensitivity and ease of handling, adults cultured from eggs are recommended in both 24-h and 96-h mortality (LC50 value) tests, as well as 96-h reproduction tests.« less

All Eggs Are Not Equal: The Maternal Environment Affects Progeny Reproduction and Developmental Fate in Caenorhabditis elegans

PubMed Central

Harvey, Simon C.; Orbidans, Helen E.

2011-01-01

Background Maternal effects on progeny traits are common and these can profoundly alter progeny life history. Maternal effects can be adaptive, representing attempts to appropriately match offspring phenotype to the expected environment and are often mediated via trade-offs between progeny number and quality. Here we have investigated the effect of maternal food availability on progeny life history in the free-living nematode Caenorhabditis elegans. Methodology/Principal Findings The maternal environment affects both reproductive traits and progeny development. Comparisons of the progeny of worms from high and low maternal food environments indicates that low maternal food availability reduces progeny reproduction in good environments, increases progeny reproduction in poor environments and decreases the likelihood that progeny will develop as dauer larvae. These analyses also indicate that the effects on progeny are not a simple consequence of changes in maternal body size, but are associated with an increase in the size of eggs produced by worms at low maternal food availabilities. Conclusions/Significance These results indicate that the maternal environment affects both progeny reproduction and development in C. elegans and therefore that all progeny are not equal. The observed effects are consistent with changes to egg provisioning, which are beneficial in harsh environments, and of changes to progeny development, which are beneficial in harsh environments and detrimental in benign environments. These changes in progeny life history suggest that mothers in poor quality environments may be producing larger eggs that are better suited to poor conditions. PMID:21991370

A comparison of mutations induced by accelerated iron particles versus those induced by low earth orbit space radiation in the FEM-3 gene of Caenorhabditis elegans

NASA Technical Reports Server (NTRS)

Hartman, P. S.; Hlavacek, A.; Wilde, H.; Lewicki, D.; Schubert, W.; Kern, R. G.; Kazarians, G. A.; Benton, E. V.; Benton, E. R.; Nelson, G. A.

2001-01-01

The fem-3 gene of Caenorhabditis elegans was employed to determine the mutation frequency as well as the nature of mutations induced by low earth orbit space radiation ambient to Space Shuttle flight STS-76. Recovered mutations were compared to those induced by accelerated iron ions generated by the AGS synchrotron accelerator at Brookhaven National Laboratory. For logistical reasons, dauer larvae were prepared at TCU, transported to either Kennedy Space Center or Brookhaven National Laboratory, flown in space or irradiated, returned to TCU and screened for mutants. A total of 25 fem-3 mutants were recovered after the shuttle flight and yielded a mutation frequency of 2.1x10(-5), roughly 3.3-fold higher than the spontaneous rate of 6.3x10(-6). Four of the mutations were homozygous inviable, suggesting that they were large deletions encompassing fem-3 as well as neighboring, essential genes. Southern blot analyses revealed that one of the 25 contained a polymorphism in fem-3, further evidence that space radiation can induce deletions. While no polymorphisms were detected among the iron ion-induced mutations, three of the 15 mutants were homozygous inviable, which is in keeping with previous observations that high LET iron particles generate deficiencies. These data provide evidence, albeit indirect, that an important mutagenic component of ambient space radiation is high LET charged particles such as iron ions.

Neuronal regulation of ascaroside response during mate response behavior in the nematode Caenorhabditis elegans

USDA-ARS?s Scientific Manuscript database

Small-molecule signaling plays an important role in the biology of Caenorhabditis elegans. We have previously shown that ascarosides, glycosides of the dideoxysugar ascarylose regulate both development and behavior in C. elegans The mating signal consists of a synergistic blend of three dauer-induc...

Influence of cell density and phase variants of bacterial symbionts (Xenorhabdus spp.) on dauer juvenile recovery and development of biocontrol nematodes Steinernema carpocapsae and S. feltiae (Nematoda: Rhabditida).

PubMed

Hirao, A; Ehlers, R-U

2009-08-01

The rhabditid nematodes Steinernema carpocapsae and Steinernema feltiae are used in biological control of insect pests. Mass production is done in liquid culture media pre-incubated with their bacterial symbionts Xenorhabdus nematophila and Xenorhabdus bovienii, respectively, before nematode dauer juveniles (DJs) are inoculated. As a response to food signals produced by the bacterial symbionts, the DJs exit from the developmentally arrested dauer stage (they recover development) and grow to adults, which produce DJ offspring. Variable DJ recovery after inoculation often causes process failure due to non-synchronous population development and low numbers of adult nematodes. This contribution investigated the influence of the bacterial cell density on DJ recovery and development to adults. At higher density of 10(10) bacterial cells ml(-1), a higher percentage of DJ recovery was induced, and adults occurred earlier in both Steinernema spp. than at lower density of 10(9) and 10(8) cells ml(-1). Xenorhabdus symbionts produce phase variants. Recovery in bacteria-free supernatants was lower than in supernatants containing bacterial cells for both primary and secondary phase Xenorhabdus spp. and lower in secondary than in primary phase supernatants or cell suspensions. In general, recovery was lower for Steinernema feltiae and the time at which 50% of the population had recovered after exposure to the food signal was longer (RT(50) = 17.1 h) than for Steinernema carpocapsae (RT(50) = 6.6 h). Whereas >90% S. carpocapsae DJs recovered in hemolymph serum of the lepidopteran insect Galleria mellonella, recovery of S. feltiae only reached 31%. Penetration into a host insect prior to exposure to the insect's food signal did not enhance DJ recovery. Consequences for liquid culture mass production of the nematodes and differences between species of the genera Steinernema and Heterorhabditis are discussed.

The DAF-16 FOXO Transcription Factor Regulates natc-1 to Modulate Stress Resistance in Caenorhabditis elegans, Linking Insulin/IGF-1 Signaling to Protein N-Terminal Acetylation

PubMed Central

Warnhoff, Kurt; Murphy, John T.; Kumar, Sandeep; Schneider, Daniel L.; Peterson, Michelle; Hsu, Simon; Guthrie, James; Robertson, J. David; Kornfeld, Kerry

2014-01-01

The insulin/IGF-1 signaling pathway plays a critical role in stress resistance and longevity, but the mechanisms are not fully characterized. To identify genes that mediate stress resistance, we screened for C. elegans mutants that can tolerate high levels of dietary zinc. We identified natc-1, which encodes an evolutionarily conserved subunit of the N-terminal acetyltransferase C (NAT) complex. N-terminal acetylation is a widespread modification of eukaryotic proteins; however, relatively little is known about the biological functions of NATs. We demonstrated that loss-of-function mutations in natc-1 cause resistance to a broad-spectrum of physiologic stressors, including multiple metals, heat, and oxidation. The C. elegans FOXO transcription factor DAF-16 is a critical target of the insulin/IGF-1 signaling pathway that mediates stress resistance, and DAF-16 is predicted to directly bind the natc-1 promoter. To characterize the regulation of natc-1 by DAF-16 and the function of natc-1 in insulin/IGF-1 signaling, we analyzed molecular and genetic interactions with key components of the insulin/IGF-1 pathway. natc-1 mRNA levels were repressed by DAF-16 activity, indicating natc-1 is a physiological target of DAF-16. Genetic studies suggested that natc-1 functions downstream of daf-16 to mediate stress resistance and dauer formation. Based on these findings, we hypothesize that natc-1 is directly regulated by the DAF-16 transcription factor, and natc-1 is a physiologically significant effector of the insulin/IGF-1 signaling pathway that mediates stress resistance and dauer formation. These studies identify a novel biological function for natc-1 as a modulator of stress resistance and dauer formation and define a functionally significant downstream effector of the insulin/IGF-1 signaling pathway. Protein N-terminal acetylation mediated by the NatC complex may play an evolutionarily conserved role in regulating stress resistance. PMID:25330323

Chitinolytic activities in Bacillus thuringiensis and their synergistic effects on larvicidal activity.

PubMed

Liu, M; Cai, Q X; Liu, H Z; Zhang, B H; Yan, J P; Yuan, Z M

2002-01-01

To investigate the distribution of chitinase in Bacillus thuringiensis strains, and the enhancing effects of the chitinase-producing B. thuringiensis strains on insecticidal toxicity of active B. thuringiensis strain against Spodoptera exigua larvae. The chitinolytic activities of B.thuringiensis strains representing the 70 serotypes were investigated by the whitish opaque halo and the colorimetric method. Thirty-eight strains produced different levels of chitinase at pH 7.0, and so did 17 strains at pH 10.0. The strain T04A001 exhibited the highest production, reaching a specific activity of 355 U ml(-1) in liquid medium. SDS-PAGE and Western blotting showed that the chitinase produced by some B. thuringiensis strains had a molecular weight of about 61 kDa. The bioassay results indicated that the chitinase-producing B. thuringiensis strains could enhance the insecticidal activity of B. thuringiensis strain DL5789 against S. exigua larvae, with an enhancing ratio of 2.35-fold. This study demonstrated that chitinase was widely produced in B. thuringiensis strains and some of the strains could enhance the toxicity of active B. thuringiensis strain. This is the first investigation devoted exclusively to analyse the distribution of chitinase in B. thuringiensis. It infers that the chitinase produced by B. thuringiensis might play a role in the activity of the biopesticide.

Complex small-molecule architectures regulate phenotypic plasticity in a nematode.

PubMed

Bose, Neelanjan; Ogawa, Akira; von Reuss, Stephan H; Yim, Joshua J; Ragsdale, Erik J; Sommer, Ralf J; Schroeder, Frank C

2012-12-07

Chemistry the worm's way: The nematode Pristionchus pacificus constructs elaborate small molecules from modified building blocks of primary metabolism, including an unusual xylopyranose-based nucleoside (see scheme). These compounds act as signaling molecules to control adult phenotypic plasticity and dauer development and provide examples of modular generation of structural diversity in metazoans. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morphological, molecular and biological characterization of Mehdinema alii (Nematoda: Diplogasterida) from the decorated cricket (Gryllodes sigillatus).

PubMed

Luong, L T; Platzer, E G; De Ley, P; Thomas, W K

1999-12-01

The nematode Mehdinema alii was recovered from the decorated cricket Gryllodes sigillatus (Walker). Morphometric comparisons are presented from 3 populations. The nematode is characterized by dense arrays of spines on the cuticle of the anterior half of the body and a highly elongate, tubular stoma with a dorsal denticle in the glottoid region. Females have a protruding vulva. Young females are amphidelphic, but the anterior ovary disappears in older females bearing multiple developing juveniles. The male is monorchic with asymmetrically placed genital papillae, distally fused spicules, and a highly complex gubernaculum bearing 2 cuticularized thorns that protrude through a separate, postcloacal opening. Adult nematodes are located primarily in the hindgut, whereas juveniles or dauers occur mainly in the genital chamber of both male and female crickets. Male crickets are significantly more likely to be infected than females. This male-biased infection may be linked to the venereal transmission mechanism of the dauers. Although morphologically unusual in many respects, placement of M. alii in Diplogasterida is supported by both the morphology of the anterior digestive tract as well as analysis of its 18S rDNA sequence. These sequence data suggest that M. alii groups most closely with members of the Cylindrocorporidae.

Host-finding behaviour in the nematode Pristionchus pacificus.

PubMed

Brown, Federico D; D'Anna, Isabella; Sommer, Ralf J

2011-11-07

Costs and benefits of foraging have been studied in predatory animals. In nematodes, ambushing or cruising behaviours represent adaptations that optimize foraging strategies for survival and host finding. A behaviour associated with host finding of ambushing nematode dauer juveniles is a sit-and-wait behaviour, otherwise known as nictation. Here, we test the function of nictation by relating occurrence of nictation in Pristionchus pacificus dauer juveniles to the ability to attach to laboratory host Galleria mellonella. We used populations of recently isolated and mutagenized laboratory strains. We found that nictation can be disrupted using a classical forward genetic approach and characterized two novel nictation-defective mutant strains. We identified two recently isolated strains from la Réunion island, one with a higher proportion of nictating individuals than the laboratory strain P. pacificus PS312. We found a positive correlation between nictation frequencies and host attachment in these strains. Taken together, our combination of genetic analyses with natural variation studies presents a new approach to the investigation of behavioural and ecological functionality. We show that nictation behaviour in P. pacificus nematodes serves as a host-finding behaviour. Our results suggest that nictation plays a role in the evolution of new life-history strategies, such as the evolution of parasitism.

Comparison of immunogenicity and protective efficacy of genital herpes vaccine candidates herpes simplex virus 2 dl5-29 and dl5-29-41L in mice and guinea pigs.

PubMed

Hoshino, Yo; Pesnicak, Lesley; Dowdell, Kennichi C; Lacayo, Juan; Dudek, Timothy; Knipe, David M; Straus, Stephen E; Cohen, Jeffrey I

2008-07-29

A replication-defective herpes simplex virus (HSV)-2 vaccine, dl5-29, which is deleted for two essential early genes, UL5 and UL29, is highly immunogenic and protective in mice and guinea pigs. In a prior study, a derivative of HSV-2 dl5-29 termed dl5-29-41L, which has an additional deletion in UL41 (that encodes the virion-host shut-off protein), was more immunogenic and protective against challenge with wild-type HSV-2 in mice when compared with dl5-29. To determine if deletion of UL41 improves the efficacy of dl5-29 in protecting guinea pigs from HSV-2, animals were immunized with dl5-29, dl5-29-41L, or PBS. The geometric mean neutralizing antibody titers from the dl5-29 and dl5-29-41L recipients were comparable (10(1.97) and 10(2.19), respectively, p=0.15). After intravaginal challenge with wild-type HSV-2, the dl5-29-41L and dl5-29 recipients shed similar titers of HSV-2 from the vagina. Mean acute disease severity scores, numbers of recurrences during 3 months after infection, and latent viral loads in sacral ganglia were similar for dl5-29 and dl5-29-41L (all p values >0.05). dl5-29 and dl5-29-41L completely protected mice from lethal challenge with HSV-2 and induced virus-specific CD8(+) T cells in the spleens of the animals. Thus, dl5-29 was as immunogenic and protective as dl5-29-41L under these conditions. dl5-29 was at least 250,000-fold less virulent than parental virus by intracranial inoculation in healthy mice, and caused no disease in SCID mice. Both dl5-29-41L and dl5-29 are equally effective and immunogenic in guinea pigs, and dl5-29 is very safe in immunocompromised animals.

AVIATION COMPETITION: Regional Jet Service Yet to Reach Many Small Communities

DTIC Science & Technology

2001-02-01

1997), AA (2000), NW (2000) Colorado Springs CO DL (1997), CO (1999), HP (1999) Columbia SC DL (1997), CO (1998), UA (1999), US (1999) Corpus...DL (1999) Small cities Bangor ME DL (1999) Bozeman MT DL (1997), UA (2000) Butte MT DL (1997) Casper WY DL (1997) Durango CO HP (1999) Grand Forks ND

Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miah, Aisha B.; Bhide, Shreerang A.; Guerrero-Urbano, M. Teresa

2012-02-01

Purpose: To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). Methods and Materials: A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and latemore » toxicities and tumor control rates were recorded. Results: Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. Conclusions: At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III study.« less

LC–MS Proteomics Analysis of the Insulin/IGF-1-Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

PubMed Central

2015-01-01

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC–MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediary metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity. PMID:24555535

Two GH3 genes from longan are differentially regulated during fruit growth and development.

PubMed

Kuang, Jian-Fei; Zhang, Yu; Chen, Jian-ye; Chen, Qiu-Jin; Jiang, Yue-Ming; Lin, He-Tong; Xu, Shi-Juan; Lu, Wang-Jin

2011-10-01

In the present work, two full length cDNAs of GH3 genes, named DlGH3.1 and DlGH3.2 were cloned from pericarp and aril tissues of the longan fruit, respectively. Three conserved motifs, SSGTSAGERK, YASSE and YRVGD, as a characteristic of the acyladenylate/thioester forming enzyme superfamily were observed in DlGH3.1 and DlGH3.2 proteins. DlGH3.1 mainly expressed in pericarp tissues while DlGH3.2 accumulated in both the pericarp and aril tissues during fruit growth and development. In addition, NAA treatment induced the expression of DlGH3.1 and DlGH3.2 in the pericarp tissues at 21 and 77days after anthesis (DAA), while only DlGH3.2 in the aril tissues could be induced by NAA at 77DAA. More importantly, ABA and ethrel treatments suppressed the accumulations of DlGH3.1 and DlGH3.2 in the pericarp tissues of longan fruit at 21DAA (a rapid growth stage of pericarp), but enhanced DlGH3.2 expression in the aril tissues at 77DAA (a fruit ripening stage). Furthermore, the expression patterns of DlGH3.1 and DlGH3.2 showed different tissue specificity. Thus, our results suggest that DlGH3.1 gene expression might be associated with pericarp growth, while DlGH3.2 accumulation is likely to be related to both pericarp growth and fruit ripening, and the responses of DlGH3s to plant growth hormones are different and dependent on fruit development stage and fruit tissue. Copyright © 2011 Elsevier B.V. All rights reserved.

Alternative Dispute Resolution : A Viable Method for Settling Government Contract Disputes

DTIC Science & Technology

1993-06-01

S. Rept. 543, 101st Congress, 2d Session. 14. Page, Reba and Lees, Frederick J., "Roles of Participants in Mini-Trial," Public Contract Law Journal...15. Brittin, Alexander J., "Alternative Dispute Resolution in Government Contract Appeals," Public Contract Law Journal. 16. Dauer, "Litigation v...International Law and Economics. Vol. 20, No. 3, 1987. 22. Page, Reba and Lees, Frederick J., "Roles of Participants in Mini-Trial," Public Contract Law Journal

Carob pod insoluble fiber exerts anti-atherosclerotic effects in rabbits through sirtuin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α.

PubMed

Valero-Muñoz, María; Martín-Fernández, Beatriz; Ballesteros, Sandra; Lahera, Vicente; de las Heras, Natalia

2014-09-01

The aim of this study was to evaluate the potential effects of an insoluble dietary fiber from carob pod (IFC) (1 g ⋅ kg(-1) ⋅ d(-1) in the diet) on alterations associated with atherosclerosis in rabbits with dyslipidemia. Male New Zealand rabbits (n = 30) were fed the following diets for 8 wk: 1) a control diet (SF412; Panlab) as a control group representing normal conditions; 2) a control supplemented with 0.5% cholesterol + 14% coconut oil (DL) (SF302; Panlab) for 8 wk as a dyslipidemic group; and 3) a control containing 0.5% cholesterol + 14% coconut oil plus IFC (1 g ⋅ kg(-1) ⋅ d(-1)) (DL+IFC) for 8 wk. IFC was administered in a pellet mixed with the DL diet. The DL-fed group developed mixed dyslipidemia and atherosclerotic lesions, which were associated with endothelial dysfunction, inflammation, and fibrosis. Furthermore, sirtuin-1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein expression in the aorta were reduced to 77% and 63% of the control group, respectively (P < 0.05), in these rabbits. Administration of IFC to DL-fed rabbits reduced the size of the aortic lesion significantly (DL, 15.2% and DL+IFC, 2.6%) and normalized acetylcholine-induced relaxation (maximal response: control, 89.3%; DL, 61.6%; DL+IFC, 87.1%; P < 0.05) and endothelial nitric oxide synthase expression (DL, 52% and DL+IFC, 104% of the control group). IFC administration to DL-fed rabbits also reduced cluster of differentiation 36 (DL, 148% and DL+IFC, 104% of the control group; P < 0.05), plasminogen activator inhibitor-1 (DL, 141% and DL+IFC, 107% of the control group), tumor necrosis factor-α (DL, 166% and DL+IFC, 120% of the control group), vascular cell adhesion molecule-1 (DL, 153% and DL+IFC, 110% of the control group), transforming growth factor-β (DL, 173% and DL+IFC, 99% of the control group), and collagen I (DL, 157% and DL+IFC, 112% of the control group) in the aorta. These effects were accompanied by an enhancement of SIRT1 and PGC-1α (160% and 121% of the control group, respectively; P < 0.05) vascular expression. In summary, we demonstrated for the first time, to our knowledge, that administration of IFC reduces the development of atherosclerosis in rabbits. This effect seems to be related to an improvement in endothelial function and a reduction of inflammation and fibrosis, most probably as a consequence of the reduction of serum concentrations of cholesterol and triglycerides. Increased expression of aortic SIRT1 and PGC-1α could play an important role in the observed effects of IFC in rabbits with dyslipidemia. © 2014 American Society for Nutrition.

LC-MS Proteomics Analysis of the Insulin/IGF-1 Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Depuydt, Geert G.; Xie, Fang; Petyuk, Vladislav A.

2014-02-20

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity and metabolism in C. elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass-spectrometry (LC-MS) based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2); daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the up-regulation of many core intermediarymore » metabolic pathways. These include, glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complex I, II, III and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative for spatio-temporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. This restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves, possibly also shunting metabolites through alternative energy-generating pathways, in order to sustain longevity.« less

LC–MS Proteomics Analysis of the Insulin/IGF-1-Deficient Caenorhabditis elegans daf-2(e1370) Mutant Reveals Extensive Restructuring of Intermediary Metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.

2014-04-04

The insulin/IGF-1 receptor is a major known determinant of dauer formation, stress resistance, longevity, and metabolism in Caenorhabditis elegans. In the past, whole-genome transcript profiling was used extensively to study differential gene expression in response to reduced insulin/IGF-1 signaling, including the expression levels of metabolism-associated genes. Taking advantage of the recent developments in quantitative liquid chromatography mass spectrometry (LC–MS)-based proteomics, we profiled the proteomic changes that occur in response to activation of the DAF-16 transcription factor in the germline-less glp-4(bn2);daf-2(e1370) receptor mutant. Strikingly, the daf-2 profile suggests extensive reorganization of intermediary metabolism, characterized by the upregulation of many core intermediarymore » metabolic pathways. These include glycolysis/gluconeogenesis, glycogenesis, pentose phosphate cycle, citric acid cycle, glyoxylate shunt, fatty acid β-oxidation, one-carbon metabolism, propionate and tyrosine catabolism, and complexes I, II, III, and V of the electron transport chain. Interestingly, we found simultaneous activation of reciprocally regulated metabolic pathways, which is indicative of spatiotemporal coordination of energy metabolism and/or extensive post-translational regulation of these enzymes. Finally, this restructuring of daf-2 metabolism is reminiscent to that of hypometabolic dauers, allowing the efficient and economical utilization of internal nutrient reserves and possibly also shunting metabolites through alternative energy-generating pathways to sustain longevity.« less

Cocrystallization out of the blue: DL-mandelic acid/ethyl-DL-mandelate cocrystal

NASA Astrophysics Data System (ADS)

Tumanova, Natalia; Payen, Ricky; Springuel, Géraldine; Norberg, Bernadette; Robeyns, Koen; Le Duff, Cécile; Wouters, Johan; Leyssens, Tom

2017-01-01

This work focuses on a peculiar behavior of racemic mandelic acid in ethanol solution. Dissolution of racemic mandelic acid in ethanol followed by evaporation to dryness results in a DL-mandelic acid/ethyl-DL-mandelate cocrystal. This behavior indicates that racemic mandelic acid tends not only to transform into an ester in ethanol, but also to cocrystallize with untransformed acid molecules. Cocrystal formation for mandelic acid in ethanol was found to be reproducible under various conditions. DL-tropic acid and DL-phenyllactic acid that contain similar functional groups and that were tested as well, on the other hand, showed no cocrystal formation: DL-phenyllactic acid partly converted into an ester, whereas DL-tropic acid mostly recrystallized.

Racemic resolution of some DL-amino acids using Aspergillus fumigatus L-amino acid oxidase.

PubMed

Singh, Susmita; Gogoi, Binod K; Bezbaruah, Rajib L

2011-07-01

The ability of Aspergillus fumigatus L-amino acid oxidase (L-aao) to cause the resolution of racemic mixtures of DL-amino acids was investigated with DL-alanine, DL-phenylalanine, DL-tyrosine, and DL-aspartic acid. A chiral column, Crownpak CR+ was used for the analysis of the amino acids. The enzyme was able to cause the resolution of the three DL-amino acids resulting in the production of optically pure D-alanine (100% resolution), D-phenylalanine (80.2%), and D-tyrosine (84.1%), respectively. The optically pure D-amino acids have many uses and thus can be exploited industrially. This is the first report of the use of A. fumigatus L: -amino acid oxidase for racemic resolution of DL-amino acids.

The virtual revolution: implications for academe.

PubMed

Pardue, S L

2001-05-01

The global expansion and acceptance of the Internet as been unprecedented. The emergence of the potential for distance learning (DL) has altered the way in which faculty, university administrators, and for-profit corporations view the educational process. In 1998, nearly 80% of public 4-yr institutions offered some DL courses. However, DL courses in agriculture and natural resources represented less than 1% of the total enrollment. Like any technology that ushers in a new era of change, DL has attracted enthusiastic supporters and detractors. Few view DL with neutrality. It is this divergence of opinion that has fueled the debate over the academic value of DL. A valid evaluation of the educational benefits or deficiencies of DL may require additional long-term studies. For some academic traditionalists, DL is viewed as the fusion of education and commerce and borders on the repugnant. Others embrace DL not only because it may provide a source of much needed revenue, but also because it allows for the low-cost delivery of information to a nontraditional pool of students. Well-funded, private, for-profit organizations and universities have developed a number of DL models. Some hybrid DL models exist in which public institutions have created independent for-profit corporations to develop and distribute their web-based courses. The question is not if DL will be a part of the educational landscape; it surely will. The challenge is to define the role DL can most effectively fulfill.

Post-task Effects on EEG Brain Activity Differ for Various Differential Learning and Contextual Interference Protocols

PubMed Central

Henz, Diana; John, Alexander; Merz, Christian; Schöllhorn, Wolfgang I.

2018-01-01

A large body of research has shown superior learning rates in variable practice compared to repetitive practice. More specifically, this has been demonstrated in the contextual interference (CI) and in the differential learning (DL) approach that are both representatives of variable practice. Behavioral studies have indicate different learning processes in CI and DL. Aim of the present study was to examine immediate post-task effects on electroencephalographic (EEG) brain activation patterns after CI and DL protocols that reveal underlying neural processes at the early stage of motor consolidation. Additionally, we tested two DL protocols (gradual DL, chaotic DL) to examine the effect of different degrees of stochastic fluctuations within the DL approach with a low degree of fluctuations in gradual DL and a high degree of fluctuations in chaotic DL. Twenty-two subjects performed badminton serves according to three variable practice protocols (CI, gradual DL, chaotic DL), and a repetitive learning protocol in a within-subjects design. Spontaneous EEG activity was measured before, and immediately after each 20-min practice session from 19 electrodes. Results showed distinguishable neural processes after CI, DL, and repetitive learning. Increases in EEG theta and alpha power were obtained in somatosensory regions (electrodes P3, P7, Pz, P4, P8) in both DL conditions compared to CI, and repetitive learning. Increases in theta and alpha activity in motor areas (electrodes C3, Cz, C4) were found after chaotic DL compared to gradual DL, and CI. Anterior areas (electrodes F3, F7, Fz, F4, F8) showed increased activity in the beta and gamma bands after CI. Alpha activity was increased in occipital areas (electrodes O1, O2) after repetitive learning. Post-task EEG brain activation patterns suggest that DL stimulates the somatosensory and motor system, and engages more regions of the cortex than repetitive learning due to a tighter stimulation of the motor and somatosensory system during DL practice. CI seems to activate specifically executively controlled processing in anterior brain areas. We discuss the obtained patterns of post-training EEG traces as evidence for different underlying neural processes in CI, DL, and repetitive learning at the early stage of motor learning. PMID:29445334

Dioxins, DL-PCB and NDL-PCB accumulation profiles in livers from sheep and cattle reared in North-western Italy.

PubMed

Benedetto, A; Brizio, P; Guaraldo, P; Stella, C; Cappa, C; Baioni, E; Spalenza, V; Nebbia, C; Abete, M C

2016-06-01

Products of animal origin represent the main route of human exposure to dioxins and dioxin-like PCBs (DL-compounds). Recently, concerns have been raised about ovine products, particularly the liver, in which relatively high levels of DL-compounds have been reported. We surveyed ovine and bovine livers in areas with no known sources of dioxin or DL-PCB contamination, in order to assess accumulation patterns for both DL-compounds and non-DL (NDL-) PCBs. None of the ovine and bovine samples exceeded the current Maximum Limits (MLs) for DL-compounds. Liver DL-compound TEQ concentrations were up to 5-fold higher in sheep than in cows. No statistically significant differences in total NDL-PCBs levels were found. The main contributors to TEQ levels were the Penta- and Hexa-chlorinated PCDFs and PCB 126. The results confirm the increased bioaccumulation in ovine liver towards specific DL-compounds even in ewes reared in areas with no known sources of PCDD/Fs or DL-PCBs contamination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differential Transcription Factor Use by the KIR2DL4 Promoter Under Constitutive and IL-2/15-Treated Conditions

PubMed Central

Presnell, Steven R.; Zhang, Lei; Chlebowy, Corrin N.; Al-Attar, Ahmad; Lutz, Charles T.

2012-01-01

KIR2DL4 is unique among human KIR genes in expression, cellular localization, structure, and function, yet the transcription factors required for its expression have not been identified. Using mutagenesis, electrophoretic mobility shift assay, and co-transfection assays, we identified two redundant Runx binding sites in the 2DL4 promoter as essential for constitutive 2DL4 transcription, with contributions by a CRE site and initiator elements. IL-2-and IL-15-stimulated human NK cell lines increased 2DL4 promoter activity, which required functional Runx, CRE, and Ets sites. Chromatin immunoprecipitation experiments show that Runx3 and Ets1 bind the 2DL4 promoter in situ. 2DL4 promoter activity had similar transcription factor requirements in T cells. Runx, CRE, and Ets binding motifs are present in 2DL4 promoters from across primate species, but other postulated transcription factor binding sites are not preserved. Differences between 2DL4 and clonally-restricted KIR promoters suggest a model that explains the unique 2DL4 expression pattern in human NK cells. PMID:22467658

Validated chiral high performance liquid chromatography separation method and simulation studies of dipeptides on amylose chiral column.

PubMed

Ali, Imran; Sahoo, Dibya Ranjan; ALOthman, Zeid A; Alwarthan, Abdulrahman A; Asnin, Leonid; Larsson, Bernt

2015-08-07

Chiral resolution of dl-alanine-dl-tyrosine and dl-leucine-dl-phenylalanine dipeptides was achieved on AmyCoat-RP column. The mobile phase used for dl-alanine-dl-tyrosine was acetonitrile-ammonium acetate (10mM, pH 6.0) [50:50, v/v]. It was acetonitrile-methanol-ammonium acetate (10mM; pH adjusted to 4.5 with glacial acetic acid) [50:20:30, v/v] for dl-leucine-dl-phenylalanine. The flow rate of the mobile phases was 0.8mL/min with UV detection at 275nm. The values of retention factors for ll-, dd-, dl- and ld-stereomers of dl-alanine-dl-tyrosine were 1.71, 2.86, 5.43 and 9.42, respectively. The values of separation and resolution factors were 1.67, 1.90 and 1.73 and 2.88, 6.43 and 7.90, respectively. Similarly, these values for dl-leucine-dl-phenylalanine stereomers were 1.50, 2.88, 3.50 and 4.07 (retention factors), 1.92, 1.22 and 1.62 (separation factors) and 2.67, 1.55 and 2.30 (resolution factors). The limits of detections and quantitation were ranged from 2.03 to 6.40 and 6.79 to 21.30μg/mL, respectively. The modeling studies were in agreement with the elution orders. The mechanism of chiral recognition was established by modeling and chromatographic studies. It was observed that hydrogen bondings and π-π interactions are the major forces for chiral separation. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential Training Facilitates Early Consolidation in Motor Learning

PubMed Central

Henz, Diana; Schöllhorn, Wolfgang I.

2016-01-01

Current research demonstrates increased learning rates in differential learning (DL) compared to repetitive training. To date, little is known on the underlying neurophysiological processes in DL that contribute to superior performance over repetitive practice. In the present study, we measured electroencephalographic (EEG) brain activation patterns after DL and repetitive badminton serve training. Twenty-four semi-professional badminton players performed badminton serves in a DL and repetitive training schedule in a within-subjects design. EEG activity was recorded from 19 electrodes according to the 10–20 system before and immediately after each 20-min exercise. Increased theta activity was obtained in contralateral parieto-occipital regions after DL. Further, increased posterior alpha activity was obtained in DL compared to repetitive training. Results indicate different underlying neuronal processes in DL and repetitive training with a higher involvement of parieto-occipital areas in DL. We argue that DL facilitates early consolidation in motor learning indicated by post-training increases in theta and alpha activity. Further, brain activation patterns indicate somatosensory working memory processes where attentional resources are allocated in processing of somatosensory information in DL. Reinforcing a somatosensory memory trace might explain increased motor learning rates in DL. Finally, this memory trace is more stable against interference from internal and external disturbances that afford executively controlled processing such as attentional processes. PMID:27818627

Changes in miRNA expression profile of space-flown Caenorhabditis elegans during Shenzhou-8 mission

NASA Astrophysics Data System (ADS)

Xu, Dan; Gao, Ying; Huang, Lei; Sun, Yeqing

2014-04-01

Recent advances in the field of molecular biology have demonstrated that small non-coding microRNAs (miRNAs) have a broad effect on gene expression networks and play a key role in biological responses to environmental stressors. However, little is known about how space radiation exposure and altered gravity affect miRNA expression. The "International Space Biological Experiments" project was carried out in November 2011 by an international collaboration between China and Germany during the Shenzhou-8 (SZ-8) mission. To study the effects of spaceflight on Caenorhabditis elegans (C. elegans), we explored the expression profile miRNA changes in space-flown C. elegans. Dauer C. elegans larvae were taken by SZ-8 spacecraft and experienced the 16.5-day shuttle spaceflight. We performed miRNA microarray analysis, and the results showed that 23 miRNAs were altered in a complex space environment and different expression patterns were observed in the space synthetic and radiation environments. Most putative target genes of the altered miRNAs in the space synthetic environment were predicted to be involved in developmental processes instead of in the regulation of transcription, and the enrichment of these genes was due to space radiation. Furthermore, integration analysis of the miRNA and mRNA expression profiles confirmed that twelve genes were differently regulated by seven miRNAs. These genes may be involved in embryonic development, reproduction, transcription factor activity, oviposition in a space synthetic environment, positive regulation of growth and body morphogenesis in a space radiation environment. Specifically, we found that cel-miR-52, -55, and -56 of the miR-51 family were sensitive to space environmental stressors and could regulate biological behavioural responses and neprilysin activity through the different isoforms of T01C4.1 and F18A12.8. These findings suggest that C. elegans responded to spaceflight by altering the expression of miRNAs and some target genes that function in diverse regulatory pathways.

Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor KIR2DL4: heparan sulfate directly modulates KIR2DL4-mediated responses

PubMed Central

Brusilovsky, Michael; Cordoba, Moti; Rosental, Benyamin; Hershkovitz, Oren; Andrake, Mark D.; Pecherskaya, Anna; Einarson, Margret B.; Zhou, Yan; Braiman, Alex

2013-01-01

KIR2DL4 (CD158d) is a distinct member of the killer cell Ig-like receptor (KIR) family in human NK cells that can induce cytokine production and cytolytic activity in resting NK cells. Soluble HLA-G, normally expressed only by fetal-derived trophoblast cells, was reported to be a ligand for KIR2DL4; however, KIR2DL4 expression is not restricted to the placenta and can be found in CD56high subset of peripheral blood NK cells. We demonstrated that KIR2DL4 can interact with alternative ligand(s), expressed by cells of epithelial or fibroblast origin. A genome-wide high-throughput siRNA screen revealed that KIR2DL4 recognition of cells surface ligand(s) is directly regulated by heparan sulfate (HS) glucosamine 3-O-sulfotransferase 3B1 (HS3ST3B1). KIR2DL4 was found to directly interact with HS/heparin, and the D0-domain of KIR2DL4 was essential for this interaction. Accordingly, exogenous HS/heparin can regulate cytokine production by KIR2DL4-expressing NK cells and HEK293T cells (HEK293T-2DL4) and induces differential localization of KIR2DL4 to rab5+ and rab7+ endosomes, thus leading to down-regulation of cytokine production and degradation of the receptor. Furthermore, we showed that intimate interaction of syndecan-4 (SDC4) HS Proteo-Glycan (HSPG) and KIR2DL4 directly affects receptor endocytosis and membrane trafficking. PMID:24127555

[Cloning and sequencing of KIR2DL1 framework gene cDNA and identification of a novel allele].

PubMed

Sun, Ge; Wang, Chang; Zhen, Jianxin; Zhang, Guobin; Xu, Yunping; Deng, Zhihui

2016-10-01

To develop an assay for cDNA cloning and haplotype sequencing of KIR2DL1 framework gene and determine the genotype of an ethnic Han from southern China. Total RNA was isolated from peripheral blood sample, and complementary DNA (cDNA) transcript was synthesized by RT-PCR. The entire coding sequence of the KIR2DL1 framework gene was amplified with a pair of KIR2DL1-specific PCR primers. The PCR products with a length of approximately 1.2 kb were then subjected to cloning and haplotype sequencing. A specific target fragment of the KIR2DL1 framework gene was obtained. Following allele separation, a wild-type KIR2DL1*00302 allele and a novel variant allele, KIR2DL1*031, were identified. Sequence alignment with KIR2DL1 alleles from the IPD-KIR Database showed that the novel allele KIR2DL1*031 has differed from the closest allele KIR2DL1*00302 by a non-synonymous mutation at CDS nt 188A>G (codon 42 GAG>GGG) in exon 4, which has caused an amino acid change Glu42Gly. The sequence of the novel allele KIR2DL1*031 was submitted to GenBank under the accession number KP025960 and to the IPD-KIR Database under the submission number IWS40001982. A name KIR2DL1*031 has been officially assigned by the World Health Organization (WHO) Nomenclature Committee. An assay for cDNA cloning and haplotype sequencing of KIR2DL1 has been established, which has a broad applications in KIR studies at allelic level.

HLA and killer cell immunoglobulin-like receptor (KIRs) genotyping in patients with acute viral encephalitis

PubMed Central

Tuttolomondo, Antonino; Colomba, Claudia; Di Bona, Danilo; Casuccio, Alessandra; Di Raimondo, Domenico; Clemente, Giuseppe; Arnao, Valentina; Pecoraro, Rosaria; Ragonese, Paolo; Aiello, Anna; Accardi, Giulia; Maugeri, Rosario; Maida, Carlo; Simonetta, Irene; Della Corte, Vittoriano; Iacopino, Domenico Gerardo; Caruso, Calogero; Cascio, Antonio; Pinto, Antonio

2018-01-01

Introduction The HLA genes, as well as the innate immune KIR genes, are considered relevant determinants of viral outcomes but no study, to our knowledge, has evaluated their role in the clinical setting of acute viral encephalitis. Results Subjects with acute viral encephalitis in comparison to subjects without acute viral encephalitis showed a significantly higher frequency of 2DL1 KIR gene and AA KIR haplotypes and of HLA-C2 and HLA-A-Bw4 alleles. Subjects without acute viral encephalitis showed a higher frequency of interaction between KIR2DL2 and HLAC1. Multiple logistic regression analysis showed the detrimental effect of HLA-A haplotype and HLA-C1, HLA-A-BW4 HLA-B-BW4T alleles, whereas multiple logistic regression showed a protective effect of AB+BB KIR haplotype and a detrimental effect of interaction between KIR3DL1 and HLA-A-Bw4. Discussion Our findings of a lower frequency of activating receptors in patients with acute encephalitis compared to controls could result in a less efficient response of NK cells. This finding could represent a possible pathogenetic explanation of susceptibility to acute symptomatic encephalitis in patients with viral infection from potentially responsible viruses such as Herpes virus. Materials and Methods 30 Consecutive patients with symptomatic acute viral encephalitis and as controls, 36 consecutive subjects without acute encephalitis were analyzed. The following KIR genes were analyzed, KIR2DL1, 2DL2, 2DL3, 2DL5, 3DL1, 3DL2, 3DL3, 2DL4, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DS1, 2 pseudogenes (2DP1 and 3DP1) and the common variants of KIR2DL5 (KIR2DL5A, KIR2DL5B). PMID:29707126

Allelic variation in KIR2DL3 generates a KIR2DL2-like receptor with increased binding to its HLA-C ligand.

PubMed

Frazier, William R; Steiner, Noriko; Hou, Lihua; Dakshanamurthy, Sivanesan; Hurley, Carolyn Katovich

2013-06-15

Although extensive homology exists between their extracellular domains, NK cell inhibitory receptors killer Ig-like receptor (KIR) 2DL2*001 and KIR2DL3*001 have previously been shown to differ substantially in their HLA-C binding avidity. To explore the largely uncharacterized impact of allelic diversity, the most common KIR2DL2/3 allelic products in European American and African American populations were evaluated for surface expression and binding affinity to their HLA-C group 1 and 2 ligands. Although no significant differences in the degree of cell membrane localization were detected in a transfected human NKL cell line by flow cytometry, surface plasmon resonance and KIR binding to a panel of HLA allotypes demonstrated that KIR2DL3*005 differed significantly from other KIR2DL3 allelic products in its ability to bind HLA-C. The increased affinity and avidity of KIR2DL3*005 for its ligand was also demonstrated to have a larger impact on the inhibition of IFN-γ production by the human KHYG-1 NK cell line compared with KIR2DL3*001, a low-affinity allelic product. Site-directed mutagenesis established that the combination of arginine at residue 11 and glutamic acid at residue 35 in KIR2DL3*005 were critical to the observed phenotype. Although these residues are distal to the KIR/HLA-C interface, molecular modeling suggests that alteration in the interdomain hinge angle of KIR2DL3*005 toward that found in KIR2DL2*001, another strong receptor of the KIR2DL2/3 family, may be the cause of this increased affinity. The regain of inhibitory capacity by KIR2DL3*005 suggests that the rapidly evolving KIR locus may be responding to relatively recent selective pressures placed upon certain human populations.

Allelic Variation in KIR2DL3 Generates a KIR2DL2-like Receptor with Increased Binding to Its HLA-C Ligand12

PubMed Central

Frazier, William R.; Steiner, Noriko; Hou, Lihua; Dakshanamurthy, Sivanesan; Hurley, Carolyn Katovich

2013-01-01

Although extensive homology exists between their extracellular domains, natural killer cell inhibitory receptors KIR2DL2*001 and KIR2DL3*001 have previously been shown to differ substantially in their HLA-C binding avidity. To explore the largely uncharacterized impact of allelic diversity, the most common KIR2DL2/3 allelic products in European American and African American populations were evaluated for surface expression and binding affinity to their HLA-C group 1 and 2 ligands. Although no significant differences in the degree of cell membrane localization were detected in a transfected human NKL cell line by flow cytometry, surface plasmon resonance and KIR binding to a panel of HLA allotypes demonstrated that KIR2DL3*005 differed significantly from other KIR2DL3 allelic products in its ability to bind HLA-C. The increased affinity and avidity of KIR2DL3*005 for its ligand was also demonstrated to have a larger impact on the inhibition of IFN-γ production by the human KHYG-1 NK cell line compared to KIR2DL3*001, a low affinity allelic product. Site-directed mutagenesis established that the combination of arginine at residue 11 and glutamic acid at residue 35 in KIR2DL3*005 were critical to the observed phenotype. Although these residues are distal to the KIR/HLA-C interface, molecular modeling suggests that alteration in the interdomain hinge angle of KIR2DL3*005 towards that found in KIR2DL2*001, another strong receptor of the KIR2DL2/3 family, may be the cause of this increased affinity. The regain of inhibitory capacity by KIR2DL3*005 suggests that the rapidly evolving KIR locus may be responding to relatively recent selective pressures placed upon certain human populations. PMID:23686481

DL-2-amino-3-phosphonopropionic acid protects primary neurons from oxygen-glucose deprivation induced injury.

PubMed

Cui, Di; Xu, Jun; Xu, Quanyi; Zuo, Guokun

2017-02-21

Cerebral infarction is a type of ischemic stroke and is one of the main causes of irreversible brain damage. Although multiple neuroprotective agents have been investigated recently, the potential of DL-2-amino-3-phosphonopropionic acid (DL-AP3) in treating oxygen-glucose deprivation (OGD)-induced neuronal injury, has not been clarified yet. This study was aimed to explore the role of DL-AP3 in primary neuronal cell cultures. Primary neurons were divided into four groups: (1) a control group that was not treated; (2) DL-AP3 group treated with 10 μM of DL-AP3; (3) OGD group, in which neurons were cultured under OGD conditions; and (4) OGD + DL-AP3 group, in which OGD model was first established and then the cells were treated with 10 μM of DL-AP3. Neuronal viability and apoptosis were measured using Cell Counting Kit-8 and flow cytometry. Expressions of phospho-Akt1 (p-Akt1) and cytochrome c were detected using Western blot. The results showed that DL-AP3 did not affect neuronal viability and apoptosis in DL-AP3 group, nor it changed p-Akt1 and cytochrome c expression (p > 0.05). In OGD + DL-AP3 group, DL-AP3 significantly attenuated the inhibitory effects of OGD on neuronal viability (p < 0.001), and reduced OGD induced apoptosis (p < 0.01). Additionally, the down-regulation of p-Akt1 and up-regulation of cytochrome c, induced by OGD, were recovered to some extent after DL-AP3 treatment (p < 0.05 or p < 0.001). Overall, DL-AP3 could protect primary neurons from OGD-induced injury by affecting the viability and apoptosis of neurons, and by regulating the expressions of p-Akt1 and cytochrome c.

Regularized spherical polar fourier diffusion MRI with optimal dictionary learning.

PubMed

Cheng, Jian; Jiang, Tianzi; Deriche, Rachid; Shen, Dinggang; Yap, Pew-Thian

2013-01-01

Compressed Sensing (CS) takes advantage of signal sparsity or compressibility and allows superb signal reconstruction from relatively few measurements. Based on CS theory, a suitable dictionary for sparse representation of the signal is required. In diffusion MRI (dMRI), CS methods proposed for reconstruction of diffusion-weighted signal and the Ensemble Average Propagator (EAP) utilize two kinds of Dictionary Learning (DL) methods: 1) Discrete Representation DL (DR-DL), and 2) Continuous Representation DL (CR-DL). DR-DL is susceptible to numerical inaccuracy owing to interpolation and regridding errors in a discretized q-space. In this paper, we propose a novel CR-DL approach, called Dictionary Learning - Spherical Polar Fourier Imaging (DL-SPFI) for effective compressed-sensing reconstruction of the q-space diffusion-weighted signal and the EAP. In DL-SPFI, a dictionary that sparsifies the signal is learned from the space of continuous Gaussian diffusion signals. The learned dictionary is then adaptively applied to different voxels using a weighted LASSO framework for robust signal reconstruction. Compared with the start-of-the-art CR-DL and DR-DL methods proposed by Merlet et al. and Bilgic et al., respectively, our work offers the following advantages. First, the learned dictionary is proved to be optimal for Gaussian diffusion signals. Second, to our knowledge, this is the first work to learn a voxel-adaptive dictionary. The importance of the adaptive dictionary in EAP reconstruction will be demonstrated theoretically and empirically. Third, optimization in DL-SPFI is only performed in a small subspace resided by the SPF coefficients, as opposed to the q-space approach utilized by Merlet et al. We experimentally evaluated DL-SPFI with respect to L1-norm regularized SPFI (L1-SPFI), which uses the original SPF basis, and the DR-DL method proposed by Bilgic et al. The experiment results on synthetic and real data indicate that the learned dictionary produces sparser coefficients than the original SPF basis and results in significantly lower reconstruction error than Bilgic et al.'s method.

Translating effective web-based self-help for problem drinking into the real world.

PubMed

Riper, Heleen; Kramer, Jeannet; Conijn, Barbara; Smit, Filip; Schippers, Gerard; Cuijpers, Pim

2009-08-01

Drinking Less (DL) is a 24/7 free-access anonymous interactive web-based self-help intervention without therapeutic guidance for adult problem drinkers in the community. In a randomized controlled trial (referred to here as DL-RCT), DL has been shown effective in reducing risky alcohol consumption. To assess whether the findings of DL-RCT are generalizable to a naturalistic setting (DL-RW) in terms of ability to reach the target group and alcohol treatment response. Pretest-posttest study with 6-month follow-up. An online survey was conducted of 378 of the 1,625 people who used DL-RW from May to November 2007. Primary outcome measures were (1) problem drinking, defined as alcohol consumption in the previous 4 weeks averaging >21 or >14 standard units (male/female) per week or >or=6 or >or=4 units (m/f) on 1 or more days per week; and (2) mean weekly alcohol consumption. DL-RW and DL-RCT data were compared and pooled. Intention-to-treat (ITT) analysis was performed to analyze and compare changes in drinking from baseline to follow-up. In the DL-RW group, 18.8% (n = 71) were drinking successfully within the limits of the Dutch guideline for low-risk drinking (p < 0.001) 6 months after baseline (ITT). The DL-RW group also decreased its mean weekly alcohol intake by 7.4 units, t(377) = 6.67, p < 0.001, d = 0.29. Drinking reduction in DL-RW was of a similar magnitude to that in the DL-RCT condition in terms of drinking within the guideline [chi(2)(1) = 1.83, CI: 0.82-3.00, p = 0.18, RD = 0.05, OR = 1.55] and mean weekly consumption (a negligible difference of d = 0.03 in favor of DL-RW group). The results from DL-RCT and DL-RW were similar, and they demonstrate that web-based self-help without therapeutic guidance is feasible, well accepted, and effective for curbing adult problem drinking in the community.

Spontaneous resolution of binary copper(II) complexes with racemic dipeptides: crystal structures of glycyl-L-alpha-amino-n-butyrato copper(II) monohydrate, glycyl-D-valinato copper(II) hemihydrate, and glycyl-L-valinato copper(II) hemihydrate.

PubMed

Inomata, Yoshie; Yamaguchi, Takeshi; Tomita, Airi; Yamada, Dai; Howell, F Scott

2005-08-01

Copper(II) complexes with glycyl-DL-alpha-amino-n-butyric acid (H2gly-DL-but), glycyl-DL-valine (H2gly-DL-val), glycyl-DL-norleucine (H2gly-DL-norleu), glycyl-DL-threonine (H2gly-DL-thr), glycyl-DL-serine (H2gly-DL-ser), glycyl-DL-phenylalanine (H2gly-DL-phe), and glycyl-L-valine (H2gly-L-val), have been prepared and characterized by IR, powder diffuse reflection, CD and ORD spectra, and magnetic susceptibility measurements, and by single-crystal X-ray diffraction. The crystal structures of the copper complex with H2gly-DL-but, the copper complex with H2gly-DL-val, and [Cu(gly-L-val)]n.0.5nH2O have been determined by a single-crystal X-ray diffraction method. As for the structure of the copper complex with H2gly-DL-but, the configuration around the asymmetric carbon atom is similar to that of [Cu(gly-L-val)]n.0.5nH2O. Therefore it is concluded that the copper complex with H2gly-DL-but is [Cu(gly-L-but)]n.nH2O. On the contrary, as for the structure of the copper complex with H2gly-DL-val, the configuration around the asymmetric carbon atom is different from that of [Cu(gly-L-val)]n.0.5nH2O. Therefore it is concluded that the copper complex with H2gly-dl-val is [Cu(gly-D-val)]n.0.5nH2O. So during the crystallization of the copper(II) complexes with H2gly-DL-but and H2gly-DL-val, spontaneous resolution has been observed; the four complexes have separated as [Cu(gly-D-but)]n.nH2O, [Cu(gly-L-but)]n.nH2O, [Cu(gly-D-val)]n.0.5nH2O, and [Cu(gly-L-val)]n.0.5nH2O, respectively. [Cu(gly-L-but)]n.nH2O is orthorhombic with the space group P2(1)2(1)2(1). [Cu(gly-D-val)]n.0.5nH2O and [Cu(gly-L-val)]n.0.5nH2O are monoclinic with the space group C2. In these complexes, the copper atom is in a square-pyramidal geometry, ligated by a peptide nitrogen atom, an amino nitrogen atom, a carboxyl oxygen atom, and a carboxyl oxygen atom and a peptide oxygen atom from neighboring molecules. So these complexes consist of a two-dimensional polymer chain bridged by a carboxyl oxygen atom and a peptide oxygen atom from neighboring molecules. The axial oxygen atom is located above the basal plane and the side chain of an amino acid is located below it. These polymer chains consist of only one or the other type of optical isomers; no racemic dipeptides are found. Therefore, spontaneous resolution has been observed in the crystallization of copper(II) complexes with H2gly-DL-but and H2gly-DL-val. The crystal structure of [Cu(gly-D-val)]n.0.5nH2O agrees almost completely with that of [Cu(gly-L-val)]n.0.5nH2O, except for the configuration around the asymmetric carbon atom.

Deep learning strategy for accurate carotid intima-media thickness measurement: An ultrasound study on Japanese diabetic cohort.

PubMed

Biswas, Mainak; Kuppili, Venkatanareshbabu; Araki, Tadashi; Edla, Damodar Reddy; Godia, Elisa Cuadrado; Saba, Luca; Suri, Harman S; Omerzu, Tomaž; Laird, John R; Khanna, Narendra N; Nicolaides, Andrew; Suri, Jasjit S

2018-07-01

The carotid intima-media thickness (cIMT) is an important biomarker for cardiovascular diseases and stroke monitoring. This study presents an intelligence-based, novel, robust, and clinically-strong strategy that uses a combination of deep-learning (DL) and machine-learning (ML) paradigms. A two-stage DL-based system (a class of AtheroEdge™ systems) was proposed for cIMT measurements. Stage I consisted of a convolution layer-based encoder for feature extraction and a fully convolutional network-based decoder for image segmentation. This stage generated the raw inner lumen borders and raw outer interadventitial borders. To smooth these borders, the DL system used a cascaded stage II that consisted of ML-based regression. The final outputs were the far wall lumen-intima (LI) and media-adventitia (MA) borders which were used for cIMT measurements. There were two sets of gold standards during the DL design, therefore two sets of DL systems (DL1 and DL2) were derived. A total of 396 B-mode ultrasound images of the right and left common carotid artery were used from 203 patients (Institutional Review Board approved, Toho University, Japan). For the test set, the cIMT error for the DL1 and DL2 systems with respect to the gold standard was 0.126 ± 0.134 and 0.124 ± 0.100 mm, respectively. The corresponding LI error for the DL1 and DL2 systems was 0.077 ± 0.057 and 0.077 ± 0.049 mm, respectively, while the corresponding MA error for DL1 and DL2 was 0.113 ± 0.105 and 0.109 ± 0.088 mm, respectively. The results showed up to 20% improvement in cIMT readings for the DL system compared to the sonographer's readings. Four statistical tests were conducted to evaluate reliability, stability, and statistical significance. The results showed that the performance of the DL-based approach was superior to the nonintelligence-based conventional methods that use spatial intensities alone. The DL system can be used for stroke risk assessment during routine or clinical trial modes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Emergency department blood alcohol level associates with injury factors and six-month outcome after uncomplicated mild traumatic brain injury.

PubMed

Yue, John K; Ngwenya, Laura B; Upadhyayula, Pavan S; Deng, Hansen; Winkler, Ethan A; Burke, John F; Lee, Young M; Robinson, Caitlin K; Ferguson, Adam R; Lingsma, Hester F; Cnossen, Maryse C; Pirracchio, Romain; Korley, Frederick K; Vassar, Mary J; Yuh, Esther L; Mukherjee, Pratik; Gordon, Wayne A; Valadka, Alex B; Okonkwo, David O; Manley, Geoffrey T

2017-11-01

The relationship between blood alcohol level (BAL) and mild traumatic brain injury (mTBI) remains in need of improved characterization. Adult patients suffering mTBI without intracranial pathology on computed tomography (CT) from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with emergency department (ED) Glasgow Coma Scale (GCS) 13-15 and recorded blood alcohol level (BAL) were extracted. BAL≥80-mg/dl was set as proxy for excessive use. Multivariable regression was performed for patients with six-month Glasgow Outcome Scale-Extended (GOSE; functional recovery) and Wechsler Adult Intelligence Scale Processing Speed Index Composite Score (WAIS-PSI; nonverbal processing speed), using BAL≥80-mg/dl and <80-mg/dl cohorts, adjusting for demographic/injury factors. Overall, 107 patients were aged 42.7±16.8-years, 67.3%-male, and 80.4%-Caucasian; 65.4% had BAL=0-mg/dl, 4.6% BAL<80-mg/dl, and 30.0% BAL≥80-mg/dl (range 100-440-mg/dl). BAL differed across loss of consciousness (LOC; none: median 0-mg/dl [interquartile range (IQR) 0-0], <30-min: 0-mg/dl [0-43], ≥30-min: 224-mg/dl [50-269], unknown: 108-mg/dl [0-232]; p=0.002). GCS<15 associated with higher BAL (19-mg/dl [0-204] vs. 0-mg/dl [0-20]; p=0.013). On univariate analysis, BAL≥80-mg/dl associated with less-than-full functional recovery (GOSE≤7; 38.1% vs. 11.5%; p=0.025) and lower WAIS-PSI (92.4±12.7, 30th-percentile vs. 105.1±11.7, 63rd-percentile; p<0.001). On multivariable regression BAL≥80-mg/dl demonstrated an odds ratio of 8.05 (95% CI [1.35-47.92]; p=0.022) for GOSE≤7 and an adjusted mean decrease of 8.88-points (95% CI [0.67-17.09]; p=0.035) on WAIS-PSI. Day-of-injury BAL>80-mg/dl after uncomplicated mTBI was associated with decreased GCS score and prolongation of reported LOC. BAL may be a biomarker for impaired return to baseline function and decreased nonverbal processing speed at six-months postinjury. Future confirmatory studies are needed. Published by Elsevier Ltd.

Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex.

PubMed

Fan, Q R; Long, E O; Wiley, D C

2001-05-01

Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to its class I MHC ligand, HLA-Cw4. The KIR2DL1-HLA-Cw4 interface exhibits charge and shape complementarity. Specificity is mediated by a pocket in KIR2DL1 that hosts the Lys80 residue of HLA-Cw4. Many residues conserved in HLA-C and in KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a previously reported KIR2DL2-HLA-Cw3 complex. A dimeric aggregate of KIR-HLA-C complexes was observed in one KIR2DL1-HLA-Cw4 crystal. Most of the amino acids that differ between human and chimpanzee KIRs with HLA-C specificities form solvent-accessible clusters outside the KIR-HLA interface, which suggests undiscovered interactions by KIRs.

Killer cell immunoglobulin-like receptor gene diversity in the Tibetan ethnic minority group of China.

PubMed

Zhu, Bo-feng; Wang, Hong-dan; Shen, Chun-mei; Deng, Ya-jun; Yang, Guang; Wu, Qing-ju; Xu, Peng; Qin, Hai-xia; Fan, Shuan-liang; Huang, Ping; Deng, Li-bin; Lucas, Rudolf; Wang, Zhen-Yuan

2010-11-01

The aim of this study was to analyze killer immunoglobulin-like receptor (KIR) gene polymorphisms in the Tibetan ethnic minority of China. To that purpose, we have studied KIR gene frequencies and genotype diversities of 16 KIR genes and three pseudogenes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B, 2DS1, 2DS2, 2DS3, 2DS4*001/002, 2DS4*003-007, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1, 3DP1*001/002/004, and 3DP1*003) in a population sample of 102 unrelated healthy individuals of the Tibetan population living in Lhasa city, Tibet Autonomous Region of China. Tibetans mainly live in "the roof of the world," the Qinghai-Tibet Plateau of China and surrounding areas stretching from central Asia in the North and West to Myanmar and mainland China in the East, and India, Nepal, and Bhutan to the south. KIR gene frequencies and statistical parameters of Tibetan ethnic minority were calculated. Fifteen KIR genes were observed in the 102 tested Tibetan individuals with different frequencies. The allelic frequencies of the 15 KIR genes ranged from 0.06 to 0.86. In addition, KIR 2DL1, 2DL4, 3DL2, and 3DL3 were found to be present in every individual. Variable gene content, together with allelic polymorphisms, can result in individualized human KIR genotypes and haplotypes, with the A haplotypes being predominantly observed. The results of tested linkage disequilibrium (LD) among KIR genes demonstrated that KIR genes present a wide range of linkage disequilibrium. Moreover, a comparison of the population data of our study with previously published population data of other ethnic groups or areas was performed. The differences of allelic frequency distribution in KIR2DL2, 2DL3, 2DL5, 3DL1, 2DS1, 2DS2, 2DS3, 3DS1, and 2DP1 were statistically significant among different populations using the statistical method of the standard χ(2) test. In conclusion, the results of the present study can be valuable for enriching the Chinese ethnical gene information resources of the KIR gene pool and for anthological studies, as well as for KIR-related disease research. Copyright © 2010. Published by Elsevier Inc.

Improved Understanding of Sources of Variability in Groundwater Sampling for Long-Term Monitoring Programs

DTIC Science & Technology

2013-02-01

20000 18200 ug/L 91 60 - 140 Styrene - DL 70 10000 10900 ug/L 109 60 - 140 1,1,2,2-Tetrachloroethane - DL 220 10000 12600 ug/L 126 60 - 140...L 110 60 - 140 Trichloroethene - DL2 180 10000 12600 F ug/L 126 56 - 118 Vinyl acetate - DL2 210 10000 4630 F ug/L 46 60 - 140 Vinyl chloride - DL2

The morphologic characteristics of the distolingual roots of mandibular first molars in a Taiwanese population.

PubMed

Chen, Yi-Chen; Lee, Ya-Yun; Pai, Sheng-Fang; Yang, Shue-Fen

2009-05-01

The prevalence of extra distolingual (DL) roots in mandibular first molars in Chinese population is about 20%. The purpose of this study was to evaluate the difference of root length and root curvatures between distobuccal (DB) and DL roots of three-rooted mandibular first molars in a Taiwanese (Chinese) population. Of the 293 extracted mandibular first molars, DL roots were present in 29 (9.9%) teeth. Excluding teeth with fractured DB or DL roots, 21 mandibular first molars were further investigated. DB and DL root lengths were measured from the lower level of furcation at the distal surface to the root apex. The curvature of the DL root was measured on mesial-distal and buccal-lingual radiographs by Schneider's technique. The DL roots were significantly (p < 0.001) shorter than the DB roots with an average of 1.48 +/- 0.81 mm. Most DL roots had a greater curvature in a buccal-lingual orientation (36.35 degrees +/- 9.38 degrees ) than a mesial-distal orientation (9.24 degrees +/- 6.10 degrees ) and 28.57% of the curved DL roots had the curvature at the apical one third (p < 0.001). The results of this study verified the characteristics of shorter root length and severe buccal-lingual inclination of DL roots in three-rooted mandibular first molars.

In Vivo Efficacy of Latex from Calotropis procera in Ameliorating Fever-Biochemical Characteristics and Plausible Mechanism.

PubMed

Kumar, Vijay L; Guruprasad, B; Fatmi, Syed Meraj A; Chaudhary, Priyanka; Alencar, Nylane Maria Nunes; Lima-Filho, José Vitor Moreira; Ramos, Márcio Viana

2017-07-01

Calotropis procera latex fractions possessing anti-inflammatory property were characterized for their biochemical properties, compared for their efficacy in ameliorating fever in rats and their mechanism of action was elucidated. Aqueous fraction and methanol extract (AqDL and MeDL) were derived from the dried latex (DL) and proteins were separated from the fresh latex (LP). Polyacrylamide gel electrophoresis carried out under denaturing conditions showed the presence of proteins with some similarity in LP and AqDL and both of these fractions exhibited proteinase activity by gelatin zymography. A further analysis revealed that only the LP fraction possesses cysteine proteinase activity. Oral administration of both AqDL and MeDL produced a dose-dependent reduction in body temperature in rats where fever was induced by yeast and their effect was comparable to that of standard drug paracetamol while intravenous administration of LP was not so effective. Both AqDL and MeDL produced a significant reduction in the levels of TNF-α, PGE 2 , and immunoreactivity of COX-2 in the hypothalamus as compared to yeast control group. This study shows that both AqDL and MeDL, the orally effective anti-inflammatory fractions of latex, have therapeutic potential in treating various febrile conditions.

Amino Acid and Vitamin Requirements of Several Bacteroides Strains

PubMed Central

Quinto, Grace

1966-01-01

Nutritional studies were performed on nine Bacteroides strains, by use of the methodology and media of anaerobic rumen microbiology. Ristella perfoetens CCI required l-arginine hydrochloride, l-tryptophan, l-leucine, l-histidine hydrochloride, l-cysteine hydrochloride, dl-valine, dl-tyrosine, and the vitamin calcium-d-pantothenate, since scant turbidity developed in media without these nutrients. R. perfoetens was stimulated by glycine, dl-lysine hydrochloride, dl-isoleucine, l-proline, l-glutamic acid, dl-alanine, dl-phenylalanine, dl-methionine, and the vitamins nicotinamide and p-aminobenzoic acid, since maximal turbidity developed more slowly in media without these nutrients than in complete medium. Medium A-23, which was devised for R. perfoetens, contained salts, 0.0002% nicotinamide and calcium d-pantothenate, 0.00001% p-aminobenzoic acid, 0.044% l-tryptophan, 0.09% l-glutamic acid, and 0.1% of the other 13 amino acids listed above. Zuberella clostridiformis and seven strains of R. pseudoinsolita did not require vitamins, and showed no absolute requirement for any one amino acid. Various strains produced maximal turbidity more slowly in media deficient in l-proline, glycine, l-glutamic acid, dl-serine, l-histidine hydrochloride, dl-alanine, or l-cysteine hydrochloride, than in complete medium. These eight strains grew optimally in medium A-23 plus 0.1% dl-serine but without vitamins. PMID:16349673

KIR2DL2/2DL3-E35 alleles are functionally stronger than -Q35 alleles

NASA Astrophysics Data System (ADS)

Bari, Rafijul; Thapa, Rajoo; Bao, Ju; Li, Ying; Zheng, Jie; Leung, Wing

2016-03-01

KIR2DL2 and KIR2DL3 segregate as alleles of a single locus in the centromeric motif of the killer cell immunoglobulin-like receptor (KIR) gene family. Although KIR2DL2/L3 polymorphism is known to be associated with many human diseases and is an important factor for donor selection in allogeneic hematopoietic stem cell transplantation, the molecular determinant of functional diversity among various alleles is unclear. In this study we found that KIR2DL2/L3 with glutamic acid at position 35 (E35) are functionally stronger than those with glutamine at the same position (Q35). Cytotoxicity assay showed that NK cells from HLA-C1 positive donors with KIR2DL2/L3-E35 could kill more target cells lacking their ligands than NK cells with the weaker -Q35 alleles, indicating better licensing of KIR2DL2/L3+ NK cells with the stronger alleles. Molecular modeling analysis reveals that the glutamic acid, which is negatively charged, interacts with positively charged histidine located at position 55, thereby stabilizing KIR2DL2/L3 dimer and reducing entropy loss when KIR2DL2/3 binds to HLA-C ligand. The results of this study will be important for future studies of KIR2DL2/L3-associated diseases as well as for donor selection in allogeneic stem cell transplantation.

Analytical Performance Evaluation of Infopia Element™ Auto-coding Blood Glucose Monitoring System for Self-Monitoring of Blood Glucose.

PubMed

Park, Hae-Il; Lee, Seong-Su; Son, Jang-Won; Kwon, Hee-Sun; Kim, Sung Rae; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo; Yoo, Soonjib

2016-11-01

Element™ Auto-coding Blood Glucose Monitoring System (BGMS; Infopia Co., Ltd., Anyang-si, Korea) was developed for self-monitoring of blood glucose (SMBG). Precision, linearity, and interference were tested. Eighty-four capillary blood samples measured by Element™ BGMS were compared with central laboratory method (CLM) results in venous serum. Accuracy was evaluated using ISO 15197:2013 criteria. Coefficients of variation (CVs; mean) were 2.4% (44.2 mg/dl), 3.7% (100.6 mg/dl), and 2.1% (259.8 mg/dl). Linearity was shown at concentrations 39.25-456.25 mg/l (y = 0.989 + 0.984x, SE = 17.63). Up to 15 mg/dl of galactose, ascorbic acid, and acetaminophen, interference > 10.4% was not observed. Element™ BGMS glucose was higher than CLM levels by 3.2 mg/dl (at 200 mg/dl) to 8.2 mg/dl (at 100 mg/dl). The minimum specification for bias (3.3%) was met at 140 and 200 mg/l glucose. In the Clarke and consensus error grids, 100% of specimens were within zone A and B. For Element™ BGMS values, 92.9% (78/84) to 94.0% (79/84) were within a 15 mg/dl (< 100 mg/dl) or 15% (> 100 mg/dl) of the average CLM value. Element™ BGMS was considered an appropriate SMBG for home use; however, the positive bias at low-to-mid glucose levels requires further improvement. © 2016 Wiley Periodicals, Inc.

Modified cuspal relationships of mandibular molar teeth in children with Down's syndrome

PubMed Central

PERETZ, BENJAMIN; SHAPIRA, JOSEPH; FARBSTEIN, HANNA; ARIELI, ELIAHU; SMITH, PATRICIA

1998-01-01

A total of 50 permanent mandibular 1st molars of 26 children with Down's syndrome (DS) were examined from dental casts and 59 permanent mandibular 1st molars of normal children were examined from 33 individuals. The following measurements were performed on both right and left molars (teeth 46 and 36 respectively): (a) the intercusp distances (mb-db, mb-d, mb-dl, db-ml, db-d, db-dl, db-ml, d-dl, d-ml, dl-ml); (b) the db-mb-ml, mb-db-ml, mb-ml-db, d-mb-dl, mb-d-dl, mb-dl-d angles; (c) the area of the pentagon formed by connecting the cusp tips. All intercusp distances were significantly smaller in the DS group. Stepwise logistic regression, applied to all the intercusp distances, was used to design a multivariate probability model for DS and normals. A model based on 2 distances only, mb-dl and mb-db, proved sufficient to discriminate between the teeth of DS and the normal population. The model for tooth 36 for example was as follows: formula here A similar model for tooth 46 was also created, as well as a model which incorporated both teeth. With respect to the angles, significant differences between DS and normals were found in 3 out of the 6 angles which were measured: the d-mb-dl angle was smaller than in normals, the mb-d-dl angle was higher, and the mb-dl-d angle was smaller. The dl cusp was located closer to the centre of the tooth. The change in size occurs at an early stage, while the change in shape occurs in a later stage of tooth formation in the DS population. PMID:10029186

Sustainable Development under Population Pressure: Lessons from Developed Land Consumption in the Conterminous U.S.

PubMed Central

2015-01-01

Population growth will result in a significant anthropogenic environmental change worldwide through increases in developed land (DL) consumption. DL consumption is an important environmental and socioeconomic process affecting humans and ecosystems. Attention has been given to DL modeling inside highly populated cities. However, modeling DL consumption should expand to non-metropolitan areas where arguably the environmental consequences are more significant. Here, we study all counties within the conterminous U.S. and based on satellite-derived product (National Land Cover Dataset 2001) we calculate the associated DL for each county. By using county population data from the 2000 census we present a comparative study on DL consumption and we propose a model linking population with expected DL consumption. Results indicate distinct geographic patterns of comparatively low and high consuming counties moving from east to west. We also demonstrate that the relationship of DL consumption with population is mostly linear, altering the notion that expected population growth will have lower DL consumption if added in counties with larger population. Added DL consumption is independent of a county’s starting population and only dependent on whether the county belongs to a Metropolitan Statistical Area (MSA). In the overlapping MSA and non-MSA population range there is also a constant DL efficiency gain of approximately 20km2 for a given population for MSA counties which suggests that transitioning from rural to urban counties has significantly higher benefits in lower populations. In addition, we analyze the socioeconomic composition of counties with extremely high or low DL consumption. High DL consumption counties have statistically lower Black/African American population, higher poverty rate and lower income per capita than average in both NMSA and MSA counties. Our analysis offers a baseline to investigate further land consumption strategies in anticipation of growing population pressures. PMID:25806525

Asian population frequencies and haplotype distribution of killer cell immunoglobulin-like receptor (KIR) genes among Chinese, Malay, and Indian in Singapore.

PubMed

Lee, Yi Chuan; Chan, Soh Ha; Ren, Ee Chee

2008-11-01

Killer cell immunoglobulin-like receptors (KIR) gene frequencies have been shown to be distinctly different between populations and contribute to functional variation in the immune response. We have investigated KIR gene frequencies in 370 individuals representing three Asian populations in Singapore and report here the distribution of 14 KIR genes (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1) with two pseudogenes (2DP1, 3DP1) among Singapore Chinese (n = 210); Singapore Malay (n = 80), and Singapore Indian (n = 80). Four framework genes (KIR3DL3, 3DP1, 2DL4, 3DL2) and a nonframework pseudogene 2DP1 were detected in all samples while KIR2DS2, 2DL2, 2DL5, and 2DS5 had the greatest significant variation across the three populations. Fifteen significant linkage patterns, consistent with associations between genes of A and B haplotypes, were observed. Eighty-four distinct KIR profiles were determined in our populations, 38 of which had not been described in other populations. KIR haplotype studies were performed using nine Singapore Chinese families comprising 34 individuals. All genotypes could be resolved into corresponding pairs of existing haplotypes with eight distinct KIR genotypes and eight different haplotypes. The haplotype A2 with frequency of 63.9% was dominant in Singapore Chinese, comparable to that reported in Korean and Chinese Han. The A haplotypes predominate in Singapore Chinese, with ratio of A to B haplotypes of approximately 3:1. Comparison with KIR frequencies in other populations showed that Singapore Chinese shared similar distributions with Chinese Han, Japanese, and Korean; Singapore Indian was found to be comparable with North Indian Hindus while Singapore Malay resembled the Thai.

Expressed sequence tag (EST) analysis of the pine wood nematode Bursaphelenchus xylophilus and B. mucronatus.

PubMed

Kikuchi, Taisei; Aikawa, Takuya; Kosaka, Hajime; Pritchard, Leighton; Ogura, Nobuo; Jones, John T

2007-09-01

Most Bursaphelenchus species feed on fungi that colonise dead or dying trees. However, Bursaphelenchus xylophilus is unique in that in addition to feeding on fungi it has the capacity to be a parasite of live pine trees. We present an analysis of over 13,000 expressed sequence tags (ESTs) from B. xylophilus and, by way of contrast, over 3000 ESTs from a closely related species that does not parasitise plants as readily; B. mucronatus. Four libraries from B. xylophilus, from a variety of life stages including fungal feeding nematodes, nematodes extracted from plants and dauer-like stage nematodes, and one library from B. mucronatus were constructed and used to generate ESTs. Contig analysis showed that the 13,327 B. xylophilus ESTs could be grouped into 2110 contigs and 4377 singletons giving a total of 6487 identified genes. Similarly the 3193 B. mucronatus ESTs yielded a total of 2219 identified genes from 425 contigs and 1794 singletons. A variety of proteins potentially important in the parasitic process of B. xylophilus and B. mucronatus, including plant and fungal cell wall degrading enzymes and a novel gene potentially encoding a expansin-like protein that may disrupt non-covalent bonds in the plant cell wall were identified in the libraries. Additionally several gene candidates potentially involved in dauer entry or maintenance were also identified in the EST dataset. The EST sequences from this study will provide a solid base for future research on the biology, pathogenicity and evolutionary history of this nematode group.

KIR3DL2 binds to HLA-B27 dimers and free heavy chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis

PubMed Central

Wong-Baeza, Isabel; Ridley, Anna; Shaw, Jackie; Hatano, Hiroko; Rysnik, Oliwia; McHugh, Kirsty; Piper, Christopher; Brackenbridge, Simon; Fernandes, Ricardo; Chan, Anthoni; Bowness, Paul; Kollnberger, Simon

2013-01-01

1Abstract The Human Leukocyte Antigen HLA-B27(B27) is strongly associated with the spondyloarthritides. B27 can be expressed at the cell surface of antigen presenting cells (APC) as both classical β2m-associated B27 and as B27 free heavy chain forms (FHC) including disulphide-bonded heavy chain homodimers (termed B272). B27 FHC forms but not classical B27 bind to KIR3DL2. HLA-A3 which is not associated with spondyloarthritis (SpA) is also a ligand for KIR3DL2. Here we show that B272 and B27 FHC bind more strongly to KIR3DL2 than other HLA-class I, including HLA-A3. B272 tetramers bound KIR3DL2 transfected cells more strongly than HLA-A3. KIR3DL2Fc bound to HLA-B27-transfected cells more strongly than to cells transfected with other HLA-class I. KIR3DL2Fc pulled down multimeric, dimeric and monomeric free heavy chains from HLA-B27 expressing cell lines. Binding to B272 and B27 FHC stimulated greater KIR3DL2 phosphorylation than HLA-A3. B272 and B27 FHC stimulated KIR3DL2CD3ε–transduced T cell IL-2 production to a greater extent than control HLA-class I. KIR3DL2 binding to B27 inhibited NK IFNγ secretion and promoted greater survival of KIR3DL2+CD4 T and NK cells than binding to other HLA-class I. KIR3DL2+ T cells from B27+SpA patients proliferated more in response to antigen presented by syngeneic APC than the same T cell subset from healthy and disease controls. Our results suggest that expansion of KIR3DL2-expressing leukocytes observed in B27+ SpA may be explained by the stronger interaction of KIR3DL2 with B27 FHC. PMID:23440420

Activation‐Induced Killer Cell Immunoglobulin‐like Receptor 3DL2 Binding to HLA–B27 Licenses Pathogenic T Cell Differentiation in Spondyloarthritis

PubMed Central

Ridley, Anna; Hatano, Hiroko; Wong‐Baeza, Isabel; Shaw, Jacqueline; Matthews, Katherine K.; Al‐Mossawi, Hussein; Ladell, Kristin; Price, David A.; Bowness, Paul

2016-01-01

Objective In the spondyloarthritides (SpA), increased numbers of CD4+ T cells express killer cell immunoglobulin‐like receptor 3DL2 (KIR‐3DL2). The aim of this study was to determine the factors that induce KIR‐3DL2 expression, and to characterize the relationship between HLA–B27 and the phenotype and function of KIR‐3DL2–expressing CD4+ T cells in SpA. Methods In total, 34 B27+ patients with SpA, 28 age‐ and sex‐matched healthy controls (20 B27− and 8 B27+), and 9 patients with rheumatoid arthritis were studied. KIR-3DL2 expression and other phenotypic characteristics of peripheral blood and synovial fluid CD4+ T cells were studied by flow cytometry, quantitative polymerase chain reaction, and Western blotting. T cell receptor clonality was determined by template‐switch anchored reverse transcription–polymerase chain reaction and sequencing analysis. Cytokines were measured by enzyme‐linked immunosorbent assay. Results Cellular activation induced KIR‐3DL2 expression on both naive and effector CD4+ T cells. KIR‐3DL2 binding to B27+ cells promoted expression of KIR‐3DL2, the Th17‐specific transcription factor retinoic acid receptor–related orphan nuclear receptor γt, and the antiapoptotic factor B cell lymphoma 2. KIR‐3DL2+CD4+ T cells in patients with ankylosing spondylitis were oligoclonal and enriched for markers of T cell activation and for the gut homing receptor CCR9. In the presence of B27+ antigen‐presenting cells, KIR‐3DL2+CD4+ T cells produced less interleukin‐2 (IL‐2) but more IL‐17. This effect was blocked by HC10, an antibody that inhibits the binding of KIR‐3DL2 to B27 heavy chains. Conclusion KIR‐3DL2 binding to HLA–B27 licenses Th17 cell differentiation in SpA. These findings raise the therapeutic potential of targeting HLA–B27–KIR‐3DL2 interactions for the treatment of B27+ patients with SpA. PMID:26841353

KIR3DL2 binds to HLA-B27 dimers and free H chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis.

PubMed

Wong-Baeza, Isabel; Ridley, Anna; Shaw, Jackie; Hatano, Hiroko; Rysnik, Oliwia; McHugh, Kirsty; Piper, Christopher; Brackenbridge, Simon; Fernandes, Ricardo; Chan, Anthoni; Bowness, Paul; Kollnberger, Simon

2013-04-01

The human leukocyte Ag HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 can be expressed at the cell surface of APC as both classical β2-microglobulin-associated B27 and B27 free H chain forms (FHC), including disulfide-bonded H chain homodimers (termed B27(2)). B27 FHC forms, but not classical B27, bind to KIR3DL2. HLA-A3, which is not associated with spondyloarthritis (SpA), is also a ligand for KIR3DL2. In this study, we show that B27(2) and B27 FHC bind more strongly to KIR3DL2 than other HLA-class I, including HLA-A3. B27(2) tetramers bound KIR3DL2-transfected cells more strongly than HLA-A3. KIR3DL2Fc bound to HLA-B27-transfected cells more strongly than to cells transfected with other HLA-class I. KIR3DL2Fc pulled down multimeric, dimeric, and monomeric FHC from HLA-B27-expressing cell lines. Binding to B27(2) and B27 FHC stimulated greater KIR3DL2 phosphorylation than HLA-A3. B27(2) and B27 FHC stimulated KIR3DL2CD3ε-transduced T cell IL-2 production to a greater extent than control HLA-class I. KIR3DL2 binding to B27 inhibited NK IFN-γ secretion and promoted greater survival of KIR3DL2(+) CD4 T and NK cells than binding to other HLA-class I. KIR3DL2(+) T cells from B27(+) SpA patients proliferated more in response to Ag presented by syngeneic APC than the same T cell subset from healthy and disease controls. Our results suggest that expansion of KIR3DL2-expressing leukocytes observed in B27(+) SpA may be explained by the stronger interaction of KIR3DL2 with B27 FHC.

Descriptions and Implementations of DL_F Notation: A Natural Chemical Expression System of Atom Types for Molecular Simulations.

PubMed

Yong, Chin W

2016-08-22

DL_F Notation is an easy-to-understand, standardized atom typesetting expression for molecular simulations for a range of organic force field (FF) schemes such as OPLSAA, PCFF, and CVFF. It is implemented within DL_FIELD, a software program that facilitates the setting up of molecular FF models for DL_POLY molecular dynamics simulation software. By making use of the Notation, a single core conversion module (the DL_F conversion Engine) implemented within DL_FIELD can be used to analyze a molecular structure and determine the types of atoms for a given FF scheme. Users only need to provide the molecular input structure in a simple xyz format and DL_FIELD can produce the necessary force field file for DL_POLY automatically. In commensurate with the development concept of DL_FIELD, which placed emphasis on robustness and user friendliness, the Engine provides a single-step solution to setup complex FF models. This allows users to switch from one of the above-mentioned FF seamlessly to another while at the same time provides a consistent atom typing that is expressed in a natural chemical sense.

A monoclonal antibody, DL10, which recognizes a sugar moiety of MHC class I antigens expressed on NK cells, NK+ T cells, and granulocytes in humans.

PubMed

Shirai, K; Watanabe, H; Weerasinghe, A; Sakai, T; Sekikawa, H; Abo, T

1997-11-01

One mAb, DL10, was established from mice injected with dolphin lymphocytes. In addition to its reactivity against all dolphin lymphocytes, it reacted with some human leukocytes, including NK cells, NK+ T cells, and granulocytes. When its reactivity was examined in various animals, bovine, ovine, and equine leukocytes were DL10+. Murine, rat, and canine leukocytes were DL10-. Although the reactivity of DL10+ was similar to those of CD56 and CD57 antigens in humans, the actual molecules it recognized were different. Thus, all reactivity of DL10 disappeared after treatment of cells with glycopeptidase or after culture of cells with tunicamycin. Furthermore, the immunoprecipitation method revealed that DL10 indirectly recognized the heavy chain (45kD) of MHC class I antigen in humans and animals. Considering data from analysis of the N-terminal amino acid sequence of the DL10 molecule and the HLA typing of reactive cells, DL10 recognized a sugar moiety of some monomorphic MHC antigens and polymorphic MHC antigens such as HLA-B60 and -B61. If the donors are HLA-B60- and -B61 (> 80% in Japan and > 95% in the United States), DL10 would appear to be a very useful agent for the detection of pan-NK+ T cells.

Protective effect of latex of Calotropis procera in Freund's Complete Adjuvant induced monoarthritis.

PubMed

Kumar, V L; Roy, S

2009-01-01

The protective effect of latex of Calotropis procera in Freund's Complete Adjuvant (FCA) induced monoarticular arthritis was evaluated in rats. Arthritis was induced by a single intra-articular injection of 0.1 mL of 0.1% FCA in the right ankle joint. The effect of dried latex (DL, 200 and 400 mg/kg) and its methanol extract (MeDL, 50 and 500 mg/kg) following oral administration was evaluated on joint inflammation, hyperalgesia, locomotor function and histology at the time of peak inflammation. The effects of DL and MeDL were compared with antiinflammatory drugs phenylbutazone (100 mg/kg), prednisolone (20 mg/kg), rofecoxib (20 and 100 mg/kg) and immuno-suppressant methotrexate (0.3 mg/kg). Daily oral administration of DL and its methanol extract (MeDL) produced a significant reduction in joint inflammation (about 50% and 80% inhibition) and associated hyperalgesia. The antihyperalgesic effect of MeDL was comparable to that of rofecoxib. Both DL and MeDL produced a marked improvement in the motility and stair climbing ability of the rats. The histological analysis of the arthritic joint also revealed significant reduction in oedema and cellular infiltration by MeDL that was comparable to that of rofecoxib. Thus, our study suggests that the latex of C. procera has the potential to be used as an antiarthritic agent. Copyright 2008 John Wiley & Sons, Ltd.

The potential use of novel chitosan-coated deformable liposomes in an ocular drug delivery system.

PubMed

Chen, Hongdan; Pan, Hao; Li, Panpan; Wang, Hui; Wang, Xin; Pan, Weisan; Yuan, Yue

2016-07-01

In this study, novel chitosan-coated deformable liposomes (DL-CS) were proposed as an ocular drug delivery system to prolong pre-corneal retention, and improve transcorneal penetration and absorption. Flurbiprofen-loaded deformable liposomes (FP-DL) were prepared by a modified ethanol injection method and then coated with chitosan. Both DL and DL-CS exhibited a homogeneous particle size distribution, high encapsulation efficiency and good stability. After coating with 0.1% CS, the zeta potential was shifted from negative to positive. The apparent permeability coefficient of FP-DL-0.1% CS evaluated using isolated rabbit corneas was 1.29-, 1.95- and 4.59- fold greater than that of uncoated FP-DL, conventional liposomes and FP solution (P<0.01), respectively. The in vivo pre-corneal retention time and elimination dynamics were assessed using gamma scintigraphy technology. The area under the remaining activity-time of FP-DL-0.1% CS was prolonged 2.84- and 1.53-fold compared with that of the FP solution and FP-DL groups, respectively. Moreover, the ocular irritation test in vivo revealed that DL-0.1% CS produced no ocular damage or abnormal clinical signs. These results indicate that DL-CS appears to be a novel ophthalmic drug delivery strategy with the potential to overcome the limitations of conventional eye drops. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison between McMaster and Mini-FLOTAC methods for the enumeration of Eimeria maxima oocysts in poultry excreta.

PubMed

Bortoluzzi, C; Paras, K L; Applegate, T J; Verocai, G G

2018-04-30

Monitoring Eimeria shedding has become more important due to the recent restrictions to the use of antibiotics within the poultry industry. Therefore, there is a need for the implementation of more precise and accurate quantitative diagnostic techniques. The objective of this study was to compare the precision and accuracy between the Mini-FLOTAC and the McMaster techniques for quantitative diagnosis of Eimeria maxima oocyst in poultry. Twelve pools of excreta samples of broiler chickens experimentally infected with E. maxima were analyzed for the comparison between Mini-FLOTAC and McMaster technique using, the detection limits (dl) of 23 and 25, respectively. Additionally, six excreta samples were used to compare the precision of different dl (5, 10, 23, and 46) using the Mini-FLOTAC technique. For precision comparisons, five technical replicates of each sample (five replicate slides on one excreta slurry) were read for calculating the mean oocyst per gram of excreta (OPG) count, standard deviation (SD), coefficient of variation (CV), and precision of both aforementioned comparisons. To compare accuracy between the methods (McMaster, and Mini-FLOTAC dl 5 and 23), excreta from uninfected chickens was spiked with 100, 500, 1,000, 5,000, or 10,000 OPG; additional samples remained unspiked (negative control). For each spiking level, three samples were read in triplicate, totaling nine reads per spiking level per technique. Data were transformed using log10 to obtain normality and homogeneity of variances. A significant correlation (R = 0.74; p = 0.006) was observed between the mean OPG of the McMaster dl 25 and the Mini-FLOTAC dl 23. Mean OPG, CV, SD, and precision were not statistically different between the McMaster dl 25 and Mini-FLOTAC dl 23. Despite the absence of statistical difference (p > 0.05), Mini-FLOTAC dl 5 showed a numerically lower SD and CV than Mini-FLOTAC dl 23. The Pearson correlation coefficient revealed significant and positive correlation among the four dl (p ≤ 0.05). In the accuracy study, it was observed that the Mini-FLOTAC dl 5 and 23 were more accurate than the McMaster for 100 OPG, and the Mini-FLOTAC dl 23 had the highest accuracy for 500 OPG. The McMaster and Mini-FLOTAC dl 23 techniques were more accurate than the Mini-FLOTAC dl 5 for 5,000 OPG, and both dl of the Mini-FLOTAC were less accurate for 10,000 OPG counts than the McMaster technique. However, the overall accuracy of the Mini-FLOTAC dl 23 was higher than the McMaster and Mini-FLOTAC dl 5 techniques. Copyright © 2018 Elsevier B.V. All rights reserved.

HIV-1 Control by NK Cells via Reduced Interaction between KIR2DL2 and HLA-C∗12:02/C∗14:03.

PubMed

Lin, Zhansong; Kuroki, Kimiko; Kuse, Nozomi; Sun, Xiaoming; Akahoshi, Tomohiro; Qi, Ying; Chikata, Takayuki; Naruto, Takuya; Koyanagi, Madoka; Murakoshi, Hayato; Gatanaga, Hiroyuki; Oka, Shinichi; Carrington, Mary; Maenaka, Katsumi; Takiguchi, Masafumi

2016-11-22

Natural killer (NK) cells control viral infection in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands. We investigated 504 anti-retroviral (ART)-free Japanese patients chronically infected with HIV-1 and identified two KIR/HLA combinations, KIR2DL2/HLA-C ∗ 12:02 and KIR2DL2/HLA-C ∗ 14:03, that impact suppression of HIV-1 replication. KIR2DL2 + NK cells suppressed viral replication in HLA-C ∗ 14:03 + or HLA-C ∗ 12:02 + cells to a significantly greater extent than did KIR2DL2 - NK cells in vitro. Functional analysis showed that the binding between HIV-1-derived peptide and HLA-C ∗ 14:03 or HLA-C ∗ 12:02 influenced KIR2DL2 + NK cell activity through reduced expression of the peptide-HLA (pHLA) complex on the cell surface (i.e., reduced KIR2DL2 ligand expression), rather than through reduced binding affinity of KIR2DL2 to the respective pHLA complexes. Thus, KIR2DL2/HLA-C ∗ 12:02 and KIR2DL2/HLA-C ∗ 14:03 compound genotypes have protective effects on control of HIV-1 through a mechanism involving KIR2DL2-mediated NK cell recognition of virus-infected cells, providing additional understanding of NK cells in HIV-1 infection. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Synthesis and Hydrolytic Degradation of Substituted Poly(DL-Lactic Acid)s

PubMed Central

Tsuji, Hideto; Eto, Takehiko; Sakamoto, Yuzuru

2011-01-01

Non-substituted racemic poly(DL-lactic acid) (PLA) and substituted racemic poly(DL-lactic acid)s or poly(DL-2-hydroxyalkanoic acid)s with different side-chain lengths, i.e., poly(DL-2-hydroxybutanoic acid) (PBA), poly(DL-2-hydroxyhexanoic acid) (PHA), and poly(DL-2-hydroxydecanoic acid) (PDA) were synthesized by acid-catalyzed polycondensation of DL-lactic acid (LA), DL-2-hydroxybutanoic acid (BA), DL-2-hydroxyhexanoic acid (HA), and DL-2-hydroxydecanoic acid (DA), respectively. The hydrolytic degradation behavior was investigated in phosphate-buffered solution at 80 and 37 °C by gravimetry and gel permeation chromatography. It was found that the reactivity of monomers during polycondensation as monitored by the degree of polymerization (DP) decreased in the following order: LA > DA > BA > HA. The hydrolytic degradation rate traced by DP and weight loss at 80 °C decreased in the following order: PLA > PDA > PHA > PBA and that monitored by DP at 37 °C decreased in the following order: PLA > PDA > PBA > PHA. LA and PLA had the highest reactivity during polymerization and hydrolytic degradation rate, respectively, and were followed by DA and PDA. BA, HA, PBA, and PHA had the lowest reactivity during polymerization and hydrolytic degradation rate. The findings of the present study strongly suggest that inter-chain interactions play a major role in the reactivity of non-substituted and substituted LA monomers and degradation rate of the non-substituted and substituted PLA, along with steric hindrance of the side chains as can be expected. PMID:28824149

Investigation of the influence of the composition on mechanical properties poly(glycolide-DL-lactide)

NASA Astrophysics Data System (ADS)

Baikin, A. S.; Sevostyanov, M. A.; Nasakina, E. O.; Sergienko, K. V.; Kaplan, M. A.; Konushkin, S. V.; Kolmakova, A. A.; Yakubov, A. D.; Kolmakov, A. G.

2018-04-01

In this paper we describe the creation of films from poly (glycolide-DL-lactide). Studied the mechanical properties of developed polymer films of poly (glycolide-DL-lactide). The effect of the molecular weight of poly (glycolide-DL-lactide) on the mechanical properties of the resulting polymer films is shown. The dependence of the mechanical properties of poly (glycolide-DL-lactide) films on the polymer concentration in chloroform was studied. The possibility of creating biodegradable films with specified mechanical properties is shown.

Direct Loan Update, 2002-2003. EDExpress Training. Participant Guide.

ERIC Educational Resources Information Center

Office of Student Financial Assistance (ED), Washington, DC.

This participant guide is an update to basic training in the Direct Loan (DL) portion of the EDExpress system designed for financial aid professionals who have already participated in the basic training. The first session considers new aspects of DL processing, focusing on DL process changes and EDExpress DL changes. Session 2 contains three…

Thermochemistry of the Dissolution of Dipeptides Containing DL-α-Alanine in Aqueous Solutions of Sodium Dodecyl Sulfate at 298.15 K

NASA Astrophysics Data System (ADS)

Smirnov, V. I.; Badelin, V. G.

2018-05-01

Enthalpies of the dissolution of DL-α-alanylglycine (AlaGly), DL-α-alanyl-DL-α-alanine (AlaAla), DL-α-alanyl-DL-α-valine (AlaVal), and DL-α-alanyl-DL-norleucine (AlaNln) in an aqueous solution of sodium dodecyl sulfate (SDS) at SDS concentration of m = 0-0.07 mol kg-1 and temperature T = 298.15 K are measured via calorimetry. The standard values of the enthalpy of dissolution (Δsol H m ) and the transfer of dipeptides (Δtr H m ) from water to aqueous SDS solutions are calculated using the experimental data. The dependences of Δsol H m and Δtr H m the SDS concentration at a constant concentration of dipeptide are established. Thermochemical characteristics of the transfer of AlaGly, AlaAla, AlaVal, and AlaNln in the investigated range of SDS concentrations are compared. The results are interpreted by considering ion-ion, ion-polar, and hydrophobic-hydrophobic interactions between SDS and dipeptide molecules.

Stereospecificity of mushroom tyrosinase immobilized on a chiral and a nonchiral support.

PubMed

Marín-Zamora, María Elisa; Rojas-Melgarejo, Francisco; García-Canovas, Francisco; García-Ruiz, Pedro Antonio

2007-05-30

Mushroom tyrosinase was immobilized from an extract onto glass beads covered with the cross-linked totally cinnamoylated derivates of d-sorbitol (sorbitol cinnamate) and glycerine (glycerine cinnamate). The enzyme was immobilized onto the support by direct adsorption, and the quantity of immobilized tyrosinase was higher for sorbitol cinnamate, the support with the higher number of esterified hydroxyls per unit of monosacharide, than for glycerine cinnamate. The results obtained from the stereospecificity study of the monophenolase and diphenolase activity of immobilized mushroom tyrosinase are reported. The enantiomers L-tyrosine, DL-tyrosine, D-tyrosine, L-dopa, DL-dopa, D-dopa, L-alpha-methyldopa, DL-alpha-methyldopa, L-isoprenaline, DL-isoprenaline, L-adrenaline, DL-adrenaline, L-noradrenaline, and D-noradrenaline were assayed with tyrosinase immobilized on a chiral support (sorbitol cinnamate), whereas L-tyrosine, DL-tyrosine, D-tyrosine, L-dopa, DL-dopa, D-dopa, L-alpha-methyldopa, and DL-alpha-methyldopa were assayed with tyrosinase immobilized on a nonchiral support (glycerine cinnamate). The same Vmax(app) values for each series of enantiomers were obtained. However, the Km(app) values were different, the l isomers showing lower values than the dl isomers, whereas the highest Km(app) value was obtained with d isomers. No difference was observed in the stereospecificity of tyrosinase immobilized on a chiral (sorbitol cinnamate) or nonchiral (glycerine cinnamate) support.

Can PEP-3 Provide a Cognitive Profile in Children with ASD? A Comparison Between the Developmental Ages of PEP-3 and IQ of Leiter-R.

PubMed

De Giacomo, Andrea; Craig, Francesco; Cristella, Arcangelo; Terenzio, Vanessa; Buttiglione, Maura; Margari, Lucia

2016-11-01

The assessment of the intelligence quotient (IQ) in children with autism spectrum disorder (ASD) is important to plan a detailed therapeutic-educative programme. The aim of the study was to evaluate the usefulness of the Psychoeducational Profile-third edition (PEP-3) to estimate the general cognitive development of children with ASD. We recruited 30 children with ASD assessed with the Leiter International Performance Scale-Revised (Leiter-R) and the PEP-3. We compared the IQ of the Leiter-R with the developmental level (DL) of PEP-3. The findings showed a significant positive correlation between IQ with DL of the cognitive verbal/pre-verbal (P = 0.0005), DL of the area of expressive language (P = 0.0004), DL of the area of receptive language (P = 0.0001), DL of fine motor (P = 0.0066), DL of gross motor (P = 0.0217), DL of visuo-motor imitation (P = 0.02), DL of communication (P = 0.0001) and DL of motor (P = 0.0063). These findings show that the DLs could be considered as indicators of cognitive functioning in ASD. © 2015 John Wiley & Sons Ltd.

Development of Long-Circulating pH-Sensitive Liposomes to Circumvent Gemcitabine Resistance in Pancreatic Cancer Cells.

PubMed

Xu, Hongtao; Paxton, James W; Wu, Zimei

2016-07-01

To develop pH-sensitive liposomes (PSL) containing a high content of gemcitabine; and to investigate whether drug loading (DL) would alter the in vitro and pharmacokinetic properties. PSL with a high DL were obtained using a modified small-volume incubation method. The DL effects on drug release rate and in vitro cytotoxicity of PSL were evaluated using MIA PaCa-2 pancreatic cancer cells and their pharmacokinetics investigated in rats. The highest DL of 4.5 ± 0.1% was achieved for gemcitabine in PSL with 145 ± 5 nm diameter. DL did not alter the in vitro release rate from PSL. The IC50 (48 h) of PSL (DL 0.5 and 4.5%) and non pH-sensitive liposomes (NPSL, DL 4.2%) were 1.1 ± 0.1, 0.7 ± 0.1 and 37.0 ± 7.5 μM, respectively. The PSL resulted in a 4.2-fold increase in its elimination half-life (6.2 h) compared to gemcitabine solution (1.4 h) in rats. No significant difference in pharmacokinetic parameters was observed between the two PSL (DL 0.5 and 4.5%). The PSL offered advantages over NPSL in restoring the sensitivity of pancreatic cancer cells to gemcitabine without requiring a high DL. DL in the PSL did not alter release rate, cytotoxicity or their long-circulating properties. Graphical Abstract ᅟ.

Hematologic and serum biochemical reference intervals for Florida panthers.

USGS Publications Warehouse

Dunbar, M.R.; Nol, P.; Linda, S.B.

1997-01-01

Ninety-four blood samples were collected from 48 (29 males and 19 females) free-ranging Florida panthers (Felis concolor coryi) captured in southern Florida (USA) from 1983 to 1994 for routine hematological and serum biochemical analysis. Florida panthers in the northern portion of their range had significantly higher red blood cell (mean +/- SD = 7.923 x 10(6) +/- 0.854 x 10(6)/microliter), hemoglobin (12.53 +/- 1.66 g/dl), and packed cell volume (36.97 +/- 4.27%) values compared to those of panthers localized in more southern parts of Florida (7.148 x 10(6) +/- 1.045 x 10(6)/microliter, 11.60 +/- 1.62 g/dl, and 34.82 +/- 5.99%, respectively). Adults had significantly higher mean serum total protein (7.50 +/- 0.59 g/dl) and packed cell volume (36.90 +/- 4.97%) values than juveniles (6.88 +/- 0.49 g/dl and 34.54 +/- 5.30%). However, mean serum albumin concentrations were significantly higher in juveniles (3.80 +/- 0.26 g/dl) when compared to adult values (3.58 +/- 0.26 g/dl). Mean serum calcium concentrations were significantly higher in juveniles (10.33 +/- 0.39 mg/dl) than in adults (9.66 +/- 0.45 mg/dl). Additionally, mean serum iron concentrations were significantly higher in those panthers of intergrade genetic stock compared to values in those of authentic genetic stock (105.6 +/- 72.1 micrograms/dl versus 59.3 +/- 19.7 micrograms/dl, respectively).

Management of anaemia in haemodialysis and peritoneal dialysis patients (chapter 8).

PubMed

Richardson, Donald; Hodsman, Alex; van Schalkwyk, Dirk; Tomson, Charlie; Warwick, Graham

2007-08-01

Forty-one percent of UK patients commence RRT with an Hb < 10.0 g/dl. The mean Hb at commencement of RRT is 10.3 g/dl. Eighty-five percent of patients on dialysis in the UK have an Hb > or = 10.0 g/dl by 6 months after commencement of RRT. The median Hb on haemodialysis in the UK is 11.8 g/dl with an IQR of 10.7-12.8 g/dl. Eighty-six percent of haemodialysis patients in the UK have a Hb > or = 10.0 g/dl. The median Hb on peritoneal dialysis in the UK is 12.0 g/dl with an IQR of 11.0-12.9 g/dl. Ninety percent of peritoneal dialysis patients in the UK have an Hb > or = 10.0 g/dl. In the UK, 49% of patients on PD and 48% of patients on haemodialysis have an Hb between 10.5-12.5 g/dl. The median ferritin in UK haemodialysis patients is 413 microg/l (IQR 262-623), 95% of UK haemodialysis patients have a ferritin > or =100 microg/l. The median ferritin in UK PD patients is 256 microg/l (IQR 147-421), 86% of UK peritoneal dialysis patients have a ferritin > or = 100 microg/l. A higher proportion of HD patients than PD patients receive ESA therapy (88% vs 76%). The ESA dose is higher for HD than PD patients (9204 vs 6080 IU/week).

Serum 3,3'-L-diiodothyronine, a direct radioimmunoassay in human serum: method and clinical results. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burger, A.; Sakoloff, C.

1977-09-01

A specific radioimmunoassay for 3,3'-diiodothyronine (T/sub 2/) is described which is capable of detecting as little as 1.3 ng/dl. The antiserum recognizes mainly T/sub 2/; biliary conjugates of T/sub 2/ bind slightly to the antibody. The intraassay and interassay coefficients of variation were, respectively, 5.7% and 13.1%. T/sub 2/ was detected in the serum of hypothyroid patients treated with triiodothyronine (T/sub 3/) and in euthyroid subjects treated with reverse triiodothyronine (rT/sub 3/). These results suggest that both T/sub 3/ and rT/sub 3/ are deiodinated to T/sub 2/. Serum concentrations of T/sub 2/ in normal subjects decreased with age. Between 20more » and 40 years the mean concentration was 4.3 +- 2.0 ng/dl (2 SD), between 41 and 60 years it varied from 1.9 to 5.8 ng/dl (3.8 +- 0.3 ng/dl, SE) and in elderly subjects have 60 years concentrations varied from unmeasurable to 4 ng/dl (2.9 +- 0.4 ng/dl, SE). Low serum T/sub 2/ concentrations were found in anorexia nervosa (2.5 +- 0.3 ng/dl, SE). In hypothyroidism the serum concentrations were low or unmeasurable. As most of the hypothyroid subjects were elderly their serum T/sub 2/ concentrations overlapped with the low values found in the elderly euthyroid subjects. In classical hyperthyroidism serum T/sub 2/ concentrations were greatly increased (3.3 to 31 ng/dl (11.8 +- 2.7 ng/dl, SE) but in ''T/sub 3/ toxicosis'' the concentrations were only modestly increased (2.4 to 8.8 ng/dl, 5.2 +- 0.8 ng/dl, SE).« less

HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS

PubMed Central

Dausset, Jean; Rapaport, Felix T.; Cannon, Frances D.; Ferrebee, Joseph W.

1971-01-01

The segregation of the canine DL-A leukocyte group antigen(s) b, c, d, e, f, g, h, k, l, and m has been traced in 141 consecutive matings in the Cooperstown Colony of beagles. All of the leukocyte antigen(s) were regularly transmitted en bloc from parent to offspring, with no instance of independent segregation. A total of 23 haplotypes, including six different DL-A antigen patterns (gl, bkhfm, bkcd, e, be, fgl) was observed. 31 different DL-A phenotypes were observed in a population of 100 mongrel dogs. A number of statistically significant positive and negative associations between individual DL-A antigenic components occurred in this population. The results support the concept of the DL-A system as a complex immunogenetic system governed by a single region (or locus) of an autosomal pair of chromosomes. Studies of skin, kidney, heart, and liver allografts in the Cooperstown Colony indicated that the longest allograft survivals occur under genetically and serologically defined conditions of donor-recipient DL-A compatibility. Skin and renal allografts generally behaved in parallel fashion, while cardiac allografts survived for longer periods of time (MST = 47.1 days) than kidneys (MST = 28.1 days) or skin (MST = 25.1 days) under conditions of DL-A identity. Heart transplants were rejected at a more rapid rate than kidney, however, in DL-A-incompatible donor-recipient combinations. Liver transplants were accorded the longest survival time (MST = 76.2 days) under conditions of DL-A identity, but were rejected at a rapid rate (MST = 5 days) in DL-A-incompatible nonlittermate donor-recipient pairs. The results provide further evidence that the DL-A system is the principal system of histocompatibility in the canine species. The differences in survival of different organs under similar conditions of donor-recipient DL-A compatibility suggest, however, the existence of a number of unknown variables which may also be capable of significantly affecting allograft behavior. PMID:4939370

Activation-Induced Killer Cell Immunoglobulin-like Receptor 3DL2 Binding to HLA-B27 Licenses Pathogenic T Cell Differentiation in Spondyloarthritis.

PubMed

Ridley, Anna; Hatano, Hiroko; Wong-Baeza, Isabel; Shaw, Jacqueline; Matthews, Katherine K; Al-Mossawi, Hussein; Ladell, Kristin; Price, David A; Bowness, Paul; Kollnberger, Simon

2016-04-01

In the spondyloarthritides (SpA), increased numbers of CD4+ T cells express killer cell immunoglobulin-like receptor 3DL2 (KIR-3DL2). The aim of this study was to determine the factors that induce KIR-3DL2 expression, and to characterize the relationship between HLA-B27 and the phenotype and function of KIR-3DL2-expressing CD4+ T cells in SpA. In total, 34 B27+ patients with SpA, 28 age- and sex-matched healthy controls (20 B27- and 8 B27+), and 9 patients with rheumatoid arthritis were studied. KIR-3DL2 expression and other phenotypic characteristics of peripheral blood and synovial fluid CD4+ T cells were studied by flow cytometry, quantitative polymerase chain reaction, and Western blotting. T cell receptor clonality was determined by template-switch anchored reverse transcription-polymerase chain reaction and sequencing analysis. Cytokines were measured by enzyme-linked immunosorbent assay. Cellular activation induced KIR-3DL2 expression on both naive and effector CD4+ T cells. KIR-3DL2 binding to B27+ cells promoted expression of KIR-3DL2, the Th17-specific transcription factor retinoic acid receptor-related orphan nuclear receptor γt, and the antiapoptotic factor B cell lymphoma 2. KIR-3DL2+CD4+ T cells in patients with ankylosing spondylitis were oligoclonal and enriched for markers of T cell activation and for the gut homing receptor CCR9. In the presence of B27+ antigen-presenting cells, KIR-3DL2+CD4+ T cells produced less interleukin-2 (IL-2) but more IL-17. This effect was blocked by HC10, an antibody that inhibits the binding of KIR-3DL2 to B27 heavy chains. KIR-3DL2 binding to HLA-B27 licenses Th17 cell differentiation in SpA. These findings raise the therapeutic potential of targeting HLA-B27-KIR-3DL2 interactions for the treatment of B27+ patients with SpA. © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Effects of homocysteine and its related compounds on oxygen consumption of the rat heart tissue homogenate: the role of different gasotransmitters.

PubMed

Uzelac, Jovana Jakovljević; Stanić, Marina; Krstić, Danijela; Čolović, Mirjana; Djurić, Dragan

2017-11-29

The objective of this study was to investigate in vitro effects of 10 µM DL-homocysteine (DL-Hcy), DL-homocysteine thiolactone-hydrochloride (DL-Hcy TLHC), and L-homocysteine thiolactone-hydrochloride (L-Hcy TLHC) on the oxygen consumption of rat heart tissue homogenate, as well as the involvement of the gasotransmitters NO, H 2 S and CO in the effects of the most toxic homocysteine compound, DL-Hcy TLHC. The possible contribution of the gasotransmitters in these effects was estimated by using the appropriate inhibitors of their synthesis (N ω -nitro-L-arginine methyl ester (L-NAME), DL-propargylglycine (DL-PAG), and zinc protoporphyrin IX (ZnPPR IX), respectively). The oxygen consumption of rat heart tissue homogenate was measured by Clark/type oxygen electrode in the absence and presence of the investigated compounds. All three homocysteine-based compounds caused a similar decrease in the oxygen consumption rate compared to control: 15.19 ± 4.01%, 12.42 ± 1.01%, and 16.43 ± 4.52% for DL-Hcy, DL-Hcy TLHC, or L-Hcy TLHC, respectively. All applied inhibitors of gasotransmitter synthesis also decreased the oxygen consumption rate of tissue homogenate related to control: 13.53 ± 1.35% for L-NAME (30 µM), 5.32 ± 1.23% for DL-PAG (10 µM), and 5.56 ± 1.39% for ZnPPR IX (10 µM). Simultaneous effect of L-NAME (30 µM) or ZnPPR IX (10 µM) with DL-Hcy TLHC (10 µM) caused a larger decrease of oxygen consumption compared to each of the substances individually. However, when DL-PAG (10 µM) was applied together with DL-Hcy TLHC (10 µM), it attenuated the effect of DL-Hcy TLHC from 12.42 ± 1.01 to 9.22 ± 1.58%. In conclusion, cardiotoxicity induced by Hcy-related compounds, which was shown in our previous research, could result from the inhibition of the oxygen consumption, and might be mediated by the certain gasotransmitters.

Are there sex differences in the capillary blood volume and diffusing capacity response to exercise?

PubMed

Bouwsema, Melissa M; Tedjasaputra, Vincent; Stickland, Michael K

2017-03-01

Previous work suggests that women may exhibit a greater respiratory limitation in exercise compared with height-matched men. Diffusion capacity (Dl CO ) increases with incremental exercise, and the smaller lungs of women may limit membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) in response to the increased oxygen demand. We hypothesized that women would have lower Dl CO , Dl CO relative to cardiac output (Dl CO /Q̇), Dm, Vc, and pulmonary transit time, secondary to lower Vc at peak exercise. Sixteen women (112 ± 12% predicted relative V̇o 2peak ) and sixteen men (118 ± 22% predicted relative V̇o 2peak ) were matched for height and weight. Hemoglobin-corrected diffusing capacity (Dl CO ), Vc, and Dm were determined via the multiple-[Formula: see text] Dl CO technique at rest and during incremental exercise up to 90% of V̇o 2peak Both groups increased Dl CO , Vc, and Dm with exercise intensity, but women had 20% lower Dl CO ( P < 0.001), 18% lower Vc ( P = 0.002), and 22% lower Dm ( P < 0.001) compared with men across all workloads, and neither group exhibited a plateau in Vc. When expressed relative to alveolar volume (Va), the between-sex difference was eliminated. The drop in Dl CO /Q̇ was proportionally less in women than men, and mean pulmonary transit time did not drop below 0.3 s in either group. Women demonstrate consistently lower Dl CO , Vc, and Dm compared with height-matched men during exercise; however, these differences disappear with correction for lung size. These results suggest that after differences in lung volume are accounted for there is no intrinsic sex difference in the Dl CO , Vc, or Dm response to exercise. NEW & NOTEWORTHY Women demonstrate lower diffusing capacity-to-cardiac output ratio (Dl CO /Q̇), pulmonary capillary blood volume (Vc), and membrane diffusing capacity (Dm) compared with height-matched men during exercise. However, these differences disappear after correction for lung size. The drop in Dl CO /Q̇ was proportionally less in women, and pulmonary transit time did not drop below 0.3 s in either group. After differences in lung volume are accounted for, there is no intrinsic sex difference in Dl CO , Vc, or Dm response to exercise. Copyright © 2017 the American Physiological Society.

HISTOCOMPATIBILITY STUDIES IN A CLOSELY BRED COLONY OF DOGS

PubMed Central

Rapaport, Felix T.; Boyd, Arthur D.; Spencer, Frank C.; Lower, Richard R.; Dausset, Jean; Cannon, Florence D.; Ferrebee, Joseph W.

1971-01-01

The DL-A system of histocompatibility plays an important role in conditioning the survival of cardiac allografts in the unmodified canine host. The mean survival time of six cardiac allografts performed in DL-A-compatible littermate dogs obtained from a closely bred colony of beagles was 53.2 days, while the MST of transplants performed in seven DL-A-incompatible animals was 7.3 days. The MST of cardiac allografts performed in nine DL-A-compatible nonlittermate beagles was 26.3 days, as compared with 6.3 days in six DL-A-incompatible nonlittermate transplants. The results did not appear to be affected by Swisher erythrocyte-group incompatibilities. The MST of 28 cardiac allografts performed in randomly selected mongrel dogs was 10.0 days. Incompatibilities for DL-A antigens e, f, g, l, and m may constitute major barriers to transplantation, but antigens b, c, d, and k appeared to act as weak histocompatibility antigens. Under controlled conditions of donor-recipient DL-A compatibility, cardiac allografts may be less immunogenic than renal transplants. Heart transplants performed across major donor-recipient DL-A incompatibilities appeared, however, to be more vulnerable to the events of allograft rejection than renal allografts performed under similar conditions. The selection of optimally compatible donor-recipient combinations for organ transplantation may be aided materially by genetic studies of the transmission of DL-A antigens to the animals under consideration. PMID:4943931

[Effect of smoke water and distillation liquid on the seed germination and seedling growth of Trichosathes kirilowii].

PubMed

Zhou, Jie; Bian, Li-hua; Zou, Lin; Zhou, Bin-qian; Liu, Wei; Wang, Xiao

2015-10-01

Smoke water and distillation liquid were used to treat the seeds of Trichosathes kirilowii and to study the effects of smoke water and distillation liquid on the seed germination and seedling growth of T. kirilowii. The results showed that germination rate, germination index and germination vigor of T. kirilowii all were significantly improved with the treatment of SW and DL treatment. The activity of α-amylase were significantly increased with the treatment of SW and DL at 1:2,000. SW and DL treatment showed no significant effects on the activity of SOD. The activity of POD were markedly enhanced under the treatment of SW (1:000) and DL (1:2,000). CAT activity were increased with the treatment of SW and DL at 1:2,000 while were inhibited by SW and DL at 1:500. Seedling height and root length were increased with the treatment of SW and DL (1:1,000, 1:2,000). SW and DL treaments improved the content of chlorophyll, and moreover with the concentration of SW and DL, the stimulatory were also increased. This work demonstrated that smoke water and diatillation liquid at 1:2,000 could stimulate the seed germination and seedling growth of T. kirilowii, and it provided the references for the study of seed germination technology.

Amino acid ionic liquids as chiral ligands in ligand-exchange chiral separations.

PubMed

Liu, Qian; Wu, Kangkang; Tang, Fei; Yao, Lihua; Yang, Fei; Nie, Zhou; Yao, Shouzhuo

2009-09-28

Recently, amino acid ionic liquids (AAILs) have attracted much research interest. In this paper, we present the first application of AAILs in chiral separation based on the chiral ligand exchange principle. By using 1-alkyl-3-methylimidazolium L-proline (L-Pro) as a chiral ligand coordinated with copper(II), four pairs of underivatized amino acid enantiomers-dl-phenylalanine (dl-Phe), dl-histidine (dl-His), dl-tryptophane (dl-Trp), and dl-tyrosine (dl-Tyr)-were successfully separated in two major chiral separation techniques, HPLC and capillary electrophoresis (CE), with higher enantioselectivity than conventionally used amino acid ligands (resolution (R(s))=3.26-10.81 for HPLC; R(s)=1.34-4.27 for CE). Interestingly, increasing the alkyl chain length of the AAIL cation remarkably enhanced the enantioselectivity. It was inferred that the alkylmethylimidazolium cations and L-Pro form ion pairs on the surface of the stationary phase or on the inner surface of the capillary. The ternary copper complexes with L-Pro are consequently attached to the support surface, thus inducing an ion-exchange type of retention for the dl-enantiomers. Therefore, the AAIL cation plays an essential role in the separation. This work demonstrates that AAILs are good alternatives to conventional amino acid ligands for ligand-exchange-based chiral separation. It also reveals the tremendous application potential of this new type of task-specific ILs.

Enantioselective separation of chiral aromatic amino acids with surface functionalized magnetic nanoparticles.

PubMed

Ghosh, Sudipa; Fang, Tan Hui; Uddin, M S; Hidajat, K

2013-05-01

Chiral resolution aromatic amino acids, DL-tryptophan (DL-Trp), DL-phenylalanine (DL-Phe), DL-tyrosine (DL-Tyr) from phosphate buffer solution was achieved in present study employing the concept of selective adsorption by surface functionalized magnetic nanoparticles (MNPs). Surfaces of magnetic nanoparticles were functionalized with silica and carboxymethyl-β-cyclodextrin (CMCD) to investigate their adsorption resolution characteristics. Resolution of enantiomers from racemic mixture was quantified in terms of enantiomeric excess using chromatographic method. The MNPs selectively adsorbed L-enantiomers of DL-Trp, DL-Phe, and DL-Tyr from racemic mixture and enantiomeric excesses (e.e.) were determined as 94%, 73% and 58%, respectively. FTIR studies demonstrated that hydrophobic portion of enantiomer penetrated into hydrophobic cavity of cyclodextrin molecules to form inclusion complex. Furthermore, adsorption site was explored using XPS and it was revealed that amino group at chiral center of the amino acid molecule formed hydrogen bond with secondary hydroxyl group of CMCD molecule and favorability of hydrogen bond formation resulted in selective adsorption of L-enantiomer. Finally, stability constant (K) and Gibbs free energy change (-ΔG°) for inclusion complexation of CMCD with L-/D-enantiomers of amino acids were determined using spectroflurometry in aqueous buffer solution. Higher binding constants were obtained for inclusion complexation of CMCD with L-enantiomers compared to D-enantiomers which stimulated enantioselective properties of CMCD functionalized magnetite silica nanoparticles. Copyright © 2013 Elsevier B.V. All rights reserved.

Oral and transdermal DL-methylphenidate-ethanol interactions in C57BL/6J mice: potentiation of locomotor activity with oral delivery.

PubMed

Bell, Guinevere H; Griffin, William C; Patrick, Kennerly S

2011-12-01

Many abusers of dl-methylphenidate co-abuse ethanol. The present animal study examined behavioral effects of oral or transdermal DL-methylphenidate in combination with a high, depressive dose of ethanol to model co-abuse. Locomotor activity of C57BL/6J mice was recorded for 3 h following dosing with either oral DL-methylphenidate (7.5 mg/kg) or transdermal DL-methylphenidate (Daytrana®;1/4 of a 12.5 cm(2) patch; mean dose 7.5 mg/kg), with or without oral ethanol (3 g/kg). Brains were enantiospecifically analyzed for the isomers of methylphenidate and the transesterification metabolite ethylphenidate. An otherwise depressive dose of ethanol significantly potentiated oral DL-methylphenidate induced increases in total distance traveled for the first 100 min (p<0.05). Transdermal DL-methylphenidate increased total distance traveled after a latency of 80 min, though this effect was not potentiated by concomitant ethanol. Mean 3 h brain D-methylphenidate concentrations were significantly elevated by ethanol in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding L-ethylphenidate concentrations were 10 ng/g and 130 ng/g. Stimulant induced motor activity in rodents may correlate with abuse liability. Potentiation of DL-methylphenidate motor effects by concomitant ethanol carries implications regarding increased abuse potential of DL-methylphenidate when combined with ethanol. Copyright © 2011 Elsevier Inc. All rights reserved.

Tumor-specific cytolysis caused by an E1B55K-attenuated adenovirus in nasopharyngeal carcinoma is augmented by cisplatin.

PubMed

Liu, Ran-Yi; Peng, Ji-Lin; Li, Yong-Qiang; Huang, Bi-Jun; Lin, Huan-Xin; Zhou, Ling; Luo, Hui-Ling; Huang, Wenlin

2013-12-01

An E1B55K-attenuated adenovirus, dl1520, has been shown to replicate selectively in and lyse tumor cells. In this study, the antitumor activities of dl1520, alone or in combination with the chemotherapeutic agent cisplatin, were investigated in nasopharyngeal carcinoma (NPC) cells. The results demonstrated that dl1520 replicated in and destroyed NPC cells, and induced apoptosis in vitro. In a nude mouse xenograft model, dl1520 significantly inhibited the growth of NPC cell xenografts, and the viral replication was associated with tumor regression. Importantly, the antitumor activity of dl1520 was augmented by the addition of cisplatin both in vitro and in vivo, showing that dl1520 and cisplatin have a synergistic anti-NPC effect. These data suggest that dl1520 exerts an efficient anti-NPC activity through oncolysis and the induction of apoptosis, which is enhanced synergistically by cisplatin. These findings indicate that oncolytic viral therapeutics using the E1B55K-attenuated adenovirus dl1520 could be promising in the comprehensive treatment of NPC, especially in combination with platinum-based chemotherapy. Copyright © 2013 Wiley Periodicals, Inc.

Determinants of blood-lead levels in children in Callao and Lima metropolitan area.

PubMed

Espinoza, Rocío; Hernández-Avila, Mauricio; Narciso, Juan; Castañaga, Carmen; Moscoso, Shirley; Ortiz, Georgina; Carbajal, Luz; Wegner, Steve; Noonan, Gary

2003-01-01

To determine blood lead levels in urban populations of children (n = 2,510) and women (n = 874) in the early postpartum in certain districts of Lima and Callao, and to correlate those levels with particular exposures. Between July 1998 and January 1999 cross sectional study was conducted. The study population was selected using three sampling strategies in the government operated school system and from public pediatric and maternity hospitals at Lima and Callao, Peru. Study personnel were trained to collect finger stick blood samples with a protocol that minimizes external lead contamination. Lead determinations in blood and environmental samples were performed at the study site using portable anodic striping voltamenters. To determine the simultaneous effects of different predictors on blood lead levels, multivariate regression models were used to estimate adjusted mean differences. The mean blood lead level in the children studied was 9.9 micrograms/dl ranging from 1 microgram/dl to 64 micrograms/dl with 29% of the children displaying values greater than 10 micrograms/dl and 9.4% at levels greater than 20 micrograms/dl. Among the women, the mean was 3.5 micrograms/dl (SD = 2.4 micrograms/dl), and 2.4% (n = 21) displayed levels greater than 10 micrograms/dl. Important differences were observed between the sample locations, and the highest levels were documented in the port region near Callao. The mean level of blood lead in this group was 25.6 micrograms/dl (SD = 4.6 micrograms/dl), while among the rest of the sample it was 7.1 micrograms/dl (SD = 5.1 micrograms/dl). The presence of a mineral storage area signified a difference in exposure in excess of 13 micrograms/dl for children living near the port area in contrast to the other children who were not as close to such fixed sources of lead exposure. For the participants in Lima, the risk of showing levels above 10 micrograms/dl was associated with exposure to high vehicular traffic. In metropolitan Lima, we conclude that the mean blood lead levels of the populations studied were not alarming and that a positive health impact can be made by a reduction of lead in gasoline. With regard to the port area, the study demonstrates that the presence of mineral storage areas pose a detrimental risk factor for the health of the children living in this area. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.

[The effects of the short-term regular exercise-diet program on lipid profile in sedentary subjects].

PubMed

Yalin, S; Gök, H; Toksöz, R

2001-09-01

Regular aerobic exercise leads to changes in plasma lipids, lipoprotein and apoprotein levels. The aim of this study was to examine the training effects of the intervention program consisted of regular exercise and low fat diet on plasma lipid profile. The effects of the four weeks intervention programme which consisted of walking and dietary restriction on lipid profile in sedentary subjects were investigated. Subjects, who had dyslipidemia or obesity, were instructed to walk (consecutive 60 minutes, one times daily) and to consume no more than 20% total fat and 300 mg/d of cholesterol for four weeks. At the end of fourth week, 41 subjects who had implemented exercise-diet programme, were assigned to study (intervention) group; 21 subjects who had remained sedentary, nondieting, were included into the control group. Total-C, triglycerides, LDL-C, HDL-C, Lp (a), apo A1 and apo B100 were measured in fasting blood samples before and after 4 weeks of intervention programme. At the end of four weeks, subjects in the exercise-diet group, as compared with the control group, showed a significant reduction in body weight (respectively 1.67 +/- 2.36 kg versus -0.21 +/- 1.36 kg, p = 0.001), total cholesterol (35 +/- 37 mg/dl vs -20 +/- 25 mg/dl, p < 0.001), triglycerides (30 +/- 68 mg/dl vs -10 +/- 52 mg/dl, p = 0.024) and LDL-C (29 +/- 41 mg/dl vs -18 +/- 25 mg/dl, p < 0.001) levels. However, at the end of programme, in the exercise-diet group, as compared with the control group, the changes in HDL-C (respectively -0.85 +/- 7.30 mg/dl vs 1.05 +/- 5.64 mg/dl, p = 0.302), Lp (a) (1.59 +/- 3.06 mg/dl vs -0.09 +/- 3.96 mg/dl, p = 0.069), apo A1 (0.61 +/- 22.69 mg/dl vs -0.66 +/- 17.27 mg/dl, p = 0.822) and apo B100 (5.41 +/- 19.33 mg/dl vs -4.00 +/- 20.51 mg/dl, p = 0.080) were not significant. The data of this study demonstrate that the four weeks programme based on regular daily aerobic exercise and low fat diet is capable of decreasing total cholesterol, triglycerides and LDL-C levels and that this short-term intervention is insufficient in increasing HDL-C, in decreasing Lp (a) and improving apoprotein levels.

Model-Based Closed-Loop Glucose Control in Type 1 Diabetes: The DiaCon Experience

PubMed Central

Schmidt, Signe; Boiroux, Dimitri; Duun-Henriksen, Anne Katrine; Frøssing, Laurits; Skyggebjerg, Ole; Jørgensen, John Bagterp; Poulsen, Niels Kjølstad; Madsen, Henrik; Madsbad, Sten; Nørgaard, Kirsten

2013-01-01

Background To improve type 1 diabetes mellitus (T1DM) management, we developed a model predictive control (MPC) algorithm for closed-loop (CL) glucose control based on a linear second-order deterministic-stochastic model. The deterministic part of the model is specified by three patient-specific parameters: insulin sensitivity factor, insulin action time, and basal insulin infusion rate. The stochastic part is identical for all patients but identified from data from a single patient. Results of the first clinical feasibility test of the algorithm are presented. Methods We conducted two randomized crossover studies. Study 1 compared CL with open-loop (OL) control. Study 2 compared glucose control after CL initiation in the euglycemic (CL-Eu) and hyperglycemic (CL-Hyper) ranges, respectively. Patients were studied from 22:00–07:00 on two separate nights. Results Each study included six T1DM patients (hemoglobin A1c 7.2% ± 0.4%). In study 1, hypoglycemic events (plasma glucose < 54 mg/dl) occurred on two OL and one CL nights. Average glucose from 22:00–07:00 was 90 mg/dl [74–146 mg/dl; median (interquartile range)] during OL and 108 mg/dl (101–128 mg/dl) during CL (determined by continuous glucose monitoring). However, median time spent in the range 70–144 mg/dl was 67.9% (3.0–73.3%) during OL and 80.8% (70.5–89.7%) during CL. In study 2, there was one episode of hypoglycemia with plasma glucose <54 mg/dl in a CL-Eu night. Mean glucose from 22:00–07:00 and time spent in the range 70–144 mg/dl were 121 mg/dl (117–133 mg/dl) and 69.0% (30.7–77.9%) in CL-Eu and 149 mg/dl (140–193 mg/dl) and 48.2% (34.9–72.5%) in CL-Hyper, respectively. Conclusions This study suggests that our novel MPC algorithm can safely and effectively control glucose overnight, also when CL control is initiated during hyperglycemia. PMID:24124952

CSA/AZA, in the absence of prednisone, improves linear growth in renal transplanted children.

PubMed

David-Neto, E; Nahas, W; Sampaio, E C; Ianhez, L E; Sabbaga, E; Arap, S

1992-01-01

We compared the results of 44 renal transplants in children, of whom 24 were treated with CSA/AZA and 20 with prednisone in combination with AZA and/or CSA. There were no differences in age distribution or mean ages at transplant between the two treatment groups. The CSA/AZA group had a longer follow-up (29 +/- 33 vs 17 +/- 18 months). At the last follow-up, five children in the CSA/AZA and none in the prednisone group had lost their grafts. Serum creatinine increased in both groups from 0.7 +/- 0.1 mg/dl and 0.9 +/- 0.1 mg/dl at the end of the first month to 1.1 +/- 0.2 mg/dl in the 36th month (CSA/AZA group) (P < 0.0001) and to 1.5 +/- 0.6 mg/dl in the 18th month (prednisone group) (P < 0.05), respectively. Total cholesterol level was 189 +/- 52 mg/dl and 178 +/- 60 mg/dl and LDL level was 117 +/- 48 mg/dl and 115 +/- 51 mg/dl for the prednisone and CSA/AZA groups, respectively. HDL was greater in the CSA/AZA group (50 +/- 10 vs 41 +/- 10 mg/dl) (P < 0.03), and VLDL was greater in the prednisone group (31 +/- 13 vs 22 +/- 8 mg/dl) (P < 0.05). Serum triglyceride was greater in the prednisone group (174 +/- 93 vs 112 +/- 50 mg/dl) (P < 0.03). The standard deviation score for height of the children in the prednisone group did not change (-2.4 +/- 1.4 vs -2.1 +/- 1.4 SDS), whereas the SDS height score for the CSA/AZA children increased from -3.1 +/- 1.7 to -2.6 +/- 1.5, -1.9 +/- 1.4 and -1.7 +/- 1.4, at 12, 24 and 36 months, respectively (P < 0.001). CSA/AZA is a good immunosuppressive regime for the first renal transplant in children, but only 75% tolerated AZA/CSA without same damage to their grafts.

A comparison of the enzymatic properties of three recombinant isoforms of thrombolytic and antibacterial protein--Destabilase-Lysozyme from medicinal leech.

PubMed

Kurdyumov, Alexey S; Manuvera, Valentin A; Baskova, Isolda P; Lazarev, Vassili N

2015-11-21

Destabilase-Lysozyme (mlDL) is a multifunctional i-type enzyme that has been found in the secretions from the salivary glands of medicinal leeches. mlDL has been shown to exhibit isopeptidase, muramidase and antibacterial activity. This enzyme attracts interest because it expresses thrombolytic activity through isopeptidolysis of the ε-(γ-Glu)-Lys bonds that cross-link polypeptide chains in stabilised fibrin. To date, three isoforms of mlDL have been identified. The enzymatic properties of pure mlDL isoforms have not yet been described because only destabilase complexes containing other proteins could be isolated from the salivary gland secretion and because low product yield from the generation of recombinant proteins has made comprehensive testing difficult. In the present study, we optimised the procedures related to the expression, isolation and purification of active mlDL isoforms (mlDL-Ds1, mlDL-Ds2, mlDL-Ds3) using an Escherichia coli expression system, and we detected and compared their muramidase, lytic, isopeptidase and antimicrobial activities. After optimisation, the product yield was 30 mg per litre of culture. The data obtained in our study led to the suggestion that the recombinant mlDL isoforms isolated from inclusion bodies form stable oligomeric complexes. Analyses of the tested activities revealed that all isoforms exhibited almost identical patterns of pH and ionic strength effects on the activities. We determined that mlDL-Ds1, 2, 3 possessed non-enzymatic antibacterial activity independent of their muramidase activity. For the first time, we demonstrated the fibrinolytic activity of the recombinant mlDL and showed that only intact proteins possessed this activity, suggesting their enzymatic nature. The recombinant Destabilase-Lysozyme isoforms obtained in our study may be considered potential thrombolytic agents that act through a mechanism different from that of common thrombolytics.

Methionine metabolism in piglets Fed DL-methionine or its hydroxy analogue was affected by distribution of enzymes oxidizing these sources to keto-methionine.

PubMed

Fang, Zhengfeng; Luo, Hefeng; Wei, Hongkui; Huang, Feiruo; Qi, Zhili; Jiang, Siwen; Peng, Jian

2010-02-10

Previous evidence shows that the extensive catabolism of dietary essential amino acids (AA) by the intestine results in decreased availability of these AA for protein synthesis in extraintestinal tissues. This raises the possibility that extraintestinal availability of AA may be improved by supplying the animal with an AA source more of which can bypass the intestine. To test this hypothesis, six barrows (35-day-old, 8.6 +/- 1.4 kg), implanted with arterial, portal, and mesenteric catheters, were fed a DL-methionine (DL-MET) or DL-2-hydroxy-4-methylthiobutyrate (DL-HMTB) diet once hourly and infused intramesenterically with 1% p-amino hippurate. Although the directly available L-MET in DL-MET diet was about 1.2-fold that in DL-HMTB diet, the net portal appearance of L-MET was not different between the two diets. Compared with the low mRNA abundance and low activity of D-2-hydroxy acid dehydrogenase (D-HADH) and l-2-hydroxy acid oxidase (L-HAOX) in the intestine, the high mRNA abundance and high activity of D-AA oxidase (D-AAOX) indicated that the intestine had a relatively higher capacity of D-MET utilization than of dl-HMTB utilization to L-MET synthesis and its subsequent metabolism. However, in contrast to the much lower D-AAOX activity (nmol/g tissue) in the stomach than in the liver and kidney, both d-HADH and L-HAOX activity in the stomach was comparable with those in the liver and/or kidney, indicating the substantial capacity of the stomach to convert DL-HMTB to L-MET. Collectively, the difference in distribution of activity and mRNA abundance of D-AAOX, D-HADH, and L-HAOX in the piglets may offer a biological basis for the similar portal appearance of L-MET between DL-MET and DL-HMTB diets, and thus may provide new important insights into nutritional efficiency of different L-MET sources.

KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules.

PubMed

Miah, S M Shahjahan; Hughes, Tracey L; Campbell, Kerry S

2008-03-01

KIR2DL4 (2DL4) is a member of the killer cell Ig-like receptor (KIR) family in human NK cells. It can stimulate potent cytokine production and weak cytolytic activity in resting NK cells, but the mechanism for 2DL4-mediated signaling remains unclear. In this study we characterized the signaling pathways stimulated by 2DL4 engagement. In a human NK-like cell line, KHYG-1, cross-linking of 2DL4 activated MAPKs including JNK, ERK, and p38. Furthermore, 2DL4 cross-linking resulted in phosphorylation of IkappaB kinase beta (IKKbeta) and the phosphorylation and degradation of IkappaBalpha, which indicate activation of the classical NF-kappaB pathway. Engagement of 2DL4 was also shown to activate the transcription and translation of a variety of cytokine genes, including TNF-alpha, IFN-gamma, MIP1alpha, MIP1beta, and IL-8. Pharmacological inhibitors of JNK, MEK1/2 and p38, blocked IFN-gamma, IL-8, and MIP1alpha production, suggesting that MAPKs are regulating 2DL4-mediated cytokine production in a nonredundant manner. Activation of both p38 and ERK appear to be upstream of the stimulation of NF-kappaB. Mutation of a transmembrane arginine in 2DL4 to glycine (R/G mutant) abrogated FcepsilonRI-gamma association, as well as receptor-mediated cytolytic activity and calcium responses. Surprisingly, the R/G mutant still activated MAPKs and the NF-kappaB pathway and selectively stimulated the production of MIP1alpha, but not that of IFN-gamma or IL-8. In conclusion, we provide evidence that the activating functions of 2DL4 can be compartmentalized into two distinct structural modules: 1) through transmembrane association with FcepsilonRI-gamma; and 2) through another receptor domain independent of the transmembrane arginine.

A sensory code for host seeking in parasitic nematodes

PubMed Central

Hallem, Elissa A.; Dillman, Adler R.; Hong, Annie V.; Zhang, Yuanjun; Yano, Jessica M.; DeMarco, Stephanie F.

2011-01-01

Summary Nematodes comprise a large phylum of both free-living and parasitic species that show remarkably diverse lifestyles, ecological niches, and behavioral repertoires. Parasitic species in particular often display highly specialized host-seeking behaviors that reflect their specific host preferences. Many host-seeking behaviors can be triggered by the presence of host odors, yet little is known about either the specific olfactory cues that trigger these behaviors or the neural circuits that underlie them. Heterorhabditis bacteriophora and Steinernema carpocapsae are phylogenetically distant insect-parasitic nematodes whose host-seeking and host-invasion behavior resembles that of some of the most devastating human- and plant-parasitic nematodes. Here we compare the olfactory responses of H. bacteriophora and S. carpocapsae infective juveniles (IJs) to those of Caenorhabditis elegans dauers, which are analogous life stages [1]. We show that the broad host range of these parasites results from their ability to respond to the universally-produced signal carbon dioxide (CO2) as well as a wide array of odors, including host-specific odors that we identified using TD-GC-MS. We show that CO2 is attractive for the parasitic IJs and C. elegans dauers despite being repulsive for C. elegans adults [2–4], and we identify an ancient and conserved sensory neuron that mediates CO2 response in both parasitic and free-living species regardless of whether CO2 is an attractive or a repulsive cue. Finally, we show that the parasites’ odor response profiles are more similar to each other than to that of C. elegans despite their greater phylogenetic distance, likely reflecting evolutionary convergence to insect parasitism. Our results suggest that the olfactory responses of parasitic versus free-living nematodes are highly diverse and that this diversity is critical to the evolution of nematode behavior. PMID:21353558

Mycobacterium sarraceniae sp. nov. and Mycobacterium helvum sp. nov., isolated from the pitcher plant Sarracenia purpurea.

PubMed

Tran, Phuong M; Dahl, John L

2016-11-01

Several fast- to intermediate-growing, acid-fast, scotochromogenic bacteria were isolated from Sarracenia purpurea pitcher waters in Minnesota sphagnum peat bogs. Two strains (DL734T and DL739T) were among these isolates. On the basis of 16S rRNA gene sequences, the phylogenetic positions of both strains is in the genus Mycobacterium with no obvious relation to any characterized type strains of mycobacteria. Phenotypic characterization revealed that neither strain was similar to the type strains of known species of the genus Mycobacterium in the collective properties of growth, pigmentation or fatty acid composition. Strain DL734T grew at temperatures between 28 and 32 °C, was positive for 3-day arylsulfatase production, and was negative for Tween 80 hydrolysis, urease and nitrate reduction. Strain DL739T grew at temperatures between 28 and 37 °C, and was positive for Tween 80 hydrolysis, urea, nitrate reduction and 3-day arylsulfatase production. Both strains were catalase-negative while only DL739T grew with 5 % NaCl. Fatty acid methyl ester profiles were unique for each strain. DL739T showed an ability to survive at 8 °C with little to no cellular replication and is thus considered to be psychrotolerant. Therefore, strains DL734T and DL739T represent two novel species of the genus Mycobacterium with the proposed names Mycobacterium sarraceniae sp. nov. and Mycobacterium helvum sp. nov., respectively. The type strains are DL734T (=JCM 30395T=NCCB 100519T) and DL739T (=JCM 30396T=NCCB 100520T), respectively.

Plasma iron levels appraised 15 days after spinal cord injury in a limb movement animal model.

PubMed

Reis, F M; Esteves, A M; Tufik, S; de Mello, M T

2011-03-01

Experimental, controlled trial. The purpose of this study was to evaluate plasma iron and transferrin levels in a limb movement animal model with spinal cord injury (SCI). Universidade Federal de São Paulo, Departamento de Psicobiologia. In all, 72 male Wistar rats aged 90 days were divided into four groups: (1) acute SCI (1 day, SCI1), (2) 3 days post-SCI (SCI3), (3) 7 days post-SCI (SCI7) and (4) 15 days post-SCI (SCI15). Each of these groups had corresponding control (CTRL) and SHAM groups. Plasma iron and transferrin levels of the different groups were analyzed using a one-way analysis of variance (ANOVA) followed by Tukey's test. We found a significant reduction in iron plasma levels after SCI compared with the CTRL group: SCI1 (CTRL: 175±10.58 μg dl(-1); SCI: 108.28±11.7 μg dl(-1)), SCI3 (CTRL: 195.5±11.00 μg dl(-1); SCI: 127.88±12.63 μg dl(-1)), SCI7 (CTRL: 186±2.97 μg dl(-1); SCI: 89.2±15.39 μg dl(-1)) and SCI15 (CTRL: 163±5.48 μg dl(-1); SCI: 124.44±10.30 μg dl(-1)) (P<0.05; ANOVA). The SHAM1 group demonstrated a reduction in iron plasma after acute SCI (CTRL: 175±10.58 μg dl(-1); SHAM: 114.60±7.81 μg dl(-1)) (P<0.05; ANOVA). Reduced iron metabolism after SCI may be one of the mechanisms involved in the pathogenesis of sleep-related movement disorders.

A comparative evaluation to assess the efficacy of 5% sodium fluoride varnish and diode laser and their combined application in the treatment of dentin hypersensitivity

PubMed Central

Suri, Isha; Singh, Poonam; Shakir, Quaid Johar; Shetty, Arvind; Bapat, Ranjeet; Thakur, Roshani

2016-01-01

Background: Dentin hypersensitivity (DH) is an age old complaint with a great number of treatment modalities, but none of these are totally effective till date. Lasers being one of the latest treatment options in periodontics, a study was conducted to test the efficacy of diode laser (DL) in DH alone and in comparison with 5% sodium fluoride (NaF) varnish. Aim: The aim of the present study was to compare the effectiveness of 5% topical NaF varnish and 980 nm gallium aluminum arsenide (GaAlAs) DL alone and combination of 5% NaF + 980 nm GaAlAs DL in the management of DH. Materials and Methods: The study was conducted on 120 teeth in thirty patients with DH assessed by tactile and air blast (AB) stimuli measured by visual analog scale (VAS). Teeth were randomly divided into Group 1 (P) placebo-treated control group, Group 2 (NaF) treated by 5% NaF varnish, Group 3 (DL) treated with 980 nm DL, and Group 4 (NaF + DL) treated with both 5% NaF varnish and 980 nm DL (combination group). Results: There was a significant reduction in DH. The VAS reduction percentages were calculated, and there was a significant decrease in DH above all in G4 (NaF + DL) than G3 (DL) and G2 (NaF). Conclusion: Even though all the three groups (2, 3, and 4) showed improvement in terms of DH reduction, 5% NaF varnish with DL showed the best results among all the groups. PMID:27563205

Differences in metabolic parameters and cardiovascular risk between American Diabetes Association and World Health Organization definition of impaired fasting glucose in European Caucasian subjects: a cross-sectional study

PubMed Central

Filippatos, Theodosios D.; Rizos, Evangelos C.; Gazi, Irene F.; Lagos, Konstantinos; Agouridis, Dimitrios; Mikhailidis, Dimitri P.

2013-01-01

Introduction The American Diabetes Association (ADA) defines impaired fasting glucose (IFG) as fasting plasma glucose concentration of 100–125 mg/dl, whereas the World Health Organization (WHO) and the International Diabetes Federation (IDF) define IFG as fasting plasma glucose levels of 110–125 mg/dl. We identified differences in metabolic parameters and cardiovascular disease (CVD) risk according to the ADA or WHO/IDF definition of IFG. Material and methods Healthy drug-naive Caucasian (Greek) subjects (n = 396; age 55 ±12 years) participated in this cross-sectional study. Results Diastolic blood pressure (DBP) and uric acid levels were higher in the subjects with glucose 100–109 mg/dl compared with those with glucose < 100 mg/dl (87 ±9 mm Hg vs. 84 ±11 mm Hg, p = 0.004 for DBP, 5.6 ±1.5 mg/dl vs. 5.0 ±1.0 mg/dl, p = 0.002 for uric acid), whereas triglyceride levels were lower in subjects with glucose 100–109 mg/dl compared with those with glucose ≥ 110 mg/dl (169 mg/dl (interquartile range (IQR) = 102–186) vs. 186 mg/dl (IQR = 115–242), p = 0.002). Only the ADA definition recognized subjects with significantly increased 10-year CVD risk estimation (SCORE risk calculation) compared with their respective controls (5.4% (IQR = 0.9–7.3) vs. 4.1% (IQR = 0.7–5.8), p = 0.002). Conclusions The ADA IFG definition recognized more subjects with significantly increased CVD risk (SCORE model) compared with the WHO/IDF definition. PMID:24273558

Seasonal trends in nesting leatherback turtle (Dermochelys coriacea) serum proteins further verify capital breeding hypothesis

PubMed Central

Perrault, Justin R.; Wyneken, Jeanette; Page-Karjian, Annie; Merrill, Anita; Miller, Debra L.

2014-01-01

Serum protein concentrations provide insight into the nutritional and immune status of organisms. It has been suggested that some marine turtles are capital breeders that fast during the nesting season. In this study, we documented serum proteins in neophyte and remigrant nesting leatherback sea turtles (Dermochelys coriacea). This allowed us to establish trends across the nesting season to determine whether these physiological parameters indicate if leatherbacks forage or fast while on nesting grounds. Using the biuret method and agarose gel electrophoresis, total serum protein (median = 5.0 g/dl) and protein fractions were quantified and include pre-albumin (median = 0.0 g/dl), albumin (median = 1.81 g/dl), α1-globulin (median = 0.90 g/dl), α2-globulin (median = 0.74 g/dl), total α-globulin (median = 1.64 g/dl), β-globulin (median = 0.56 g/dl), γ-globulin (median = 0.81 g/dl) and total globulin (median = 3.12 g/dl). The albumin:globulin ratio (median = 0.59) was also calculated. Confidence intervals (90%) were used to establish reference intervals. Total protein, albumin and total globulin concentrations declined in successive nesting events. Protein fractions declined at less significant rates or remained relatively constant during the nesting season. Here, we show that leatherbacks are most likely fasting during the nesting season. A minimal threshold of total serum protein concentrations of around 3.5–4.5 g/dl may physiologically signal the end of the season's nesting for individual leatherbacks. The results presented here lend further insight into the interaction between reproduction, fasting and energy reserves and will potentially improve the conservation and management of this imperiled species. PMID:27293623

Isolation and characterization of L-valine-degrading Candida maltosa DLPU-zpb for D-valine preparation from DL-valine.

PubMed

Zhang, C H; Xin, W T; Chen, M; Bi, Y; Gao, Z Q; Zhang, J

2015-11-01

To develop a practical process for D-valine preparation from DL-valine, L-valine was used as a sole source of carbon and nitrogen in basal minimal medium to isolate L-valine-degrading micro-organisms. A yeast strain DLPU-zpb was obtained, which showed asymmetric degrading activity against DL-valine. Based on the morphology, physiological and biochemical characteristics, and 26S rDNA D1/D2 domain sequence, strain DLPU-zpb was identified as Candida maltosa. The cells of this strain were used as a biocatalyst for eliminating the L-isomer from DL-valine. The L-isomer was completely degraded within 72 h under the conditions of 30°C, pH control at 6·0, 200 rev min(-1) and 50 g l(-1) DL-valine. The strain DLPU-zpb degraded L-valine effectively but not D-valine, and thus D-valine could be easily isolated from the resultant reaction mixture, which provides a new method for D-valine preparation from DL-valine. D-valine is an important raw material for medicines and its demand is increasing year by year. Several approaches for D-valine preparation have been reported, but none of them are likely to provide product at low cost. A newly isolated L-valine-degrading yeast strain Candida maltosa DLPU-zpb was described, which showed asymmetric degrading activity against DL-valine. Thus, a new and practical process for D-valine preparation from DL-valine could be developed. This is the first report of the asymmetric degrading ability of C. maltosa against DL-valine and D-valine preparation from DL-valine. © 2015 The Society for Applied Microbiology.

The D0 immunoglobulin-like domain plays a central role for the stronger binding of KIR3DL2 to B27 free heavy chain dimers

PubMed Central

Hatano, Hiroko; Shaw, Jacqueline; Marquardt, Kaitlin; Zhang, Zhiyong; Gauthier, Laurent; Chanteux, Stephanie; Rossi, Benjamin; Li, Demin; Mitchell, Julie; Kollnberger, Simon

2015-01-01

We have proposed that the killer cell immunoglobulin-like receptor KIR3DL2 binding more strongly to HLA-B27 (B27) β2m-free heavy chain (FHC) dimers regulates lymphocyte function in arthritis and infection. We compared the function of B27 FHC dimers with other class I heavy chains and identified contact residues in KIR3DL2. B27 FHC dimers interacted functionally with KIR3DL2 on NK and reporter cells more strongly than other class I FHC. Mutagenesis identified key residues in the D0 and other immunoglobulin-like domains which were shared and distinct from KIR3DL1, for KIR3DL2 binding to B27 and other class I FHC. We modeled B27 dimer binding to KIR3DL2 and compared experimental mutagenesis data with computational “hot spot” predictions. Modelling predicts the stronger binding of B27 dimers to KIR3DL2 is mediated by non-symmetrical complementary contacts of the D0 and D1 domains with the α1, α2 and α3 domains of both B27 heavy chains. By contrast, the D2 domain primarily contacts residues in the α2 domain of one B27 heavy chain. These findings both provide novel insights about the molecular basis of KIR3DL2 binding to HLA-B27 and other ligands and suggest an important role for KIR3DL2 HLA-B27 interactions in controlling the function of NK cells in HLA-B27+ individuals. PMID:25582852

Chapter 8 Haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2010: national and centre-specific analyses.

PubMed

Webb, Lynsey; Gilg, Julie; Wilkie, Martin

2012-01-01

The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published clinical practice guidelines which include recommendations for management of anaemia in established renal failure. To determine the extent to which the guidelines for anaemia management are met in the UK. Quarterly data were obtained regarding haemoglobin (Hb) and factors that influence Hb from renal centres in England, Wales, Northern Ireland (EWNI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2010. In the UK, in 2010 53.6% of patients commenced dialysis therapy with Hb ≥ 10.0 g/dl (median Hb 10.1 g/dl). The median Hb of haemodialysis (HD) patients was 11.5 g/dl with an interquartile range (IQR) of 10.5-12.3 g/dl. Of HD patients 84.6% had Hb ≥ 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.6 g/dl (IQR 10.6-12.5 g/dl). Of UK PD patients, 87.2% had Hb ≥ 10.0 g/dl. The median ferritin in HD patients in EWNI was 444 µg/L (IQR 299-635) and 96% of HD patients had a ferritin ≥ 100 µg/L. The median ferritin in PD patients was 264 µg/L (IQR 148-426) with 86% of PD patients having a ferritin ≥ 100 µg/L. In EWNI the mean Erythropoietin Stimulating Agent (ESA) dose was higher for HD than PD patients (9,020 vs. 6,202 IU/week). Of prevalent HD patients, 52.7% had Hb ≥ 10 and ≤ 12 g/dl. Of prevalent PD patients, 54.3% had Hb 10.5-12.5 g/dl. Copyright © 2012 S. Karger AG, Basel.

The utility of ductal lavage in breast cancer detection and risk assessment

PubMed Central

Domchek, Susan M

2002-01-01

Ductal lavage (DL) permits noninvasive retrieval of epithelial cells from the breast. Clinical development of this technique has been fueled largely by its potential, as yet unproven, to improve detection of breast cancer and definition of individual risk for development of breast cancer. Early studies demonstrate the feasibility of performing this technique, provide data on cellular yield and findings, and demonstrate the ability to measure molecular markers in DL fluid. However, the sensitivity and specificity of DL for the detection of breast cancer remains unknown, as does the significance of atypia, particularly mild atypia, when found in DL fluid. Although DL appears safe and the device is approved by the US Food and Drug Administration, DL is still best utilized in the setting of clinical trials designed to resolve issues of sensitivity, specificity, and localization. PMID:11879562

Marginal Shape Deep Learning: Applications to Pediatric Lung Field Segmentation.

PubMed

Mansoor, Awais; Cerrolaza, Juan J; Perez, Geovanny; Biggs, Elijah; Nino, Gustavo; Linguraru, Marius George

2017-02-11

Representation learning through deep learning (DL) architecture has shown tremendous potential for identification, localization, and texture classification in various medical imaging modalities. However, DL applications to segmentation of objects especially to deformable objects are rather limited and mostly restricted to pixel classification. In this work, we propose marginal shape deep learning (MaShDL), a framework that extends the application of DL to deformable shape segmentation by using deep classifiers to estimate the shape parameters. MaShDL combines the strength of statistical shape models with the automated feature learning architecture of DL. Unlike the iterative shape parameters estimation approach of classical shape models that often leads to a local minima, the proposed framework is robust to local minima optimization and illumination changes. Furthermore, since the direct application of DL framework to a multi-parameter estimation problem results in a very high complexity, our framework provides an excellent run-time performance solution by independently learning shape parameter classifiers in marginal eigenspaces in the decreasing order of variation. We evaluated MaShDL for segmenting the lung field from 314 normal and abnormal pediatric chest radiographs and obtained a mean Dice similarity coefficient of 0.927 using only the four highest modes of variation (compared to 0.888 with classical ASM 1 (p-value=0.01) using same configuration). To the best of our knowledge this is the first demonstration of using DL framework for parametrized shape learning for the delineation of deformable objects.

What does fault tolerant Deep Learning need from MPI?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amatya, Vinay C.; Vishnu, Abhinav; Siegel, Charles M.

Deep Learning (DL) algorithms have become the {\\em de facto} Machine Learning (ML) algorithm for large scale data analysis. DL algorithms are computationally expensive -- even distributed DL implementations which use MPI require days of training (model learning) time on commonly studied datasets. Long running DL applications become susceptible to faults -- requiring development of a fault tolerant system infrastructure, in addition to fault tolerant DL algorithms. This raises an important question: {\\em What is needed from MPI for designing fault tolerant DL implementations?} In this paper, we address this problem for permanent faults. We motivate the need for amore » fault tolerant MPI specification by an in-depth consideration of recent innovations in DL algorithms and their properties, which drive the need for specific fault tolerance features. We present an in-depth discussion on the suitability of different parallelism types (model, data and hybrid); a need (or lack thereof) for check-pointing of any critical data structures; and most importantly, consideration for several fault tolerance proposals (user-level fault mitigation (ULFM), Reinit) in MPI and their applicability to fault tolerant DL implementations. We leverage a distributed memory implementation of Caffe, currently available under the Machine Learning Toolkit for Extreme Scale (MaTEx). We implement our approaches by extending MaTEx-Caffe for using ULFM-based implementation. Our evaluation using the ImageNet dataset and AlexNet neural network topology demonstrates the effectiveness of the proposed fault tolerant DL implementation using OpenMPI based ULFM.« less

PLASMA ELECTROPHORETIC PROFILES IN THE EASTERN MASSASAUGA (SISTRURUS CATENATUS) AND INFLUENCES OF AGE, SEX, YEAR, LOCATION, AND SNAKE FUNGAL DISEASE.

PubMed

Allender, Matthew C; Junge, Randall E; Baker-Wylie, Sarah; Hileman, Eric T; Faust, Lisa J; Cray, Carolyn

2015-12-01

The purpose of this study was to establish reference intervals of the protein electrophoretic fractions and the acute-phase proteins hemoglobin binding protein (as determined by the haptoglobin assay) and C-reactive protein (CRP) and assess any possible correlations between varying age class, sex, location (Illinois or Michigan), year, or presence of snake fungal disease (SFD). Banked plasma samples were assayed from 130 eastern massasaugas from 2009 to 2014 in Illinois and Michigan. Snakes from Michigan had higher total protein (mean: 5.50 g/dl), albumin/globulin ratio (0.42), albumin (1.59 g/dl), and gamma globulins (0.55 g/dl) than from snakes in Illinois (4.72 g/dl, 0.29, 1.03 g/dl, 0.38 g/dl, respectively). Snakes in Illinois (22.19 g/ml) had higher CRP than snakes in Michigan (10.89 mg/ml). Adults had higher gamma globulins (0.47 g/dl) than juveniles (0.28 g/dl). Males had higher alpha-2 globulins (0.98 g/dl) and CRP (21.4 mg/ml) than females (0.85, 11.6, respectively). There were no significant differences in absolute plasma proteins in SFD-positive snakes, but the percentage of gamma globulins was significantly higher in positive snakes. Future research in this area can now build on this data to determine changes in population health over time or due to specific environmental or disease threats.

Marginal shape deep learning: applications to pediatric lung field segmentation

NASA Astrophysics Data System (ADS)

Mansoor, Awais; Cerrolaza, Juan J.; Perez, Geovany; Biggs, Elijah; Nino, Gustavo; Linguraru, Marius George

2017-02-01

Representation learning through deep learning (DL) architecture has shown tremendous potential for identification, local- ization, and texture classification in various medical imaging modalities. However, DL applications to segmentation of objects especially to deformable objects are rather limited and mostly restricted to pixel classification. In this work, we propose marginal shape deep learning (MaShDL), a framework that extends the application of DL to deformable shape segmentation by using deep classifiers to estimate the shape parameters. MaShDL combines the strength of statistical shape models with the automated feature learning architecture of DL. Unlike the iterative shape parameters estimation approach of classical shape models that often leads to a local minima, the proposed framework is robust to local minima optimization and illumination changes. Furthermore, since the direct application of DL framework to a multi-parameter estimation problem results in a very high complexity, our framework provides an excellent run-time performance solution by independently learning shape parameter classifiers in marginal eigenspaces in the decreasing order of variation. We evaluated MaShDL for segmenting the lung field from 314 normal and abnormal pediatric chest radiographs and obtained a mean Dice similarity coefficient of 0:927 using only the four highest modes of variation (compared to 0:888 with classical ASM1 (p-value=0:01) using same configuration). To the best of our knowledge this is the first demonstration of using DL framework for parametrized shape learning for the delineation of deformable objects.

Marginal Shape Deep Learning: Applications to Pediatric Lung Field Segmentation

PubMed Central

Mansoor, Awais; Cerrolaza, Juan J.; Perez, Geovanny; Biggs, Elijah; Nino, Gustavo; Linguraru, Marius George

2017-01-01

Representation learning through deep learning (DL) architecture has shown tremendous potential for identification, localization, and texture classification in various medical imaging modalities. However, DL applications to segmentation of objects especially to deformable objects are rather limited and mostly restricted to pixel classification. In this work, we propose marginal shape deep learning (MaShDL), a framework that extends the application of DL to deformable shape segmentation by using deep classifiers to estimate the shape parameters. MaShDL combines the strength of statistical shape models with the automated feature learning architecture of DL. Unlike the iterative shape parameters estimation approach of classical shape models that often leads to a local minima, the proposed framework is robust to local minima optimization and illumination changes. Furthermore, since the direct application of DL framework to a multi-parameter estimation problem results in a very high complexity, our framework provides an excellent run-time performance solution by independently learning shape parameter classifiers in marginal eigenspaces in the decreasing order of variation. We evaluated MaShDL for segmenting the lung field from 314 normal and abnormal pediatric chest radiographs and obtained a mean Dice similarity coefficient of 0.927 using only the four highest modes of variation (compared to 0.888 with classical ASM1 (p-value=0.01) using same configuration). To the best of our knowledge this is the first demonstration of using DL framework for parametrized shape learning for the delineation of deformable objects. PMID:28592911

Germination of Phaseolus vulgaris. II. Stimulation of axis growth by dl-fluorophenylalanines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walton, D.C.

p-, o- and m-fluoro-dl-phenylalanine have been found to stimulate the growth of excised axes of Phaseolus vulgaris. At 5 x 10/sup -4/ m p-fluoro-dl-phenylalanine stimulated growth by 20 to 40% and the other 2 isomers by 10 to 20%. L-Phenylalanine (10/sup -3/ M) essentially reversed the stimulation by 5 x 10/sup -4/ M p-fluoro-dl-phenylalanine.

Metabolic Derangement in Acute and Chronic Liver Disorders.

PubMed

Bajaj, Sarita; Kashyap, Richi; Srivastava, Anubha; Singh, Smriti

2017-01-01

This study aims to assess glycemic and lipid derangement in acute and chronic liver disorders. A cross-sectional study was conducted on 104 patients diagnosed with acute or chronic liver disorder. Acute liver disease (ALD) patients were 40 and chronic liver disease (CLD) patients were 64. The mean value of fasting plasma glucose (FPG) in patients with ALD was 91.8 ± 5.4 mg/dl and in CLD was 115.7 ± 17.9 mg/dl, the difference was significant. The mean value of A1c was 4.3 ± 0.6 in ALD and 6.1 ± 0.8 in CLD, the difference was significant. In patients with CLD mean cholesterol was higher 177.4 ± 28.8 mg/dl when compared to ALD 140 ± 35.1 mg/dl, but the difference was not significant. ALD patients' high-density lipoprotein (HDL) was 50.4 ± 5.1 mg/dl, and in CLD patients, HDL was 44.4 ± 6.1 mg/dl. In CLD mean triglyceride (T) was 148.9 ± 6.4 mg/dl while in ALD T was 134.8 ± 14.2 mg/dl, the difference was significant. CLD is associated with glycemic derangement demonstrated by deranged FPG and A1c. In patients of ALD, no metabolic derangement was observed.

High lead exposure and auditory sensory-neural function in Andean children.

PubMed Central

Counter, S A; Vahter, M; Laurell, G; Buchanan, L H; Ortega, F; Skerfving, S

1997-01-01

We investigated blood lead (B-Pb) and mercury (B-Hg) levels and auditory sensory-neural function in 62 Andean school children living in a Pb-contaminated area of Ecuador and 14 children in a neighboring gold mining area with no known Pb exposure. The median B-Pb level for 62 children in the Pb-exposed group was 52.6 micrograms/dl (range 9.9-110.0 micrograms/dl) compared with 6.4 micrograms/dl (range 3.9-12.0 micrograms/dl) for the children in the non-Pb exposed group; the differences were statistically significant (p < 0.001). Auditory thresholds for the Pb-exposed group were normal at the pure tone frequencies of 0.25-8 kHz over the entire range of B-Pb levels, Auditory brain stem response tests in seven children with high B-Pb levels showed normal absolute peak and interpeak latencies. The median B-Hg levels were 0.16 micrograms/dl (range 0.04-0.58 micrograms/dl) for children in the Pb-exposed group and 0.22 micrograms/dl (range 0.1-0.44 micrograms/dl) for children in the non-Pb exposed gold mining area, and showed no significant relationship to auditory function. Images Figure 1. Figure 3. A Figure 3. B PMID:9222138

Comprehensive survey of deep learning in remote sensing: theories, tools, and challenges for the community

NASA Astrophysics Data System (ADS)

Ball, John E.; Anderson, Derek T.; Chan, Chee Seng

2017-10-01

In recent years, deep learning (DL), a rebranding of neural networks (NNs), has risen to the top in numerous areas, namely computer vision (CV), speech recognition, and natural language processing. Whereas remote sensing (RS) possesses a number of unique challenges, primarily related to sensors and applications, inevitably RS draws from many of the same theories as CV, e.g., statistics, fusion, and machine learning, to name a few. This means that the RS community should not only be aware of advancements such as DL, but also be leading researchers in this area. Herein, we provide the most comprehensive survey of state-of-the-art RS DL research. We also review recent new developments in the DL field that can be used in DL for RS. Namely, we focus on theories, tools, and challenges for the RS community. Specifically, we focus on unsolved challenges and opportunities as they relate to (i) inadequate data sets, (ii) human-understandable solutions for modeling physical phenomena, (iii) big data, (iv) nontraditional heterogeneous data sources, (v) DL architectures and learning algorithms for spectral, spatial, and temporal data, (vi) transfer learning, (vii) an improved theoretical understanding of DL systems, (viii) high barriers to entry, and (ix) training and optimizing the DL.

A Scalable Framework for CSI Feedback in FDD Massive MIMO via DL Path Aligning

NASA Astrophysics Data System (ADS)

Luo, Xiliang; Cai, Penghao; Zhang, Xiaoyu; Hu, Die; Shen, Cong

2017-09-01

Unlike the time-division duplexing (TDD) systems, the downlink (DL) and uplink (UL) channels are not reciprocal anymore in the case of frequency-division duplexing (FDD). However, some long-term parameters, e.g. the time delays and angles of arrival (AoAs) of the channel paths, still enjoy reciprocity. In this paper, by efficiently exploiting the aforementioned limited reciprocity, we address the DL channel state information (CSI) feedback in a practical wideband massive multiple-input multiple-output (MIMO) system operating in the FDD mode. With orthogonal frequency-division multiplexing (OFDM) waveform and assuming frequency-selective fading channels, we propose a scalable framework for the DL pilots design, DL CSI acquisition, and the corresponding CSI feedback in the UL. In particular, the base station (BS) can transmit the FFT-based pilots with the carefully-selected phase shifts. Then the user can rely on the so-called time-domain aggregate channel (TAC) to derive the feedback of reduced imensionality according to either its own knowledge about the statistics of the DL channels or the instruction from the serving BS. We demonstrate that each user can just feed back one scalar number per DL channel path for the BS to recover the DL CSIs. Comprehensive numerical results further corroborate our designs.

Integrative Cardiac Health Project (ICHP)

DTIC Science & Technology

2012-09-01

Body Mass Index 88 30.92 (6.1) 30.16 (6.0) -0.8 ɘ.00001 Total Cholesterol (mg/dl) 85 187.59 (39.4) 184.28 (37.5) -3.3 0.2845 High Density ...0.001 Total Cholesterol (mg/dl) 61 189.41 (42.4) 178.25 (38.1) -11.2 ɘ.05 High Density Lipids (mg/dl) 61 49.28 (13.7) 48.44 (12.8) -0.8 0.3427 Low...3.8) -1.1 ɘ.01 Total Cholesterol (mg/dl) 14 179.14 (46.2) 175.29 (43.6) -3.9 0.6836 High Density Lipids (mg/dl) 14 52.36 (10.8) 49.21 (7.2) -3.1

[Obesity, high blood pressure, hypercholesterolaemia, and untreated diabetes in HIV-infected and HIV-uninfected Adults in Mbuji-Mayi (Democratic republic of congo)].

PubMed

Mukeba-Tshialala, D; Nachega, J B; Mutombo-Tshingwali, M; Arendt, V; Gilson, G; Moutschen, M

2017-12-01

Little is known about the major cardiovascular risk factors in HIV-infected as compared to the HIV-uninfected patients in the Democratic Republic of Congo (DR Congo). We determined the prevalence of hypertension, obesity (BMI ≥ 30 kg/m 2 ), total cholesterol > 200 mg/dl, HDLcholesterol &≤ 40 mg/dl, and glycemia > 126 mg/dl. We also calculated the average and/or median of total cholesterol, HDL-cholesterol, and glycemia among HIV-infected and HIV-uninfected patients.We conducted a cross-sectional study that enrolled 592 HIV-uninfected and 445 HIV-infected patients of whom 425 (95.5%) were on first-line antiretroviral therapy based on stavudine-lamivudine-nevirapine. Clinical and laboratory data of the patients were collected. The results were analyzed by chi-square, t-student, and Wilcoxon rank sum tests. 11.5% of HIV-infected patients had an average blood pressure suggesting hypertension versus 10.6% of HIV-uninfected (P = 0.751). But in absolute value, HIVinfected patients had a median of diastolic blood pressure of 90 mmHg versus 85 mmHg of HIV-uninfected (P < 0.001). 4.04% of HIV-infected patients had a BMI suggesting obesity versus 6.08% of HIV-uninfected patients (P = 0.187). For fasting glucose: 2.50% of HIV-infected patients versus 4.20% of HIV-uninfected patients had a serum fasting glucose suggesting diabetes (P<0.176). 11.9% of HIV-infected patients had a total cholesterol greater than 200 mg/dl versus 7.4% of HIVuninfected patients (P=0.019). For HDL-cholesterol: 36.40% of HIV-infected patients had a serum fasting ≤ 40 mg/dl versus 15.70% of HIV-uninfected patients (P < 0.001). HIV-infected patients had a median fasting total cholesterol higher (140 mg/ dl) thanHIV-uninfected patients (133mg/dl) [P=0.015].HIVuninfected patients had a median fasting HDL-cholesterol higher (58.5 mg/dl) than HIV-infected patients (49 mg/dl) [P < 0.001]. HIV-infected women were more likely to have a higher mean of total cholesterol: 147.70 #x00B1; 52.09 mg/dl versus 135.72 ± 48.23 mg/dl for the HIV-infected men (P = 0.014) and of HDL-cholesterol: 55.80 ± 30.77 mg/dl versus 48.24 ± 28.57mg/dl for the HIV-infected men (P = 0.008). In this study population, prevalence of hypertension was elevated in HIVinfected versus HIV-uninfected patients. Being HIV positive on first-line antiretroviral therapy based on stavudine-lamivudine-nevirapine was associated with high prevalence of total cholesterol > 200 mg/dl and HDL-cholesterol ≤ 40 mg/dl. Proactive screening and prompt management of dyslipidemia and hypertension in this population should be a priority.

Therapeutic effects of dl-3-n-butylphthalide in a transgenic mouse model of amyotrophic lateral sclerosis.

PubMed

Feng, Xin-Hong; Yuan, Wei; Peng, Ying; Liu, Ming-Sheng; Cui, Li-Ying

2012-05-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Transgenic mice over-expressing a mutant form of the human SOD1 gene develop an ALS-like phenotype. Currently, there is no effective treatment or drug for the fatal disease. Previous studies reported potent efficacy of dl-3-n-butylphthalide (DL-NBP) for several neurodegenerative disorders and cerebral ischemia. SOD1-G93A mice are a mouse model of ALS. In this study, we investigated the efficacy of DL-NBP on this ALS mouse model. Sixty SOD1-G93A female mice were divided into four groups. The vehicle control group received 0 mg×kg(-1)×d(-1) DL-NBP. The experimental groups received DL-NBP with doses of 30, 60 or 120 mg×kg(-1)×d(-1), respectively. For measurement of motor activity, the hanging wire test and rotarod test were performed. Survival statistics were analyzed by Kaplan-Meier survival curves. The body weight of each mouse was recorded twice per week. The statistical motor unit number estimation (MUNE) technique was used to estimate the number of functioning motor units in gastrocnemius muscle. Muscle morphology was evaluated by hematoxylin and eosin staining. Motor neuron quantitation was performed by Nissl staining and microglia activation was observed by immunohistochemistry. Oral administration of 60 mg×kg(-1)×d(-1)1 DL-NBP significantly prolonged survival ((164.78 ± 16.67) days) of SOD1-G93A mice compared with vehicle control ((140.00 ± 16.89) days). Treating mice with DL-NBP (60 mg×kg(-1)×d(-1)) significantly decreased the progression rate of motor deficits and suppressed body weight reduction. Furthermore, we found that treating SOD1-G93A mice with DL-NBP (60 mg×kg(-1)×d(-1)) slowed the rate of MUNE reduction (P < 0.01). Motor neurons were remarkably preserved in the anterior horns in mice treated with DL-NBP (60 mg×kg(-1)×d(-1)) at the stage of 19 weeks (P < 0.01). Treating mice with DL-NBP (60 mg×kg(-1)×d(-1)) significantly reduced CD11b immunoreactivity compared with vehicle control mice (P < 0.05). No significant effect was observed in mice treated with DL-NBP of 30 or 120 mg×kg(-1)×d(-1). The post-disease-onset administration of DL-NBP significantly prolonged survival and improved motor performance in SOD1-G93A mice. DL-NBP may be a potential therapeutic agent for ALS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ade, P. A. R.; Aghanim, N.; Alves, M. I. R.

In this paper, we present all-sky modelling of the high resolution Planck, IRAS, and WISE infrared (IR) observations using the physical dust model presented by Draine & Li in 2007 (DL, ApJ, 657, 810). We study the performance and results of this model, and discuss implications for future dust modelling. The present work extends the DL dust modelling carried out on nearby galaxies using Herschel and Spitzer data to Galactic dust emission. We employ the DL dust model to generate maps of the dust mass surface density Σ Md, the dust optical extinction A V, and the starlight intensity heatingmore » the bulk of the dust, parametrized by U min. The DL model reproduces the observed spectral energy distribution (SED) satisfactorily over most of the sky, with small deviations in the inner Galactic disk and in low ecliptic latitude areas, presumably due to zodiacal light contamination. In the Andromeda galaxy (M31), the present dust mass estimates agree remarkably well (within 10%) with DL estimates based on independent Spitzer and Herschel data. We compare the DL optical extinction A V for the diffuse interstellar medium (ISM) with optical estimates for approximately 2 × 10 5 quasi-stellar objects (QSOs) observed inthe Sloan Digital Sky Survey (SDSS). The DL A V estimates are larger than those determined towards QSOs by a factor of about 2, which depends on U min. The DL fitting parameter U min, effectively determined by the wavelength where the SED peaks, appears to trace variations in the far-IR opacity of the dust grains per unit A V, and not only in the starlight intensity. These results show that some of the physical assumptions of the DL model will need to be revised. To circumvent the model deficiency, we propose an empirical renormalization of the DL A V estimate, dependent of U min, which compensates for the systematic differences found with QSO observations. This renormalization, made to match the A V estimates towards QSOs, also brings into agreement the DL A V estimates with those derived for molecular clouds from the near-IR colours of stars in the 2 micron all sky survey (2MASS). The DL model and the QSOs data are also used to compress the spectral information in the Planck and IRAS observations for the diffuse ISM to a family of 20 SEDs normalized per A V, parameterized by U min, which may be used to test and empirically calibrate dust models. Finally, the family of SEDs and the maps generated with the DL model are made public in the Planck Legacy Archive.« less

CIRCULATING CONCENTRATIONS OF THYROID HORMONE IN BELUGA WHALES (DELPHINAPTERUS LEUCAS): INFLUENCE OF AGE, SEX, AND SEASON.

PubMed

Flower, Jennifer E; Allender, Matthew C; Giovanelli, Richard P; Summers, Sandra D; Spoon, Tracey R; St Leger, Judy A; Goertz, Caroline E C; Dunn, J Lawrence; Romano, Tracy A; Hobbs, Roderick C; Tuttle, Allison D

2015-09-01

Thyroid hormones play a critical physiologic role in regulating protein synthesis, growth, and metabolism. To date, because no published compilation of baseline values for thyroid hormones in beluga whales (Delphinapterus leucas) exists, assessment of thyroid hormone concentrations in this species has been underused in clinical settings. The purpose of this study was to document the concentrations of total thyroxine (tT4) and total triiodothyronine (tT3) in healthy aquarium-maintained and free-ranging beluga whales and to determine the influence of age, sex, and season on the thyroid hormone concentrations. Archived serum samples were collected from healthy aquarium-maintained (n=43) and free-ranging (n=39) belugas, and serum tT4 and tT3 were measured using chemiluminescence immunoassay. The mean tT4 concentration in aquarium-maintained belugas was 5.67±1.43 μg/dl and the mean tT3 concentration was 70.72±2.37 ng/dl. Sex comparisons showed that aquarium-maintained males had significantly greater tT4 and tT3 (9.70±4.48 μg/dl and 92.65±30.55 ng/dl, respectively) than females (7.18±2.82 μg/dl and 77.95±20.37 ng/dl) (P=0.004 and P=0.013). Age comparisons showed that aquarium-maintained whales aged 1-5 yr had the highest concentrations of tT4 and tT3 (8.17±0.17 μg/dl and 105.46±1.98 ng/dl, respectively) (P=0.002 and P<0.001). tT4 concentrations differed significantly between seasons, with concentrations in winter (4.59±1.09 μg/dl) being significantly decreased compared with spring (P=0.009), summer (P<0.0001), and fall (P<0.0001) concentrations. There was a significant difference in tT4 and tT3 concentrations between aquarium-maintained whales (5.67±1.43 μg/dl and 70.72±15.57 ng/dl, respectively) and free-ranging whales (11.71±3.36 μg/dl and 103.38±26.45 ng/dl) (P<0.0001 and P<0.001). Clinicians should consider biologic and environmental influences (age, sex, and season) for a more accurate interpretation of thyroid hormone concentrations in belugas. The findings of this study provide a baseline for thyroid health monitoring and comprehensive health assessments in both aquarium-maintained and free-ranging beluga whales.

Comparison of the DiversiLab Repetitive Element PCR System with spa Typing and Pulsed-Field Gel Electrophoresis for Clonal Characterization of Methicillin-Resistant Staphylococcus aureus▿

PubMed Central

Babouee, B.; Frei, R.; Schultheiss, E.; Widmer, A. F.; Goldenberger, D.

2011-01-01

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become an increasing problem worldwide in recent decades. Molecular typing methods have been developed to identify clonality of strains and monitor spread of MRSA. We compared a new commercially available DiversiLab (DL) repetitive element PCR system with spa typing, spa clonal cluster analysis, and pulsed-field gel electrophoresis (PFGE) in terms of discriminatory power and concordance. A collection of 106 well-defined MRSA strains from our hospital was analyzed, isolated between 1994 and 2006. In addition, we analyzed 6 USA300 strains collected in our institution. DL typing separated the 106 MRSA isolates in 10 distinct clusters and 8 singleton patterns. Clustering analysis into spa clonal complexes resulted in 3 clusters: spa-CC 067/548, spa-CC 008, and spa-CC 012. The discriminatory powers (Simpson's index of diversity) were 0.982, 0.950, 0.846, and 0.757 for PFGE, spa typing, DL typing, and spa clonal clustering, respectively. DL typing and spa clonal clustering showed the highest concordance, calculated by adjusted Rand's coefficients. The 6 USA300 isolates grouped homogeneously into distinct PFGE and DL clusters, and all belonged to spa type t008 and spa-CC 008. Among the three methods, DL proved to be rapid and easy to perform. DL typing qualifies for initial screening during outbreak investigation. However, compared to PFGE and spa typing, DL typing has limited discriminatory power and therefore should be complemented by more discriminative methods in isolates that share identical DL patterns. PMID:21307215

Comparison of Olympic and Hexagonal Barbells With Midthigh Pull, Deadlift, and Countermovement Jump.

PubMed

Malyszek, Kylie K; Harmon, RoQue A; Dunnick, Dustin D; Costa, Pablo B; Coburn, Jared W; Brown, Lee E

2017-01-01

Malyszek, KK, Harmon, RA, Dunnick, DD, Costa, PB, Coburn, JW, and Brown, LE. Comparison of olympic and hexagonal barbells with midthigh pull, deadlift, and countermovement jump. J Strength Cond Res 31(1): 140-145, 2017-Those training for strength and power commonly use different bars and different lifts. The hexagonal barbell (HBar) and Olympic barbell (OBar) are frequently used training implements, and the midthigh pull (MTP) and deadlift (DL) are 2 popular exercises. Therefore, the purpose of this study was to compare force between an HBar and OBar for a MTP, DL, and countermovement jump (CMJ). Twenty resistance-trained men (age = 24.05 ± 2.09 years, ht = 178.07 ± 7.05 cm, mass = 91.42 ± 14.44 kg) volunteered to participate and performed MTP and DL using both bars and a CMJ. Joint angles were recorded for all pulls and the bottom position of the CMJ. Peak ground reaction force (PGRF) was greater in the MTP (3,186.88 ± 543.53 N) than DL (2,501.15 ± 404.04 N) but not different between bars. Midthigh pull joint angles were more extended than DL, and the strongest correlations between isometric and dynamic performance were seen between DL PGRF and CMJ impulse (OBar r = 0.85; HBar r = 0.84). These findings are likely because of the different anatomical characteristics between the MTP and DL and the similarity in joint angles between the DL and CMJ. Therefore, the DL may be an optimal choice for athletes in jump-dependent sports, regardless of bar.

The Effect of Cloud Ear Fungus (Auricularia polytricha) on Serum Total Cholesterol, LDL And HDL Levels on Wistar Rats Induced by Reused Cooking Oil

NASA Astrophysics Data System (ADS)

Budinastiti, Ratih; Sunoko, Henna Rya; Widiastiti, Nyoman Suci

2018-02-01

The usage of reused cooking oil affects the increase of serum total cholesterol (TC) and LDL, also the decrease of serum HDL. This condition escalates the risk of atherosclerosis, which could lead to the incidence of cardiovascular disease. Cloud ear fungus is a natural antioxidant that contains polysaccharides, flavonoids, niacin, and vitamin C, which can improve the lipid profiles. Objective of this research is to analyze the impact of water from boiled cloud ear fungus on total cholesterol, LDL, and HDL level of Wistar rats that have been given reused cooking oil. This study is a true experimental research with post test only control group design, using 12 weeks-aged male Wistar rats (n = 24) that were randomly divided into 4 groups. K1 as the negative control, K2 was given reused cooking oil and standard diet, K3 was given water from boiled cloud ear fungus and standard diet, and K4 was given reused cooking oil, water from boiled cloud ear fungus and standard diet. Serum total cholesterol, LDL, and HDL levels were measured by the CHOD-PAP method after 28 days treatment. The study showed that TC mean value of K1 (80.2217 ± 3.61 mg / dL), K2 (195.8483 ± 5.47 mg / dL), K3 (75.5800 ± 4.02 mg / dL), and K4 (110.8683 ± 5.82 mg / dL); p = 0.000. LDL mean value of K1 (29.9200 ± 1.53 mg / dL), K2 (78.4167 ± 1.77 mg / dL), K3 (24.3167 ± 1.77 mg / dL), and K4 (40, 1617 ± 2.84 mg / dL); p = 0.000. HDL mean value of K1 (65.8950 ± 1.99 mg / dL), K2 (24.3233 ± 1.44 mg / dL), K3 (73.2300 ± 1.92 mg / dL), and K4 (54, 9550 ± 2.04 mg / dL); p= 0.000. Conclusion: Water from boiled cloud ear fungus decreases the serum total cholesterol and LDL, 06006 increases serum HDL levels of Wistar rats that has been given reused cooking oil.

Long-term acceptability, durability and bio-efficacy of ZeroVector® durable lining for vector control in Papua New Guinea.

PubMed

Kuadima, Joseph J; Timinao, Lincoln; Naidi, Laura; Tandrapah, Anthony; Hetzel, Manuel W; Czeher, Cyrille; Pulford, Justin

2017-02-28

This study examined the acceptability, durability and bio-efficacy of pyrethroid-impregnated durable lining (DL) over a three-year period post-installation in residential homes across Papua New Guinea (PNG). ZeroVector ® ITPS had previously been installed in 40 homes across four study sites representing a cross section of malaria transmission risk and housing style. Structured questionnaires, DL visual inspections and group interviews (GIs) were completed with household heads at 12- and 36-months post-installation. Three DL samples were collected from all households in which it remained 36-months post-installation to evaluate the bio-efficacy of DL on Anopheles mosquitoes. Bio-efficacy testing followed WHO guidelines for the evaluation of indoor residual spraying. The DL was still intact in 86 and 39% of study homes at the two time periods, respectively. In homes in which the DL was still intact, 92% of household heads considered the appearance at 12-months post installation to be the same as, or better than, that at installation compared to 59% at 36-months post-installation. GIs at both time points confirmed continuing high acceptance of DL, based in large part of the perceived attractiveness and functionality of the material. However, participants frequently asserted that they, or their family members, had ceased or reduced their use of mosquito nets as a result of the DL installation. A total of 16 houses were sampled for bio-efficacy testing across the 4 study sites at 36-months post-installation. Overall, combining all sites and samples, both knock-down at 30 min and mortality at 24 h were 100%. The ZeroVector ® DL installation remained highly acceptable at 36-months post-installation, the material and fixtures proved durable and the efficacy against malaria vectors did not decrease. However, the DL material had been removed from over 50% of the original study homes 3 years post-installation, largely due to deteriorating housing infrastructure. Furthermore, the presence of the DL installation appeared to reduce ITN use among many participating householders. The study findings suggest DL may not be an appropriate vector control method for large-scale use in the contemporary PNG malaria control programme.

Chemical Compositions of the Peel Essential Oil of Citrus aurantium and Its Natural Larvicidal Activity against the Malaria Vector Anopheles stephensi (Diptera: Culicidae) in Comparison with Citrus paradisi

PubMed Central

Sanei-Dehkordi, Alireza; Sedaghat, Mohammad Mehdi; Vatandoost, Hassan; Abai, Mohammad Reza

2016-01-01

Background: Recently, essential oils and extracts derived from plants have received much interest as potential bio-active agents against mosquito vectors. Methods: The essential oils extract from fresh peel of ripe fruit of Citrus aurantium and Citrus paradisi were tested against mosquito vector Anopheles stephensi (Diptera: Culicidae) under laboratory condition. Then chemical composition of the essential oil of C. aurantium was analyzed using gas chromatography-mass spectrometry (GC–MS). Results: The essential oils obtained from C. aurantium, and C. paradisi showed good larviciding effect against An. stephensi with LC50 values 31.20 ppm and 35.71 ppm respectively. Clear dose response relationships were established with the highest dose of 80 ppm plant extract evoking almost 100% mortality. Twenty-one (98.62%) constituents in the leaf oil were identified. The main constituent of the leaf oil was Dl-limonene (94.81). Conclusion: The results obtained from this study suggest that the limonene of peel essential oil of C. aurantium is promising as larvicide against An. stephensi larvae and could be useful in the search for new natural larvicidal compounds. PMID:28032110

Mathematical Relationships between Neuron Morphology and Neurite Growth Dynamics in Drosophila melanogaster Larva Class IV Sensory Neurons

NASA Astrophysics Data System (ADS)

Ganguly, Sujoy; Liang, Xin; Grace, Michael; Lee, Daniel; Howard, Jonathon

The morphology of neurons is diverse and reflects the diversity of neuronal functions, yet the principles that govern neuronal morphogenesis are unclear. In an effort to better understand neuronal morphogenesis we will be focusing on the development of the dendrites of class IV sensory neuron in Drosophila melanogaster. In particular we attempt to determine how the the total length, and the number of branches of dendrites are mathematically related to the dynamics of neurite growth and branching. By imaging class IV neurons during early embryogenesis we are able to measure the change in neurite length l (t) as a function of time v (t) = dl / dt . We found that the distribution of v (t) is well characterized by a hyperbolic secant distribution, and that the addition of new branches per unit time is well described by a Poisson process. Combining these measurements with the assumption that branching occurs with equal probability anywhere along the dendrite we were able to construct a mathematical model that provides reasonable agreement with the observed number of branches, and total length of the dendrites of the class IV sensory neuron.

Chemical Compositions of the Peel Essential Oil of Citrus aurantium and Its Natural Larvicidal Activity against the Malaria Vector Anopheles stephensi (Diptera: Culicidae) in Comparison with Citrus paradisi.

PubMed

Sanei-Dehkordi, Alireza; Sedaghat, Mohammad Mehdi; Vatandoost, Hassan; Abai, Mohammad Reza

2016-12-01

Recently, essential oils and extracts derived from plants have received much interest as potential bio-active agents against mosquito vectors. The essential oils extract from fresh peel of ripe fruit of Citrus aurantium and Citrus paradisi were tested against mosquito vector Anopheles stephensi (Diptera: Culicidae) under laboratory condition. Then chemical composition of the essential oil of C. aurantium was analyzed using gas chromatography-mass spectrometry (GC-MS). The essential oils obtained from C. aurantium , and C. paradisi showed good larviciding effect against An. stephensi with LC 50 values 31.20 ppm and 35.71 ppm respectively. Clear dose response relationships were established with the highest dose of 80 ppm plant extract evoking almost 100% mortality. Twenty-one (98.62%) constituents in the leaf oil were identified. The main constituent of the leaf oil was Dl-limonene (94.81). The results obtained from this study suggest that the limonene of peel essential oil of C. aurantium is promising as larvicide against An. stephensi larvae and could be useful in the search for new natural larvicidal compounds.

Replacement value of betaine for DL-methionine in male broiler chicks.

PubMed

Schutte, J B; De Jong, J; Smink, W; Pack, M

1997-02-01

The effect of DL-methionine and betaine supplementation on growth performance of 2,400 male broilers in the age period of 1 to 38 d, and on carcass composition of a subsample of 384 birds was examined. Three dose levels of DL-methionine (0, 0.05, and 0.10%) and two doses of betaine (0 and 0.04%) were supplemented in different combinations to methioninedeficient diets. Two types of diets were fed as starters and growers: either corn-soybean diets or practical diets typical for the Dutch broiler industry. All diets were fortified with 220 ppm choline in order to avoid a deficiency in methyl groups. Increasing DL-methionine supplementation significantly improved daily weight gain and feed conversion efficiency. Supplemental betaine did not affect bird growth. Betaine slightly improved feed conversion in diets without supplemental DL-methionine, but did not affect this parameter in diets with added DL-methionine. Breast meat yield was significantly increased by about 1.5 percentage points by the addition of 0.05% DL-methionine, whereas 0.04% betaine only tended to increase breast meat yield in the range of 0.3 to 0.6 percentage points. The type of diet did not have any effect on the responses obtained. In summary, there was no evidence for betaine to spare DL-methionine as an essential amino acid supplement in broiler diets.

UK Renal Registry 15th annual report: Chapter 6 haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2011: national and centre-specific analyses.

PubMed

Rao, Anirudh; Gilg, Julie; Williams, Andrew

2013-01-01

The UK Renal Association (RA) and National Institute for Health and Care Excellence (NICE) have published Clinical Practice Guidelines which include recommendations for management of anaemia in established renal failure. To determine the extent to which the guidelines for anaemia management are met in the UK. Quarterly data were obtained for haemoglobin (Hb) and factors that influence Hb from renal centres in England, Wales, Northern Ireland (E, W, NI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2011. In the UK, in 2011 51% of patients commenced dialysis therapy with Hb ≥10.0 g/dl (median Hb 10 g/dl). Of patients in the early presentation group, 55% started dialysis with Hb ≥10.0 g/dl whilst 37% of patients presenting late started dialysis with Hb ≥10.0 g/dl. The UK median Hb of haemodialysis (HD) patients was 11.2 g/dl with an inter-quartile range (IQR) of 10.3-12.1 g/dl. Of UK HD patients, 82% had Hb ≥10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.4 g/dl (IQR 10.5-12.3 g/dl). Of UK PD patients, 85% had Hb ≥10.0 g/dl. The median ferritin in HD patients in the UK was 436 mg/L (IQR 292-625) and 96% of HD patients had a ferritin ≥100 mg/ L. In EW&NI the median ferritin in PD patients was 273 mg/ L (IQR 153-446) with 86% of PD patients having a ferritin ≥100 mg/L. In EW&NI the mean erythropoietin stimulating agent (ESA) dose was higher for HD than PD patients (8,740 vs. 6,624 IU/week). Prevalent HD and PD patients had 56% and 53% respectively within the Hb ≥10 and ≤12 g/dl target. Copyright © 2013 S. Karger AG, Basel.

Response to fifty grams oral glucose challenge test and pattern of preceding fasting plasma glucose in normal pregnant Nigerians.

PubMed

Adegbola, Omololu; Ajayi, Godwin Olufemi

2014-03-01

Diabetes mellitus in pregnancy has profound implications for the baby and mother and thus active screening for this is desirable. Fifty grams oral glucose challenge test was administered after obtaining consent to 222 women in good health with singleton pregnancies without diabetes mellitus at 24 to 28 weeks gestation after an overnight fast. Venous blood sample was obtained before and 1 hour after the glucose load. A diagnostic 3-hour 100 g oral glucose tolerance test was subsequently performed in all. Two hundred and ten women had a normal response to oral glucose tolerance test i.e. venous plasma glucose below these cut-off levels: fasting 95 mg/dl (5.3 mmol/l), 1 hour 180 mg/dl (10.0 mmol/l), 2 hours 155 mg/dl (8.6 mmol/l) and 3 hours 140 mg/dl (7.8 mmol/l), while 12 were found to have gestational diabetes mellitus and were subsequently excluded from the study. They were appropriately managed. The mean maternal age was 30.9 ± 4.1 years (range 19 to 45 years) and the mean parity was 1.2 ± 1.1 (range 0 to 5). The mean fasting plasma glucose was 74.5 ± 11.5 mg/dl (range 42 to 117 mg/dl), while the mean plasma glucose 1 hour after 50 g glucose challenge test was 115.3 ± 19.1 mg/dl (range 56 to 180 mg/dl). The mean fasting plasma glucose in normal pregnant Nigerians was 74.5 ± 11.5 mg/dl (range 42 to 117 mg/dl). There is a need to re-appraise and possibly review downwards the World Health Organization fasting plasma glucose diagnostic criteria in pregnant Nigerians for better detection of gestational diabetes mellitus. Pregnant women with venous plasma glucose greater than 153.5 mg/dl (8.5 mmol/l) 1 hour after 50 g glucose challenge test are strongly recommended for diagnostic test of gestational diabetes mellitus.

UK Renal Registry 13th Annual Report (December 2010): Chapter 9: haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2009: national and centre-specific analyses.

PubMed

Gilg, Julie; Webb, Lynsey; Feest, Terry; Fogarty, Damian

2011-01-01

The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published Clinical Practice Guidelines which include recommendations for management of anaemia in established renal failure. To determine the extent to which the guidelines for anaemia management are met in the UK. Quarterly data were obtained regarding haemoglobin (Hb) and factors that influence Hb from renal centres in England, Wales, Northern Ireland (EWNI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2009. In the UK, in 2009 55% of patients commenced dialysis therapy with Hb x10.0 g/dl (median Hb 10.2 g/dl). The median Hb of haemodialysis (HD) patients was 11.6 g/dl with an interquartile range (IQR) of 10.6 - 12.4 g/dl. Of HD patients 85% had Hb ≥ 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.7 g/dl (IQR 10.7-12.6 g/dl). Of UK PD patients, 88% had Hb ≥ 10.0 g/dl. The median ferritin in HD patients in EWNI was 441 mg/L (IQR 289-629) and 96% of HD patients had a ferritin ≥ 100 mg/L. The median ferritin in PD patients was 249 mg/L (IQR 142-412) with 86% of PD patients having a ferritin 5100 mg/L. In EWNI the mean Erythropoietin Stimulating Agent (ESA) dose was higher for HD than PD patients (9,507 vs. 6,212 IU/week). In 2009, 56% of prevalent HD patients had a Hb ≥ 10.5 and ≤ 12.5 g/dl compared with 54% in 2008 and 53% in 2007. Fifty-four percent of prevalent PD patients had a Hb ≥10.5 and ≤12.5 g/dl compared to 55% in 2008. Copyright © 2011 S. Karger AG, Basel.

Quantifying the activity of adenoviral E1A CR2 deletion mutants using renilla luciferase bioluminescence and 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography imaging.

PubMed

Leyton, Julius; Lockley, Michelle; Aerts, Joeri L; Baird, Sarah K; Aboagye, Eric O; Lemoine, Nicholas R; McNeish, Iain A

2006-09-15

The adenoviral E1A CR2 mutant dl922-947 has potent activity in ovarian cancer. We have used Renilla luciferase bioluminescence imaging to monitor viral E1A expression and replication and [18F]fluorothymidine positron emission tomography ([18F]FLT-PET) to quantify the activity of dl922-947 in vivo. We created dlCR2 Ren, with the same E1A CR2 deletion as dl922-947 and the luciferase gene from Renilla reniformis downstream of E1. Light emitted from s.c. and i.p. IGROV1 ovarian carcinoma xenografts was measured following treatment with dlCR2 Ren. Mice bearing s.c. IGROV1 xenografts were injected with 2.96 to 3.7 MBq of [18F]FLT 48 and 168 hours following i.t. injection of dl922-947 or control virus Ad LM-X. The presence of Renilla luciferase in dlCR2 Ren did not reduce in vitro nor in vivo potency compared with dl922-947. Light emission correlated closely with E1A expression in vitro and peaked 48 hours after dlCR2 Ren injection in both s.c. and i.p. IGROV1 xenografts. It diminished by 168 hours in s.c. tumors but persisted for at least 2 weeks in i.p. models. Normalized tumor [18F]FLT uptake at 60 minutes (NUV60), fractional retention, and area under radioactivity curve all decreased marginally 48 hours after dl922-947 treatment and significantly at 168 hours compared with controls. There was a close linear correlation between NUV60 and both tumor proliferation (Ki67 labeling index) and thymidine kinase 1 expression. Renilla luciferase bioluminescence and [18F]FLT-PET imaging are capable of quantifying the activity and effectiveness of E1A CR2-deleted adenoviral mutants in ovarian cancer.

KIR3DL1 interaction with HLA-B27 is altered by ankylosing spondylitis associated ERAP1 and enhanced by MHC class I cross-linking.

PubMed

Abdullah, Hasan; Zhang, Zhenbo; Yee, Kirby; Haroon, Nigil

2015-01-01

Ankylosing spondylitis (AS) is a chronic, inflammatory arthritis of the spine and peripheral joints linked to the antigen presenting molecule HLA-B27. The risk of AS is increased in patients possessing endoplasmic reticulum aminopeptidase-1 (ERAP1) polymorphisms rs30187 and rs27044 encoding amino acid changes K528R and Q730E, respectively. Dysfunction of ERAP1 is hypothesized to cause changes in expression of HLA-B27 classical (pHLA) and non-classical (FHC) conformers on antigen presenting cells (APCs), which interact with the natural killer (NK) cell receptor KIR3DL1. Dysregulation of this pathway may be pathogenic in AS. APC cell lines expressing HLA-B27 were found to inhibit cytokine production in KIR3DL1+ NK cells due to decreased APC-NK cell adhesion, and possibly activation of receptor down-regulation. Blocking pHLA and FHC reveals that both conformers inhibit cytokine production through KIR3DL1. KIR3DL1 affinity and HLA-B27 surface expression studies suggest that ERAP1 R528 and E730 expression protects from AS by generating sub-optimal pHLA, causing reduced KIR3DL1 affinity and weaker cytokine inhibition. Secondarily we observed that KIR3DL1 binding to C1R-B27 APCs is enhanced by blocking pHLA, but not FHC, raising the possibility that antibody mediated HLA-B27 cross-linking may be important in enhancing KIR3DL1+ NK cell function. This study establishes the role of both FHC and pHLA in modulating NK cell cytokine secretion and adhesion functions by interacting with KIR3DL1. This interaction varies depending on the AS association status of the ERAP1 variant expressed in APCs. Additionally antibody cross-linking of HLA-B27 enhances KIR3DL1 binding and as such could be an important pathogenic mechanism in AS.

Effect of environmental lead pollution on blood lead levels in traffic police constables in Islamabad, Pakistan.

PubMed

Agha, Farida; Sadaruddin, Agha; Khatoon, Naz

2005-10-01

To determine the blood lead levels and trace elements (copper and manganese) in traffic police constables in Islamabad in order to assess the effects of environmental pollution on the levels of metals in body fluids. Blood samples were collected from 47 male traffic police constables, 21 to 45 years of age, posted in different areas of Islamabad and controlling traffic from 3 months to 18 years, 8 hours/day, 6 days/week. Adolescent males (13-19 years), residing in comparatively clean and very low traffic areas were included as controls. Blood lead, copper, and manganese concentrations were estimated by atomic absorption spectrophotometry. The mean blood lead level among constables (27.27 microg/dl) was significantly (p<0.0001) high as compared to controls (3.22 microg/dl). Twenty one percent constables had elevated blood lead levels (over 25 microg/dl) and 13% had levels above the safety limit (40 microg/dl). No correlation was found between blood lead levels and length of service. No significant difference was found in the mean values for copper between traffic constables (93.49 microg/dl) and controls (71.15 microg/dl). The mean blood manganese levels in traffic constables (21.94 microg/dl) were significantly (p<0.0001) higher than in controls (1.70 microg/dl). The mean blood lead levels were significantly high in traffic constables of Karachi (47.7 microg/dl) as compared to Islamabad (27.2 microg/dl), which shows direct relation of rise in blood lead levels with vehicle exhaust. Environmental lead pollution is associated with an increased blood lead concentration in those who are regularly exposed to vehicle exhaust in high traffic areas. The degree of lead pollution arising from vehicle exhaust differs in Karachi and Islamabad. Exposure to air containing dust particles rich in manganese may affect blood manganese levels.

Polychlorinated dibenzo-p-dioxins, dibenzofurans, and dioxin-like polychlorinated biphenyls in rice straw smoke and their origins in Japan.

PubMed

Minomo, Kotaro; Ohtsuka, Nobutoshi; Nojiri, Kiyoshi; Hosono, Shigeo; Kawamura, Kiyoshi

2011-08-01

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs) contained in the smoke generated from rice straw burning in post-harvest paddy fields in Japan were analyzed to determine their congener profiles. Both the apportionment of toxic equivalent (TEQ) by using indicative congeners and the comparison of the homolog profiles showed that the PCDDs/PCDFs/DL-PCBs present in the rice-straw smoke were greatly influenced by those present as impurities in pentachlorophenol (PCP) and chlornitrofen (CNP, 4-nitrophenyl-2,4,6-trichlorophenyl ether) formulations that had been widely used as herbicides in paddy fields in Japan. Further, in order to investigate the effects of paddy-field soil on the PCDDs/PCDFs/DL-PCBs present in rice-straw smoke, PCDD/PCDF/DL-PCB homolog profiles of rice straw, rice-straw smoke and paddy-field soil were compared. Rice-straw smoke was generated by burning rice straw on a stainless-steel tray in a laboratory. The results suggested that the herbicides-originated PCDDs/PCDFs/DL-PCBs and the atmospheric PCDDs/PCDFs/DL-PCBs contributed predominantly to the presence of PCDDs/PCDFs/DL-PCBs in the rice-straw smoke while the contribution of PCDDs/PCDFs/DL-PCBs formed during rice straw burning was relatively minimal. The major sources of the PCDDs/PCDFs/DL-PCBs found in the rice-straw smoke were attributed primarily to the paddy-field soil adhered to the rice straw surface and secondarily to the air taken by the rice straw. The principal component analysis supported these conclusions. It is concluded that rice straw burning at paddy fields acts as a driving force in the transfer of PCDDs/PCDFs/DL-PCBs from paddy-field soil to the atmosphere. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dendrimer-based Nanoparticle for Dye Sensitized Solar Cells with Improved Efficiency.

PubMed

Ghann, William; Kang, Hyeonggon; Uddin, Jamal; Gonawala, Sunalee J; Mahatabuddin, Sheikh; Ali, Meser M

2018-01-01

Dye sensitized solar cells were fabricated with DyLight680 (DL680) dye and its corresponding europium conjugated dendrimer, DL680-Eu-G5PAMAM, to study the effect of europium on the current and voltage characteristics of the DL680 dye sensitized solar cell. The dye samples were characterized by using Absorption Spectroscopy, Emission Spectroscopy, Fluorescence lifetime and Fourier Transform Infrared measurements. Transmission electron microscopy imaging was carried out on the DL680-Eu-G5PAMAM dye and DL680-Eu-G5PAMAM dye sensitized titanium dioxide nanoparticles to analyze the size of the dye molecules and examine the interaction of the dye with titanium dioxide nanoparticles. The DL680-Eu-G5PAMAM dye sensitized solar cells demonstrated an enhanced solar-to-electric energy conversion of 0.32% under full light illumination (100 mWcm -2 , AM 1.5 Global) in comparison with that of DL680 dye sensitized cells which recorded an average solar-to-electric energy conversion of only 0.19%. The improvement of the efficiency could be due to the presence of the europium that enhances the propensity of dye to absorb sunlight.

Photodynamic Therapy for Actinic Keratoses: A Randomized Prospective Non-sponsored Cost-effectiveness Study of Daylight-mediated Treatment Compared with Light-emitting Diode Treatment.

PubMed

Neittaanmäki-Perttu, Noora; Grönroos, Mari; Karppinen, Toni; Snellman, Erna; Rissanen, Pekka

2016-02-01

Daylight-mediated photodynamic therapy (DL-PDT) is considered as effective as conventional PDT using artificial light (light-emitting diode (LED)-PDT) for treatment of actinic keratoses (AK). This randomized prospective non-sponsored study assessed the cost-effectiveness of DL-PDT compared with LED-PDT. Seventy patients with 210 AKs were randomized to DL-PDT or LED-PDT groups. Effectiveness was assessed at 6 months. The costs included societal costs and private costs, including the time patients spent in treatment. Results are presented as incremental cost-effectiveness ratio (ICER). The total costs per patient were significantly lower for DL-PDT (€132) compared with LED-PDT (€170), giving a cost saving of €38 (p = 0.022). The estimated probabilities for patients' complete response were 0.429 for DL-PDT and 0.686 for LED-PDT; a difference in probability of being healed of 0.257. ICER showed a monetary gain of €147 per unit of effectiveness lost. DL-PDT is less costly and less effective than LED-PDT. In terms of cost-effectiveness analysis, DL-PDT provides lower value for money compared with LED-PDT.

Enhancement of bioavailability of cinnarizine from its beta-cyclodextrin complex on oral administration with DL-phenylalanine as a competing agent.

PubMed

Tokumura, T; Nanba, M; Tsushima, Y; Tatsuishi, K; Kayano, M; Machida, Y; Nagai, T

1986-04-01

The present investigation is concerned with an improvement of the bioavailability of cinnarizine by administering its beta-cyclodextrin complex together with another compound which competes with the beta-cyclodextrin molecule in complex formation in aqueous solution (competing agent). The bioavailability of cinnarizine on oral administration of the cinnarizine-beta-cyclodextrin inclusion complex was enhanced by the simultaneous administration of DL-phenylalanine as a competing agent, e.g., the AUC was 1.9 and 2.7 times as large as those of the cinnarizine-beta-cyclodextrin complex alone and cinnarizine alone, respectively. The enhancement of AUC and Cmax completely depended on the dose of DL-phenylalanine. It was found from these results that DL-phenylalanine acted as a competing agent in the GI tract and the minimum effective dose required of DL-phenylalanine might be 1 g for 50 mg of cinnarizine in the cinnarizine-beta-cyclodextrin complex. Evaluating the competing effect of DL-phenylalanine in vitro using an absorption simulator, it was found that the decreased penetration rate of cinnarizine through the artificial lipid barrier with addition of beta-cyclodextrin was restored with the addition of DL-phenylalanine.

Review on occurrence and behavior of PCDD/Fs and dl-PCBs in atmosphere of East Asia

NASA Astrophysics Data System (ADS)

Trinh, Minh Man; Chang, Moo Been

2018-05-01

This paper reviews the data from studies mainly published after 2000 to provide the current understanding of the physicochemical properties, atmospheric occurrence, gas/particle partitioning, fate and temporal trends in atmospheric matrix of PCDD/Fs and dl-PCBs of East Asia. Ambient PCDD/Fs and dl-PCBs concentrations in East Asia are found to be tens to hundreds times higher than that measured in Europe and North America. After strict regulations on PCDD/Fs and dl-PCBs emissions are enacted, the concentrations of these compounds decrease dramatically in Eastern Asian countries. In general, most of PCDD/Fs distribute in particle phase while dl-PCBs majorly exist in gas phase. Three main factors including physicochemical properties of the compounds, properties of particle and atmospheric condition affect the gas/particle partitioning of PCDD/Fs and dl-PCBs. The accuracy of absorption and adsorption models on predicting gas/particle partitioning of PCDD/Fs and dl-PCBs is evaluated. Gas-phase compounds are mostly removed from the atmosphere via reactions with OH radicals while those in particle phase are majorly removed by wet/dry deposition processes. The effects of removing processes and long-range transport on gas/particle partitioning are also discussed.

A comparative biochemical profile of some cyprinids fish in Dukan Lake, Kurdistan-Iraq

NASA Astrophysics Data System (ADS)

Azeez, Darya Mohammed; Mohammed, Sarbaz Ibrahim

2017-09-01

The present study was carried out to demonstrate the baseline values for some serum biochemical parameters for 64 adult freshwater fish including seven species belong to family Cyprinidae, have been collected in Dukan Lake, Kurdistan region-Iraq. Fishes were weighed, measured, and collect blood for blood chemistry. Serum biochemical analyses were determined using (Cobas C 311) full automatic chemical analyzer. The result of comparative study of serum biochemical parameters of all Cyprinidae species showed that serum glucose was (459.10±106.99 mg/dl) and direct bilirubin was (0.056±0.021mg/dl) in Barbus grypus, serum total protein (3.511± 0.0484gm/dl) and HDL (133.11±0.4231mg/dl) in Cyprinus carpio, serum cholesterol (338.33±43.923 mg/dl) and LDL (86.11±11.871mg/dl) in Carassius carassius, serum triglyceride (420.0±28.8mg/dl) and ALK (113.93±20.65U/L) in Chondrostoma regium, serum AST and serum ALT in Capoeta trutta, were significantly higher when compared to other species. In a conclusion there is variation in biochemical values among species of same family.

Influence of highly distinctive structural properties on the excitability of pyramidal neurons in monkey visual and prefrontal cortices

PubMed Central

Amatrudo, Joseph M.; Weaver, Christina M.; Crimins, Johanna L.; Hof, Patrick R.; Rosene, Douglas L.; Luebke, Jennifer I.

2012-01-01

Whole-cell patch-clamp recordings and high-resolution 3D morphometric analyses of layer 3 pyramidal neurons in in vitro slices of monkey primary visual cortex (V1) and dorsolateral granular prefrontal cortex (dlPFC) revealed that neurons in these two brain areas possess highly distinctive structural and functional properties. Area V1 pyramidal neurons are much smaller than dlPFC neurons, with significantly less extensive dendritic arbors and far fewer dendritic spines. Relative to dlPFC neurons, V1 neurons have a significantly higher input resistance, depolarized resting membrane potential and higher action potential (AP) firing rates. Most V1 neurons exhibit both phasic and regular-spiking tonic AP firing patterns, while dlPFC neurons exhibit only tonic firing. Spontaneous postsynaptic currents are lower in amplitude and have faster kinetics in V1 than in dlPFC neurons, but are no different in frequency. Three-dimensional reconstructions of V1 and dlPFC neurons were incorporated into computational models containing Hodgkin-Huxley and AMPA- and GABAA-receptor gated channels. Morphology alone largely accounted for observed passive physiological properties, but led to AP firing rates that differed more than observed empirically, and to synaptic responses that opposed empirical results. Accordingly, modeling predicts that active channel conductances differ between V1 and dlPFC neurons. The unique features of V1 and dlPFC neurons are likely fundamental determinants of area-specific network behavior. The compact electrotonic arbor and increased excitability of V1 neurons support the rapid signal integration required for early processing of visual information. The greater connectivity and dendritic complexity of dlPFC neurons likely support higher level cognitive functions including working memory and planning. PMID:23035077

Novel device-based acne treatments: comparison of a 1450-nm diode laser and microneedling radiofrequency on mild-to-moderate acne vulgaris and seborrhoea in Korean patients through a 20-week prospective, randomized, split-face study.

PubMed

Kwon, H H; Park, H Y; Choi, S C; Bae, Y; Jung, J Y; Park, G-H

2018-04-01

While device-based acne treatments are widely applied for patients not tolerating conventional medications, related controlled studies have been still limited. Recently, non-ablative 1450-nm diode laser (DL) and fractional microneedling radiofrequency (FMR) have been effectively used for acne, in addition to well-recognized dermal remodelling effects. To compare the clinical course of acne treatment between DL and FMR. Twenty-five Korean patients with mild-to-moderate facial acne completed treatments with DL and FMR through a 20-week, randomized split-face study. One randomly assigned half side of each patient's face received DL and the other side by FMR. Treatments were scheduled to receive three consecutive sessions at 4-week intervals. Objective assessments including revised Leeds grades, lesion counts, sebum output measurements, and patients' subjective satisfaction were investigated. Both DL and FMR demonstrated steady improvement of acne and seborrhoea during treatment sessions. While results between two devices were similar during treatment sessions, FMR was superior to DL in the 12-week follow-up. Patients' subjective assessments for seborrhoea improvement were similar between two devices, while those for acne, skin texture, and acne scars were more satisfactory for FMR. For safety profile, no significant difference was observed between two regimens, while mild postinflammatory hyperpigmentation was observed only in DL side. Both DL and FMR demonstrated efficacies for acne and seborrhoea, with reasonable safety profile. FMR was more effective than DL for the long-term maintenance, and subjective assessments for texture and scar improvements. Therefore, a few sessions of these devices would be a viable option for acne treatments. © 2017 European Academy of Dermatology and Venereology.

Comparison of serum trace element levels in patients with or without pre-eclampsia.

PubMed

Farzin, Leila; Sajadi, Fattaneh

2012-10-01

In developing countries, nutritional deficiency of essential trace elements is a common health problem, particularly among pregnant women because of increased requirements of various nutrients. Accordingly, this study was initiated to compare trace elements status in women with or without pre-eclampsia. In this study, serum trace elements including zinc (Zn), selenium (Se), copper (Cu), calcium (Ca) and magnesium (Mg) were determined by using atomic absorption spectrometry (AAS) in 60 patients and 60 healthy subjects. There was no significant difference in the values of Cu between two groups (P > 0.05). A significant difference in Zn, Se, Ca and Mg levels were observed between patients with pre-eclampsia and control group (P < 0.001, P<0.01, P<0.01 and P<0.001, respectively). Zn, Se, Ca and Mg levels were found to be 76.49 ± 17.62 μg/ dl, 8.82 ± 2.10 μg/ dl, 8.65 ± 2.14 mg/dl and 1.51 ± 0.34 mg/dl in Pre-eclamptic cases, and these values were found statistically lower compared to the controls (100.61 ± 20.12 μg/dl, 10.47 ± 2.78 μg/dl, 9.77 ± 3.02 mg/dl and 1.78 ± 0.27 mg/dl, respectively). While Cu levels were 118.28 ± 16.92 and 116.55 ± 15.23 μg/dl in the patients and the healthy subjects, respectively. In addition, no significant difference was found between two groups with respect to Hemoglobin Concentration (HbC) and Total White Blood Cell Count (TWBC) (P>0.05). Our findings indicate that the levels of Zn, Se, Ca and Mg are significantly altered in pregnant women with pre-eclampsia. This research shows that these deficiencies can not due to hemodilution.

Study of axial double layer in helicon plasma by optical emission spectroscopy and simple probe

NASA Astrophysics Data System (ADS)

Gao, ZHAO; Wanying, ZHU; Huihui, WANG; Qiang, CHEN; Chang, TAN; Jiting, OUYANG

2018-07-01

In this work we used a passive measurement method based on a high-impedance electrostatic probe and an optical emission spectroscope (OES) to investigate the characteristics of the double layer (DL) in an argon helicon plasma. The DL can be confirmed by a rapid change in the plasma potential along the axis. The axial potential variation of the passive measurement shows that the DL forms near a region of strong magnetic field gradient when the plasma is operated in wave-coupled mode, and the DL strength increases at higher powers in this experiment. The emission intensity of the argon atom line, which is strongly dependent on the metastable atom concentration, shows a similar spatial distribution to the plasma potential along the axis. The emission intensity of the argon atom line and the argon ion line in the DL suggests the existence of an energetic electron population upstream of the DL. The electron density upstream is much higher than that downstream, which is mainly caused by these energetic electrons.

Planck intermediate results: XXIX. All-sky dust modelling with Planck, IRAS, and WISE observations

DOE PAGES

Ade, P. A. R.; Aghanim, N.; Alves, M. I. R.; ...

2016-02-09

In this paper, we present all-sky modelling of the high resolution Planck, IRAS, and WISE infrared (IR) observations using the physical dust model presented by Draine & Li in 2007 (DL, ApJ, 657, 810). We study the performance and results of this model, and discuss implications for future dust modelling. The present work extends the DL dust modelling carried out on nearby galaxies using Herschel and Spitzer data to Galactic dust emission. We employ the DL dust model to generate maps of the dust mass surface density Σ Md, the dust optical extinction A V, and the starlight intensity heatingmore » the bulk of the dust, parametrized by U min. The DL model reproduces the observed spectral energy distribution (SED) satisfactorily over most of the sky, with small deviations in the inner Galactic disk and in low ecliptic latitude areas, presumably due to zodiacal light contamination. In the Andromeda galaxy (M31), the present dust mass estimates agree remarkably well (within 10%) with DL estimates based on independent Spitzer and Herschel data. We compare the DL optical extinction A V for the diffuse interstellar medium (ISM) with optical estimates for approximately 2 × 10 5 quasi-stellar objects (QSOs) observed inthe Sloan Digital Sky Survey (SDSS). The DL A V estimates are larger than those determined towards QSOs by a factor of about 2, which depends on U min. The DL fitting parameter U min, effectively determined by the wavelength where the SED peaks, appears to trace variations in the far-IR opacity of the dust grains per unit A V, and not only in the starlight intensity. These results show that some of the physical assumptions of the DL model will need to be revised. To circumvent the model deficiency, we propose an empirical renormalization of the DL A V estimate, dependent of U min, which compensates for the systematic differences found with QSO observations. This renormalization, made to match the A V estimates towards QSOs, also brings into agreement the DL A V estimates with those derived for molecular clouds from the near-IR colours of stars in the 2 micron all sky survey (2MASS). The DL model and the QSOs data are also used to compress the spectral information in the Planck and IRAS observations for the diffuse ISM to a family of 20 SEDs normalized per A V, parameterized by U min, which may be used to test and empirically calibrate dust models. Finally, the family of SEDs and the maps generated with the DL model are made public in the Planck Legacy Archive.« less

The effect of dys-1 mutation on miRNA expression profile in Caenorhabditis elegans during Shenzhou-8 mission

NASA Astrophysics Data System (ADS)

Xu, Dan; Sun, Yeqing; Gao, Ying; Xing, Yanfang

microRNAs (miRNAs) is reported to be sensitive to radiation exposure and altered gravity, involved in a variety of biological processes through negative regulation of gene expression. Dystrophin-like dys-1 gene is expressed and required in muscle tissue, which plays a vital role in mechanical transduction when gravity varies. In the present study, we investigated the effect of dys-1 mutation on miRNA expression profile in Caenorhabditis elegans (C. elegans) under space radiation associated with microgravity (R+M) and radiation alone (R) environment during Shenzhou-8 mission. We performed miRNA microarray analysis in dys-1 mutant and wide-type (WT) of dauer larvae and found that 27 miRNAs changed in abundance after spaceflight. Compared with WT, there was different miRNA expression pattern in different treatments in dys-1 mutant. Cel-miR-796 and miR-124 were reversely expressed under R+M and R environment in WT and dys-1 mutant, respectively, indicating they might be affected by microgravity. Mutation of dys-1 remarkably reduced the number of altered miRNAs under space environment, resulting in the decrease of genes in biological categories of “body morphogenesis”, “behavior”, “cell adhesion” and so on. Particularly, we found that those genes controlling regulation of locomotion in WT were lost in dys-1 mutant, while genes in positive regulation of developmental process only existed in dys-1 mutant. miR-796 was predicted to target genes ace-1 and dyc-1 that are functionally linked to dys-1. Integration analysis of miRNA and mRNA expression profile revealed that miR-56 and miR-124 were involved in behavior and locomotion by regulating different target genes under space environment, among which nep-11, deb-1, C07H4.1 and F11H8.2 might be associated with neuromuscular system. Our findings suggest that dys-1 could cause alteration of miRNAs and target genes, involved in regulating the response of C. elegans to space microgravity in neuromuscular system. This research will provide new insight for better understanding of the mechanism in microgravity-induced muscular dystrophy.

Assessment of the Thermodynamic Properties of DL-p-Mentha-1,8-diene, 4-Isopropyl-1-Methylcyclohexene (DL-limonene) by Inverse Gas Chromatography (IGC).

PubMed

Farshchi, Negin; Abbasian, Ali; Larijani, Kambiz

2018-05-10

Limonene is a colorless liquid hydrocarbon and had been investigated as a plasticizer for many plastics. Prediction of solubility between different materials is an advantage in many ways, one of the most convenient ways to know the compatibility of materials is to determine the degree of solubility of them in each other. The concept of "solubility parameter" can help practitioners in this way.In this study, inverse gas chromatography (IGC) method at infinite dilution was used for determination of the thermodynamic properties of DL-p-mentha-1,8-diene, 4-Isopropyl-1-methylcyclohexene (DL-limonene). The interaction between DL-limonene and 13 solvents were examined in the temperature range of 63-123°C through the assessment of the thermodynamic sorption parameters, the parameters of mixing at infinite dilution, the weight fraction activity coefficient and the Flory-Huggins interaction parameters. Additionally, the solubility parameter for DL-limonene and the temperature dependence of these parameters was investigated as well.Results show that there is a temperature dependence in solubility parameter, which increases by decreasing temperature. However, there were no specific dependence between interaction parameters and temperature, but chemical structure appeared to have a significant effect on them as well as on the type and strength of intermolecular interactions between DL-limonene and investigated solvents. The solubility parameter δ2 of DL-limonene determined to be 19.20 (J/cm3)0.5 at 25°C.

Impact of low level radiation on concentrations of some trace elements in radiation workers.

PubMed

Rostampour, Nima; Almasi, Tinoosh; Rostampour, Masoumeh; Sadeghi, Hamid Reza; Khodamoradi, Ehsan; Razi, Reyhaneh; Derakhsh, Zahra

2018-05-01

Small variations in trace element levels may cause important physiological changes in the human body. This study aims to evaluate five important trace elements in radiation workers. In this study, 44 radiation workers and an equal number of non-radiation workers were selected as the case and control group, respectively. The concentrations of iron, magnesium, zinc, copper, and selenium in the serum of the participants were measured using an Atomic Absorption Spectrometry (AAS). The mean concentrations of iron, magnesium, zinc, copper, and selenium for the case group were 107.3 µg/dl, 2.3 mg/dl, 80.9 µg/dl, 112.6 µg/dl and 216.7 ng/ml, respectively. The results for the control group were 121.9 µg/dl, 2.3 mg/dl, 82.3 µg/dl, 112.8 µg/dl and 225.2 ng/ml, respectively. The mean concentration of iron in the case group was significantly lower than the control group (p-value = 0.012), while the concentrations of other elements in both of the groups were not significantly different. In the case group, except magnesium (p-value = 0.021), no significant relationship was found between age and the elemental concentrations. According to Spearman's test, there was a meaningful statistical correlation between the sex and concentration of iron, Mg, Zn, and Se. Also, the correlation between the concentration of magnesium and the weights of radiation workers was significant (p-value =0.044). © 2018 Old City Publishing, Inc.

A phase I trial of imatinib in combination with mFOLFOX6-bevacizumab in patients with advanced colorectal cancer.

PubMed

Michael, M; Zalcberg, J; Gibbs, P; Lipton, L; Gouillou, M; Jefford, M; McArthur, G; Copeman, M; Lynch, K; Tebbutt, N C

2013-02-01

Platelet-derived growth factor receptor (PDGFR) inhibition by reducing tumoral interstitial fluid pressure might increase the efficacy of chemotherapy. Imatinib inhibits PDGFR kinase activity at therapeutically relevant doses. This phase I study aimed to assess the maximal tolerated dose (MTD) of imatinib in combination with mFOLFOX6-bevacizumab in patients with advanced colorectal cancer and to identify pharmacokinetic (PK) interactions and toxicities. Eligible patients had measurable disease and adequate organ function. On day-14, patients commenced imatinib daily plus bevacizumab (5 mg/kg/2 weekly). Two weeks later (day 1), patients were also treated with full dose mFOLFOX6-bevacizumab for 12 cycles. Blood samples were taken for PK. DLTs defined in the first 6 weeks. Standard dose escalation of imatinib, with 3 patient cohorts: planned dose levels (DL): DL1; 400 mg, DL2; 600 mg, DL3; 800 mg daily. Ten patients enrolled. DL1 3 patients, DL2 7 patients. DLTs observed in 3 of 6 patients in DL2: febrile neutropenia (2); Grade 3 infection and Grade 4 neutropenia (1). Neutropenia was most frequent AEs: Grade 3/4 in >60 % of patients overall. In DL2 pts, imatinib clearance was reduced post-chemotherapy (P < 0.05). Oxaliplatin and 5FU PK unchanged by imatinib. MTD was imatinib 400 mg plus full dose mFOLFOX-bevacizumab. Dose escalation of imatinib limited by neutropenia. Further study is warranted as imatinib can be delivered at levels that inhibit PDGFR.

Possible Role of HLA-G, LILRB1 and KIR2DL4 Gene Polymorphisms in Spontaneous Miscarriage.

PubMed

Nowak, Izabela; Malinowski, Andrzej; Barcz, Ewa; Wilczyński, Jacek R; Wagner, Marta; Majorczyk, Edyta; Motak-Pochrzęst, Hanna; Banasik, Małgorzata; Kuśnierczyk, Piotr

2016-12-01

The KIR2DL4 receptor and its ligand HLA-G are considered important for fetal-maternal immune tolerance and successful pregnancy. The absence of a particular variant of KIR2DL4 might be a bad prognostic factor for pregnancy outcome. However, it could be compensated by the presence of the respective LILRB1 allele. Therefore, we investigated the KIR2DL4, LILRB1 and HLA-G polymorphisms in 277 couples with spontaneous abortion and 219 control couples by HRM, PCR-SSP and RFLP methods. We found a protective effect of women's heterozygosity in -716 HLA-G (p = 0.0206) and LILRB1 (p = 0.0131) against spontaneous abortion. Surprisingly, we observed more 9A/10A genotypes of KIR2DL4 gene carriers in the group of male partners from the miscarriage group in comparison to the men from the control group (p = 0.0288). Furthermore, there was no association of women's KIR2DL4 polymorphism with susceptibility to spontaneous abortion. Multivariate analysis indicated that women's -716 HLA-G and LILRB1 and men's KIR2DL4 9A/10A are important in terms of the protection or susceptibility to miscarriage, respectively (p = 0.00968). In conclusion, a woman's heterozygosity in HLA-G and LILRB1 might be an advantage for a success of reproduction, but the partner's heterozygosity in 9A/10A KIR2DL4 alleles might not.

Atmospheric concentrations and gas-particle partitioning of PCDD/Fs and dioxin-like PCBs around Hochiminh city.

PubMed

Trinh, Minh Man; Tsai, Ching Lan; Hien, To Thi; Thuan, Ngo Thi; Chi, Kai Hsien; Lien, Chien Guo; Chang, Moo Been

2018-07-01

Atmospheric PCDD/Fs and dl-PCBs samples were collected in Hochiminh city, Vietnam to address the effect of meteorological parameters, especially rainfall, on the occurrence and gas/particle partitioning of these persistent organic pollutants. The results indicate that PCDD/Fs and dl-PCBs concentrations in industrial site are higher than those measured in commercial and rural sites during both rainy and dry seasons. In terms of mass concentration, ambient PCDD/F levels measured in dry season are significantly higher than those measured in rainy season while dl-PCB levels do not vary significantly between rainy and dry seasons. The difference could be attributed to different gas/particle partitioning characteristics between PCDD/Fs and dl-PCBs. PCDD/Fs are found to be mainly distributed in particle phase while dl- PCBs are predominantly distributed in gas phase in both rainy and dry seasons. Additionally, Junge-Pankow and Harner-Bidleman models are applied to better understand the gas/particle partitioning of these pollutants in atmosphere. As a results, both PCDD/Fs and dl-PCBs are under non-equilibrium gas/particle partitioning condition, and PCDD/Fs tend to reach equilibrium easier in rainy season while there are no clear trend for dl-PCBs. Harner-Bidleman model performs better in evaluating the gas/particle partitioning of PCDD/Fs while Junge-Pankow model results in better prediction for dl-PCBs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cytotoxic effects of some animal and vegetable extracts and some chemicals on liver and colon carcinoma and myosarcoma.

PubMed

Bayazit, Vahdettin

2004-02-01

To study, the cytotoxic effects of some biological and chemical agents on G1, S, G2, M and G0 phases of liver and colon carcinomas and myosarcoma cells obtained with chemical carcinogens dimethylbenzanthracene (DMBA) and cadmium chloride. Eight rabbit livers, colon carcinoma and myosarcoma cell lines were obtained by injection of DMBA in the Biology Laboratory, of the University of Dumlupinar, Kutahya, Turkey between January 2001 and June 2003. All lines were grown at 37 degrees celsius and 5% carbon dioxide in sterile RPMI-1640 medium with 10% fetal bovine serum after addition of glutamate, penicillin (50 units/ml) and streptomycin (50 ug/ml) (complete medium). Cells were grown on standard tissue culture plastic flasks to 80% confluence and passed by trypsinization. Tortoise (Testudo graeca) shell, sponge (Geodia cydonium), medusa (Aurelia aurita), meat flies (Calliphora erythrocephala) larva, frog (Rana ridibunda) larva and juniper (Juniperus communis) berry extracts killed a large amount of the liver and colon carcinomas and the myosarcoma cells in G2, M and G0 phases (p<0.01). The mistletoe (Viscum album) extract had more effect in only the G0 phase (p<0.05). Genistein, genistin, glycitein, glycitin, daitzein and daitzin have significantly decreased in the cancer cells tests, particularly, genistein and daitzein caused the apoptotic effect in G2, M and G0 phases (p<0.01). Cesium chloride, a mixture of cesium chloride with magnesium chloride had the most effect on tumor cells (p<0.01). AzhexSi, Azhex-AzhepSi, Et-Azhex-AzhepSi, AzhepSi, Hexamine and DL 54 have been inhibited in various levels of the cancer cells (p<0.05, p<0.01). This data suggest that some biological extracts and chemicals tested may be useful chemotherapeutic agents to inhibit the growth of cancer cells. This study sheds some light for new anti cancerogenic experiments preventing various cancers on humans.

Yellow mealworm larvae (Tenebrio molitor, L.) as a possible alternative to soybean meal in broiler diets.

PubMed

Bovera, F; Piccolo, G; Gasco, L; Marono, S; Loponte, R; Vassalotti, G; Mastellone, V; Lombardi, P; Attia, Y A; Nizza, A

2015-01-01

The aim of the study was to evaluate the feasibility of replacing soybean meal (SBM) with Tenebrio molitor larvae (TML) meal in broiler diets. A total of 80 30-d-old male Shaver brown broilers were divided into two groups fed on two isoproteic and isoenergetic diets differing for protein source (SBM vs. TML). Up to 62 d of age, body weight and feed intake were recorded weekly and body weight gain, feed conversion ratio (FCR), protein efficiency ratio (PER) and European efficiency factor (EEF) were calculated. At 62 d, blood samples were collected from 16 birds/group for evaluation of blood profiles. Feed intake was not different between groups considering the entire period of the trial. The FCR was more favourable in the TML than SBM group from 46 d of age and in the entire period of the trial (4.13 vs. 3.62). The PER was higher in the SBM than in the TML group (1.92 vs. 1.37) while the EEF was higher in broilers fed on the TML diet (132.6 vs. 156.2). Albumin-to-globulin ratio was higher in broilers fed on SBM than in the other group (0.44 vs. 0.30). aspartate aminotransferase and alanine aminotransferase were higher in TML than SBM (195.1 vs. 178.6 U/l and 82.07 vs. 46.71 U/l, respectively). Uric acid was higher in broilers fed on SBM than TML (5.40 vs. 4.16 mg/dl). TML did not affect feed intake and growth rate of broilers from 30 to 62 d of age when compared to an isoproteic and isoenergetic SBM diet, but FCR of the TML group was more favourable than that of the SBM group. The lowest albumin-to-globulin ratio in broilers fed on TML suggests a higher immune response, probably due to the prebiotic effects of chitin.

48 CFR 2953.102 - Quotation for Simplified Acquisitions DL 1-2078.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Quotation for Simplified Acquisitions DL 1-2078. 2953.102 Section 2953.102 Federal Acquisition Regulations System DEPARTMENT OF LABOR CLAUSE AND FORMS FORMS General 2953.102 Quotation for Simplified Acquisitions DL 1-2078. The following...

Dichotic Listening and Left-Right Confusion

ERIC Educational Resources Information Center

Hirnstein, Marco

2011-01-01

The present study examined the relationship between individual differences in dichotic listening (DL) and the susceptibility to left-right confusion (LRC). Thirty-six men and 59 women completed a consonant-vowel DL test, a behavioral LRC task, and an LRC self-rating questionnaire. Significant negative correlations between overall DL accuracy and…

7 CFR 205.603 - Synthetic substances allowed for use in organic livestock production.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Water Act. (i) Calcium hypochlorite. (ii) Chlorine dioxide. (iii) Sodium hypochlorite. (8) Electrolytes... additives. (1) DL-Methionine, DL-Methionine—hydroxy analog, and DL-Methionine—hydroxy analog calcium (CAS... following maximum levels of synthetic methionine per ton of feed: laying chickens—4 pounds; broiler chickens...

7 CFR 205.603 - Synthetic substances allowed for use in organic livestock production.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Water Act. (i) Calcium hypochlorite. (ii) Chlorine dioxide. (iii) Sodium hypochlorite. (8) Electrolytes... additives. (1) DL-Methionine, DL-Methionine—hydroxy analog, and DL-Methionine—hydroxy analog calcium (CAS... following maximum levels of synthetic methionine per ton of feed: laying chickens—4 pounds; broiler chickens...

7 CFR 205.603 - Synthetic substances allowed for use in organic livestock production.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Water Act. (i) Calcium hypochlorite. (ii) Chlorine dioxide. (iii) Sodium hypochlorite. (8) Electrolytes.... (1) DL-Methionine, DL-Methionine-hydroxy analog, and DL-Methionine-hydroxy analog calcium (CAS #'s 59... maximum levels of synthetic methionine per ton of feed: Laying and broiler chickens—2 pounds; turkeys and...

7 CFR 205.603 - Synthetic substances allowed for use in organic livestock production.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Water Act. (i) Calcium hypochlorite. (ii) Chlorine dioxide. (iii) Sodium hypochlorite. (8) Electrolytes.... (1) DL-Methionine, DL-Methionine-hydroxy analog, and DL-Methionine-hydroxy analog calcium (CAS #'s 59... maximum levels of synthetic methionine per ton of feed: Laying and broiler chickens—2 pounds; turkeys and...

Dorsolateral Prefrontal Contributions to Human Intelligence

PubMed Central

Barbey, Aron K.; Colom, Roberto; Grafman, Jordan

2012-01-01

Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in executive control functions for human intelligence, the necessity of the dorsolateral prefrontal cortex (dlPFC) for key competencies of general intelligence and executive function remains to be well established. Here we studied human brain lesion patients with dlPFC lesions to investigate whether this region is computationally necessary for performance on neuropsychological tests of general intelligence and executive function, administering the Wechsler Adult Intelligence Scale (WAIS) and subtests of the Delis Kaplan Executive Function System (D-KEFS) to three groups: dlPFC lesions (n = 19), non-dlPFC lesions (n = 152), and no brain lesions (n = 55). The key results indicate that: (1) patients with focal dlPFC damage exhibit lower scores, at the latent variable level, than controls in general intelligence (g) and executive function; (2) dlPFC patients demonstrate lower scores than controls in several executive measures; and (3) these latter differences are no longer significant when the pervasive influence of the general factor of intelligence (g) is statistically removed. The observed findings support a central role for the dlPFC in general intelligence and make specific recommendations for the interpretation and application of the WAIS and D-KEFS to the study of high-level cognition in health and disease. PMID:22634247

Evaluation of a childhood lead questionnaire in predicting elevated blood lead levels in a rural community.

PubMed

Muñiz, Marco A; Dundas, Robert; Mahoney, Martin C

2003-01-01

The accuracy of a lead screening questionnaire in predicting elevated blood lead levels was examined in a pediatric practice in a rural part of New York state. A retrospective chart review was used to collect data on children ages 9 to 24 months who presented for well-child visits. Children with both questionnaire and lead level results available in the chart were included in the study (n = 171). The mean blood lead level among all children was 1.6 microg/dl (median = 2.0 microg/dl, range 0 to 24 microg/dl). Four children (2.3%) had elevated lead levels (greater than 10 microg/dl), with levels for two of these children being greater than 20 microg/dl. Although our lead screening questionnaire was expanded from the standard 1991 CDC questionnaire by the inclusion of six additional items, it was not especially useful in predicting elevated blood lead levels above 10 microg/dl. However, the questionnaire exhibited some utility in predicting marked elevations in blood lead levels (over 20 microg/dl). Although results in other geographic areas might differ, the lead questionnaire may have value by enhancing parents' awareness of potential lead hazards in their children's environment and may prove to be more useful in areas of high risk to lead exposure.

Internal coordination between hydraulics and stomatal control in leaves.

PubMed

Brodribb, Tim J; Jordan, Gregory J

2008-11-01

The stomatal response to changing leaf-atmospheric vapour pressure gradient (D(l)) is a crucial yet enigmatic process that defines the daily course of leaf gas exchange. Changes in the hydration of epidermal cells are thought to drive this response, mediated by the transpiration rate and hydraulic conductance of the leaf. Here, we examine whether species-specific variation in the sensitivity of leaves to perturbation of D(l) is related to the efficiency of water transport in the leaf (leaf hydraulic conductivity, K(leaf)). We found good correlation between maximum liquid (K(leaf)) and gas phase conductances (g(max)) in leaves, but there was no direct correlation between normalized D(l) sensitivity and K(leaf). The impact of K(leaf) on D(l) sensitivity in our diverse sample of eight species was important only after accounting for the strong relationship between K(leaf) and g(max). Thus, the ratio of g(max)/K(leaf) was strongly correlated with stomatal sensitivity to D(l). This ratio is an index of the degree of hydraulic buffering of the stomata against changes in D(l), and species with high g(max) relative to K(leaf) were the most sensitive to D(l) perturbation. Despite the potentially high adaptive significance of this phenomenon, we found no significant phylogenetic or ecological trend in our species.

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 associations in DILI, although our findings do not support evidence of these genetic variations playing a major role in AC DILI development.

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 associations in DILI, although our findings do not support evidence of these genetic variations playing a major role in AC DILI development. PMID:27616993

The arthritis-associated HLA-B*27:05 allele forms more cell surface B27 dimer and free heavy chain ligands for KIR3DL2 than HLA-B*27:09

PubMed Central

Shaw, Jacqueline; Giles, Joanna; Hatano, Hiroko; Rysnik, Oliwia; Payeli, Sravan; McHugh, Kirsty; Dessole, Grazia; Porru, Giovanni; Desogus, Elisabetta; Fiedler, Sarah; Hölper, Soraya; Carette, Amanda; Blanco-Gelaz, Miguel Angel; Vacca, Alessandra; Piga, Matteo; Ibba, Valentina; Garau, Pietro; La Nasa, Giorgio; López-Larrea, Carlos; Mathieu, Alessandro; Renner, Christoph; Bowness, Paul; Kollnberger, Simon

2013-01-01

Objectives. HLA-B*27:05 is associated with AS whereas HLA-B*27:09 is not associated. We hypothesized that different interactions with KIR immune receptors could contribute to the difference in disease association between HLA-B*27:05 and HLAB*27:09. Thus, the objective of this study was to compare the formation of β2m-free heavy chain (FHC) including B27 dimers (B272) by HLA-B*27:05 and HLA-B*27:09 and their binding to KIR immunoreceptors. Methods. We studied the formation of HLA-B*27:05 and HLA-B*27:09 heterotrimers and FHC forms including dimers in vitro and in transfected cells. We investigated HLA-B*27:05 and HLA-B*27:09 binding to KIR3DL1, KIR3DL2 and LILRB2 by FACS staining with class I tetramers and by quantifying interactions with KIR3DL2CD3ε-reporter cells and KIR3DL2-expressing NK cells. We also measured KIR expression on peripheral blood NK and CD4 T cells from 18 HLA-B*27:05 AS patients, 8 HLA-B27 negative and 12 HLA-B*27:05+ and HLA-B*27:09+ healthy controls by FACS staining. Results. HLA-B*27:09 formed less B272 and FHC than HLA-B*27:05. HLA-B*27:05-expressing cells stimulated KIR3DL2CD3ε-reporter T cells more effectively. Cells expressing HLA-B*27:05 promoted KIR3DL2+ NK cell survival more strongly than HLA-B*27:09. HLA-B*27:05 and HLA-B*27:09 dimer tetramers stained KIR3DL1, KIR3DL2 and LILRB2 equivalently. Increased proportions of NK and CD4 T cells expressed KIR3DL2 in HLA-B*27:05+ AS patients compared with HLA-B*27:05+, HLA-B*27:09+ and HLA-B27− healthy controls. Conclusion. Differences in the formation of FHC ligands for KIR3DL2 by HLA-B*27:05 and HLA-B*27:09 could contribute to the differential association of these alleles with AS. PMID:23804219

Effects of hyperglycemia on fluorine-18-fluorodeoxyglucose biodistribution in a large oncology clinical practice.

PubMed

Rosica, Dillenia; Cheng, Su-Chun; Hudson, Margo; Sakellis, Christopher; Van den Abbeele, Annick D; Kim, Chun K; Jacene, Heather A

2018-05-01

Suggested cutoff points of blood glucose levels (BGL) before F-FDG PET/CT scanning vary between 120 and 200 mg/dl in current guidelines. This study's purpose was to compare the frequency of abnormal fluorine-18-fluorodeoxyglucose (F-FDG) biodistribution on PET/CT scans of patients with various ranges of abnormal BGL and to determine the effect of BGL greater than 200 mg/dl on F-FDG uptake in various organs. F-FDG PET/CT scans were retrospectively reviewed for 325 patients with BGL greater than 120 mg/dl at the time of scan and 112 with BGL less than or equal to 120 mg/dl. F-FDG biodistribution was categorized as normal, mildly abnormal, or abnormal by visual analysis of brain, background soft tissue, and muscle. Mean standardized uptake values (SUVmean) in brain, liver, fat (flank), gluteal muscle, and blood pool (aorta) were recorded. F-FDG biodistribution frequencies were assessed using a nonparametric χ-test for trend. Normal organ SUVs were compared using Kruskal-Wallis tests using the following BGL groupings: ≤120, 121-150, 151-200, and ≥201 mg/dl. Although higher BGL were significantly associated with an increased proportion of abnormal biodistribution (P<0.001), most patients with BGL less than or equal to 200 mg/dl had normal or mildly abnormal biodistribution. Average brain SUVmean significantly decreased with higher BGL groupings (P<0.001). Average aorta, gluteal muscle, and liver SUVmean did not significantly differ among groups with BGL greater than 120 mg/dl (P=0.66, 0.84, and 0.39, respectively), but were significantly lower in those with BGL less than or equal to 120 mg/dl (P≤0.001). Flank fat SUVmean was not significantly different among BGL groups (P=0.67). Abnormal F-FDG biodistribution is associated with higher BGL at the time of scan, but the effects are negligible or mild in most patients with BGL less than 200 mg/dl. Although mildly increased soft tissue uptake is seen with BGL greater than 120 mg/dl, decline in brain metabolic activity correlated the most with various BGL.

Effect of ketogenic Mediterranean diet with phytoextracts and low carbohydrates/high-protein meals on weight, cardiovascular risk factors, body composition and diet compliance in Italian council employees.

PubMed

Paoli, Antonio; Cenci, Lorenzo; Grimaldi, Keith A

2011-10-12

There has been increased interest in recent years in very low carbohydrate ketogenic diets (VLCKD) that, even though they are much discussed and often opposed, have undoubtedly been shown to be effective, at least in the short to medium term, as a tool to tackle obesity, hyperlipidemia and some cardiovascular risk factors. For this reason the ketogenic diet represents an interesting option but unfortunately suffers from a low compliance. The aim of this pilot study is to ascertain the safety and effects of a modified ketogenic diet that utilizes ingredients which are low in carbohydrates but are formulated to simulate its aspect and taste and also contain phytoextracts to add beneficial effects of important vegetable components. The study group consisted of 106 Rome council employees with a body mass index of ≥ 25, age between 18 and 65 years (19 male and 87 female; mean age 48.49 ± 10.3). We investigated the effects of a modified ketogenic diet based on green vegetables, olive oil, fish and meat plus dishes composed of high quality protein and virtually zero carbohydrate but which mimic their taste, with the addition of some herbal extracts (KEMEPHY ketogenic Mediterranean with phytoextracts). Calories in the diet were unlimited. Measurements were taken before and after 6 weeks of diet. There were no significant changes in BUN, ALT, AST, GGT and blood creatinine. We detected a significant (p < 0.0001) reduction in BMI (31.45 Kg/m2 to 29.01 Kg/m2), body weight (86.15 kg to 79.43 Kg), percentage of fat mass (41.24% to 34.99%), waist circumference (106.56 cm to 97.10 cm), total cholesterol (204 mg/dl to 181 mg/dl), LDLc (150 mg/dl to 136 mg/dl), triglycerides (119 mg/dl to 93 mg/dl) and blood glucose (96 mg/dl to 91 mg/dl). There was a significant (p < 0.0001) increase in HDLc (46 mg/dl to 52 mg/dl). The KEMEPHY diet lead to weight reduction, improvements in cardiovascular risk markers, reduction in waist circumference and showed good compliance.

The Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis is straightforward and considerably outperforms the standard DerSimonian-Laird method

PubMed Central

2014-01-01

Background The DerSimonian and Laird approach (DL) is widely used for random effects meta-analysis, but this often results in inappropriate type I error rates. The method described by Hartung, Knapp, Sidik and Jonkman (HKSJ) is known to perform better when trials of similar size are combined. However evidence in realistic situations, where one trial might be much larger than the other trials, is lacking. We aimed to evaluate the relative performance of the DL and HKSJ methods when studies of different sizes are combined and to develop a simple method to convert DL results to HKSJ results. Methods We evaluated the performance of the HKSJ versus DL approach in simulated meta-analyses of 2–20 trials with varying sample sizes and between-study heterogeneity, and allowing trials to have various sizes, e.g. 25% of the trials being 10-times larger than the smaller trials. We also compared the number of “positive” (statistically significant at p < 0.05) findings using empirical data of recent meta-analyses with > = 3 studies of interventions from the Cochrane Database of Systematic Reviews. Results The simulations showed that the HKSJ method consistently resulted in more adequate error rates than the DL method. When the significance level was 5%, the HKSJ error rates at most doubled, whereas for DL they could be over 30%. DL, and, far less so, HKSJ had more inflated error rates when the combined studies had unequal sizes and between-study heterogeneity. The empirical data from 689 meta-analyses showed that 25.1% of the significant findings for the DL method were non-significant with the HKSJ method. DL results can be easily converted into HKSJ results. Conclusions Our simulations showed that the HKSJ method consistently results in more adequate error rates than the DL method, especially when the number of studies is small, and can easily be applied routinely in meta-analyses. Even with the HKSJ method, extra caution is needed when there are = <5 studies of very unequal sizes. PMID:24548571

Entrococcus faecalis Elimination in Root Canals Using Silver Nanoparticles, Photodynamic Therapy, Diode Laser, or Laser-activated Nanoparticles: An In Vitro Study.

PubMed

Afkhami, Farzaneh; Akbari, Saba; Chiniforush, Nasim

2017-02-01

The aim of this study was to compare the efficacy of silver nanoparticles (AgNPs), an 810-nm diode laser (DL), conventional photodynamic therapy (PDT) with the use of indocyanine green (ICG) photosensitizer, and modified PDT with the use of AgNPs for the disinfection of root canals inoculated with Enterococcus faecalis. The root canals of 65 extracted human single-rooted teeth were prepared, and E. faecalis was incubated in the root canals for 4 weeks. The teeth were then randomly divided into the following 4 experimental groups: the DL group: 810-nm DL irradiation (1 W, 4 times for 10 seconds), the AN group: 5 minutes of irrigation with 5 mL AgNPs (100 ppm), the ICG/DL group: conventional PDT with ICG (1 mg/mL)/810-nm DL (200 mW, 30 seconds), and the AN/ICG/DL group: modified PDT with AgNPs/ICG/810-nm DL (200 mW, 30 seconds). There was also a control group, which consisted of 5 minutes of irrigation with 5 mL 2.5% sodium hypochlorite (n = 9). Samples were obtained from dentin chips before and after the interventions. A reduction in colony count was assessed by counting the colony-forming units. Significant reductions were noted in E. faecalis colony counts in all groups (P < .05). The greatest reduction in colony count (99.12%) was noted in the AN/ICG/DL group (AgNPs/ICG/810-nm diode laser); however, the differences in this respect between the AN/ICG/DL group and the DL (97.41%), AN (94.42%), and control groups (94.61%) were not significant (P > .05). PDT with ICG, an 810-nm diode laser, and AgNPs has the potential to be used as an adjunct for disinfection of the root canal system. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Multifractal Approaches of the Ring Tensile Rupture Patterns of Dried Laver (Porphyra) as Affected by the Relative Humidity.

PubMed

Jung, Hwabin; Yoon, Won Byong

2017-12-01

The effect of water activity (a w ) or the relative humidity (RH) on the tensile rupture properties of dried laver (DL) associated with structures formed with phycocolloids was investigated. The morphological characteristics of tensile ruptured DL samples at various relative humidities were evaluated by multifractal analysis. The RH of the microclimate was controlled from 10% to 90% at 25 °C using supersaturated salt solutions. The sorption isotherm of DL was experimentally obtained and quantitatively analyzed using mathematical models. The monolayer moisture contents from the Guggenheim-Anderson-de Boer (GAB) model was 5.92% (w.b.). An increase in the RH resulted in increasing ring tensile stress and maintaining constant ring tensile strain up to 58% to 75% RH, whereas the ring tensile stress and the ring tensile strain rapidly decreased and increased, respectively, when the RH was higher than 75%. The general fractal dimensions and the multifractal spectra f(α) manifested that the patterns of the lowest and the highest moisture content of dried laver showed high irregularity. The different multifractal parameters obtained from the DL at various RHs well-represented the transient moment of the structures from the monolayer moisture to texture changes associated with RH. Overall, the ring tensile test and the multifractal analysis were useful tools to analyze the change of crispness of DL from its structural characteristics. In addition, the results of this study revealed that the integration and disintegration properties of DL occurred through the networks of phycocolloids at various moisture contents. Texture properties are the most important quality attributes for commercial dried laver (DL) products. The relative humidity influences the texture properties of DL during production, storage, shipping, and consuming. This study well characterized the effect of the relative humidity on the texture properties of DL using the tensile tests under microclimate conditions. This information is very practical and can be immediately applied to control the relative humidity of the packaging and the storage room for DL. © 2017 Institute of Food Technologists®.

TU-F-CAMPUS-J-03: Evaluation of a New GE Device-Less Cine 4D-CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, R; Pan, T; Chandler, A

2015-06-15

Purpose: Standard cine 4D-CT (S-4DCT) is the cine CT scan of the thorax followed by image sorting with the respiratory signal recorded by the RPM. Although the feasibility of cine 4D-CT without RPM or device-less 4DCT (DL-4DCT) has been reported in a laboratory setting, the only commercial implementation of DL-4DCT was made recently by GE based on the measurements of the lung, body and air area and density. We report the initial results of this new DL-4DCT on its determination of gross tumor volume (GTV). Methods: 30 stereotactic body radiation therapy (SBRT) patients with NSCLC were included in the study.more » All patients received the S-4DCT for their treatment planning. Their cine CT data without the respiratory signal from RPM were submitted to the DL-4DCT. The DL-4DCT image quality was assessed in reference to S-4DCT. Using maximum intensity projection (MIP) images, the GTVs of the S-4DCT and DL-4DCT were compared on a subset of 9 patients whose tumors in the low density lung regions could be contoured using a region growing algorithm in MIM without contouring bias from the user. A lower threshold of −424 HU was used for all patients and other algorithm parameters were held constant for each patient. Results: The DL-4DCT was able to produce the 4DCT images on 29 out of the 30 SBRT cases. One case failed due to the enhanced calcification surrounding both the breast implants. The GTVs determined on the 9 patients with DL-4DCT were 4.2 ± 4.8% smaller than the GTVs with S-4DCT. However, this was statistically insignificant (p=0.15). The Dice similarity coefficients were 95.1 ± 1.8%. The image quality of DL-4DCT and S-4DCT was similar on the 29 cases. Conclusion: The first commercial DL-4DCT was promising in generating 4D-CT images without a respiratory monitoring device in this preliminary study of 30 patients.« less

Metabolic control and chronic complications during a 3-year follow-up period in a cohort of type 2 diabetic patients attended in primary care in the Community of Madrid (Spain).

PubMed

Arrieta, Francisco; Piñera, Marbella; Iglesias, Pedro; Nogales, Pedro; Salinero-Fort, Miguel Angel; Abanades, Juan Carlos; Botella-Carretero, José Ignacio; Calañas, Alfonso; Balsa, José Antonio; Zamarrón, Isabel; Rovira, Adela; Vázquez, Clotilde

2014-01-01

Our aim was to analyze both metabolic control and chronic complications of type 2 diabetes mellitus (T2D) patients regularly attended in primary care during a 3 years of follow-up in the Community of Madrid (Spain). From 2007 to 2010 we prospectively included 3268 patients with T2D attended by 153 primary care physicians from 51 family health centers. An prospective cohort study with annual evaluation over 3 years to the same population was performed. We measured the goals of control in diabetic patients and the incidence of chronic complications of diabetes during the study period. A significant decrease in serum glucose levels (143±42mg/dl vs 137±43mg/dl, p<0.00), HbA1c (7.09±1.2% vs 7.02±1.2%, p<0.00), total cholesterol (191.4±38mg/dl vs 181.5±36mg/dl, p<0.00), LDL cholesterol (114.7±31mg/dl vs 105.5±30mg/dl, p<0.00) and triglyceride levels (144.5±93mg/dl vs 138±84mg/dl, p<0.00) during study period was documented. On the contrary, a significant elevation in HDL cholesterol levels was observed (49.2±14mg/dl vs 49.9±16mg/dl, p<0.00). The incidence of diabetic complications throughout the study period was low, with a incidence of coronary heart disease of 6.2%, peripheral arterial disease 3%, ischemic stroke 2.8%, diabetic foot 11.2%, nephropathy 5.9%, retinopathy 4.5%, and neuropathy 3%. Metabolic control in T2D patients attended in primary care in the Community of Madrid throughout 3 years is adequate and is accompanied by low percent of chronic diabetic complications during this period of follow-up. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

A variant of green fluorescent protein exclusively deposited to active intracellular inclusion bodies

PubMed Central

2014-01-01

Background Inclusion bodies (IBs) were generally considered to be inactive protein deposits and did not hold any attractive values in biotechnological applications. Recently, some IBs of recombinant proteins were confirmed to show their functional properties such as enzyme activities, fluorescence, etc. Such biologically active IBs are not commonly formed, but they have great potentials in the fields of biocatalysis, material science and nanotechnology. Results In this study, we characterized the IBs of DL4, a deletion variant of green fluorescent protein which forms active intracellular aggregates. The DL4 proteins expressed in Escherichia coli were exclusively deposited to IBs, and the IBs were estimated to be mostly composed of active proteins. The spectral properties and quantum yield of the DL4 variant in the active IBs were almost same with those of its native protein. Refolding and stability studies revealed that the deletion mutation in DL4 didn’t affect the folding efficiency of the protein, but destabilized its structure. Analyses specific for amyloid-like structures informed that the inner architecture of DL4 IBs might be amorphous rather than well-organized. The diameter of fluorescent DL4 IBs could be decreased up to 100–200 nm by reducing the expression time of the protein in vivo. Conclusions To our knowledge, DL4 is the first GFP variant that folds correctly but aggregates exclusively in vivo without any self-aggregating/assembling tags. The fluorescent DL4 IBs have potentials to be used as fluorescent biomaterials. This study also suggests that biologically active IBs can be achieved through engineering a target protein itself. PMID:24885571

Blood lead survey of children, pregnant women, professional drivers, street workers, and office workers in Trujillo, Peru.

PubMed

Naeher, Luke P; Aguilar-Villalobos, Manuel; Miller, Todd

2004-07-01

In this pilot study, conducted in summer 2002, the authors measured blood lead levels (BLLs) for 118 subjects in the city of Trujillo, Peru, where leaded gasoline is in the process of being phased out. Subjects included bus drivers, combi (minivan) drivers, street vendors, newspaper vendors, traffic police, taxi drivers, gas station attendants, children living both near and distant from gas stations, pregnant women, and office workers (controls). The highest BLLs were 9.2 microg/dl and 9.3 microg/dl from a child who lived near a gas station and from a traffic policeman, respectively; however, all BLLs were below the U.S. Centers for Disease Control and Prevention's advisory level of concern (10 microg/dl). Office workers (n = 8) and pregnant women (n = 36) had significantly lower BLLs (geometric mean +/- standard deviation = 2.1 +/- 0.7 microg/dl, p < 0.022; and 2.5 +/- 1.1 microg/dl, p < 0.008, respectively) than total traffic-exposed workers (n = 48; 3.2 +/- 1.8 microg/dl). BLLs of children living near gas stations (n = 17; 3.7 +/- 2.2 microg/dl) were marginally higher (p = 0.07) than for children not living near gas stations (n = 9; 2.9 +/- 1.1 microg/dl). The study was limited by small sample size and the fact that the data were based on a convenience sample not fully representative of the cohorts studied. Nevertheless, the authors' findings suggest that leaded gasoline use in Trujillo continues to affect BLLs in traffic-exposed populations.

THE AP-2 CLATHRIN ADAPTOR MEDIATES ENDOCYTOSIS OF AN INHIBITORY KILLER CELL Ig-LIKE RECEPTOR (KIR) IN HUMAN NK CELLS1

PubMed Central

Purdy, Amanda K.; Alvarez-Arias, Diana A.; Oshinsky, Jennifer; James, Ashley M.; Serebriiskii, Ilya; Campbell, Kerry S.

2014-01-01

Stable surface expression of human inhibitory killer cell immunoglobulin-like receptors (KIR) is critical for controlling NK cell function and maintaining NK cell tolerance toward normal MHC-I+ cells. Our recent experiments, however, have found that antibody-bound KIR3DL1 (3DL1) readily leaves the cell surface and undergoes endocytosis to early/recycling endosomes and subsequently to late endosomes. We found that 3DL1 internalization is at least partially mediated by an interaction between the μ2 subunit of the AP-2 clathrin adaptor complex and ITIM tyrosine residues in the cytoplasmic domain of 3DL1. Disruption of the 3DL1/μ2 interaction, either by mutation of the ITIM tyrosines in 3DL1 or mutation of μ2, significantly diminished endocytosis and increased surface expression of 3DL1 in human primary NK cells and cell lines. Furthermore, we found that the 3DL1/AP-2 interaction is diminished upon antibody engagement with the receptor, as compared to untreated cells. Thus, we have identified AP-2-mediated endocytosis as a mechanism regulating the surface levels of inhibitory KIR though their ITIM domains. Based upon our results, we propose a model in which non-engaged KIR are internalized by this mechanism, whereas engagement with MHC-I ligand would diminish AP-2 binding, thereby prolonging stable receptor surface expression and promoting inhibitory function. Furthermore, this ITIM-mediated mechanism may similarly regulate the surface expression of other inhibitory immune receptors. PMID:25238755

Pharmacokinetics of orally administered DL-α-lipoic acid in dogs.

PubMed

Zicker, Steven C; Avila, Albert; Joshi, Dinesh K; Gross, Kathy L

2010-11-01

To determine the pharmacokinetics of DL-α-lipoic acid in dogs when administered at 3 dosages via 3 methods of delivery. 27 clinically normal Beagles. In a 3 × 3 factorial Latin square design, 3 dosages (2.5, 12.5, and 25 mg/kg) of DL-α-lipoic acid were administered orally in a capsule form and provided without a meal, in a capsule form and provided with a meal, and as an ingredient included in an extruded dog food. Food was withheld for 12 hours prior to DL-α-lipoic acid administration. Blood samples were collected before (0 minutes) and at 15, 30, 45, 60, and 120 minutes after administration. Plasma concentrations of DL-α-lipoic acid were determined via high-performance liquid chromatography. A generalized linear models procedure was used to evaluate the effects of method of delivery and dosage. Noncompartmental analysis was used to determine pharmacokinetic parameters of DL-α-lipoic acid. Nonparametric tests were used to detect significant differences between pharmacokinetic parameters among treatment groups. A significant effect of dosage was observed regardless of delivery method. Method of delivery also significantly affected plasma concentrations of DL-α-lipoic acid, with extruded foods resulting in lowest concentration for each dosage administered. Maximum plasma concentration was significantly affected by method of delivery at each dosage administered. Other significant changes in pharmacokinetic parameters were variable and dependent on dosage and method of delivery. Values for pharmacokinetic parameters of orally administered DL-α-lipoic acid may differ significantly when there are changes in dosage, method of administration, and fed status.

Effects of cocoa products/dark chocolate on serum lipids: a meta-analysis.

PubMed

Tokede, O A; Gaziano, J M; Djoussé, L

2011-08-01

Cocoa products, which are rich sources of flavonoids, have been shown to reduce blood pressure and the risk of cardiovascular disease. Dark chocolate contains saturated fat and is a source of dietary calories; consequently, it is important to determine whether consumption of dark chocolate adversely affects the blood lipid profile. The objective was to examine the effects of dark chocolate/cocoa product consumption on the lipid profile using published trials. A detailed literature search was conducted via MEDLINE (from 1966 to May 2010), CENTRAL and ClinicalTrials.gov for randomized controlled clinical trials assessing the effects of flavanol-rich cocoa products or dark chocolate on lipid profile. The primary effect measure was the difference in means of the final measurements between the intervention and control groups. In all, 10 clinical trials consisting of 320 participants were included in the analysis. Treatment duration ranged from 2 to 12 weeks. Intervention with dark chocolate/cocoa products significantly reduced serum low-density lipoprotein (LDL) and total cholesterol (TC) levels (differences in means (95% CI) were -5.90 mg/dl (-10.47, -1.32 mg/dl) and -6.23 mg/dl (-11.60, -0.85 mg/dl), respectively). No statistically significant effects were observed for high-density lipoprotein (HDL) (difference in means (95% CI): -0.76 mg/dl (-3.02 to 1.51 mg/dl)) and triglyceride (TG) (-5.06 mg/dl (-13.45 to 3.32 mg/dl)). These data are consistent with beneficial effects of dark chocolate/cocoa products on total and LDL cholesterol and no major effects on HDL and TG in short-term intervention trials.

Influence of triglycerides on other plasma lipids in middle-aged men intended for hypolipidaemic treatment.

PubMed

Kolovou, Genovefa D; Anagnostopoulou, Katherine K; Salpea, Klelia D; Hoursalas, Ioannis S; Petropoulos, Ilias; Bilianou, Helen I; Damaskos, Dimitris S; Giannakopoulou, Vasiliki N; Cokkinos, Dennis V

2006-01-01

The present investigation aimed to evaluate the influence of serum triglycerides (TG) on other plasma lipids in male patients less than 65 years of age intended for hypolipidaemic treatment. Lipid profiles of a cohort of 412 dyslipidaemic male patients aged 53.4 +/- 7.7 years (mean +/- standard deviation) were evaluated. Patients were stratified in accordance with their fasting plasma lipid levels. They were divided into multiple groups on the basis of serum TG (> or = 150 or < 150 mg/dl) and high-density lipoprotein cholesterol (HDL-C > or = 40 or < 40 mg/dl). Patients with TG > or = 150 mg/dl had higher total cholesterol and lower HDL-C levels compared with those with TG < 150 mg/dl (p = 0.005 and p < 0.001, respectively). Patients with HDL-C < 40 mg/dl had similar total cholesterol levels and higher TG levels compared to those with HDL-C > or = 40 mg/dl (p < 0.001). In all patients, an inverse correlation between TG and HDL-C was found (r = -0.286, p < 0.001). Additionally, HDL-C levels were inversely correlated with the TG concentration in patients with TG < 150 mg/dl (r = -0.135, p = 0.042) and TG > or = 150 mg/dl (r = -0.188, p = 0.002). An inverse correlation between TG and HDL-C levels seems to exist in the sampled population, revealing a close link between the metabolic pathways for TG and HDL-C. This inverse correlation appears to persist even in patients with low fasting TG levels.

Antidiabetic activity of Pongamia pinnata leaf extracts in alloxan-induced diabetic rats

PubMed Central

Sikarwar, Mukesh S.; Patil, M.B.

2010-01-01

The antidiabetic activity of Pongamia pinnata ( Family: Leguminosae) leaf extracts was investigated in alloxan-induced diabetic albino rats. A comparison was made between the action of different extracts of P. pinnata and a known antidiabetic drug glibenclamide (600 μg/kg b. wt.). An oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats. The petroleum ether, chloroform, alcohol and aqueous extracts of P. pinnata were obtained by simple maceration method and were subjected to standardization using pharmacognostical and phytochemical screening methods. Dose selection was made on the basis of acute oral toxicity study (50-5000 mg/kg b. w.) as per OECD guidelines. P. pinnata ethanolic extract (PPEE) and aqueous extract (PPAE) showed significant (P < 0.001) antidiabetic activity. In alloxan-induced model, blood glucose levels of these extracts on 7th day of the study were 155.83 ± 11.211mg/dl (PPEE) and 132.00 ± 4.955mg/dl (PPAE) in comparison of diabetic control (413.50 ± 4.752mg/dl) and chloroform extract (210.83 ± 14.912mg/dl). In glucose loaded rats, PPEE exhibited glucose level of 164.50 ± 6.350mg/dl after 30 min and 156.50 ± 4.089mg/dl after 90 min, whereas the levels in PPAE treated animals were 176 ± 3.724mg/dl after 30 min and 110.33 ± 6.687mg/dl after 90 min. These extracts also prevented body weight loss in diabetic rats. The drug has the potential to act as an antidiabetic drug. PMID:21455444

Comparison of the effects of seleno-l-methionine, seleno-dl-methionine, and selenized yeast on reproduction of mallards

USGS Publications Warehouse

Heinz, G.H.; Hoffman, D.J.

1996-01-01

The toxicities of seleno-L-methionine, seleno-DL-methionine, and selenized yeast were compared. Ten pairs of mallards were fed a control diet and 15 pairs were fed diets containing 10 ppm selenium as seleno-DL-methionine, seleno-L-methionine, or selenized yeast. Hatching of fertile eggs was significantly lower for females fed 10 ppm selenium as seleno-DL-methionine (7.6%) and seleno-L-methionine (6.4%) than for controls (41.3%). Survival of ducklings was lower when their parents had been fed 10 ppm selenium as seleno-L-methionine (20.0%) than for controls (98.4%). The number of 6-day-old ducklings produced per female was significantly lower for mallards fed 10 ppm selenium as seleno-DL-methionine (0.47) or selenized yeast (2.67) than for controls (6.10), and was significantly lower for mallards fed seleno-L-methionine (0.13) than for mallards fed selenized yeast. The eighth eggs of females fed the DL or L forms of selenomethionine contained means of 9.2 and 8.9 ppm selenium, wet weight; these means were higher than the mean (6.6 ppm) for females fed selenized yeast. Among embryos that died at 7 days of age or older, the percentage of embryos that were deformed was 1.3% for controls, 24.6% for seleno-DL-methionine, 28.2% for seleno-L-methionine, and 11.0% for selenized yeast. The results suggested that seleno-DL-methionine and seleno-L-methionine were of similar toxicity and were both more toxic than selenium from selenized yeast.

Use of Multichannel Near Infrared Spectroscopy to Study Relationships Between Brain Regions and Neurocognitive Tasks of Selective/Divided Attention and 2-Back Working Memory.

PubMed

Tomita, Nozomi; Imai, Shoji; Kanayama, Yusuke; Kawashima, Issaku; Kumano, Hiroaki

2017-06-01

While dichotic listening (DL) was originally intended to measure bottom-up selective attention, it has also become a tool for measuring top-down selective attention. This study investigated the brain regions related to top-down selective and divided attention DL tasks and a 2-back task using alphanumeric and Japanese numeric sounds. Thirty-six healthy participants underwent near-infrared spectroscopy scanning while performing a top-down selective attentional DL task, a top-down divided attentional DL task, and a 2-back task. Pearson's correlations were calculated to show relationships between oxy-Hb concentration in each brain region and the score of each cognitive task. Different brain regions were activated during the DL and 2-back tasks. Brain regions activated in the top-down selective attention DL task were the left inferior prefrontal gyrus and left pars opercularis. The left temporopolar area was activated in the top-down divided attention DL task, and the left frontopolar area and left dorsolateral prefrontal cortex were activated in the 2-back task. As further evidence for the finding that each task measured different cognitive and brain area functions, neither the percentages of correct answers for the three tasks nor the response times for the selective attentional task and the divided attentional task were correlated to one another. Thus, the DL and 2-back tasks used in this study can assess multiple areas of cognitive, brain-related dysfunction to explore their relationship to different psychiatric and neurodevelopmental disorders.

Comparative analysis of salivary glucose and electrolytes in diabetic individuals with periodontitis.

PubMed

Lasisi, T J; Fasanmade, A A

2012-06-01

A high incidence of periodontal disease has been reported among diabetics, however the role of saliva in the occurrence of this oral disease in these patients is yet to be understood. To determine the effects of type-2 diabetes and periodontal disease on salivary flow rate and biochemical composition. A prospective study involving 40 adult human subjects divided equally into four groups of diabetics with periodontitis (group 1), diabetics without periodontitis (group 2), non diabetics with periodontitis (group 3) and non diabetics without periodontitis (group 4). Saliva samples were collected and analyzed for salivary glucose, total protein, calcium, sodium, potassium, chloride and bicarbonate. Salivary flow rates were also determined. Salivary glucose and potassium levels were significantly higher (P = 0.002 and 0.04 respectively) in diabetic patients regardless of periodontal disease (mean = 100.7 ± 9.33 mg/dl; 111.5 ± 32.85 mg/dl and 23.79 ± 5.19 mg/dl; 22.9 ± 6.25 mg/dl respectively) compared with non diabetic participants (mean = 80.5 ± 30.85 mg/ dl; 62.5 ± 31.89 mg/dl and 19.23 ± 5.04 mg/dl; 17.74 ± 4.68 mg/dl respectively). In contrast, there was no significant difference in saliva flow rates and levels of total protein, Na(+), Ca(++), Cl(-) and HCO3 (-)between the groups. Salivary glucose and potassium levels were significantly higher among diabetics with or without periodontitis compared with non-diabetics with or without periodontitis. However, biochemical composition of saliva in diabetic individuals has probably little role in their susceptibility to periodontitis.

Analysis of Pharmacists' Attitudes toward a Distance Learning Initiative on Health Screening.

ERIC Educational Resources Information Center

Whiteman, Jane; And Others

1994-01-01

A survey of 436 community pharmacists completing a distance learning (DL) course of continuing education (CE) in health screening, and 117 nonparticipants, found participants more positively disposed toward DL. Most found DL enjoyable and more suitable than other CE methods. More females and fewer males than expected requested and completed the…

Darrieus-Landau instability of premixed flames enhanced by fuel droplets

NASA Astrophysics Data System (ADS)

Nicoli, Colette; Haldenwang, Pierre; Denet, Bruno

2017-07-01

Recent experiments on spray flames propagating in a Wilson cloud chamber have established that spray flames are much more sensitive to wrinkles or corrugations than single-phase flames. To propose certain elements of explanation, we numerically study the Darrieus-Landau (or hydrodynamic) instability (DL-instability) developing in premixtures that contain an array of fuel droplets. Two approaches are compared: numerical simulation starting from the general conservation laws in reactive media, and the numerical computation of Sivashinsky-type model equations for DL-instability. Both approaches provide us with results in deep agreement. It is first shown that the presence of droplets in fuel-air premixtures induces initial perturbations which are large enough to trigger the DL-instability. Second, the droplets are responsible for additional wrinkles when the DL-instability is developed. The latter wrinkles are of length scales shorter than those of the DL-instability, in such a way that the DL-unstable spray flames have a larger front surface and therefore propagate faster than the single-phase ones when subjected to the same instability.

Classification of Chinese herbs based on the cluster analysis of delayed luminescence.

PubMed

Pang, Jingxiang; Yang, Meina; Fu, Jialei; Zhao, Xiaolei; van Wijk, Eduard; Wang, Mei; Liu, Yanli; Zhou, Xiaoyan; Fan, Hua; Han, Jinxiang

2016-03-01

Traditional Chinese material medica are an important component of the Chinese pharmacopeia. According to the traditional Chinese medicinal concept, Chinese herbal medicines are classified into different categories based on their therapeutic effects, however, the bioactive principles cannot be solely explained by chemical analysis. The aim of this study is to classify different Chinese herbs based on their therapeutic effects by using delayed luminescence (DL). The DL of 56 Chinese herbs was measured using an ultra-sensitive luminescence detection system. The different DL parameters were used to classify Chinese herbs according to a hierarchical cluster analysis. The samples were divided into two groups based on their DL kinetic parameters. Interestingly, the DL classification results were quite consistent with classification according to the Chinese medicinal concepts of 'cold' and 'heat' properties. In this paper, we show for the first time that by using DL technology, it is possible to classify Chinese herbs according to the Chinese medicinal concept and it may even be possible to predict their therapeutic properties. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of flaxseed gum on reduction of blood glucose and cholesterol in type 2 diabetic patients.

PubMed

Thakur, Goutam; Mitra, Analava; Pal, Kunal; Rousseau, Dérick

2009-01-01

The effects of ingestion of flaxseed gum on blood glucose and cholesterol, particularly low-density lipoprotein cholesterol, in type 2 diabetes were evaluated. Flaxseed gum was incorporated in wheat flour chapattis. Sixty patients of type 2 diabetes were fed a daily diet for 3 months, along with six wheat flour chapattis containing flaxseed gum (5 g), as per the recommendations of the American Diabetic Association. The control group (60 individuals) consumed an identical diet but the chapattis were without gum. The blood biochemistry profiles monitored before starting the study and at monthly intervals showed fasting blood sugar in the experimental group decreased from 154 ± 8 mg/dl to 136 ± 7 mg/dl (P=0.03) while the total cholesterol reduced from 182 ± 11 mg/dl to 163 ± 9 mg/dl (P=0.03). Results showed a decrease in low-density lipoprotein cholesterol from 110 ± 8 mg/dl to 92 ± 9 mg/dl (P=0.02). The study demonstrated the efficacy of flax gum in the blood biochemistry profiles of type 2 diabetes.

Glutathione and 2,3-diphosphoglycerate in the blood of hypoxic ruminants.

PubMed

O'Dea, J D; Agar, N S

1980-09-01

Two merino sheep and two angora goats were subjected to simulated altitudes of up to 5500 m for about 10 h per day for 38 days. Packed cell volume (PCV), haemoglobin (Hb) concentration and red blood cell (RBC) levels of reduced glutathione (GSH) and 2,3-diphosphoglycerate (2,3-DPG) were measured at regular intervals. Mean PCV increased from 33 per cent to 60 per cent in the sheep and from 33 per cent to 45 per cent in the goats. Mean Hb concentration rose from 11.7 g/dl to 23.1 g/dl in the sheep, and from 11.4 g/dl to 16.0 g/dl in the goats. The level of GSH began to rise in the sheep only after the animals were no longer being subjected to the hypoxic stress, increasing by about 20 mg/dl RBC. In the goats, the levels of GSH rose during, as well as after, the period of hypoxic stress, also by about 20 mg/dl RBC. No change in 2,3-DPG levels was found in either species.

Using deep learning to investigate the neuroimaging correlates of psychiatric and neurological disorders: Methods and applications.

PubMed

Vieira, Sandra; Pinaya, Walter H L; Mechelli, Andrea

2017-03-01

Deep learning (DL) is a family of machine learning methods that has gained considerable attention in the scientific community, breaking benchmark records in areas such as speech and visual recognition. DL differs from conventional machine learning methods by virtue of its ability to learn the optimal representation from the raw data through consecutive nonlinear transformations, achieving increasingly higher levels of abstraction and complexity. Given its ability to detect abstract and complex patterns, DL has been applied in neuroimaging studies of psychiatric and neurological disorders, which are characterised by subtle and diffuse alterations. Here we introduce the underlying concepts of DL and review studies that have used this approach to classify brain-based disorders. The results of these studies indicate that DL could be a powerful tool in the current search for biomarkers of psychiatric and neurologic disease. We conclude our review by discussing the main promises and challenges of using DL to elucidate brain-based disorders, as well as possible directions for future research. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Coexposure of dioxin-like polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins and dibenzofurans in free-range hens and implications derived from congener profile analysis.

PubMed

Lin, Chingju; Hsu, Jing-Fang; Liao, Pao-Chi

2012-02-29

The consumption of free-range eggs is becoming more popular worldwide. We analyzed the levels of 12 dioxin-like polychlorinated biphenyls (dl-PCBs) and their congener profiles from 6 free-range and 12 caged egg samples. The mean levels of dl-PCBs in the free-range samples were 5.4 times higher than those in caged eggs. All egg samples exhibited at least two characteristic dl-PCB congener patterns, which reflected distinctive contamination sources. Additionally, for the first time, we demonstrated that the dl-PCB levels in the free-range eggs were highly correlated with elevated levels of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) (r = 0.986; p < 0.001), indicating a coexposure scenario in free-range hens. Cluster analysis of congener patterns implied that this coexposure scenario could be attributed to distinct dl-PCB and PCDD/F sources. This congener profile information provides insights from a different perspective for further identifying potential dl-PCB and PCDD/F sources in the polluted free-range eggs.

Brain tumor image segmentation using kernel dictionary learning.

PubMed

Jeon Lee; Seung-Jun Kim; Rong Chen; Herskovits, Edward H

2015-08-01

Automated brain tumor image segmentation with high accuracy and reproducibility holds a big potential to enhance the current clinical practice. Dictionary learning (DL) techniques have been applied successfully to various image processing tasks recently. In this work, kernel extensions of the DL approach are adopted. Both reconstructive and discriminative versions of the kernel DL technique are considered, which can efficiently incorporate multi-modal nonlinear feature mappings based on the kernel trick. Our novel discriminative kernel DL formulation allows joint learning of a task-driven kernel-based dictionary and a linear classifier using a K-SVD-type algorithm. The proposed approaches were tested using real brain magnetic resonance (MR) images of patients with high-grade glioma. The obtained preliminary performances are competitive with the state of the art. The discriminative kernel DL approach is seen to reduce computational burden without much sacrifice in performance.

Experimental evidence of a double layer in a large volume helicon reactor.

PubMed

Sutherland, O; Charles, C; Plihon, N; Boswell, R W

2005-11-11

The self-consistently generated current-free electric double layer (DL) is shown to scale up with the source tube diameter and appears not to be affected by rf driving frequency and changes in reactor geometry. This Letter presents the first simultaneous measurements of local plasma potential and beam energy as a function of axial position. The DL is shown to be no more than 5 mm thick (20 D lengths) and positioned just downstream of the maximum in the magnetic field gradient. Furthermore, its position relative to the magnetic field is observed to be invariant as the magnetic field is translated axially. Measurements of the potential drop across the DL are presented for pressures down to 0.09 mTorr and the DL strength (phiDL/T(e)) is determined to be between 5 and 7.

Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis. Comparison of two dosage schedules of choline magnesium trisalicylate.

PubMed

Cassell, S; Furst, D; Dromgoole, S; Paulus, H

1979-04-01

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a ddecrease of 1 mg/dl in mean minimum concentration.

The novel non-imidazole histamine H3 receptor antagonist DL77 reduces voluntary alcohol intake and ethanol-induced conditioned place preference in mice.

PubMed

Bahi, Amine; Sadek, Bassem; Nurulain, Syed M; Łażewska, Dorota; Kieć-Kononowicz, Katarzyna

2015-11-01

It has become clear that histamine H3 receptors (H3R) have been implicated in modulating ethanol intake and preference in laboratory animals. The novel non-imidazole H3R antagonist DL77 with excellent selectivity profile shows high in-vivo potency as well as in-vitro antagonist affinity with ED50 of 2.1 ± 0.2 mg/kg and pKi=8.08, respectively. In the present study, and applying an unlimited access two-bottle choice procedure, the anti-alcohol effects of the H3R antagonist, DL77 (0, 3, 10 and 30 mg/kg; i.p.), were investigated in adult mice. In this C57BL/6 line, effects of DL77 on voluntary alcohol intake and preference, as well as on total fluid intake were evaluated. Results have shown that DL77, dose-dependently, reduced both ethanol intake and preference. These effects were very selective as both saccharin and quinine, used to control for taste sensitivity, and intakes were not affected following DL77 pre-application. More importantly, systemic administration of DL77 (10 mg/kg) during acquisition inhibited ethanol-induced conditioned-place preference (EtOH-CPP) as measured using an unbiased protocol. The anti-alcohol activity observed for DL77 was abrogated when mice were pretreated with the selective H3R agonist R-(α)-methyl-histamine (RAMH) (10 mg/kg), or with the CNS penetrant H1R antagonist pyrilamine (PYR) (10mg/kg). These results suggest that DL77 has a predominant role in two in vivo effects of ethanol. Therefore, signaling via H3R is essential for ethanol-related consumption and conditioned reward and may represent a novel therapeutic pharmacological target to tackle ethanol abuse and alcoholism. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing's syndrome.

PubMed

Giordano, Roberta; Berardelli, Rita; Karamouzis, Ioannis; D'Angelo, Valentina; Picu, Andreea; Zichi, Clizia; Fussotto, Beatrice; Manzo, Maria; Mengozzi, Giulio; Ghigo, Ezio; Arvat, Emanuela

2013-09-01

The purpose of this study is to verify whether acute pre-treatment with alprazolam (ALP), a benzodiazepine that inhibits HPA secretion in normal subjects, could better characterize patients with subclinical Cushing's syndrome (SCS) than the 1-mg dexamethasone test (DST). In 22 patients with SCS, 10 with overt Cushing's syndrome (CS), 11 with non-functioning adrenal incidentalomas (NF) and 14 normal subjects (NS) we studied the effect of ALP (1 mg, p.o. at 2300 hours) on cortisol levels after 1-mg DST. Cortisol levels (mean ± SEM) after DST were lower (P = 0.012) in SCS (3.9 ± 0.3 μg/dl) than in overt CS (10.4 ± 1.9 μg/dl), while they were higher (P = 0.0005) than in NF (1.1 ± 0.1 μg/dl) and NS (1.5 ± 0.1 μg/dl). After ALP pre-treatment, cortisol levels further decreased (P = 0.004) in SCS (3.0 ± 0.3 μg/dl), but neither in CS (9.3 ± 1.3 μg/dl) nor in NF (1.3 ± 0.1 μg/dl) and in NS (1.3 ± 0.1 μg/dl). In SCS, cortisol levels after ALP + 1-mg DST persisted lower (P = 0.0005) than those in CS, but higher (P = 0.0005) than those in NF and NS. Considering individual cases, ALP pre-treatment reduced cortisol levels < 3 and < 1.8 μg/dl in 50 and 23 % of SCS patients, respectively. ALP amplifies the cortisol inhibition exerted by 1-mg DST in patients with SCS but not in those with CS. The clinical usefulness of ALP to increase the sensitivity of 1-mg DST to identify true autonomous cortisol release in patients with adrenal incidentalomas as well as to predict different clinical outcomes remains to be clarified.

Stress-induced hyperglycemia on complications in non-critically elderly hospitalized patients.

PubMed

Carrasco-Sánchez, F J; Carretero-Gómez, J; Gómez-Huelgas, R; Garcia-Ordoñez, M A; Pardo-Ortega, M V; de Escalante-Yanguela, B; Mateos-Polo, L; Formiga, F; Ena, J

Hospital complications and hyperglycemia are common in elderly patients during hospitalization. Our aim was to analyze the relationship between hyperglycemia and hospital complications in an ageing population. We conducted an observational study to evaluate the association between maximum blood glucose (MBG) levels and hospital complications. Patients were stratified according to the quartiles of MBG levels. Diabetes mellitus (DM) was determined by patient history and/or admission glycated hemoglobin (HbA1c) level ≥6.5%. Hyperglycemia in patients without DM was defined as stress-induced hyperglycemia (SH). The composite primary end-point included frequent complications and/or all-cause hospital mortality. Among 461 patients, mean age 80±7.5years, 238 (51.6%) patients had DM, 20 had undiagnosed DM, and 162 (35.1%) developed hospital complications. Patients with complications had higher mean daily BG levels (215±84 vs 195±85mg/dl, P<.01). The incidence of complications was directly associated with severity of hyperglycemia according to the quartiles of MBG levels in patients without DM, namely SH (<140 mg/dl, 22.2%; 140-185mg/dl, 40%; 186-250mg/dl, 47%; >250mg/dl, 60%; P=.002), but not in patients with DM (<140mg/dl, 26.3%; 140-185mg/dl, 40.4%; 186-250mg/dl, 35.6%; >250mg/dl, 37.4%; P=.748). In the multivariate analyses, SH was independently associated with complications: OR 2.60 (CI95%: 1.2-5.6), 2.82 (CI95%: 1.2-6.5), 5.50 (CI95%: 1.4-20.8) for the second, third and fourth quartile respectively (P=.01), as compared to the first quartile. We found no association with readmissions and all-cause mortality. SH in elderly patients is associated with hospital complications, but not with all-cause mortality, compared to patients with diabetes or normoglycemia. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Role of dorsolateral periaqueductal grey in the coordinated regulation of cardiovascular and respiratory function.

PubMed

Dampney, Roger A L; Furlong, Teri M; Horiuchi, Jouji; Iigaya, Kamon

2013-04-01

The midbrain periaqueductal grey (PAG) contains four longitudinal columns, referred to as the dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG) subdivisions, which collectively have a pivotal role in integrating behavioural and physiological responses to external stressors as well as other functions. This review is focussed on the dlPAG, which is believed to be an important component of the central mechanisms that generate the defensive response to acute psychological stressors, such as the presence of a predator or other immediate threat. The anatomical connections of the dlPAG are highly specific and distinctly different from those of the other PAG subregions. The chemical properties of the dlPAG are also distinctly different from the other PAG subregions (e.g. there is a very high density of neurons that synthesize nitric oxide in the dlPAG but very few such neurons in the other PAG subregions). Recent functional studies have demonstrated that neurons in the dlPAG exert a powerful control over both sympathetic and respiratory activity, and that the pattern of the evoked respiratory changes is also distinctly different from those evoked from other PAG subregions. These studies also showed that the sympathetic and respiratory changes evoked from the dlPAG are highly correlated, suggesting the possibility that a common population of "command neurons" within this region may generate the sympathetic and respiratory changes that accompany defensive behavioural responses to acute psychological stressors. Finally, although the anatomical connections and functional properties of the dlPAG are distinctly different from the other PAG subregions, they have many similarities with adjacent parts of the superior colliculus, suggesting that the dlPAG and deep layers of the superior colliculus may be part of a common defence system in the midbrain. Copyright © 2013 Elsevier B.V. All rights reserved.

Analysis of the vp2 gene sequence of a new mutated mink enteritis parvovirus strain in PR China

PubMed Central

2010-01-01

Background Mink enteritis virus (MEV) causes a highly contagious viral disease of mink with a worldwide distribution. MEV has a linear, single-stranded, negative-sense DNA with a genome length of approximately 5,000 bp. The VP2 protein is the major structural protein of the parvovirus encoded by the vp2 gene. VP2 is highly antigenic and plays important roles in determining viral host ranges and tissue tropisms. This study describes the bionomics and vp2 gene analysis of a mutated strain, MEV-DL, which was isolated recently in China and outlines its homologous relationships with other selected strains registered in Genbank. Results The MEV-DL strain can infect F81 cells with cytopathic effects. Pig erythrocytes were agglutinated by the MEV-DL strain. The generation of MEV-DL in F81 cells could infect mink within three months and cause a disease that was similar to that caused by wild-type MEV. A comparative analysis of the vp2 gene nucleotide (nt) sequence of MEV-DL showed that this was more than 99% homologous with other mink enteritis parvoviruses in Genbank. However, the nucleotide residues at positions 1,065 and 1,238 in the MEV-DL strain of the vp2 gene differed from those of all the other MEV strains described previously. It is noteworthy that the mutation at the nucleotide residues position 1,238 led to Asp/Gly replacement. This may lead to structural changes. A phylogenetic tree and sequence distance table were obtained, which showed that the MEV-DL and ZYL-1 strains had the closest inheritance distance. Conclusions A new variation of the vp2 gene exists in the MEV-DL strain, which may lead to structural changes of the VP2 protein. Phylogenetic analysis showed that MEV-DL may originate from the ZYL-1 strain in DaLian. PMID:20540765

Comparison of serum trace element levels in patients with or without pre-eclampsia

PubMed Central

Farzin, Leila; Sajadi, Fattaneh

2012-01-01

Objective: In developing countries, nutritional deficiency of essential trace elements is a common health problem, particularly among pregnant women because of increased requirements of various nutrients. Accordingly, this study was initiated to compare trace elements status in women with or without pre-eclampsia. Materials and Methods: In this study, serum trace elements including zinc (Zn), selenium (Se), copper (Cu), calcium (Ca) and magnesium (Mg) were determined by using atomic absorption spectrometry (AAS) in 60 patients and 60 healthy subjects. Results: There was no significant difference in the values of Cu between two groups (P > 0.05). A significant difference in Zn, Se, Ca and Mg levels were observed between patients with pre-eclampsia and control group (P < 0.001, P<0.01, P<0.01 and P<0.001, respectively). Zn, Se, Ca and Mg levels were found to be 76.49 ± 17.62 μg/ dl, 8.82 ± 2.10 μg/ dl, 8.65 ± 2.14 mg/dl and 1.51 ± 0.34 mg/dl in Pre-eclamptic cases, and these values were found statistically lower compared to the controls (100.61 ± 20.12 μg/dl, 10.47 ± 2.78 μg/dl, 9.77 ± 3.02 mg/dl and 1.78 ± 0.27 mg/dl, respectively). While Cu levels were 118.28 ± 16.92 and 116.55 ± 15.23 μg/dl in the patients and the healthy subjects, respectively. In addition, no significant difference was found between two groups with respect to Hemoglobin Concentration (HbC) and Total White Blood Cell Count (TWBC) (P>0.05). Conclusion: Our findings indicate that the levels of Zn, Se, Ca and Mg are significantly altered in pregnant women with pre-eclampsia. This research shows that these deficiencies can not due to hemodilution. PMID:23825993

Rotavirus-like particles primary recovery from insect cells in aqueous two-phase systems.

PubMed

Benavides, Jorge; Mena, Jimmy A; Cisneros-Ruiz, Mayra; Ramírez, Octavio T; Palomares, Laura A; Rito-Palomares, Marco

2006-09-14

Virus-like particles have a wide range of applications, including vaccination, gene therapy, and even as nanomaterials. Their successful utilization depends on the availability of selective and scalable methods of product recovery and purification that integrate effectively with upstream operations. In this work, a strategy based on aqueous two phase system (ATPS) was developed for the recovery of double-layered rotavirus-like particles (dlRLP) produced by the insect cell-baculovirus expression system. Polyethylene glycol (PEG) molecular mass, PEG and salt concentrations, and volume ratio (Vr, volume of top phase/volume of bottom phase) were evaluated in order to determine the conditions where dlRLP and contaminants concentrated to opposite phases. Two-stage ATPS consisting of PEG 400-phosphate with a Vr of 13.0 and a tie-line length (TLL) of 35% (w/w) at pH 7.0 provided the best conditions for processing highly concentrated crude extract from disrupted cells (dlRLP concentration of 5 microg/mL). In such conditions intracellular dlRLP accumulated in the top phase (recovery of 90%), whereas cell debris remained in the interface. Furthermore, dlRLP from culture supernatants accumulated preferentially in the interface (recovery of 82%) using ATPS with a Vr of 1.0, pH of 7.0, PEG 3350 (10.1%, w/w) and phosphate (10.9%, w/w). The purity of dlRLP from culture supernatant increased up to 55 times after ATPS. The use of ATPS resulted in a recovery process that produced dlRLP with a purity between 6 and 11% and an overall product yield of 85% (w/w), considering purification from intracellular and extracellular dlRLP. Overall, the strategy proposed in this study is simpler than traditional methods for recovering dlRLP, and represents a scalable and economically viable alternative for production processes of vaccines against rotavirus infection with significant scope for generic commercial application.

Possible selective adsorption of enantiomers by Na-montmorillonite

NASA Technical Reports Server (NTRS)

Friebele, E.; Shimoyama, A.; Ponnamperuma, C.

1981-01-01

Racemic amino acids including (D,L) alpha-alamine, (D,L) alpha-aminobutyric acid, (D,L) valine, and (D,L) norvaline were incubated with Na-montmorillonite at 100% CEC at three hydrogen ion concentrations, and amino acid adsorption was determined by ion exchange chromatography. Enantiomers were analyzed by gas chromatography. Differences in the quantities of D and L enantiomers in any of the fractions was no larger than a few percent. Although a large difference in the adsorption of the amino acid enantiomers was not observed, the analysis may indicate a small preferential adsorption (0.5-2%) of L-amino acids by Na-montmorillonite.

Acceptance and Commitment Therapy in Daily Life Training: A Feasibility Study of an mHealth Intervention

PubMed Central

Bakker, Jindra; Vaessen, Thomas; Kasanova, Zuzana; Collip, Dina; van Os, Jim; Wichers, Marieke; Germeys, Inez; Peeters, Frenk

2016-01-01

Background With the development of mHealth, it is possible to treat patients in their natural environment. Mobile technology helps to bridge the gap between the therapist’s office and the “real world.” The ACT in Daily Life training (ACT-DL) was designed as an add-on intervention to help patients practice with acceptance and commitment therapy in their daily lives. The ACT-DL consists of two main components: daily monitoring using experience sampling and ACT training in daily life. Objectives To assess the acceptability and feasibility of the ACT-DL in a general outpatient population. A secondary objective was to conduct a preliminary examination of the effectiveness of the ACT-DL. Methods An observational comparative study was conducted. The experimental group consisted of 49 patients who volunteered for ACT-DL, and the control group consisted of 112 patients who did not volunteer. As part of an inpatient treatment program, both groups received a 6-week ACT training. Participants went home to continue their treatment on an outpatient basis, during which time the experimental group received the 4-week add-on ACT-DL. Acceptability and feasibility of the ACT-DL was assessed weekly by telephone survey. Effectiveness of the ACT-DL was evaluated with several self-report questionnaires ( Flexibility Index Test (FIT-60): psychological flexibility, Brief Symptom Inventory: symptoms, Utrechtse Coping List: coping, and Quality of life visual analog scale (QoL-VAS): quality of life). Results More than three-quarters of the participants (76%) completed the full 4-week training. User evaluations showed that ACT-DL stimulated the use of ACT in daily life: participants practiced over an hour a week (mean 78.8 minutes, standard deviation 54.4), doing 10.4 exercises (standard deviation 6.0) on average. Both ACT exercises and metaphors were experienced as useful components of the training (rated 5 out of 7). Repeated measures ANCOVA did not show significant effects of the ACT-DL on psychological flexibility (P=.88), symptoms (P=.39), avoidant coping (P=.28), or quality of life (P=.15). Conclusions This is the first study that uses experience sampling to foster awareness in daily life in combination with acceptance and commitment therapy to foster skill building. Adherence to the ACT-DL was high for an intensive mHealth intervention. ACT-DL appears to be an acceptable and feasible mHealth intervention, suitable for a broad range of mental health problems. However, short-term effectiveness could not be demonstrated. Additional clinical trials are needed to examine both short-term and long-term effects. PMID:27634747

Lipid levels among African and Middle-Eastern Bedouin populations.

PubMed

Dreiher, Jacob; Cohen, Arnon D; Weitzman, Shimon; Sharf, Amir; Shvartzman, Pesach

2008-06-01

Previous studies observed higher high-density lipoprotein (HDL) levels and lower triglycerides levels among people of African ancestry. The goal of this study was to characterize lipid levels in Bedouins of African vs. Middle-Eastern ethnicity. A cross-sectional study was conducted in a Bedouin primary care clinic in southern Israel, with 4470 listed individuals over the age of 21, of whom 402 (9%) were of African origin. A stratified random sample was included in the analysis. Associations between ethnicity, age, gender and lipid levels were assessed. Multiple linear regression and logistic regression models were used for multivariate analysis. The study included 261 African Bedouins and 406 Middle-Eastern Bedouins. (median age: 37 years, 58.6% females). The average total cholesterol and low-density lipoprotein (LDL) levels were 10 mg/dl lower among African Bedouins as compared to Middle-Eastern Bedouins (total cholesterol: 168.6 vs. 179.6 mg/dl, p<0.001; LDL: 99.5 vs. 109.0 mg/dl, respectively, p<0.001). Average triglycerides levels were 36 mg/dl lower among African Bedouins as compared to Middle-Eastern Bedouins (102.8 vs. 138.9 mg/dl, respectively, p<0.001). Average HDL levels were 3 mg/dl higher among African Bedouins as compared to Middle-Eastern Bedouins (48.3 vs. 44.6 mg/dl, respectively, p<0.001). A lower prevalence of dyslipidemia was found in African Bedouins, as compared with Middle-Eastern Bedouins.

Conversion from cyclosporine to tacrolimus improves renal function and lipid profile after cardiac transplantation.

PubMed

Garlicki, Mirosław; Czub, Paweł; Labuś, Krzysztof; Ehrlich, Marek P; Rdzanek, Hanna

2006-01-01

Calcineurin inhibitors (CNIs) have become the cornerstone of immunosuppressive regimens following heart transplantation, but their use is associated with nephrotoxicity. The impact on renal function after conversion from cyclosporine (CsA) to tacrolimus (TAC) is reported. Fifteen patients (men age 42 +/- 11 years) after cardiac transplantation (HTX) were switched from CsA to TAC (mean time after HTX 21 +/- 6 months). There were 13 male and 2 female patients. Mean cholesterol and LDL level at the time of conversion were 217 +/- 65 ml/dl and and 136 +/- 51 mg/100 ml respectively. Indication for HTX was ischemic cardiomyopathy (CMP) in 8, congenital in 3 and dilatative CMP in the remaining 4 patients. Mean tacrolimus level (microg/dl) at 1, 3, 6 and 12 months were 8.6 +/- 3.3, 8.6 +/- 1.4, 9.2 +/- 2.8 and 9.8 +/- 2.5 respectively. There was a statistically significant improvement in creatinine levels at 1, 3, 6 and 12 months after conversion from baseline 1.9 +/- 0.7 mg/dl to 1.4 +/- 0.5 mg/dl, 1.4 +/- 0.4 mg/dl, 1.3 +/- 0.4 mg/dl and 1.2 +/- 0.4 mg/dl, respectively (p < 0.05). Furthermore, TAC decreased cholesterol as well as LDL-levels during this one-year time frame. This study shows that conversion from CsA to tacrolimus after orthotopic heart transplantation improves renal function.

Anodal transcranial direct current stimulation over right dorsolateral prefrontal cortex alters decision making during approach-avoidance conflict.

PubMed

Chrysikou, Evangelia G; Gorey, Claire; Aupperle, Robin L

2017-03-01

Approach-avoidance conflict (AAC) refers to situations associated with both rewarding and threatening outcomes. The AAC task was developed to measure AAC decision-making. Approach behavior during this task has been linked to self-reported anxiety sensitivity and has elicited anterior cingulate, insula, caudate and right dorsolateral prefrontal cortex (dlPFC) activity, with right lateral PFC tracking the extent of approach behavior. Guided by these results, we used excitatory transcranial direct current stimulation (tDCS) to demonstrate the causal involvement of right dlPFC in AAC decision-making. Participants received anodal tDCS at 1.5mA over either left or right dlPFC or sham stimulation, while performing the AAC task and a control short-term memory task. Analyses of variance (ANOVA) revealed that for individuals with high anxiety sensitivity excitatory right (but not left or sham) dlPFC stimulation elicited measurable decreases in approach behavior during conflict. Excitatory left (but not right or sham) dlPFC simulation improved performance on the control task. These results support a possible asymmetry between the contributions of right and left dlPFC to AAC resolution during emotional decision-making. Increased activity in right dlPFC may contribute to anxiety-related symptoms and, as such, serve as a neurobehavioral target of anxiolytic treatments aiming to decrease avoidance behavior. © The Author (2016). Published by Oxford University Press.

Students' Perceived Service Quality of Distance Learning Courses in a Dual-Mode Education System

ERIC Educational Resources Information Center

Yener, Dursun

2013-01-01

Distance learning (DL) has become an important part of university education. In the past DL was applied in different universities with different forms. With rapid technological developments, DL gained a new format through the Internet. Students can take courses online wherever they are geographically. Therefore, working people and adults can…

Comparing the NPS MBA Resident and Distance Programs

DTIC Science & Technology

2017-06-01

17 D. ARTICLES ON HYBRID DELIVERY OF EDUCATION .................21 E. BENEFITS AND COSTS OF DL...isolation, potentially reducing the student stress reported by Ni (2013) that can occur in DL programs. E. BENEFITS AND COSTS OF DL Both tangible...PROGRAMS June 2017 By: Mara F. Rosenthal Advisors: Marigee Bacolod Latika Hartmann Approved for public release. Distribution

21 CFR 172.540 - DL-Alanine.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Agents and Related Substances § 172.540 DL-Alanine. DL-Alanine (a racemic mixture of D- and L-alanine; CAS Reg. No. 302-72-7) may be safely used as a flavor enhancer for sweeteners in pickling mixtures at a level not to exceed 1 percent of the pickling spice that is added to the pickling brine. [56 FR...

Association of anaemia in primary care patients with chronic kidney disease: cross sectional study of quality improvement in chronic kidney disease (QICKD) trial data

PubMed Central

2013-01-01

Background Anaemia is a known risk factor for cardiovascular disease and treating anaemia in chronic kidney disease (CKD) may improve outcomes. However, little is known about the scope to improve primary care management of anaemia in CKD. Methods An observational study (N = 1,099,292) with a nationally representative sample using anonymised routine primary care data from 127 Quality Improvement in CKD trial practices (ISRCTN5631023731). We explored variables associated with anaemia in CKD: eGFR, haemoglobin (Hb), mean corpuscular volume (MCV), iron status, cardiovascular comorbidities, and use of therapy which associated with gastrointestinal bleeding, oral iron and deprivation score. We developed a linear regression model to identify variables amenable to improved primary care management. Results The prevalence of Stage 3–5 CKD was 6.76%. Hb was lower in CKD (13.2 g/dl) than without (13.7 g/dl). 22.2% of people with CKD had World Health Organization defined anaemia; 8.6% had Hb ≤ 11 g/dl; 3% Hb ≤ 10 g/dl; and 1% Hb ≤ 9 g/dl. Normocytic anaemia was present in 80.5% with Hb ≤ 11; 72.7% with Hb ≤ 10 g/dl; and 67.6% with Hb ≤ 9 g/dl; microcytic anaemia in 13.4% with Hb ≤ 11 g/dl; 20.8% with Hb ≤ 10 g/dl; and 24.9% where Hb ≤ 9 g/dl. 82.7% of people with microcytic and 58.8% with normocytic anaemia (Hb ≤ 11 g/dl) had a low ferritin (<100ug/mL). Hypertension (67.2% vs. 54%) and diabetes (30.7% vs. 15.4%) were more prevalent in CKD and anaemia; 61% had been prescribed aspirin; 73% non-steroidal anti-inflammatory drugs (NSAIDs); 14.1% warfarin 12.4% clopidogrel; and 53.1% aspirin and NSAID. 56.3% of people with CKD and anaemia had been prescribed oral iron. The main limitations of the study are that routine data are inevitably incomplete and definitions of anaemia have not been standardised. Conclusions Medication review is needed in people with CKD and anaemia prior to considering erythropoietin or parenteral iron. Iron stores may be depleted in over >60% of people with normocytic anaemia. Prescribing oral iron has not corrected anaemia. PMID:23351270

Identification of mildly oxidized low-density lipoprotein (electronegative LDL) and its auto-antibodies IgG in children and adolescents hypercholesterolemic offsprings.

PubMed

Barros, Marcos Roberto Andrade Costa; Bertolami, Marcelo Chiara; Abdalla, Dulcinéia Saes Parra; Ferreira, Waldinai Pereira

2006-01-01

Oxidative modification of low-density lipoproteins (LDL) is an essential step in atherogenesis, generating minimally oxidized LDL, also called electronegative LDL [LDL(-)], which has chemotactic, cytotoxic and immunogenic properties. Serum LDL(-) and anti-LDL(-) auto-antibodies (IgG) were evaluated in 28 children and adolescents with familial hypercholesterolemia (FH) antecedents, with or without early coronary artery disease in first-degree relatives (eCAD), hypercholesterolemic (hc) or normocholesterolemic (nc) versus a control group of normocholesterolemic children without pathologic antecedents (C). ELISA method was used for detection of LDL(-) and anti-LDL(-) IgG. LDL(-) serum levels did not differ among the four groups (FH-eCAD-hc 41.4 +/- 24.9 microg/dl; FH-hc 38.3 +/- 11.2 microg/dl; FH-nc 47.3 +/- 17.0 microg/dl and C 44.2 +/- 28.8 microg/dl, p = 0.659). However, IgG anti-LDL(-) auto-antibodies were significantly higher in the control group in comparison to the FH groups with or without eCAD, independent of hypercholesterolemia or normocholesterolemia (FH-eCAD-hc 0.825 +/- 0.289 microg/dl; FH-hc 0.667 +/- 0.307 microg/dl; FH-nc 0.763 +/- 0.204 microg/dl and C 1.105 +/- 0.233 microg/dl, p = 0.006). When the auto-antibodies of groups with FH, with or without eCAD and with or without hypercholesterolemia were compared, no differences were found (p = 0.509). These results showed that FH and/or eCAD children and adolescents have lower titers of auto-antibodies anti-LDL(-) than children from normal families, independent of serum LDL-cholesterol or serum LDL(-).

Maternal hemoglobin concentration and adverse pregnancy outcomes at low and moderate altitudes in Peru.

PubMed

Gonzales, Gustavo F; Tapia, Vilma; Gasco, Manuel; Carrillo, Carlos E

2012-07-01

To identify associations of maternal hemoglobin (Hb) with perinatal outcomes at low and moderate altitudes in Peru. Study of records with sequential information using perinatal database system. The study included 295 651 pregnant women with their products. Using multiple logistic regression analysis, we estimated the probability of stillbirths, preterm and small for gestational age (SGA) births associated with maternal Hb levels at low (0-1999 m) and moderate altitudes (2000-2999 m). Maternal Hb decreased as pregnancy progressed from first to third trimester at both altitudes. Hb was higher at moderate than at low altitude (p < 0.001). Risks for stillbirths increased with low maternal Hb (odds ratio [OR]: 1.39 for Hb 9-9.9; OR: 1.84 for Hb 8-8.9; OR: 3.25 for Hb 7-7.9; and OR: 7.8 for Hb <7 g/dl); with Hb higher than 14.5 g/dl (OR: 1.31) and with altitudes ≥ 2000 m (OR: 1.2). High preterm rates were also observed with low Hbs (OR: 1.16 for Hb 9-9.9; OR: 1.64 for Hb 8-8.9; OR: 2.25 for Hb 7-7.9; and OR:2.87 for Hb<7 g/dl) and with Hb higher than 14.5 g/dl (OR: 1.14). High SGA rates were observed in neonates with maternal Hb of 7-7.9 (OR: 1.35) and <7 g/dl (OR:1.57), and higher than 14.5 g/dl (OR: 1.33), and with moderate altitudes (OR: 1.12). The cut-off points for lower risks of stillbirth and preterm births was 10 g/dl, and for SGA 9 g/dl of hemoglobin. Low and high maternal Hb levels and moderate altitude were independent risk factors for adverse perinatal outcomes.

Impact of radiation therapy on the oncolytic adenovirus dl520: implications on the treatment of glioblastoma.

PubMed

Bieler, Alexa; Mantwill, Klaus; Holzmüller, Regina; Jürchott, Karsten; Kaszubiak, Alexander; Stärk, Sybille; Glockzin, Gabriel; Lage, Hermann; Grosu, Anca-Ligia; Gansbacher, Bernd; Holm, Per Sonne

2008-03-01

Viral oncolytic therapy is emerging as a new form of anticancer therapy and has shown promising preclinical results, especially in combination with radio- and chemotherapy. We recently reported that nuclear localization of the human transcription factor YB-1 in multidrug-resistant cells facilitates E1-independent adenoviral replication. The aim of this study was to evaluate the combined treatment of the conditionally-replicating adenovirus dl520 and radiotherapy in glioma cell lines in vitro and in human tumor xenografts. Furthermore, the dependency of YB-1 on dl520 replication was verified by shRNA directed down regulation of YB-1. Localization of YB-1 was determined by immunostaining. Glioma cell lines LN-18, U373 and U87 were infected with dl520. Induction of cytopathic effect (CPE), viral replication, viral yield and viral release were determined after viral infection, radiation therapy and the combination of both treatment modalities. The capacity of treatments alone or combined to induce tumor growth inhibition of subcutaneous U373 tumors was tested also in nude mice. Quantitative real-time PCR demonstrated that the shRNA-mediated down regulation of YB-1 is leading to a dramatic decrease in adenoviral replication of dl520. Immunostaining analysis showed that the YB-1 protein was predominantly located in the cytoplasm in the perinuclear space and less abundant in the nucleus. After irradiation we found an increase of nuclear YB-1. The addition of radiotherapy increased the oncolytic effect of dl520 with enhanced viral replication, viral yield and viral release. The oncolytic activity of dl520 plus radiation inhibited the growth of subcutaneous U373 tumors in a xenograft mouse model. Radiation mediated increase of nuclear YB-1 in glioma cells enhanced the oncolytic potential of adenovirus dl520.

Efficacy and Safety of Risedronate in Osteoporosis Subjects with Comorbid Diabetes, Hypertension, and/or Dyslipidemia: A Post Hoc Analysis of Phase III Trials Conducted in Japan.

PubMed

Inoue, Daisuke; Muraoka, Ryoichi; Okazaki, Ryo; Nishizawa, Yoshiki; Sugimoto, Toshitsugu

2016-02-01

Many osteoporotics have comorbid diabetes mellitus (DM), hypertension (HT), and dyslipidemia (DL). However, whether such comorbidities alter response to anti-osteoporotic treatment is unknown. We did post hoc analyses of combined data from three risedronate Japanese phase III trials to determine whether the presence of DM, HT, or DL affects its efficacy and safety. Data from 885 subjects who received 48-week treatment with risedronate were collected and combined from the three phase III trials. They were divided into two groups by the presence or absence of comorbidities: DM (n = 53) versus non-DM (n = 832); HT (n = 278) versus non-HT (n = 607); and DL (n = 292) versus non-DL (n = 593). Bone mineral density (BMD), urinary type 1 collagen N-telopeptide (uNTX), and serum bone-specific alkaline phosphatase (BAP) were measured at baseline and sequentially until 48 weeks. BMD or bone markers were not different between any of the two groups. Overall, BMD was increased by 5.52%, and uNTX and BAP were decreased by 35.4 and 33.8%, respectively. Some bone markers were slightly lower in DM and DL subjects, but the responses to risedronate were not significantly different. Statin users had lower uNTX and BAP, but showed no difference in the treatment response. All the other medications had no apparent effect. Adverse event incidence was marginally higher in DL compared with non-DL (Relative risk 1.06; 95% confidence interval 1.01-1.11), but was not related to increase in any specific events. Risedronate shows consistent safety and efficacy in suppressing bone turnover and increasing BMD in osteoporosis patients with comorbid DM, HT, and/or DL.

Lower Glucose Target is Associated with Improved 30-Day Mortality in Cardiac and Cardiothoracic Patients.

PubMed

Hersh, Andrew M; Hirshberg, Eliotte L; Wilson, Emily L; Orme, James F; Morris, Alan H; Lanspa, Michael J

2018-04-26

Practice guidelines recommend against Intensive Insulin Therapy (IIT) in critically ill patients based on trials that had high rates of severe hypoglycemia. Intermountain Healthcare uses a computerized intravenous insulin protocol (eProtocol-insulin) that allows choice of blood glucose (BG) targets (80-110 mg/dl versus 90-140 mg/dl), and has low rates of severe hypoglycemia. We sought to study the effects of BG target on mortality in adult patients in cardiac intensive care units (ICUs) that have very low rates of severe hypoglycemia. Critically ill patients receiving intravenous insulin were treated with either of two BG targets (80-110 mg/dl versus 90-140 mg/dl). We created a propensity score for BG target using factors believed to have influenced clinicians' choice, and then performed a propensity-score-adjusted regression analysis for 30-day mortality. 1809 patients met inclusion criteria. Baseline patient characteristics were similar. Median glucose was lower in the 80-110 mg/dl group (104 mg/dl vs. 122 mg/dl, p<0.001). Severe hypoglycemia occurred at very low rates in both groups (1.16% vs. 0.35%, p=0.051). Unadjusted 30-day mortality was lower in the 80-110 mg/dl group (4.3% vs 9.2%, p<0.001). This remained after propensity-score-adjusted regression (OR 0.65; 95% CI, 0.43-0.98; p=0.04). Tight glucose control can be achieved with low rates of severe hypoglycemia, and is associated with decreased 30-day mortality in a cohort of largely cardiac patients. While such findings should not be used to guide clinical practice at present, the use of tight glucose control should be re-examined using a protocol that has low rates of severe hypoglycemia. Copyright © 2018. Published by Elsevier Inc.

Bedside hemoglobinometry in hemodialysis patients: lessons from point-of-care testing.

PubMed

Agarwal, R; Heinz, T

2001-01-01

The HemoCue B-hemoglobin test system (HemoCue, Inc., Mission Viejo, CA) is a photometric method for rapid bedside determination of hemoglobin (Hb). We compared the performance of HemoCue measured Hb against Coulter STK-S (CSTK) measured Hb in chronic hemodialysis (HD) patients in two different settings. In the first setting, Hemocue analysis was performed by multiple HD technicians (n = 132). In the second setting, a nurse trained in proper specimen handling performed the HemoCue analysis (n = 74). Simultaneous measurement of Hb by the CSTK method was performed. First setting: Hb was 11.1+/-1.66 (SD) g/dl by CSTK and 11.7+/-2.29 g/dl by HemoCue. The HemoCue method consistently overestimated Hb by an average (SD) of 0.63 (1.267) g/dl (95% CI = 0.42 to 0.85). Hb was overestimated in 25.7% and underestimated in 2.3% of the patients by 1 g/dl or more. Thus, the HemoCue system was accurate within 1 g/dl only 72% of the time. Second setting: HemoCue overestimated Hb by an average (SD) of 0.29 (0.52) g/dl (95% CI, 0.17 to 0.41). Only 4% of all patients had errors in estimation of 1 g/dl or more. Thus, HemoCue was accurate in 96% of the patients within 1 g/dl. After reviewing the two protocols, the primary difference in the two studies was the technique used to obtain the specimens. When performed properly, Hb testing using the HemoCue testing system had a high level of agreement with CSTK. Appropriate training in specimen handling, as well as test performance, will increase accuracy and reliability of bedside hemoglobinometry.

Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes

PubMed Central

Norman, Paul J.; Abi-Rached, Laurent; Gendzekhadze, Ketevan; Hammond, John A.; Moesta, Achim K.; Sharma, Deepti; Graef, Thorsten; McQueen, Karina L.; Guethlein, Lisbeth A.; Carrington, Christine V.F.; Chandanayingyong, Dasdayanee; Chang, Yih-Hsin; Crespí, Catalina; Saruhan-Direskeneli, Güher; Hameed, Kamran; Kamkamidze, Giorgi; Koram, Kwadwo A.; Layrisse, Zulay; Matamoros, Nuria; Milà, Joan; Park, Myoung Hee; Pitchappan, Ramasamy M.; Ramdath, D. Dan; Shiau, Ming-Yuh; Stephens, Henry A.F.; Struik, Siske; Tyan, Dolly; Verity, David H.; Vaughan, Robert W.; Davis, Ronald W.; Fraser, Patricia A.; Riley, Eleanor M.; Ronaghi, Mostafa; Parham, Peter

2009-01-01

Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here is KIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the 3DL1 and 3DL2 genes produced a deleted KIR haplotype in which the telomeric “half” was reduced to a single fusion gene with functional properties distinct from its 3DL1 and 3DL2 parents. Conversely, in Eurasian populations, duplication of the KIR3DL1/S1 locus by unequal crossing over has enabled individuals to carry and express alleles of all three KIR3DL1/S1 lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving human KIR gene family. PMID:19411600

A 1-year trial of repeated high-dose intravenous iron isomaltoside 1000 to maintain stable hemoglobin levels in inflammatory bowel disease.

PubMed

Reinisch, Walter; Altorjay, Istvan; Zsigmond, Ferenc; Primas, Christian; Vogelsang, Harald; Novacek, Gottfried; Reinisch, Sieglinde; Thomsen, Lars L

2015-01-01

Iron isomaltoside 1000 (Monofer®) is a high-dose intravenous (IV) iron, which in a recent 8 weeks trial in inflammatory bowel disease (IBD) subjects with iron deficiency anemia (IDA) demonstrated good tolerability and efficacy. The present trial is an extension to this trial, which evaluates the need for additional high IV iron doses to maintain a stable hemoglobin (Hb) ≥12.0 g/dl. This was a prospective, open-label, 12 months trial of European IBD subjects willing to participate after completing the lead-in trial. Subjects were allowed re-dosing with 500-2000 mg single doses of iron isomaltoside 1000 infused over ∼15 min at 3 months intervals depending on a predefined algorithm. Outcome measures included Hb, safety parameters and need for additional iron dosing. A total of 39 subjects were enrolled of which 34 subjects required re-dosing with a median cumulative 1-year dose of 1.8 g (mean cumulative dose 2.2 g). The mean (SD) Hb was 12.3 (1.5) g/dl at baseline, 12.8 (1.6) g/dl at 3 months, 12.8 (1.6) g/dl at 6 months, 12.9 (1.4) g/dl at 9 months and 12.9 (1.6) g/dl at 12 months. Seventy-four percent of subjects who had an Hb ≥12.0 g/dl at baseline were able to maintain Hb ≥12.0 g/dl till the end of the trial at 12 months. Nonserious probably related hypersensitivity reactions without significant hypotension were reported at the beginning of the infusion in two subjects, who recovered without sequelae. Repeated treatment of iron deficiency with iron isomaltoside 1000 could avoid episodes of IDA without major safety issues.

Oligopeptides and copeptides of homochiral sequence, via beta-sheets, from mixtures of racemic alpha-amino acids, in a one-pot reaction in water; relevance to biochirogenesis.

PubMed

Illos, Roni A; Bisogno, Fabricio R; Clodic, Gilles; Bolbach, Gerard; Weissbuch, Isabelle; Lahav, Meir

2008-07-09

As part of our studies on the biochirogenesis of peptides of homochiral sequence during early evolution, the formation of oligopeptides composed of 14-24 residues of the same handedness in the polymerization of dl-leucine (Leu), dl-phenylalanine (Phe), and dl-valine (Val) in aqueous solutions, by activation with N, N'-carbonyldiimidazole and then initiation with a primary amine, in a one-pot reaction, was demonstrated by MALDI-TOF MS using deuterium enantio-labeled alpha-amino acids. The formation of long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of l-Leu with l-isoleucine (Ile) or l-Phe with l- (1) N-Me-histidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of l- + d-alpha-amino acids, the long oligopeptides were composed mainly from oligo- l-Leu and oligo- d-Ile in the first system and oligo- d-Phe in the second. Furthermore, in the polymerization of mixtures of hydrophobic racemic alpha-amino acids dl-Leu, dl-Val, and dl-Phe and with added racemic dl-alanine and dl-tyrosine, copeptides of homochiral sequences are most dominantly represented. Possible routes for a spontaneous "mirror-symmetry breaking" process of the racemic mixtures of homochiral peptides are presented.

TOLERANCE TO AMINO ACID MIXTURES AND CASEIN DIGESTS GIVEN INTRAVENOUSLY

PubMed Central

Madden, S. C.; Woods, R. R.; Shull, F. W.; Remington, J. H.; Whipple, G. H.

1945-01-01

Several synthetic mixtures of natural and racemic crystalline amino acids suitable for the daily nitrogen requirement are tested in dogs for their tolerance upon intravenous injection. Certain mixtures of the ten essential amino acids plus non-essential amino acids exclusive of glutamic acid are accepted without any obvious sign of disturbance even at rates above 10 mg. nitrogen per kilo per minute for quantities greater than 300 mg. per kilo. One such mixture consists in parts per 100 of dl-threonine 7, dl-valine 15, l(-)-leucine 10.9, dl-isoleucine 9.9, l(+)-lysine· HCl·H2O 10.9, dl-tryptophane 3, dl-phenylalanine 9.9, dl-methionine 6, l(+)-histidine·HCl·H2O 5, l(+)-arginine-HCl 5, glycine 9.9, dl-α-alanine 4, dl-serine 2, l(-)-cystine 0.5, and l(-)-tyrosine 1. In addition other well tolerated mixtures included the prolines. When glutamic acid, natural or racemic, is included in similar mixtures vomiting reactions frequently occur at nitrogen rates above 4 mg. per kilo per minute. Vomiting almost always occurs on the first daily injection containing glutamic acid and usually on any subsequent injection containing more than 100 mg. glutamic acid per kilo unless given very slowly. Upon the addition of glycine certain mixtures of the ten essential amino acids show an improved tolerance. Two casein digests tested usually produced vomiting at injection rates above 2 mg. nitrogen per kilo per minute, probably because of their glutamic acid content. No serious reaction has ever occurrred to any mixture of amino acids or casein digest tested. Elimination of minor reactions such as vomiting appears possible and desirable for greater usefulness of these solutions in parenteral feeding. PMID:19871468

Differential Functional Connectivity Alterations of Two Subdivisions within the Right dlPFC in Parkinson's Disease

PubMed Central

Caspers, Julian; Mathys, Christian; Hoffstaedter, Felix; Südmeyer, Martin; Cieslik, Edna C.; Rubbert, Christian; Hartmann, Christian J.; Eickhoff, Claudia R.; Reetz, Kathrin; Grefkes, Christian; Michely, Jochen; Turowski, Bernd; Schnitzler, Alfons; Eickhoff, Simon B.

2017-01-01

Patients suffering from Parkinson's disease (PD) often show impairments in executive function (EF) like decision-making and action control. The right dorsolateral prefrontal cortex (dlPFC) has been strongly implicated in EF in healthy subjects and has repeatedly been reported to show alterations related to EF impairment in PD. Recently, two key regions for cognitive action control have been identified within the right dlPFC by co-activation based parcellation. While the posterior region is engaged in rather basal EF like stimulus integration and working memory, the anterior region has a more abstract, supervisory function. To investigate whether these functionally distinct subdivisions of right dlPFC are differentially affected in PD, we analyzed resting-state functional connectivity (FC) in 39 PD patients and 44 age- and gender-matched healthy controls. Patients were examined both after at least 12 h withdrawal of dopaminergic drugs (OFF) and under their regular dopaminergic medication (ON). We found that only the posterior right dlPFC subdivision shows FC alterations in PD, while the anterior part remains unaffected. PD-related decreased FC with posterior right dlPFC was found in the bilateral medial posterior parietal cortex (mPPC) and left dorsal premotor region (PMd) in the OFF state. In the medical ON, FC with left PMd normalized, while decoupling with bilateral mPPC remained. Furthermore, we observed increased FC between posterior right dlPFC and the bilateral dorsomedial prefrontal cortex (dmPFC) in PD in the ON state. Our findings point to differential disturbances of right dlPFC connectivity in PD, which relate to its hierarchical organization of EF processing by stronger affecting the functionally basal posterior aspect than the hierarchically higher anterior part. PMID:28611616

Soluble NKG2D ligands: prevalence, release, and functional impact.

PubMed

Salih, Helmut Rainer; Holdenrieder, Stefan; Steinle, Alexander

2008-05-01

Natural Killer (NK) cells are capable to recognize and eliminate malignant cells. Anti-tumor responses of NK cells are promoted by the tumor-associated expression of cell stress-inducible ligands of the activating NK receptor NKG2D. Current evidence suggests that established tumors subvert NKG2D-mediated tumor immunosurveillance by releasing NKG2D ligands (NKG2DL). Release of NKG2DL has been observed in a broad variety of human tumor entities and is thought to interfere with NKG2D-mediated tumor immunity in several ways. Further, levels of soluble NKG2DL (sNKG2DL) were also found to be elevated under various non-malignant conditions, although the functional implications remain largely unclear. Here we review and discuss the available data on the prevalence, release, functional impact, and potential clinical value of sNKG2DL.

Biology of Paenibacillus larvae, a deadly pathogen of honey bee larvae.

PubMed

Ebeling, Julia; Knispel, Henriette; Hertlein, Gillian; Fünfhaus, Anne; Genersch, Elke

2016-09-01

The gram-positive bacterium Paenibacillus larvae is the etiological agent of American Foulbrood of honey bees, a notifiable disease in many countries. Hence, P. larvae can be considered as an entomopathogen of considerable relevance in veterinary medicine. P. larvae is a highly specialized pathogen with only one established host, the honey bee larva. No other natural environment supporting germination and proliferation of P. larvae is known. Over the last decade, tremendous progress in the understanding of P. larvae and its interactions with honey bee larvae at a molecular level has been made. In this review, we will present the recent highlights and developments in P. larvae research and discuss the impact of some of the findings in a broader context to demonstrate what we can learn from studying "exotic" pathogens.

Effect of amino acids and vitamins on laccase production by the bird's nest fungus Cyathus bulleri.

PubMed

Dhawan, Shikha; Kuhad, Ramesh Chander

2002-08-01

Various amino acids, their analogues and vitamins have shown stimulatory as well as inhibitory effects on laccase production by Cyathus bulleri. DL-methionine, DL-tryptophan, glycine and DL-valine stimulated laccase production, while L-cysteine monohydrochloride completely inhibited the enzyme production. Among vitamins tested biotin, riboflavin and pyridoxine hydrochloride were found to induce laccase production.

New Tools and Metrics for Evaluating Army Distributed Learning. Monograph

ERIC Educational Resources Information Center

Straus, Susan G.; Shanley, Michael G.; Yeung, Douglas; Rothenberg, Jeff; Steiner, Elizabeth D.; Leuschner, Kristin J.

2011-01-01

Distributed learning (DL) is a key element of the Army's training strategy, and the Army has ambitious goals for expanding the future use of DL and for changing how it is developed and delivered. Program-level evaluation of DL can play an essential role in accomplishing those goals and in identifying strategic directions for the overall program.…

X-ray and conformational investigations of a 4:1 mixture of 6-(N-benzyl-N-tert-butoxycarbonylamino)-2,3,6,7-tetradeoxy-alpha- DL-ery thro- and -beta-DL-threo-hept-2-enopyranos-4-uloses.

PubMed

Krajewski, J W; Urbańczyk-Lipkowska, Z; Gluziński, P; Jurczak, J; Raczko, J; Gołebiowski, A

1990-07-01

The crystals of a 4:1 mixture of 6-(N-benzyl-N-tert-butoxycarbonylamino)-2,3,6,7-tetradeoxy-a-DL-er ythro- and -beta-DL-threo-hept-2-enopyranos-4-ulose were monoclinic, space group P2(1)/c, with cell dimensions: a = 9.490(2), b = 21.516(5), c = 10.279(2) A, beta = 115.31(1) degrees, Z = 4. The ulose ring had a half-chair conformation deformed towards the sofa (envelope) form.

Potential challenges facing distributed leadership in health care: evidence from the UK National Health Service.

PubMed

Martin, Graeme; Beech, Nic; MacIntosh, Robert; Bushfield, Stacey

2015-01-01

The discourse of leaderism in health care has been a subject of much academic and practical debate. Recently, distributed leadership (DL) has been adopted as a key strand of policy in the UK National Health Service (NHS). However, there is some confusion over the meaning of DL and uncertainty over its application to clinical and non-clinical staff. This article examines the potential for DL in the NHS by drawing on qualitative data from three co-located health-care organisations that embraced DL as part of their organisational strategy. Recent theorising positions DL as a hybrid model combining focused and dispersed leadership; however, our data raise important challenges for policymakers and senior managers who are implementing such a leadership policy. We show that there are three distinct forms of disconnect and that these pose a significant problem for DL. However, we argue that instead of these disconnects posing a significant problem for the discourse of leaderism, they enable a fantasy of leadership that draws on and supports the discourse. © 2014 The Authors. Sociology of Health & Illness © 2014 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.

Deep learning based classification of breast tumors with shear-wave elastography.

PubMed

Zhang, Qi; Xiao, Yang; Dai, Wei; Suo, Jingfeng; Wang, Congzhi; Shi, Jun; Zheng, Hairong

2016-12-01

This study aims to build a deep learning (DL) architecture for automated extraction of learned-from-data image features from the shear-wave elastography (SWE), and to evaluate the DL architecture in differentiation between benign and malignant breast tumors. We construct a two-layer DL architecture for SWE feature extraction, comprised of the point-wise gated Boltzmann machine (PGBM) and the restricted Boltzmann machine (RBM). The PGBM contains task-relevant and task-irrelevant hidden units, and the task-relevant units are connected to the RBM. Experimental evaluation was performed with five-fold cross validation on a set of 227 SWE images, 135 of benign tumors and 92 of malignant tumors, from 121 patients. The features learned with our DL architecture were compared with the statistical features quantifying image intensity and texture. Results showed that the DL features achieved better classification performance with an accuracy of 93.4%, a sensitivity of 88.6%, a specificity of 97.1%, and an area under the receiver operating characteristic curve of 0.947. The DL-based method integrates feature learning with feature selection on SWE. It may be potentially used in clinical computer-aided diagnosis of breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Black sexuality, social construction, and research targeting 'The Down Low' ('The DL').

PubMed

Ford, Chandra L; Whetten, Kathryn D; Hall, Susan A; Kaufman, Jay S; Thrasher, Angela D

2007-03-01

The purpose of this commentary is to explain how social constructions of black sexuality are relevant to research targeting black sexual behavior and the ostensibly new and race-specific phenomenon known as "the Down Low" (the DL). The term "the DL" is widely used to refer to black men publicly presenting as heterosexual while secretly having sex with other men and presumably spreading human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) to unsuspecting women. We briefly review lay and public health literature from 1998 to 2004 about the DL, describe existing social constructions of black sexuality, discuss two implications for epidemiologic research, and offer recommendations to guide future research. The lifestyle referenced by the term the DL is neither new nor limited to blacks, and sufficient data linking it to HIV/AIDS disparities currently are lacking. Common perceptions about the DL reflect social constructions of black sexuality as generally excessive, deviant, diseased, and predatory. Research targeting black sexual behavior that ignores these constructions may unwittingly reinforce them. Unaddressed social constructions of black sexuality have implications for epidemiologic research targeting black sexual behavior. Explicit examination of these concerns is necessary to eliminate fundamental causes of health disparities.

Origins of hydration differences in homochiral and racemic crystals of aspartic acid.

PubMed

Juliano, Thomas R; Korter, Timothy M

2015-02-26

The propensity for crystalline hydrates of organic molecules to form is related to the strength of the interactions between molecules, including the chiral composition of the molecular solids. Specifically, homochiral versus racemic crystalline samples can exhibit distinct differences in their ability to form energetically stable hydrates. The focus of the current study is a comparison of the crystal structures and intermolecular forces found in solid-state L-aspartic acid, DL-aspartic acid, and L-aspartic acid monohydrate. The absence of experimental evidence for the DL-aspartic acid monohydrate is considered here in terms of the enhanced thermodynamic stability of the DL-aspartic acid anhydrate crystal as compared to the L-aspartic acid anhydrate as revealed through solid-state density functional theory calculations and terahertz spectroscopic measurements. The results indicate that anhydrous DL-aspartic acid is the more stable solid, not due to intermolecular forces alone but also due to the improved conformations of the molecules within the racemic solid. Hemihydrated and monohydrated forms of DL-aspartic acid have been computationally evaluated, and in each case, the hydrates produce destabilized aspartic acid conformations that prevent DL-aspartic acid hydrate formation from occurring.

Serum protein electrophoretic pattern in one-humped camels (Camelus dromedarius) in Tripoli, Libya.

PubMed

Abdoslam, Omran; Bayt-Almal, Mahmoud; Almghrbe, Abdullah; Algriany, Omran

2018-01-01

The aim of this study was to characterize serum protein capillary electrophoretic pattern in apparently healthy adult male (age: 3-7 years) dromedary camels and also evaluate total protein and albumin levels using automated analyzer. Blood samples were taken from 20 camels. 5ml of blood was collected from the jugular vein and serum was separated from samples by centrifugation. Capillary electrophoresis of serum proteins identified six protein fractions in adult camels, including albumin, alpha1, alpha2, beta1, beta2 and gamma globulins, serum levels of these parameters were 3.9±0.04 g/dl, 0.16±0.01 g/dl, 0.39±0.03 g/dl, 0.515±0.03 g/dl, 0.205±0.01 g/dl and 0.61±0.04 g/dl, and 65.42±0.62 g/l, respectively. The total protein concentration was 65.42±0.62 g/L, while, the albumin/globulin (A/G) ratio was 2.4±0.14. The present study indicates six peaks with minicapillary electrophoresis and the results obtained were compared and interpreted in the light of finding reported by other investigators in camels.

Caudal migration and proliferation of renal progenitors regulates early nephron segment size in zebrafish.

PubMed

Naylor, Richard W; Dodd, Rachel C; Davidson, Alan J

2016-10-19

The nephron is the functional unit of the kidney and is divided into distinct proximal and distal segments. The factors determining nephron segment size are not fully understood. In zebrafish, the embryonic kidney has long been thought to differentiate in situ into two proximal tubule segments and two distal tubule segments (distal early; DE, and distal late; DL) with little involvement of cell movement. Here, we overturn this notion by performing lineage-labelling experiments that reveal extensive caudal movement of the proximal and DE segments and a concomitant compaction of the DL segment as it fuses with the cloaca. Laser-mediated severing of the tubule, such that the DE and DL are disconnected or that the DL and cloaca do not fuse, results in a reduction in tubule cell proliferation and significantly shortens the DE segment while the caudal movement of the DL is unaffected. These results suggest that the DL mechanically pulls the more proximal segments, thereby driving both their caudal extension and their proliferation. Together, these data provide new insights into early nephron morphogenesis and demonstrate the importance of cell movement and proliferation in determining initial nephron segment size.

New aspects of the pathogenesis of canine distemper leukoencephalitis.

PubMed

Lempp, Charlotte; Spitzbarth, Ingo; Puff, Christina; Cana, Armend; Kegler, Kristel; Techangamsuwan, Somporn; Baumgärtner, Wolfgang; Seehusen, Frauke

2014-07-02

Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL). In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo and in vitro investigations provided new insights into its pathogenesis with special emphasis on axon-myelin-glia interaction, potential endogenous mechanisms of regeneration, and astroglial plasticity. CDV-DL is characterized by lesions with a variable degree of demyelination and mononuclear inflammation accompanied by a dysregulated orchestration of cytokines as well as matrix metalloproteinases and their inhibitors. Despite decades of research, several new aspects of the neuropathogenesis of CDV-DL have been described only recently. Early axonal damage seems to represent an initial and progressive lesion in CDV-DL, which interestingly precedes demyelination. Axonopathy may, thus, function as a potential trigger for subsequent disturbed axon-myelin-glia interactions. In particular, the detection of early axonal damage suggests that demyelination is at least in part a secondary event in CDV-DL, thus challenging the dogma of CDV as a purely primary demyelinating disease. Another unexpected finding refers to the appearance of p75 neurotrophin (NTR)-positive bipolar cells during CDV-DL. As p75NTR is a prototype marker for immature Schwann cells, this finding suggests that Schwann cell remyelination might represent a so far underestimated endogenous mechanism of regeneration, though this hypothesis still remains to be proven. Although it is well known that astrocytes represent the major target of CDV infection in CDV-DL, the detection of infected vimentin-positive astrocytes in chronic lesions indicates a crucial role of this cell population in nervous distemper. While glial fibrillary acidic protein represents the characteristic intermediate filament of mature astrocytes, expression of vimentin is generally restricted to immature or reactive astrocytes. Thus, vimentin-positive astrocytes might constitute an important cell population for CDV persistence and spread, as well as lesion progression. In vitro models, such as dissociated glial cell cultures, as well as organotypic brain slice cultures have contributed to a better insight into mechanisms of infection and certain morphological and molecular aspects of CDV-DL. Summarized, recent in vivo and in vitro studies revealed remarkable new aspects of nervous distemper. These new perceptions substantially improved our understanding of the pathogenesis of CDV-DL and might represent new starting points to develop novel treatment strategies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pangaro, L.; Burman, K.D.; Wartofsky, L.

The present report describes a RIA for 3,5-diiodothyronine (3,5T/sub 2/) which uses inner ring-labeled 3,5-(/sup 125/I)T/sub 2/ as the ligand and has a lower limit of detectability of 0.5 ng/dl. Cross-reaction was 0.14% with T/sub 3/, less than 0.001% with T/sub 4/, 1.2% with 3,3',5-triiodothyroacetic acid, and 6.1% with 3,5-diiodothyroacetic acid. No cross-reaction was detectable for iodothyronines within their physiological ranges. Intraassay variation ranged from 2.2 to 7.8%, and interassay variation ranged from 12.7 to 14%. The mean (+-SE) serum 3.5T/sub 2/ concentration in 70 normal subjects was 4.3 +- 0.2 ng/dl. The mean (+-SE) 3.5T/sub 2/ in 14 hyperthyroidmore » patients was increased to 18.4 +- 2.3 ng/dl (P < 0.001), and all but 1 patient had an elevated level. In 10 hypothyroid patients the mean (+-SE) 3,5T/sub 2/ level was decreased to 1.4 +- 0.3 ng/dl (P < 0.001). In 4 patients, levels overlapped with the normal range. In 4 hypothyroid subjects treated with L-T/sub 1/, 3,5T/sub 2/ levels were normal, suggesting that the majority of 3,5T/sub 2/ originates from extrathyroidal conversion from T/sub 3/. Studies in fasting obese subjects demonstrated that serum 3,5T/sub 2/ (mean +- SE) levels fell from 3.4 +- 0.3 to 2.5 +- 0.7 ng/dl during fasting. This fall was significant (P < 0.001) and in parallel with the fall in T/sub 3/ levels of 182 +- 20 to 126 +- 12 ng/dl. In fasting subjects given 100 ..mu..g oral L-T/sub 3//day T/sub 3/ levels rose from 138 +- 11 to 362 +- 26 ng/dl. 3,5T/sub 2/ levels (corrected for cross-reaction and for contamination of oral T/sub 3/ with 3,5T/sub 2/) rose from 2.2 +- 0.7 to 6.4 +- 1.0 ng/dl. In fasting subjects given 25 ..mu..g oral L-T/sub 3//day, T/sub 3/ levels fell from 165 +- 5.1 to 139 +- 6.9 ng/dl. Corrected 3,5T/sub 2/ levels changed from 3.7 +- 0.4 to 2.5 +- 0.3 ng/dl. Neither change were significant.« less

Urnaloricus gadi nov. gen. et nov. sp. (Loricifera, Urnaloricidae nov. fam.), an aberrant Loricifera with a viviparous pedogenetic life cycle.

PubMed

Heiner, Iben; Kristensen, Reinhardt Møbjerg

2009-02-01

A new species of Loricifera, Urnaloricus gadi nov. gen. et nov. sp., is described from the Faroe Bank, located Southwest of the Faroe Islands, North Atlantic. The new species does not fit into any known families of Loricifera and therefore it is grouped into a new family Urnaloricidae nov. fam. The new species is characterized by having a very complicated life cycle that involves a large cyst-like mega-larva, two reduced larval instars and the Higgins-larvae eating their maternal stage from within. An adult stage is missing. This form of reproduction is called viviparous pedogenesis and normally is found only in nematodes and insects. In the life cycle of Urnaloricidae nov. fam., there are two types of free-living larval stages: a Higgins-larva and a mega-larva. The latter is found in two different forms, a pre- and a cyst-forming mega-larva. Additionally, there are two reduced life history stages, the reduced larval stage (probably a postlarva) and the ghost-larval stage inside the cyst-forming mega-larva. The external morphology of the two forms of mega-larvae is much reduced, e.g., the introvert has only a few rows of scalids when compared with the Higgins-larva. The pre mega-larva is free-living and can sometimes be covered with coccoliths. Internally, a large ovary with a few oocytes, a digestive system, and an internal armature with retracted scalids are present. The pre mega-larva presumably molts into a cyst-forming mega-larva and thereby the ovary is now seen inside the cyst-forming mega-larva. The cyst-forming mega-larva has the same structures as in the pre mega-larva though here the scalids are protruded and there is a gonopore. Inside the cyst-forming mega-larva the ovary produces more oocytes and begins to fill out the entire lumen. At this stage the cyst-forming mega-larva molts first to the presumed postlarval stage, and then this stage molts to a ghost-larva. Hence, the ovary now matures inside the ghost-larva, which is surrounded by both the cuticle of the reduced postlarval stage and the cuticle of the cyst-forming mega-larva. The oocytes mature into eggs, and then into embryos and finally into Higgins-larvae while reabsorbing all the tissue of their maternal stage, the ghost-larva. During this maturation the cuticle of the cyst-forming mega-larva starts to harden and become cyst-like. The fully developed Higgins-larvae emerge through the gonopore of the cyst-forming mega-larva by penetrating the thin cuticles of the ghost-larva and the postlarva. The embryos have holoblastic radial cleavage and later a fluid-filled blastocoel is formed. The eggshells are extremely elastic; hence, they can become very elongated as the embryos mature into Higgins-larvae. (c) 2008 Wiley-Liss, Inc.

Genome-wide analysis of trans-splicing in the nematode Pristionchus pacificus unravels conserved gene functions for germline and dauer development in divergent operons.

PubMed

Sinha, Amit; Langnick, Claudia; Sommer, Ralf J; Dieterich, Christoph

2014-09-01

Discovery of trans-splicing in multiple metazoan lineages led to the identification of operon-like gene organization in diverse organisms, including trypanosomes, tunicates, and nematodes, but the functional significance of such operons is not completely understood. To see whether the content or organization of operons serves similar roles across species, we experimentally defined operons in the nematode model Pristionchus pacificus. We performed affinity capture experiments on mRNA pools to specifically enrich for transcripts that are trans-spliced to either the SL1- or SL2-spliced leader, using spliced leader-specific probes. We obtained distinct trans-splicing patterns from the analysis of three mRNA pools (total mRNA, SL1 and SL2 fraction) by RNA-seq. This information was combined with a genome-wide analysis of gene orientation and spacing. We could confirm 2219 operons by RNA-seq data out of 6709 candidate operons, which were predicted by sequence information alone. Our gene order comparison of the Caenorhabditis elegans and P. pacificus genomes shows major changes in operon organization in the two species. Notably, only 128 out of 1288 operons in C. elegans are conserved in P. pacificus. However, analysis of gene-expression profiles identified conserved functions such as an enrichment of germline-expressed genes and higher expression levels of operonic genes during recovery from dauer arrest in both species. These results provide support for the model that a necessity for increased transcriptional efficiency in the context of certain developmental processes could be a selective constraint for operon evolution in metazoans. Our method is generally applicable to other metazoans to see if similar functional constraints regulate gene organization into operons. © 2014 Sinha et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Daumone fed late in life improves survival and reduces hepatic inflammation and fibrosis in mice.

PubMed

Park, Jong Hee; Chung, Hae Young; Kim, Minkyu; Lee, Jung Hwa; Jung, Mankil; Ha, Hunjoo

2014-08-01

The liver is one of the most susceptible organs to aging, and hepatic inflammation and fibrosis increase with age. Chronic inflammation has been proposed as the major molecular mechanism underlying aging and age-related diseases, whereas calorie restriction has been shown to be the most effective in extending mammalian lifespan and to have anti-aging effects through its anti-inflammatory action. Thus, it is necessary to develop effective calorie restriction mimetics. Daumone [(2)-(6R)-(3,5-dihydroxy-6-methyltetrahydropyran-2-yloxy)heptanoic acid], a pheromone secreted by Caenorhabditis elegans, forces them to enter the dauer stage when facing inadequate conditions. Because Caenorhabditis elegans live longer during the dauer stage under energy deprivation, it was hypothesized that daumone may improve survival in mammals by mimicking calorie restriction. Daumone (2 mg kg(-1) day(-1) ) was administered orally for 5 months to 24-month-old male C57BL/6J mice. Daumone was found to reduce the risk of death by 48% compared with age-matched control mice, and the increased plasma insulin normally presented in old mice was significantly reduced by daumone. The increased hepatic hypertrophy, senescence-associated β-galactosidase activity, insulin resistance, lipid accumulation, inflammation, oxidative stress, and fibrosis in old mice were significantly attenuated by daumone. From a mechanistic view, daumone reduced the phosphorylation of the IκBα and upregulation of Rela and Nfkbia mRNA in the livers of old mice. The anti-inflammatory effect of daumone was confirmed in lipopolysaccharide-induced liver injury model. Oral administration of daumone improves survival in mice and delivers anti-aging effects to the aged liver by modulating chronic inflammation, indicating that daumone could be developed as an anti-aging compound. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Intraguild predation and cannibalism among larvae of detritivorous caddisflies in subalpine wetlands

USGS Publications Warehouse

Wissinger, S.A.; Sparks, G.B.; Rouse, G.L.; Brown, W.S.; Steltzer, Heidi

1996-01-01

Comparative data from subalpine wetlands in Colorado indicate that larvae of the limnephilid caddisflies, Asynarchus nigriculus and Limnephilus externus, are reciprocally abundant among habitats - Limnephilus larvae dominate in permanent waters, whereas Asynarchus larvae dominate in temporary basins. The purpose of this paper is to report on field and laboratory experiments that link this pattern of abundance to biotic interactions among larvae. In the first field experiment, growth and survival were compared in single and mixed species treatments in littoral enclosures. Larvae, which eat mainly vascular plant detritus, grew at similar rates among treatments in both temporary and permanent habitats suggesting that exploitative competition is not important under natural food levels and caddisfly densities. However, the survival of Limnephilus larvae was reduced in the presence of Asynarchus larvae. Subsequent behavioral studies in laboratory arenas revealed that Asynarchus larvae are extremely aggressive predators on Limnephilus larvae. In a second field experiment we manipulated the relative sizes of larvae and found that Limnephilus larvae were preyed on only when Asynarchus larvae had the same size advantage observed in natural populations. Our data suggest that the dominance of Asynarchus larvae in temporary habitats is due to asymmetric intraguild predation (IGP) facilitated by a phenological head start in development. These data do not explain the dominance of Limnephilus larvae in permanent basins, which we show elsewhere to be an indirect effect of salamander predation. Behavioral observations also revealed that Asynarchus larvae are cannibalistic. In contrast to the IGP on Limnephilus larvae, Asynarchus cannibalism occurs among same-sized larvae and often involves the mobbing of one victim by several conspecifics. In a third field experiment, we found that Asynarchus cannibalism was not density-dependent and occurred even at low larval densities. We hypothesize that Asynarchus IGP and cannibalism provide a dietary supplement to detritus that may be necessary for the timely completion of development in these nutrient-poor, high-elevation wetlands.

Clinical experience with ferric carboxymaltose in the treatment of cancer- and chemotherapy-associated anaemia

PubMed Central

Steinmetz, T.; Tschechne, B.; Harlin, O.; Klement, B.; Franzem, M.; Wamhoff, J.; Tesch, H.; Rohrberg, R.; Marschner, N.

2013-01-01

Background Intravenous (i.v.) iron can improve anaemia of chronic disease and response to erythropoiesis-stimulating agents (ESAs), but data on its use in practice and without ESAs are limited. This study evaluated effectiveness and tolerability of ferric carboxymaltose (FCM) in routine treatment of anaemic cancer patients. Patients and methods Of 639 patients enrolled in 68 haematology/oncology practices in Germany, 619 received FCM at the oncologist's discretion, 420 had eligible baseline haemoglobin (Hb) measurements, and 364 at least one follow-up Hb measurement. Data of transfused patients were censored from analysis before transfusion. Results The median total iron dose was 1000 mg per patient (interquartile range 600–1500 mg). The median Hb increase was comparable in patients receiving FCM alone (1.4 g/dl [0.2–2.3 g/dl; N = 233]) or FCM + ESA (1.6 g/dl [0.7–2.4 g/dl; N = 46]). Patients with baseline Hb up to 11.0 g/dl and serum ferritin up to 500 ng/ml benefited from FCM treatment (stable Hb ≥11.0 g/dl). Also patients with ferritin >500 ng/ml but low transferrin saturation benefited from FCM treatment. FCM was well tolerated, 2.3% of patients reported putative drug-related adverse events. Conclusions The substantial Hb increase and stabilisation at 11–12 g/dl in FCM-treated patients suggest a role for i.v. iron alone in anaemia correction in cancer patients. PMID:23071262

Occupational lead exposure aboard a tall ship.

PubMed

Landrigan, P J; Straub, W E

1985-01-01

To evaluate occupational exposures to lead in shipfitters cutting and riveting lead-painted iron plates aboard an iron-hulled sailing vessel, we conducted an environmental and medical survey. Lead exposures in seven personal (breathing zone) air samples ranged from 108 to 500 micrograms/m3 (mean 257 micrograms/m3); all were above the Occupational Safety and Health Administration (OSHA) standard of 50 micrograms/m3. In two short-term air samples obtained while exhaust ventilation was temporarily disconnected, mean lead exposure rose to 547 micrograms/m3. Blood lead levels in ten shipfitters ranged from 25 to 53 micrograms/dl (mean, 37.8 micrograms/dl); levels in three of these workers exceeded the upper normal limit of 40 micrograms/dl. Blood lead levels in shipfitters were significantly higher than in other shipyard workers (mean 10.0 micrograms/dl; p less than 0.001). Smoking shipfitters (mean, 47 micrograms/dl) had significantly higher lead levels than nonsmokers (mean, 32 micrograms/dl; p = 0.03). Lead levels in shipfitters who wore respirators were not lower than in those who wore no protective gear (p = 0.68). Four shipfitters had erythrocyte protoporphyrin (EP) concentrations above the adult upper normal limit of 50 micrograms/dl. A close correlation was found between blood lead and EP levels (r = 0.70). Prevalence of lead-related symptoms was no higher in shipfitters than in other workers. No cases of symptomatic lead poisoning were noted. These data indicate that serious occupational exposure to lead can occur in a relatively small boatyard.

Predicting planning performance from structural connectivity between left and right mid-dorsolateral prefrontal cortex: moderating effects of age during postadolescence and midadulthood.

PubMed

Kaller, Christoph P; Reisert, Marco; Katzev, Michael; Umarova, Roza; Mader, Irina; Hennig, Jürgen; Weiller, Cornelius; Köstering, Lena

2015-04-01

Complex cognitive abilities such as planning are known to critically rely on activity of bilateral mid-dorsolateral prefrontal cortex (mid-dlPFC). However, the functional relevance of the structural connectivity between left and right mid-dlPFC is yet unknown. Here, we applied global tractography to derive streamline counts as estimates of the structural connectivity between mid-dlPFC homologs and related it to planning performance in the Tower of London task across early to midadulthood, assuming a moderating effect of age. Multiple regression analyses with interaction effects revealed that streamline counts between left and right mid-dlPFC were negatively associated with planning performance specifically in early postadolescence. From the fourth life decade on, there was a trend for a reversed, positive association. These differential findings were corroborated by converging results from fractional anisotropy and white-matter density estimates in the genu of the corpus callosum where fibers connecting mid-dlPFC homologs traversed. Moreover, the results for streamline counts were regionally specific, marking the strength of mid-dlPFC connectivity as critical in predicting interindividual differences in planning performance across different stages of adulthood. Taken together, present findings provide first evidence for nonadditive effects of age on the relation between complex cognitive abilities and the structural connectivity of mid-dlPFC homologs. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Random Plasma Glucose Values Measured in Community Dental Practices: Findings from The Dental Practice-Based Research Network

PubMed Central

Barasch, Andrei; Gilbert, Gregg H; Spurlock, Noel; Funkhouser, Ellen; Persson, Lise-Lotte; Safford, Monika M

2012-01-01

Objectives To examine feasibility of testing and frequency of abnormal plasma glucose among dental patients in The Dental Practice-Based Research Network. Methods Eligible dental patients were >19 years old and had at least one American Diabetes Association-defined risk factor for diabetes mellitus, or an existing diagnosis of diabetes or pre-diabetes. Random (fasting not required) plasma glucose was measured in standardized fashion using a commercial glucometer. Readings <70 mg/dl or >300 mg/dl triggered re-testing. Patients with glucose >126 mg/dl were referred for medical follow up. Results Of 498 subjects in 28 dental practices, 491 (98%) consented and 418 (85.1%) qualified for testing. Fifty-one patients (12.2%) had diabetes; 24 (5.7%) had pre-diabetes. Glucose ranged from 50 – 465 mg/dl. 129 subjects (31%) had readings outside the normal range; of these, 28 (6.7%) had readings <80 mg/dl and 101 (24.2%) had readings >126 mg/dl; in 9 patients (7 with diabetes), glucose was >200 mg/dl. Conclusions A significant proportion of patients tested had abnormal blood glucose. Routine glucose testing in dental practice of populations at risk or diagnosed with diabetes may be beneficial and community dental practices hold promise as settings for diabetes and pre-diabetes screening and monitoring. Clinical Relevance Results suggest that implementation of glucose measurement in dental practice may provide important clinical and health information for both patients and practitioners. PMID:22903529

Evaluation of cell proliferation in malignant and potentially malignant oral lesions

PubMed Central

Madan, Mani; Chandra, Shaleen; Raj, Vineet; Madan, Rohit

2015-01-01

Aims: To evaluate the cell proliferation rate by the expression of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizing region (AgNOR) counts and to assess its usefulness as a marker for malignant potential in oral epithelial lesions. Materials and Methods: The study group included 30 cases of leukoplakia, 15 nondysplastic (NDL), 15 dysplastic (DL), 15 cases of oral squamous cell carcinoma (OSCC) and 5 cases of normal oral mucosa. Formalin fixed paraffin embedded tissues were subjected to immunohistochemical staining for PCNA and AgNOR technique. The PCNA labeling index (LI) and the AgNOR dots were evaluated for the entire sample. Statistical Analysis Used: ANOVA, Tukey honestly significant difference, Pearson's correlation. Results: In this study, the AgNOR count of OSCC was lower than the DL lesions moreover the AgNOR counts were found to be higher in normal mucosa as compared to the DL and the NDL epithelium. The study results also showed that the mean AgNOR count failed to distinguish between DL and NDL lesions. Overall we observed increased PCNA expression from normal epithelium to NDL to DL lesion. Conclusions: Based on the findings of the present study on oral epithelial precancerous and cancerous lesions we conclude that mean AgNOR count alone cannot be a valuable parameter to distinguish between the normal, NDL, DL epithelium and OSCC but, on the other hand, we found out that PCNA can be a useful biomarker for delineating normal epithelium from DL epithelium and OSCC. PMID:26980956

Evaluation of cell proliferation in malignant and potentially malignant oral lesions.

PubMed

Madan, Mani; Chandra, Shaleen; Raj, Vineet; Madan, Rohit

2015-01-01

To evaluate the cell proliferation rate by the expression of proliferating cell nuclear antigen (PCNA) and argyrophilic nucleolar organizing region (AgNOR) counts and to assess its usefulness as a marker for malignant potential in oral epithelial lesions. The study group included 30 cases of leukoplakia, 15 nondysplastic (NDL), 15 dysplastic (DL), 15 cases of oral squamous cell carcinoma (OSCC) and 5 cases of normal oral mucosa. Formalin fixed paraffin embedded tissues were subjected to immunohistochemical staining for PCNA and AgNOR technique. The PCNA labeling index (LI) and the AgNOR dots were evaluated for the entire sample. ANOVA, Tukey honestly significant difference, Pearson's correlation. In this study, the AgNOR count of OSCC was lower than the DL lesions moreover the AgNOR counts were found to be higher in normal mucosa as compared to the DL and the NDL epithelium. The study results also showed that the mean AgNOR count failed to distinguish between DL and NDL lesions. Overall we observed increased PCNA expression from normal epithelium to NDL to DL lesion. Based on the findings of the present study on oral epithelial precancerous and cancerous lesions we conclude that mean AgNOR count alone cannot be a valuable parameter to distinguish between the normal, NDL, DL epithelium and OSCC but, on the other hand, we found out that PCNA can be a useful biomarker for delineating normal epithelium from DL epithelium and OSCC.

Comparative Ethanol-Induced Potentiation of Stimulatory Responses to Dexmethylphenidate Versus Methylphenidate.

PubMed

Patrick, Kennerly S; Straughn, Arthur B; Reeves, Owen T; Bernstein, Hilary; Malcolm, Robert

2015-08-01

The potentiation of positive subjective responses to immediate-release dexmethylphenidate (d-MPH) or dl-methylphenidate (dl-MPH) by ethanol was investigated over the time course of maximal drug exposure after a single dose. In a 4-way, randomized, crossover study design, 12 men and 12 women normal volunteers received d-MPH (0.15 mg/kg) or dl-MPH (0.3 mg/kg) with or without ethanol (0.6 g/kg). Serial visual analog scales were used as surrogates for drug abuse liability ("high," "good," "like," "stimulated," and "any drug effect"). Combining pure d-MPH with ethanol significantly (P < 0.005) increased the area under the effect curves (AUC(0-5.25h)) of all 5 subscales. The dl-MPH-ethanol combination significantly (P < 0.05) increased these AUCs with the exception of like (P = 0.08). Effects of the pure d-MPH-ethanol combination exhibited delayed potentiation relative to dl-MPH-ethanol. A pharmacokinetic interaction between the l-isomer of dl-MPH and ethanol has previously been shown to increase early exposure to d-MPH. Administration of the pure isomer d-MPH precludes this absorption phase pharmacokinetic interaction with ethanol. This notwithstanding, the pure d-MPH-ethanol combination resulted in comparable, if not greater, cumulative stimulant potentiation than the dl-MPH-ethanol combination. These findings provide evidence of a pharmacodynamic component to d-MPH-ethanol synergistic interactions and carry implications for the rational drug individualization in the treatment of attention-deficit/hyperactivity disorder.

Vibration exercise as a warm-up modality for deadlift power output.

PubMed

Cochrane, Darryl J; Coley, Karl W; Pritchard, Hayden J; Barnes, Matthew J

2015-04-01

Vibration exercise (VbX) has gained popularity as a warm-up modality to enhance performance in golf, baseball, and sprint cycling, but little is known about the efficacy of using VbX as a warm-up before resistance exercise, such as deadlifting. The aim of this study was to compare the effects of a deadlift (DL)-specific warm-up, VbX warm-up, and Control on DL power output (PO). The DL warm-up (DL-WU) included 10, 8, and 5 repetitions performed at 30, 40, and 50% 1-repetition maximum (1RM), respectively, where the number of repetitions was matched by body-weight squats performed with vibration and without vibration (Control). The warm-up conditions were randomized and performed at least 2 days apart. Peak power (PP), mean power, rate of force development (RFD), and electromyography (EMG) were measured during the concentric phase of 2 consecutive DLs (75% 1RM) at 30 seconds and 2:30 minutes after the warm-up conditions. There was no significant (p > 0.05) main effect or interaction effect between the DL-WU, VbX warm-up, and Control for PP, mean power, RFD, and EMG. Vibration exercise warm-up did not exhibit an ergogenic effect to potentiate muscle activity more than the specific DL-WU and Control. Therefore, DL PO is affected to a similar extent, irrespective of the type of stimuli, when the warm-up is not focused on raising muscle temperature.

A unified model of density limit in fusion plasmas

NASA Astrophysics Data System (ADS)

Zanca, P.; Sattin, F.; Escande, D. F.; Pucella, G.; Tudisco, O.

2017-05-01

In this work we identify by analytical and numerical means the conditions for the existence of a magnetic and thermal equilibrium of a cylindrical plasma, in the presence of Ohmic and/or additional power sources, heat conduction and radiation losses by light impurities. The boundary defining the solutions’ space having realistic temperature profile with small edge value takes mathematically the form of a density limit (DL). Compared to previous similar analyses the present work benefits from dealing with a more accurate set of equations. This refinement is elementary, but decisive, since it discloses a tenuous dependence of the DL on the thermal transport for configurations with an applied electric field. Thanks to this property, the DL scaling law is recovered almost identical for two largely different devices such as the ohmic tokamak and the reversed field pinch. In particular, they have in common a Greenwald scaling, linearly depending on the plasma current, quantitatively consistent with experimental results. In the tokamak case the DL dependence on any additional heating approximately follows a 0.5 power law, which is compatible with L-mode experiments. For a purely externally heated configuration, taken as a cylindrical approximation of the stellarator, the DL dependence on transport is found stronger. By adopting suitable transport models, DL takes on a Sudo-like form, in fair agreement with LHD experiments. Overall, the model provides a good zeroth-order quantitative description of the DL, applicable to widely different configurations.

Lipid and fatty acid analysis of uninfected and granulosis virus-infected Plodia interpunctella larvae

NASA Technical Reports Server (NTRS)

Shastri-Bhalla, K.; Consigli, R. A.; Spooner, B. S. (Principal Investigator)

1994-01-01

A comparative study on the lipid and fatty acid composition of the uninfected and GV-infected Plodia interpunctella larvae was performed. Higher levels of free fatty acids were found in GV-infected larvae compared to those of the uninfected larvae, while the latter had more triacylglycerol compared to the former. The known identified phospholipids were fewer in the GV-infected larvae compared to those in the uninfected larvae. However, an unidentified phospholipid was found to be approximately two times higher in GV-infected larvae. The total lipid of both larvae had palmitic, oleic, and linoleic as the major fatty acids. The fatty acid composition of the GV-infected larval phospholipid differed considerably compared to that of the uninfected larvae, in that the ratio of unsaturated fatty acid to saturated fatty acid was 3.5 times less in the GV-infected larvae.

Fasting glucose and cardiovascular risk factors in an urban population.

PubMed

Gupta, R; Sarna, M; Thanvi, Jyoti; Sharma, Vibha; Gupta, V P

2007-10-01

To test the hypothesis that blood glucose levels in the range of normoglycemia are associated with increased cardiovascular risk we performed an epidemiological study in an urban population. Randomly selected adults > or = 20 years were studied using stratified sampling. Target sample was 1800 (men 960, women 840) of which 1123 subjects participated. Blood samples were available in 1091 subjects (60.6%, men 532, women 559). Measurement of anthropometric variables, blood pressure, fasting blood glucose and lipids was performed. Cardiovascular risk factors were determined using US Adult Treatment Panel-3 guidelines. Pearson's correlation coefficients (r) of fasting glucose with various risk factors were determined. Fasting glucose levels were classified into various groups as < 75 mg/dl, 75-89 mg/dl, 90-109 mg/dl, 110-125 mg/dl and > 126 mg/dl or known diabetes. Prevalence of cardiovascular risk factors was determined in each group. There was a significant positive correlation of fasting glucose in men and women with body mass index (r = 0.20, 0.12), waist-hip ratio (0.17, 0.09), systolic blood pressure (0.07, 0.22), total cholesterol (0.21, 0.15) and triglycerides (0.21, 0.25). Prevalence (%) of cardiovascular risk factors in men and women was smoking/tobacco use in 37.6 and 11.6, hypertension in 37.0 and 37.6, overweight and obesity in 37.8 and 50.3, truncal obesity in 57.3 and 68.0, high cholesterol > or = 200 mg/dl in 37.4 and 45.8, high triglycerides > or = 150 mg/dl in 32.3 and 28.6 and metabolic syndrome in 22.9 and 31.6 percent. In various groups of fasting glucose there was an increasing trend in prevalence of overweight/obesity, hypertension, hypercholesterolaemia, hypertriglyceridaemia, and metabolic syndrome (Mantel-Haenzel X2 for trend, p < 0.05) and fasting glucose < 75 mg/dl was associated with the lowest prevalence of these risk factors. There is a continuous relationship of fasting glucose levels with many cardiovascular risk factors and level < 75 mg/dl is associated with the lowest prevalence.

Effect of Threat on Right dlPFC Activity during Behavioral Pattern Separation

PubMed Central

Hsiung, Abigail; Ernst, Monique; Grillon, Christian

2017-01-01

It has long been established that individuals with anxiety disorders tend to overgeneralize attributes of fearful stimuli to nonfearful stimuli, but there is little mechanistic understanding of the neural system that supports overgeneralization. To address this gap in our knowledge, this study examined effect of experimentally induced anxiety in humans on generalization using the behavioral pattern separation (BPS) paradigm. Healthy subjects of both sexes encoded and retrieved novel objects during periods of safety and threat of unpredictable shocks while we recorded brain activity with fMRI. During retrieval, subjects were instructed to differentiate among new, old, and altered images. We hypothesized that the hippocampus and dorsolateral prefrontal cortex (dlPFC) would play a key role in the effect of anxiety on BPS. The dlPFC, but not the hippocampus, showed increased activity for altered images compared with old images when retrieval occurred during periods of threat compared with safety. In addition, accuracy for altered items retrieved during threat was correlated with dlPFC activity. Together, these results suggest that overgeneralization in anxiety patients may be mediated by an inability to recruit the dlPFC, which mediates the cognitive control needed to overcome anxiety and differentiate between old and altered items during periods of threat. SIGNIFICANCE STATEMENT Anxiety and posttraumatic stress disorder patients generalize fear to nonfearful fear stimuli, making it difficult to regulate anxiety. Understanding how anxiety affects generalization is key to understanding the overgeneralization experienced by these patients. We examined this relationship in healthy subjects by studying how threat of shock affects neural responses to previously encountered stimuli. Although previous studies point to hippocampal involvement, we found that threat affected activity in the dorsolateral prefrontal cortex (dlPFC), rather than the hippocampus, when subjects encountered slightly altered versions of the previously encountered items. Importantly, this dlPFC activity predicted performance for these items. Together, these results suggest that the dlPFC is important for discrimination during elevated anxiety and that overgeneralization may reflect a deficit in dlPFC-mediated cognitive control. PMID:28842415

Ubiquitylation of an internalized NK cell receptor by Triad3A disrupts sustained NF-κB signaling1

PubMed Central

Shahjahan Miah, S. M.; Purdy, Amanda K.; Rodin, Nicholas B.; MacFarlane, Alexander W.; Oshinsky, Jennifer; Alvarez-Arias, Diana A.; Campbell, Kerry S.

2011-01-01

KIR2DL4 (2DL4, CD158d) is a unique killer cell Ig-like receptor (KIR) expressed on human NK cells, which stimulates cytokine production, but mechanisms regulating its expression and function are poorly understood. By yeast two-hybrid screening, we identified the E3 ubiquitin ligase, Triad3A, as an interaction partner for the 2DL4 cytoplasmic domain. The protein interaction was confirmed in vivo, and Triad3A expression induced polyubiquitylation and degradation of 2DL4. Overexpression of Triad3A selectively abrogated cytokine-producing function of 2DL4, while Triad3A shRNA reversed ubiquitylation and restored cytokine production. Expression of Triad3A in an NK cell line did not affect receptor surface expression, internalization, or early signaling, but significantly reduced receptor turnover and suppressed sustained NF-κB activation. 2DL4 endocytosis was found to be vital to stimulate cytokine production, and Triad3A expression diminished localization of internalized receptor in early endosomes. Our results reveal a critical role for endocytosed 2DL4 receptor to generate sustained NF-κB signaling and drive cytokine production. We conclude that Triad3A is a key negative regulator of sustained 2DL4-mediated NF-κB signaling from internalized 2DL4, which functions by promoting ubiquitylation and degradation of endocytosed receptor from early endosomes. “This is an author-produced version of a manuscript accepted for publication in The Journal of Immunology (The JI). The American Association of Immunologists, Inc. (AAI), publisher of The JI, holds the copyright to this manuscript. This version of the manuscript has not yet been copyedited or subjected to editorial proofreading by The JI; hence, it may differ from the final version published in The JI (online and in print). AAI (The JI) is not liable for errors or omissions in this author-produced version of the manuscript or in any version derived from it by the U.S. National Institutes of Health or any other third party. The final, citable version of record can be found at www.jimmunol.org.” PMID:21270397

Comparison of the force applied on oral structures during intubation attempts by novice physicians between the Macintosh direct laryngoscope, Airway Scope and C-MAC PM: a high-fidelity simulator-based study.

PubMed

Nakanishi, Taizo; Shiga, Takashi; Homma, Yosuke; Koyama, Yasuaki; Goto, Tadahiro

2016-05-23

We examined whether the use of Airway Scope (AWS) and C-MAC PM (C-MAC) decreased the force applied on oral structures during intubation attempts as compared with the force applied with the use of Macintosh direct laryngoscope (DL). Prospective cross-over study. A total of 35 novice physicians participated. We used 6 simulation scenarios based on the difficulty of intubation and intubation devices. Our primary outcome measures were the maximum force applied on the maxillary incisors and tongue during intubation attempts, measured by a high-fidelity simulator. The maximum force applied on maxillary incisors was higher with the use of the C-MAC than with the DL and AWS in the normal airway scenario (DL, 26 Newton (N); AWS, 18 N; C-MAC, 52 N; p<0.01) and the difficult airway scenario (DL, 42 N; AWS, 24 N; C-MAC, 68 N; p<0.01). In contrast, the maximum force applied on the tongue was higher with the use of the DL than with the AWS and C-MAC in both airway scenarios (DL, 16 N; AWS, 1 N; C-MAC, 7 N; p<0.01 in the normal airway scenario; DL, 12 N; AWS, 4 N; C-MAC, 7 N; p<0.01 in the difficult airway scenario). The use of C-MAC, compared with the DL and AWS, was associated with the higher maximum force applied on maxillary incisors during intubation attempts. In contrast, the use of video laryngoscopes was associated with the lower force applied on the tongue in both airway scenarios, compared with the DL. Our study was a simulation-based study, and further research on living patients would be warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Differential Association of Gene Content Polymorphisms of Killer Cell Immunoglobulin-Like Receptors with Placental Malaria in HIV− and HIV+ Mothers

PubMed Central

Hightower, Allen; van Eijk, Anne Maria; Ayisi, John; Otieno, Juliana; Lal, Renu B.; Steketee, Richard; Nahlen, Bernard; ter Kuile, Feiko O.; Slutsker, Laurence; Shi, Ya Ping

2012-01-01

Pregnant women have abundant natural killer (NK) cells in their placenta, and NK cell function is regulated by polymorphisms of killer cell immunoglobulin-like receptors (KIRs). Previous studies report different roles of NK cells in the immune responses to placental malaria (PM) and human immunodeficiency virus (HIV-1) infections. Given these references, the aim of this study was to determine the association between KIR gene content polymorphism and PM infection in pregnant women of known HIV-1 status. Sixteen genes in the KIR family were analyzed in 688 pregnant Kenyan women. Gene content polymorphisms were assessed in relation to PM in HIV-1 negative and HIV-1 positive women, respectively. Results showed that in HIV-1 negative women, the presence of the individual genes KIR2DL1 and KIR2DL3 increased the odds of having PM, and the KIR2DL2/KIR2DL2 homozygotes were associated with protection from PM. However, the reverse relationship was observed in HIV-1 positive women, where the presence of individual KIR2DL3 was associated with protection from PM, and KIR2DL2/KIR2DL2 homozygotes increased the odds for susceptibility to PM. Further analysis of the HIV-1 positive women stratified by CD4 counts showed that this reverse association between KIR genes and PM remained only in the individuals with high CD4 cell counts but not in those with low CD4 cell counts. Collectively, these results suggest that inhibitory KIR2DL2 and KIR2DL3, which are alleles of the same locus, play a role in the inverse effects on PM and PM/HIV co-infection and the effect of KIR genes on PM in HIV positive women is dependent on high CD4 cell counts. In addition, analysis of linkage disequilibrium (LD) of the PM relevant KIR genes showed strong LD in women without PM regardless of their HIV status while LD was broken in those with PM, indicating possible selection pressure by malaria infection on the KIR genes. PMID:22715396

Description of larva and puparium of Oplodontha rubrithorax (Diptera: Stratiomyidae) from the Oriental Region.

PubMed

Nerudová, Jana; Kovac, Damir; Tóthová, Andrea

2015-05-01

This is the first description of larva and puparium of Oplodontha rubrithorax (Macquart, 1838) from the Oriental Region. Larvae were found at a hot spring in North Thailand. The morphological features and cuticular structures of the larva are documented by drawings and SEM micrographs and the main characters are compared with the European O. viridula (Fabricius, 1775), the only described larva of this genus. Differences between larvae of both species were only found in pubescence. The characteristic, somewhat dilated and slightly clavate hairs on the dorsal surface of the body segments of O. viridula larva are apparently lacking in the larva of O. rubrithorax.

Effect of tributyltin on veliger larvae of the Manila clam, Ruditapes philippinarum.

PubMed

Inoue, Suguru; Oshima, Yuji; Usuki, Hironori; Hamaguchi, Masami; Hanamura, Yukio; Kai, Norihisa; Shimasaki, Yohei; Honjo, Tsuneo

2007-01-01

We investigated the effects of waterborne and maternal exposure to tributyltin (TBT) on veliger larvae of the Manila clam, Ruditapes philippinarum. In a waterborne exposure test, veliger larvae (D-larvae stage: 24h after fertilization) were exposed to TBT at measured concentrations of <0.01 (control), 0.055, 0.130, 0.340, and 0.600microg/l for 13d. The percentage of normal veliger larvae (the ratio of normal veliger larvae to all larvae) decreased significantly in all TBT treatment groups compared with that in the control group. In a maternal exposure test, 100 clams were exposed to TBT at measured concentrations of <0.01 (control), 0.061, and 0.310microg/l at 20-22 degrees C for 3 weeks, and the percentage of normal veliger larvae assessed for 13d. No maternal effects on veliger larvae from TBT were observed in TBT treatment groups as compared with the control group. These results demonstrate that waterborne TBT affects Manila clam veliger larvae, and indicates that TBT may have reduced Manila clam populations by preventing the development and survival of veliger larvae.

Superior short-term cholesterol control and achievement of the adult treatment panel III low-density lipoprotein goals with initiation of statin therapy by the time of hospital discharge following acute myocardial infarction.

PubMed

Bybee, Kevin A; Powell, Brian D; Williams, Brent A; Murphy, Joseph G; Kopecky, Stephen L; Wright, R Scott

2004-03-15

In a community-based population, we compared serum cholesterol concentrations following hospital discharge after acute myocardial infarction based on statin therapy at the time of hospital discharge. At the time of follow-up cholesterol measurement, patients discharged from the hospital on a statin had lower mean low-density lipoprotein (LDL) (106.4 vs 116.7 mg/dl, p <0.01) and total cholesterol (182.2 vs 193.6 mg/dl, p <0.01) concentrations, larger absolute reductions in LDL (-24.7 vs -4.7 mg/dl, p <0.01) and total cholesterol (-24.2 vs -0.1 mg/dl, p <0.01) from pre-myocardial infarction levels, and superior attainment of the Adult Treatment Panel III LDL goal of <100 mg/dl at the time of follow-up compared with patients who were discharged without a statin (49% vs 33%; adjusted odds ratio 2.56; p <0.01).

Stereoselective aminoacylation of a dinucleoside monophosphate by the imidazolides of DL-alanine and N-(tert-butoxycarbonyl)-DL-alanine

NASA Technical Reports Server (NTRS)

Profy, A. T.; Usher, D. A.

1984-01-01

The aminoacylation of diinosine monophosphate was studied experimentally. When the acylating agent was the imidazolide of N-(tert-butoxycarbonyl)-DL-alanine, a 40 percent enantiomeric excess of the isomer was incorporated at the 2' site and the positions of equilibrium for the reversible 2'-3' migration reaction differed for the D and L enantiomers. The reactivity of the nucleoside hydroxyl groups was found to decrease on the order 2'(3') less than internal 2' and less than 5', and the extent of the reaction was affected by the concentration of the imidazole buffer. Reaction of IpI with imidazolide of unprotected DL-alanine, by contrast, led to an excess of the D isomer at the internal 2' site. Finally, reaction with the N-carboxy anhydride of DL-alanine occurred without stereoselection. These results are found to be relevant to the study of the evolution of optical chemical activity and the origin of genetically directed protein synthesis.

Total staff costs to implement a decision support system in nursing.

PubMed

Castilho, Valéria; Lima, Antônio Fernandes Costa; Fugulin, Fernanda Maria Togeiro; Peres, Heloisa Helena Ciqueto; Gaidzinski, Raquel Rapone

2014-01-01

to identify the direct labor (DL) costs to put in practice a decision support system (DSS) in nursing at the University Hospital of the University of São Paulo (HU-USP). the development of the DSS was mapped in four sub-processes: Conception, Elaboration, Construction and Transition. To calculate the DL, the baseline salary per professional category was added to the five-year additional remuneration, representation fees and social charges, and then divided by the number of hours contracted, resulting in the hour wage/professional, which was multiplied by the time spend on each activity in the sub-processes. the DL cost corresponded to R$ 752,618.56 (100%), R$ 26,000.00 (3.45%) of which were funded by a funding agency, while R$ 726,618.56 (96,55%) came from Hospital and University resources. considering the total DL cost, 72.1% related to staff wages for the informatics consulting company and 27.9% to the DL of professionals at the HU and the School of Nursing.

Dairy fat blend improves brain DHA and neuroplasticity and regulates corticosterone in mice.

PubMed

Dinel, A L; Rey, C; Bonhomme, C; Le Ruyet, P; Joffre, C; Layé, S

2016-06-01

Mimicking the breast milk lipid composition appears to be necessary for infant formula to cover the brain's needs in n-3 PUFA. In this study, we evaluated the impact of partial replacement of vegetable oil (VL) in infant formula by dairy fat (DL) on docosahexaenoic acid (DHA) brain level, neuroplasticity and corticosterone in mice. Mice were fed with balanced VL or balanced DL diets enriched or not in DHA and arachidonic acid (ARA) from the first day of gestation. Brain DHA level, microglia number, neurogenesis, corticosterone and glucocorticoid receptor expression were measured in the offsprings. DL diet increased DHA and neuroplasticity in the brain of mice at postnatal day (PND) 14 and at adulthood compared to VL. At PND14, ARA and DHA supplementation increased DHA in VL but not in DL mice brain. Importantly, DHA and ARA supplementation further improved neurogenesis and decreased corticosterone level in DL mice at adulthood. In conclusion, dairy lipids improve brain DHA level and neuroplasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dioxin-like polychlorinated biphenyls in marine fish from Shandong, China, and human dietary exposure.

PubMed

Cao, Yanping; Jiang, Dafeng; Li, Fenghua; Chen, Jindong; Li, Wei; Jiao, Yanni; Li, Lu

2018-05-22

The occurrence and human dietary exposure of 12 dioxin-like polychlorinated biphenyls (DL-PCBs) in 41 marine fish samples from Shandong Province of China were investigated. The DL-PCB congeners were extracted using automated Soxhlet extraction, purified via a composite column cleanup procedure and analyzed by gas chromatography-triple quadrupole mass spectrometry. DL-PCB congeners were found in all analyzed samples, with a mean concentration of 0.887 ng/g ww (wet weight). The TEQ concentrations of DL-PCBs in individual fish samples ranged from 0.011 to 9.214 pg WHO TEQ/g ww. The mean dietary intake for all fish species was 36.5 pg TEQ/kg bw/month, which was lower than the provisional tolerable monthly intake of 70 pg TEQ/kg bw/month set by the Joint FAO/WHO Expert Committee on Food Additives. To monitor the trend of DL-PCBs in fish for food safety control it is necessary to maintain a surveillance program.

Discover the pythagorean theorem using interactive multimedia learning

NASA Astrophysics Data System (ADS)

Adhitama, I.; Sujadi, I.; Pramudya, I.

2018-04-01

In learning process students are required to play an active role in learning. They do not just accept the concept directly from teachers, but also build their own knowledge so that the learning process becomes more meaningful. Based on the observation, when learning Pythagorean theorem, students got difficulty on determining hypotenuse. One of the solution to solve this problem is using an interactive multimedia learning. This article aims to discuss the interactive multimedia as learning media for students. This was a Research and Development (R&D) by using ADDIE model of development. The results obtained was multimedia which was developed proper for students as learning media. Besides, on Phytagorian theorem learning activity we also compare Discovery Learning (DL) model with interactive multimedia and DL without interactive multimedia, and obtained that DL with interactive gave positive effect better than DL without interactive multimedia. It was also obtainde that interactive multimedia can attract and increase the interest ot the students on learning math. Therefore, the use of interactive multimedia on DL procees can improve student learning achievement.

Chemical composition, rheological, quality characteristics and storage stability of buns enriched with coriander and curry leaves.

PubMed

Sudha, M L; Rajeswari, G; Venkateswara Rao, G

2014-12-01

Effect of addition of normal (NL) and dehydrated (DL) curry leaves (Murraya koeniggi) and coriander leaves (Corinadrum sativum) in the ratio of 1:1 to refined wheat flour (WF) or a blend of refined wheat flour-whole wheat flour (WF-WWF, 1:1) on the rheological, nutritional, storage and quality characteristics of the buns were studied. Water absorption increased on addition of increasing levels of DL from 0 to 7.5 % to WF-WWF when compared to WF. Dough weakening was greater when DL was added to WF-WWF as seen in decrease in dough stability and abscissa at rupture values. Addition of gluten and emulsifiers improved the quality characteristics of buns prepared using either 25 % NL or 5 % DL. Storage stability of buns with DL was better. The protein, dietary fiber, iron and carotenoids in buns prepared from WF-WWF were higher. The results indicate the utilization of leaves in dehydrated form in the preparation of nutritionally improved buns.

Evaluation of Venturi Oxygen Stripping (trademark) as a Ballast Water Treatment to Prevent Aquatic Invasions and Ship Corrosion

DTIC Science & Technology

2003-01-01

that can withstand low oxygen levels (e.g., resistant cysts of dinoflagellates, Hallegraeff 1998). Marine bacteria, in particular, will have...Chesapeake Bay zooplankton (copepods, barnacle larvae, polychaete larvae, cladocerans, crustacean nauplii, bivalve larvae, and nematodes ) in less than...zooplankton (copepods, barnacle larvae, polychaete larvae, cladocerans, crustacean nauplii, bivalve larvae, and nematodes ) in control and treated

Predaceous diving beetle, Dytiscus sharpi sharpi (Coleoptera: Dytiscidae) larvae avoid cannibalism by recognizing prey.

PubMed

Inoda, Toshio

2012-09-01

Larvae of diving beetles such as the various Dytiscus species (Coleoptera: Dytiscidae) are carnivorous and usually prey on other aquatic animals. Cannibalism among larvae of Dytiscus sharpi sharpi (Wehncke) was observed to begin when they were starved for more than two days under artificial breeding conditions. However, the 2-day starved larvae did not show cannibalism in the presence of intact, motionless, frozen tadpoles, or frozen shrimps. The beetle larvae attacked and captured intact tadpoles faster (15 sec) than other motionless and frozen tadpoles (120 sec), indicating that prey movement was an important factor in stimulating feeding behavior in larvae. Prey density does not have an effect on larval cannibalism. In cases in which preys are present at lower densities than that of larvae, a group of beetle larvae frequently fed on single prey. This feeding behavior, therefore, provides direct evidence of self-other recognition at the species level. Using two traps in one aquarium that allows the larvae to detect only prey smell, one containing tadpoles and another empty, the beetle larvae were attracted to the trap with tadpoles at high frequency, but not to the empty trap. In another experiment, the beetle larvae were not attracted to the trap containing a beetle larva. These results suggest that the larvae of D. sharpi sharpi are capable of recognizing prey scent, which enables the promotion of foraging behavior and the prevention of cannibalism.

Biological Role of Paenilarvins, Iturin-Like Lipopeptide Secondary Metabolites Produced by the Honey Bee Pathogen Paenibacillus larvae

PubMed Central

Gensel, Sebastian; Garcia-Gonzalez, Eva; Ebeling, Julia; Skobalj, Ranko; Kuthning, Anja; Süssmuth, Roderich D.

2016-01-01

The Gram-positive bacterium Paenibacillus larvae (P. larvae) is the causative agent of a deadly honey bee brood disease called American Foulbrood (AFB). AFB is a notifiable epizootic in most countries and, hence, P. larvae is of considerable relevance for veterinarians and apiculturists alike. Over the last decade, much progress has been made in the understanding of the (patho)biology of P. larvae. Recently, several non-ribosomally produced peptides (NRP) and peptide/polyketide (NRP/PK) hybrids produced by P. larvae were identified. Among these NRPs were iturin-like lipopeptides, the paenilarvins A-C. Iturins are known to exhibit strong anti-fungal activity; for some iturins, cytotoxic activity towards mammalian erythrocytes and human cancer cell lines are described. We here present our results on the analysis of the natural function of the paenilarvins during pathogenesis of P. larvae infections. We demonstrated production of paenilarvins in infected larvae. However, we could neither demonstrate cytotoxicity of paenilarvins towards cultured insect cells nor towards larvae in feeding assays. Accordingly, exposure bioassays performed with larvae infected by wild-type P. larvae and a knockout mutant of P. larvae lacking production of paenilarvins did not substantiate a role for the paenilarvins as virulence factor. Further experiments are necessary to analyze the relevance of the paenilarvins’ anti-fungal activity for P. larvae infections in the presence of fungal competitors in the larval midgut or cadaver. PMID:27760211

Biological Role of Paenilarvins, Iturin-Like Lipopeptide Secondary Metabolites Produced by the Honey Bee Pathogen Paenibacillus larvae.

PubMed

Hertlein, Gillian; Seiffert, Marlene; Gensel, Sebastian; Garcia-Gonzalez, Eva; Ebeling, Julia; Skobalj, Ranko; Kuthning, Anja; Süssmuth, Roderich D; Genersch, Elke

2016-01-01

The Gram-positive bacterium Paenibacillus larvae (P. larvae) is the causative agent of a deadly honey bee brood disease called American Foulbrood (AFB). AFB is a notifiable epizootic in most countries and, hence, P. larvae is of considerable relevance for veterinarians and apiculturists alike. Over the last decade, much progress has been made in the understanding of the (patho)biology of P. larvae. Recently, several non-ribosomally produced peptides (NRP) and peptide/polyketide (NRP/PK) hybrids produced by P. larvae were identified. Among these NRPs were iturin-like lipopeptides, the paenilarvins A-C. Iturins are known to exhibit strong anti-fungal activity; for some iturins, cytotoxic activity towards mammalian erythrocytes and human cancer cell lines are described. We here present our results on the analysis of the natural function of the paenilarvins during pathogenesis of P. larvae infections. We demonstrated production of paenilarvins in infected larvae. However, we could neither demonstrate cytotoxicity of paenilarvins towards cultured insect cells nor towards larvae in feeding assays. Accordingly, exposure bioassays performed with larvae infected by wild-type P. larvae and a knockout mutant of P. larvae lacking production of paenilarvins did not substantiate a role for the paenilarvins as virulence factor. Further experiments are necessary to analyze the relevance of the paenilarvins' anti-fungal activity for P. larvae infections in the presence of fungal competitors in the larval midgut or cadaver.

Thermodynamic characteristics of protolytic equilibria in aqueous solutions of glycyl peptides

NASA Astrophysics Data System (ADS)

Gridchin, S. N.

2016-11-01

Protolytic equilibria in aqueous solutions of glycyl-DL-serine, glycyl-DL-threonine, and glycyl-DL-valine are investigated by means of potentiometry and calorimetry. Dissociation constants and heat effects of the above dipeptides are determined. Standard thermodynamic characteristics (p K°, Δdis G°, Δdis H°, Δdis S°) of the investigated equilibria are calculated. The obtained results are compared to corresponding data on relative compounds.

Covalent trapping of human DNA polymerase beta by the oxidative DNA lesion 2-deoxyribonolactone.

PubMed

DeMott, Michael S; Beyret, Ergin; Wong, Donny; Bales, Brian C; Hwang, Jae-Taeg; Greenberg, Marc M; Demple, Bruce

2002-03-08

Oxidized abasic residues in DNA constitute a major class of radiation and oxidative damage. Free radical attack on the nucleotidyl C-1' carbon yields 2-deoxyribonolactone (dL) as a significant lesion. Although dL residues are efficiently incised by the main human abasic endonuclease enzyme Ape1, we show here that subsequent excision by human DNA polymerase beta is impaired at dL compared with unmodified abasic sites. This inhibition is accompanied by accumulation of a protein-DNA cross-link not observed in reactions of polymerase beta with unmodified abasic sites, although a similar form can be trapped by reduction with sodium borohydride. The formation of the stably cross-linked species with dL depends on the polymerase lysine 72 residue, which forms a Schiff base with the C-1 aldehyde during excision of an unmodified abasic site. In the case of a dL residue, attack on the lactone C-1 by lysine 72 proceeds more slowly and evidently produces an amide linkage, which resists further processing. Consequently dL residues may not be readily repaired by "short-patch" base excision repair but instead function as suicide substrates in the formation of protein-DNA cross-links that may require alternative modes of repair.

Diagnostic laparoscopy should be performed before definitive resection for pancreatic cancer: a financial argument.

PubMed

Jayakrishnan, Thejus T; Nadeem, Hasan; Groeschl, Ryan T; George, Ben; Thomas, James P; Ritch, Paul S; Christians, Kathleen K; Tsai, Susan; Evans, Douglas B; Pappas, Sam G; Gamblin, T Clark; Turaga, Kiran K

2015-02-01

Laparoscopy is recommended to detect radiographically occult metastases in patients with pancreatic cancer before curative resection. This study was conducted to test the hypothesis that diagnostic laparoscopy (DL) is cost-effective in patients undergoing curative resection with or without neoadjuvant therapy (NAT). Decision tree modelling compared routine DL with exploratory laparotomy (ExLap) at the time of curative resection in resectable cancer treated with surgery first, (SF) and borderline resectable cancer treated with NAT. Costs (US$) from the payer's perspective, quality-adjusted life months (QALMs) and incremental cost-effectiveness ratios (ICERs) were calculated. Base case estimates and multi-way sensitivity analyses were performed. Willingness to pay (WtP) was US$4166/QALM (or US$50,000/quality-adjusted life year). Base case costs were US$34,921 for ExLap and US$33,442 for DL in SF patients, and US$39,633 for ExLap and US$39,713 for DL in NAT patients. Routine DL is the dominant (preferred) strategy in both treatment types: it allows for cost reductions of US$10,695/QALM in SF and US$4158/QALM in NAT patients. The present analysis supports the cost-effectiveness of routine DL before curative resection in pancreatic cancer patients treated with either SF or NAT. © 2014 International Hepato-Pancreato-Biliary Association.

Utilization of exploration-based learning and video-assisted learning to teach GlideScope videolaryngoscopy.

PubMed

Johnston, Lindsay C; Auerbach, Marc; Kappus, Liana; Emerson, Beth; Zigmont, Jason; Sudikoff, Stephanie N

2014-01-01

GlideScope (GS) is used in pediatric endotracheal intubation (ETI) but requires a different technique compared to direct laryngoscopy (DL). This article was written to evaluate the efficacy of exploration-based learning on procedural performance using GS for ETI of simulated pediatric airways and establish baseline success rates and procedural duration using DL in airway trainers among pediatric providers at various levels. Fifty-five pediatric residents, fellows, and faculty from Pediatric Critical Care, NICU, and Pediatric Emergency Medicine were enrolled. Nine physicians from Pediatric Anesthesia benchmarked expert performance. Participants completed a demographic survey and viewed a video by the GS manufacturer. Subjects spent 15 minutes exploring GS equipment and practicing the intubation procedure. Participants then intubated neonatal, infant, child, and adult airway simulators, using GS and DL, in random order. Time to ETI was recorded. Procedural performance after exploration-based learning, measured as time to successful ETI, was shorter for DL than for GS for neonatal and child airways at the.05 significance level. Time to ETI in adult airway using DL was correlated with experience level (p =.01). Failure rates were not different among subgroups. A brief video and period of exploration-based learning is insufficient for implementing a new technology. Pediatricians at various levels of training intubated simulated airways faster using DL than GS.

Self-reinforced bioresorbable poly-L/DL-lactide [SR-P(L/DL)LA] 70/30 miniplates and miniscrews are reliable for fixation of anterior mandibular fractures: a pilot study.

PubMed

Ylikontiola, Leena; Sundqvuist, Kai; Sàndor, George K B; Törmälä, Pertti; Ashammakhi, Nureddin

2004-03-01

Bioresorbable osteofixation devices are being increasingly used in orthognathic surgery and in cases of trauma to avoid problems associated with conventional metal osteofixation devices. The aim of this clinical study was to assess the reliability and efficacy of bioresorbable self-reinforced poly-L/DL-lactide (SR-P(L/DL)LA 70/30) plates and screws in the fixation of mandibular fractures in adults. Ten patients (20 to 49 years old) with isolated anterior mandibular parasymphyseal fractures were treated by means of open reduction and internal fixation using SR-P(L/DL)LA 70/30 bioresorbable plates and screws. During the minimum of 6 months of follow-up, no problems were encountered except for 1 case where a plate became exposed intraorally and infected. This required debridement and later excision of the exposed part of the plate. Despite this setback the fractured bone healed well. SR-P(L/DL)LA 70/30 plates and screws are reliable for internal fixation of anterior mandibular fractures in adults. Proper soft tissue coverage should be ensured to avoid plate exposure. Should implant exposure occur, it might be necessary to excise the exposed part after fracture healing (6-8 weeks postoperatively).

Clinical assessment of a radioimmunoassay for free thyroxine using a modified tracer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, D.W.; Waud, J.M.; Hsu, T.H.

1983-06-01

A radioimmunoassay for measuring free thyroxine in plasma was introduced by Amersham using a I-125-labeled T4 derivative that does not bind significantly to the thyroxine-binding proteins. We evaluated this RIA for its clinical utility in assessing 278 patients with thyroid and nonthyroidal diseases. The precision of the Amerlex free T4 assay, expressed as coefficient of variation, was 20% at 0.16 ng/dl, 6.9% at 0.55 ng/dl, 4.2% at 1.08 ng/dl, 5.3% at 2.29 ng/dl, and 6.3% at 3.18 ng/dl. A reference range for free T4 was established as 0.68-1.8 ng/dl, n . 171. The correlation coefficients (r) of a dialysis methodmore » and a free thyroxine index were 0.871 and 0.911, respectively. Free T4 correctly classified 98% euthyroid, 92% hypothyroid, 100% hyperthyroid, 100% euthyroid with elevated TBG, and 87% of phenytoin patients. In addition, 80 patients with acute nonthyroidal illness were studied. Most of these patients have normal to low free T4, very low T3, and elevated rT3. We found this free T4 assay to be precise, easy to perform, and reliable in classifying thyroid status in most patients.« less

Stability of maxillary position after Le Fort I osteotomy using self-reinforced biodegradable poly-70L/30DL-lactide miniplates and screws.

PubMed

Kim, Bong Chul; Padwa, Bonnie L; Park, Hyung-Sik; Jung, Young-Soo

2011-05-01

The purpose of this study was to evaluate the stability of Le Fort I osteotomy using self-reinforced biodegradable poly-70L/30DL-lactide miniplates and screws. Nineteen patients who had Le Fort I osteotomy and internal fixation using self-reinforced biodegradable poly-70L/30DL-lactide miniplates and screws were evaluated both radiographically and clinically. Changes in maxillary position after operation were documented 1 week, 1, 3, 6 mo, and/or 1-yr postoperatively with lateral cephalometric tracings. Complications of the self-reinforced biodegradable poly-70L/30DL-lactide miniplates and screws were evaluated by follow-up roentgenograms and clinical observation. A mixed model analysis for repeated measures was used for statistical analysis. Maxillary position was stable after operation with no change between time points (P > .05). There were no complications with the self-reinforced biodegradable poly-70L/30DL-lactide miniplates and screws. Internal fixation of the maxilla after Le Fort I osteotomy with self-reinforced biodegradable poly-70L/30DL-lactide miniplates and screws is a reliable method for maintaining the postoperative maxillary position after Le Fort I osteotomy. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Dissemination and Implementation of Cognitive Behavioral Therapy for Stimulant Dependence: A Randomized Trial Comparison of Three Approaches

PubMed Central

Rawson, Richard A.; Rataemane, Solomon; Rataemane, Lusanda; Ntlhe, Nomvuyo; Fox, Ruthlyn Sodano; McCuller, Jason; Brecht, Mary-Lynn

2012-01-01

This study evaluated the effectiveness of 3 approaches to transferring cognitive behavioral therapy (CBT) to addiction clinicians in the Republic of South Africa (RSA). Clinicians (N = 143) were assigned to 3 training conditions: (1) An in vivo (IV) approach in which clinicians received in-person training and coaching; (2) A distance learning (DL) approach providing training via video conference and coaching through teleconferencing; and (3) A control condition (C) providing a manual and 2-hour orientation. Frequency of use of CBT skills increased significantly with the IV and DL approaches compared to the C approach, and the IV approach facilitated greater use of CBT skills than the DL approach. During the active phase of the study, skill quality declined significantly for clinicians trained in the C condition, whereas those in the DL approach maintained skill quality and those in the IV approach improved skill quality. After coaching was discontinued, clinicians in the IV and DL approaches declined in skill quality. However, those in the IV approach maintained a higher level of skill quality compared to the other approaches. Cost of the IV condition was double that of the DL condition and 10 times greater than the C condition. PMID:23577903

Prevalence of Three-Rooted Mandibular First Molars among Indians Using SCT

PubMed Central

Garg, Amit Kumar; Tewari, Rajendra Kumar; Agrawal, Neha

2013-01-01

Undetected extra roots or root canals are a major reason for failure of endodontic treatment. Failure to recognize an extra distolingual (DL) root in mandibular first molar may lead to incomplete debridement of the root canal system and eventually treatment failure. Therefore, it is crucial that atypical anatomy is identified before and during dental treatment. Spiral computed tomography (SCT) images can show 3D images, and therefore much detail can be used when traditional methods prevent adequate endodontic treatment. The overall incidence of DL roots on the mandibular first molars was 6.40% for all patients and 5.00% for all teeth, respectively. The occurrence of DL roots on the right side and on the left side showed a statistically significant difference. The bilateral incidence of symmetrical distribution of DL roots was 56.25%. The DL root canal orifice was separated from DB canal orifice by 2.79 ± 0.34 mm, from the MB canal orifice by 4.23 ± 0.81 mm, and from the ML canal orifice by 3.29 ± 0.52 mm. The high prevalence of the DL root in permanent mandibular first molars among the Indian population by using SCT and estimations of the interorifice distance of such teeth might be useful for successful endodontic treatments. PMID:23840212

Methodological considerations of task and shoe wear on joint energetics during landing.

PubMed

Shultz, Sandra J; Schmitz, Randy J; Tritsch, Amanda J; Montgomery, Melissa M

2012-02-01

To better understand methodological factors that alter landings strategies, we compared sagittal plane joint energetics during the initial landing phase of drop jumps (DJ) vs. drop landings (DL), and when shod vs. barefoot. Surface electromyography, kinematic and kinetic data were obtained on 10 males and 10 females during five consecutive drop landings and five consecutive drop jumps (0.45m) when shod and when barefoot. Energy absorption was greater in the DJ vs. DL (P=.002), due to increased energy absorption at the hip during the DJ. Joint stiffness/impedance was more affected by shoe condition, where overall stiffness/impedance was greater in shod compared to barefoot conditions (P=.036). Further, hip impedance was greater in shod vs. barefoot for the DL only (via increased peak hip extensor moment in DL), while ankle stiffness was greater in the barefoot vs. shod condition for the DJ only (via decreased joint excursion and increased peak joint moment in DJ vs. DL) (P=.011). DJ and DL place different neuromechanical demands upon the lower extremities, and shoe wear may alter impact forces that modulate stiffness/impedance strategies. The impact of these methodological differences should be considered when comparing landing biomechanics across studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Occurrence, variability and human exposure to Polychlorinated Dibenzo-p-dioxins (PCDDs), Polychlorinated Dibenzofurans (PCDFs) and Dioxin-Like Polychlorinated Biphenyls (DL-PCBs) in dairy products from Chile during the 2011-2013 survey.

PubMed

Pizarro-Aránguiz, N; Galbán-Malagón, C J; Ruiz-Rudolph, P; Araya-Jordan, C; Maddaleno, A; San Martin, B

2015-05-01

Levels, congener profiles of PCDD/Fs, DL-PCBs and human exposure for these xenobiotics never have been reported in Chile. For that purpose 102 raw cow milk samples were collected from seven different regions of Chile during 2011 until 2013. The highest mean level for PCDD/Fs, corresponds to 0.32 pg WHO-TEQ2005 g(-1) fat (2012) and for DL-PCBs 0.17 pg WHO-TEQ2005 g(-1) fat (2011), using the upper bound approach. Penta and tetra chlorinated congeners dominated PCDD/Fs profiles in a WHO-TEQ2005 basis during the survey. In the case of DL-PCBs, PCB 126 dominated the profiles with 89%. Statistical analysis showed significant difference among years only in DL-PCBs residues. Also dietary intake was estimated, and the highest level for total sum of PCDD/Fs and DL-PCBs for adult was 0.16 pg WHO-TEQ kg(-1) b.w d(-1) (2011) and for children correspond to 0.65 pg WHO-TEQ kg(-1) b.wd(-1) (2011). Concentrations and dietary intake for the studied compounds in milk and butter samples were below international and national regulations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Activity of Selected Formulated Biorational and Synthetic Insecticides Against Larvae of Helicoverpa armigera (Lepidoptera: Noctuidae).

PubMed

Vivan, L M; Torres, J B; Fernandes, P L S

2017-02-01

This work studied 17 insecticides belonging to nucleopolyhedrovirus (NPV), Bacillus thuringiensis (Bt kurstaki and Bt aizawai), benzoylureas (insect growth regulators [IGRs]), carbamates, organophosphates, spinosyns, and diamides against larvae of Helicoverpa armigera (Hübner), invasive species in the South American continent. Larvae of different instars were fed for 7 d with untreated or insecticide-treated diets. Mortality was recorded daily for 7 d, and surviving larvae were individually weighed on the seventh day. The NPV and Bt insecticides caused 100% mortality of first-instar larvae and first-instar and second-instar larvae, respectively. However, both NPV and Bt-based products caused low mortality of third-instar larvae and did not kill older larvae. The IGR lufenuron was highly effective against all three ages of larvae tested, whereas teflubenzuron and triflumuron produced maximum 60% mortality of second-instar larvae and lower than 50% to older larvae. Thiodicarb, chlorantraniliprole, indoxacarb, chlorpyrifos, and chlorfenapyr, irrespective of tested age, caused 100% mortality of larvae, with the last two insecticides reaching 100% mortality within 2 d of feeding on the treated diet. Flubendiamide caused lower mortality but significantly affected the weight of surviving larvae, whereas neither spinosad nor methomyl produced significant mortality or affected the weight of larvae. Based on the results, the age of H. armigera larvae plays an important role in the recommendation of NPV and Bt insecticides. Furthermore, there are potential options between biological and synthetic insecticides tested against H. armigera, and recording larval size during monitoring, in addition to the infestation level, should be considered when recommending biological-based insecticides to control this pest. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cognitive regulation during decision making shifts behavioral control between ventromedial and dorsolateral prefrontal value systems.

PubMed

Hutcherson, Cendri A; Plassmann, Hilke; Gross, James J; Rangel, Antonio

2012-09-26

Cognitive regulation is often used to influence behavioral outcomes. However, the computational and neurobiological mechanisms by which it affects behavior remain unknown. We studied this issue using an fMRI task in which human participants used cognitive regulation to upregulate and downregulate their cravings for foods at the time of choice. We found that activity in both ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) correlated with value. We also found evidence that two distinct regulatory mechanisms were at work: value modulation, which operates by changing the values assigned to foods in vmPFC and dlPFC at the time of choice, and behavioral control modulation, which operates by changing the relative influence of the vmPFC and dlPFC value signals on the action selection process used to make choices. In particular, during downregulation, activation decreased in the value-sensitive region of dlPFC (indicating value modulation) but not in vmPFC, and the relative contribution of the two value signals to behavior shifted toward the dlPFC (indicating behavioral control modulation). The opposite pattern was observed during upregulation: activation increased in vmPFC but not dlPFC, and the relative contribution to behavior shifted toward the vmPFC. Finally, ventrolateral PFC and posterior parietal cortex were more active during both upregulation and downregulation, and were functionally connected with vmPFC and dlPFC during cognitive regulation, which suggests that they help to implement the changes to the decision-making circuitry generated by cognitive regulation.

Cognitive Regulation during Decision Making Shifts Behavioral Control between Ventromedial and Dorsolateral Prefrontal Value Systems

PubMed Central

Plassmann, Hilke; Gross, James J.; Rangel, Antonio

2012-01-01

Cognitive regulation is often used to influence behavioral outcomes. However, the computational and neurobiological mechanisms by which it affects behavior remain unknown. We studied this issue using an fMRI task in which human participants used cognitive regulation to upregulate and downregulate their cravings for foods at the time of choice. We found that activity in both ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) correlated with value. We also found evidence that two distinct regulatory mechanisms were at work: value modulation, which operates by changing the values assigned to foods in vmPFC and dlPFC at the time of choice, and behavioral control modulation, which operates by changing the relative influence of the vmPFC and dlPFC value signals on the action selection process used to make choices. In particular, during downregulation, activation decreased in the value-sensitive region of dlPFC (indicating value modulation) but not in vmPFC, and the relative contribution of the two value signals to behavior shifted toward the dlPFC (indicating behavioral control modulation). The opposite pattern was observed during upregulation: activation increased in vmPFC but not dlPFC, and the relative contribution to behavior shifted toward the vmPFC. Finally, ventrolateral PFC and posterior parietal cortex were more active during both upregulation and downregulation, and were functionally connected with vmPFC and dlPFC during cognitive regulation, which suggests that they help to implement the changes to the decision-making circuitry generated by cognitive regulation. PMID:23015444

Methyl salicylate 2-O-β-D-lactoside, a novel salicylic acid analogue, acts as an anti-inflammatory agent on microglia and astrocytes

PubMed Central

2011-01-01

Background Neuroinflammation has been known to play a critical role in the pathogenesis of Alzheimer's disease (AD). Activation of microglia and astrocytes is a characteristic of brain inflammation. Epidemiological studies have shown that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) delays the onset of AD and suppresses its progression. Methyl salicylate-2-O-β-D-lactoside (DL0309) is a new molecule chemically related to salicylic acid. The present study aimed to evaluate the anti-inflammatory effects of DL0309. Findings Our studies show that DL0309 significantly inhibits lipopolysaccharide (LPS)-induced release of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α; and the expression of the inflammation-related proteins iNOS, COX-1, and COX-2 by microglia and astrocytes. At a concentration of 10 μM, DL0309 prominently inhibited LPS-induced activation of NF-κB in glial cells by blocking phosphorylation of IKK and p65, and by blocking IκB degradation. Conclusions We demonstrate here for the first time that DL0309 exerts anti-inflammatory effects in glial cells by suppressing different pro-inflammatory cytokines and iNOS/NO. Furthermore, it also regulates the NF-κB signaling pathway by blocking IKK and p65 activation and IκB degradation. DL0309 also acts as a non-selective COX inhibitor in glial cells. These studies suggest that DL0309 may be effective in the treatment of neuroinflammatory disorders, including AD. PMID:21831328

Alarm characterization for continuous glucose monitors used as adjuncts to self-monitoring of blood glucose.

PubMed

McGarraugh, Geoffrey

2010-01-01

Continuous glucose monitoring (CGM) devices available in the United States are approved for use as adjuncts to self-monitoring of blood glucose (SMBG). Alarm evaluation in the Clinical and Laboratory Standards Institute (CLSI) guideline for CGM does not specifically address devices that employ both CGM and SMBG. In this report, an alarm evaluation method is proposed for these devices. The proposed method builds on the CLSI method using data from an in-clinic study of subjects with type 1 diabetes. CGM was used to detect glycemic events, and SMBG was used to determine treatment. To optimize detection of a single glucose level, such as 70 mg/dl, a range of alarm threshold settings was evaluated. The alarm characterization provides a choice of alarm settings that trade off detection and false alarms. Detection of a range of high glucose levels was similarly evaluated. Using low glucose alarms, detection of 70 mg/dl within 30 minutes increased from 64 to 97% as alarm settings increased from 70 to 100 mg/dl, and alarms that did not require treatment (SMBG >85 mg/dl) increased from 18 to 52%. Using high glucose alarms, detection of 180 mg/dl within 30 minutes increased from 87 to 96% as alarm settings decreased from 180 to 165 mg/dl, and alarms that did not require treatment (SMBG <180 mg/dl) increased from 24 to 42%. The proposed alarm evaluation method provides information for choosing appropriate alarm thresholds and reflects the clinical utility of CGM alarms. 2010 Diabetes Technology Society.

Endocrine-metabolic responses to military field operations: Effects of cold and moderate altitude exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Floyd, E.; Hackney, A.C.; Hodgdon, J.A.

1991-03-11

Select endocrine-metabolic responses of US Marines to 4.5 day field operations (FOPS) in different environments were examined. Blood and urine samples were collected in the field immediately before and after FOPS at: (1) sea level, neutral temperatures (Ts) (SLN; n = 14), (2) sea level, cold Ts (SLC; n = 16), (3) 2,500 M altitude, neutral Ts (ALN; n = 16), and (4) 2,500 M altitude, cold Ts (ALC; n = 45). Measures examined were testosterone (T), cortisol (C), glucose (Glu), triglycerides (Tg), and urinary ketones (Uket). T decreased pre-post the FOPS in the cold conditions ({bar X}; 6.7 tomore » 5.5 hg/ml; n = 61) but did not change in neutral conditions. C increased pre-post FOPS at SLC (12.1 to 19.8 ug/dl, p < 0.01), ALN (9.3 to 13.9 ug/dl, p < 0.01), and ALC (16.7 to 19.0 ug/dl, p = 0.08). Normoglycemia was maintained under each condition. Tg decreased (p < 0.01) at SLC, ALN, and ALC ({bar X}{triangle}: {minus}59.1, {minus}102.2, {minus}93.3 mg/dl, respectively), but increased at SLN (+74.0 mg/dl). Uket increased post FOPS only at ALN and ALC ({bar X}{triangle}: 3.4 mg/dl and +11.3 mg/dl). The Uket increases were correlated to Tg decreases. Results suggest FOPS induces a slight endocrine stress response, which is augmented with moderate altitude or cold exposure. Furthermore FOPS at altitude, especially in the cold, seems to shift the body towards fat metabolism.« less

Liver condition of Holstein cows affects mitochondrial function and fertilization ability of oocytes

PubMed Central

TANAKA, Hiroshi; TAKEO, Shun; ABE, Takahito; KIN, Airi; SHIRASUNA, Koumei; KUWAYAMA, Takehito; IWATA, Hisataka

2016-01-01

The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts. PMID:26832309

Diagnostic Laparoscopy for Trauma: How Not to Miss Injuries.

PubMed

Koto, Modise Z; Matsevych, Oleh Y; Aldous, Colleen

2018-05-01

Diagnostic laparoscopy (DL) is a well-accepted approach for penetrating abdominal trauma (PAT). However, the steps of procedure and the systematic laparoscopic examination are not clearly defined in the literature. The aim of this study was to clarify the definition of DL in trauma surgery by auditing DL performed for PAT at our institution, and to describe the strategies on how to avoid missed injuries. The data of patients managed with laparoscopy for PAT from January 2012 to December 2015 were retrospectively analyzed. The details of operative technique and strategies on how to avoid missed injuries were discussed. Out of 250 patients managed with laparoscopy for PAT, 113 (45%) patients underwent DL. Stab wounds sustained 94 (83%) patients. The penetration of the peritoneal cavity or retroperitoneum was documented in 67 (59%) of patients. Organ evisceration was present in 21 (19%) patients. Multiple injuries were present in 22% of cases. The chest was the most common associated injury. Two (1.8%) iatrogenic injuries were recorded. The conversion rate was 1.7% (2/115). The mean length of hospital stay was 4 days. There were no missed injuries. In the therapeutic laparoscopy (TL) group, DL was performed as the initial part and identified all injuries. There were no missed injuries in the TL group. The predetermined sequential steps of DL and the standard systematic examination of intraabdominal organs were described. DL is a feasible and safe procedure. It accurately identifies intraabdominal injuries. The selected use of preoperative imaging, adherence to the predetermined steps of procedure and the standard systematic laparoscopic examination will minimize the rate of missed injuries.

Liver condition of Holstein cows affects mitochondrial function and fertilization ability of oocytes.

PubMed

Tanaka, Hiroshi; Takeo, Shun; Abe, Takahito; Kin, Airi; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

2016-06-17

The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts.

Correlation between synergistic action of Radix Angelica dahurica extracts on analgesic effects of Corydalis alkaloid and plasma concentration of dl-THP.

PubMed

Liao, Zheng-Gen; Liang, Xin-Li; Zhu, Jing-Yun; Zhao, Guo-Wei; Yang, Ming; Wang, Guang-Fa; Jiang, Qie-Ying; Chen, Xu-Long

2010-05-04

Yuanhu Zhitong prescription that consists of Corydalis yanhusuo and Radix Angelicae dahuricae has been used for the treatment of gastralgia, costalgia, headache and dysmenorrhea in Traditional Chinese Medicine. Our previous studies demonstrated that Corydalis alkaloid (CA, derived from the root of Corydalis yanhusu) had potent analgesic properties, and the total coumarins of Angelica dahurica (Cou) and volatile oil (VO) that derived from the root of Radix Angelicae dahuricae all could increase the analgesic effect of CA. The major objective of this paper was to investigate the mechanism that leading the analgesia of CA increased by Cou and (or) VO. The relationship between analgesic effect of CA and the plasma concentration of Dl-tetrahydropalmatine (dl-THP, active component of CA) was assayed in mice writhing test. The CA (34, 68 and 134 mg/kg) reduced the nociception by acetic acid intraperitoneal injection in a dose-dependent manner, and there was a significant linear relationship between the analgesic effect of CA and the plasma concentration of dl-THP. Then the plasma concentration of dl-THP at different time intervals in rats after oral administration of CA, CA-Cou, CA-VO and CA-Cou-VO were examined by using HPLC. The results indicated that Cou and (or) VO raised the plasma concentration of dl-THP prominently. In conclusion, the reason that Radix Angelica dahurica extracts reinforced the analgesic effects of Corydalis alkaloid was related to the improvement of the plasma concentration of dl-THP. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Dual-layer DECT for multiphasic hepatic CT with 50 percent iodine load: a matched-pair comparison with a 120 kVp protocol.

PubMed

Nagayama, Yasunori; Nakaura, Takeshi; Oda, Seitaro; Utsunomiya, Daisuke; Funama, Yoshinori; Iyama, Yuji; Taguchi, Narumi; Namimoto, Tomohiro; Yuki, Hideaki; Kidoh, Masafumi; Hirata, Kenichiro; Nakagawa, Masataka; Yamashita, Yasuyuki

2018-04-01

To evaluate the image quality and lesion conspicuity of virtual-monochromatic-imaging (VMI) with dual-layer DECT (DL-DECT) for reduced-iodine-load multiphasic-hepatic CT. Forty-five adults with renal dysfunction who had undergone hepatic DL-DECT with 300-mgI/kg were included. VMI (40-70-keV, DL-DECT-VMI) was generated at each enhancement phase. As controls, 45 matched patients undergoing standard 120-kVp protocol (120-kVp, 600-mgI/kg, and iterative reconstruction) were included. We compared the size-specific dose estimate (SSDE), image noise, CT attenuation, and contrast-to-noise ratio (CNR) between protocols. Two radiologists scored the image quality and lesion conspicuity. SSDE was significantly lower in DL-DECT group (p < 0.01). Image noise of DL-DECT-VMI was almost constant at each keV (differences of ≤15%) and equivalent to or lower than of 120-kVp. As the energy decreased, CT attenuation and CNR gradually increased; the values of 55-60 keV images were almost equivalent to those of standard 120-kVp. The highest scores for overall quality and lesion conspicuity were assigned at 40-keV followed by 45 to 55-keV, all of which were similar to or better than of 120-kVp. For multiphasic-hepatic CT with 50% iodine-load, DL-DECT-VMI at 40- to 55-keV provides equivalent or better image quality and lesion conspicuity without increasing radiation dose compared with standard 120-kVp protocol. • 40-55-keV yields optimal image quality for half-iodine-load multiphasic-hepatic CT with DL-DECT. • DL-DECT protocol decreases radiation exposure compared with 120-kVp scans with iterative reconstruction. • 40-keV images maximise conspicuity of hepatocellular carcinoma especially at hepatic-arterial phase.

Genomic instability related to zinc deficiency and excess in an in vitro model: is the upper estimate of the physiological requirements recommended for children safe?

PubMed

Padula, Gisel; Ponzinibbio, María Virginia; Gambaro, Rocío Celeste; Seoane, Analía Isabel

2017-08-01

Micronutrients are important for the prevention of degenerative diseases due to their role in maintaining genomic stability. Therefore, there is international concern about the need to redefine the optimal mineral and vitamin requirements to prevent DNA damage. We analyzed the cytostatic, cytotoxic, and genotoxic effect of in vitro zinc supplementation to determine the effects of zinc deficiency and excess and whether the upper estimate of the physiological requirement recommended for children is safe. To achieve zinc deficiency, DMEM/Ham's F12 medium (HF12) was chelated (HF12Q). Lymphocytes were isolated from healthy female donors (age range, 5-10 yr) and cultured for 7 d as follows: negative control (HF12, 60 μg/dl ZnSO 4 ); deficient (HF12Q, 12 μg/dl ZnSO 4 ); lower level (HF12Q + 80 μg/dl ZnSO 4 ); average level (HF12Q + 180 μg/dl ZnSO 4 ); upper limit (HF12Q + 280 μg/dl ZnSO 4 ); and excess (HF12Q + 380 μg/dl ZnSO 4 ). The comet (quantitative analysis) and cytokinesis-block micronucleus cytome assays were used. Differences were evaluated with Kruskal-Wallis and ANOVA (p < 0.05). Olive tail moment, tail length, micronuclei frequency, and apoptotic and necrotic percentages were significantly higher in the deficient, upper limit, and excess cultures compared with the negative control, lower, and average limit ones. In vitro zinc supplementation at the lower and average limit (80 and 180 μg/dl ZnSO 4 ) of the physiological requirement recommended for children proved to be the most beneficial in avoiding genomic instability, whereas the deficient, upper limit, and excess (12, 280, and 380 μg/dl) cultures increased DNA and chromosomal damage and apoptotic and necrotic frequencies.

Preparation, optimisation and characterisation of novel wound healing film dressings loaded with streptomycin and diclofenac.

PubMed

Pawar, H V; Tetteh, J; Boateng, J S

2013-02-01

Streptomycin (STP) and diclofenac (DLF) loaded film dressings were prepared by blending Polyox(®) (POL) with four hydrophilic polymers [hydroxypropylmethylcellulose (HPMC), carrageenan (CAR), sodium alginate (SA) or chitosan (CS)] using glycerol (GLY) as plasticiser. The films were characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, texture analysis (tensile and swelling characteristics) and in vitro dissolution profiles using Franz diffusion cell. SEM showed homogeneous morphology for both blank (BLK) and drug loaded (DL) films. Films prepared by blending of POL with the other polymers showed a reduction in the crystallisation of POL in descending order of SA>CS>HPMC>CAR respectively. DSC and XRD showed no crystalline peaks of STP and DLF suggesting molecular dispersion of both drugs as well as possible drug interaction with negatively charged sulphate ions present in CAR. The DL films did not show any IR bands of both drugs, confirming the DSC and XRD results. POL-CAR-BLK films showed higher tensile strength (12.32±1.40 MPa) than the POL-CAR-DL films (9.52±1.12 MPa). DL films plasticised with 25%w/w GLY revealed soft and tough (tensile strength 1.02±0.28 MPa, % elongation 1031.33±16.23) formulations. The swelling capacities of POL-CAR-BLK and POL-CAR-DL films were (733.17±25.78%) and (646.39±40.39%), increasing to (1072.71±80.30%) and (1051±86.68%) for POL-CAR-BLK-25% GLY and POL-CAR-DL-25% GLY respectively. POL-CAR-DL films showed significantly (n=3, p<0.0318) lower cumulative release of STP and DLF (52.11±1.34, 55.26±2.25) compared to POL-CAR-DL-25% GLY films (60.07±1.56, 63.39±1.92) respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

Concurrence of Serum Creatinine and Albumin with Lower Risk for Death in Twice-Weekly Hemodialysis Patients

PubMed Central

Wang, Jialin; Streja, Elani; Soohoo, Melissa; Chen, Joline L.T.; Rhee, Connie M.; Kim, Taehee; Molnar, Miklos Z.; Kovesdy, Csaba P.; Mehrotra, Rajnish; Kalantar-Zadeh, Kamyar

2016-01-01

Objective Markers of better nutritional status including both higher levels of serum albumin (as a measure of visceral proteins) and creatinine (as a measure of the muscle mass) are associated with lower mortality in conventional (thrice-weekly) hemodialysis patients. However, data for these associations in twice-weekly hemodialysis patients, in whom less frequent hemodialysis may confound nutritional predictors, are lacking. Design, Settings and Subjects We identified 1,113 twice-weekly and matched 4,448 thrice-weekly hemodialysis patients from a large national dialysis cohort of incident hemodialysis patients over 5 years (2007-2011). Mortality risk, adjusted for potential confounders, was examined across two-by-two combinations of serum creatinine (<6 mg/dl vs. ≥6 mg/dl) and albumin (<3.5 g/dl vs. ≥3.5 g/dl) for each treatment frequency yielding a total of eight groups. Results Patients were 70±14 years old and included 48% women, and 55% diabetics. Using the thrice-weekly hemodialysis patients with creatinine≥6mg/dl and albumin≥3.5g/dl as reference, patients with creatinine<6mg/dl and albumin<3.5g/dl had a 1.8-fold higher risk of mortality (HR: 1.75, 95%CI: 1.33-2.30) in twice-weekly and 2.2-fold increased risk of mortality (HR: 2.21, 95%CI: 1.81-2.70) in thrice-weekly hemodialysis patients, respectively in fully adjusted models adjusted for demographics, comorbidities and markers of malnutrition and inflammation. A test for interaction showed there was no significant difference in albumin creatinine mortality associations between twice-weekly and thrice-weekly hemodialysis patients (p-for-interaction 0.7667). Conclusions Surrogate markers of higher visceral protein and muscle mass combined may confer greatest survival in both twice-weekly and thrice-weekly hemodialysis patients. PMID:27528412

Role of G308 promoter variant of tumor necrosis factor alpha gene on weight loss and metabolic parameters after a high monounsaturated versus a high polyunsaturated fat hypocaloric diets.

PubMed

de Luis, Daniel A; Aller, Rocío; Izaola, Olatz; Gonzalez Sagrado, Manuel; Conde, Rosa

2013-09-07

The aim of our study was to investigate the influence of G-308 promoter variant of the tumor necrosis factor (TNF) alpha gene on metabolic changes and weight loss secondary to a high monounsaturated fat vs a high polyunsaturated fat hypocaloric diet in obese subjects. A sample of 261 obese subjects were enrolled in a consecutive prospective way, from May 2011 to July 2012 in a tertiary hospital. In the basal visit, patients were randomly allocated during 3 months to Diet M (high monounsaturated fat hypocaloric diet) and Diet P (high polyunsaturated fat hypocaloric diet). One hundred and ninety seven patients (73.2%) had the genotype G-308G and 64 (26.8%) patients had the genotype G-308A. There were no significant differences between the effects (on weight, body mass index (BMI), waist circumference, fat mass) in either genotype group with both diets. With the diet type P and in genotype G-308G, glucose levels (-6.7(22.1)mg/dl vs -3.7(2.2)mg/dl: p = 0.02), HOMA-R (-0.6(2.1)units vs -0.26(3.1)units: p = 0.01), insulin levels (-1.7(6.6)UI/L vs -0.6(7.1)UI/L: p = 0.009), total cholesterol levels (-15.3(31.1)mg/dl vs -8.4(22.1)mg/dl: p = 0.01), LDL cholesterol levels (-10.7(28.1)mg/dl vs -3.8(21.1)mg/dl: p = 0.008) and triglycerides (-12.1(52.1)mg/dl vs -6.6(43.1)mg/dl: p = 0.02) decreased. Carriers of the G-308G promoter variant of TNF alpha gene have a better metabolic response than A-308 obese with a high polyunsaturated fat hypocaloric diet. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex

PubMed Central

Yang, Yang; Paspalas, Constantinos D.; Jin, Lu E.; Picciotto, Marina R.; Arnsten, Amy F. T.; Wang, Min

2013-01-01

The cognitive function of the highly evolved dorsolateral prefrontal cortex (dlPFC) is greatly influenced by arousal state, and is gravely afflicted in disorders such as schizophrenia, where there are genetic insults in α7 nicotinic acetylcholine receptors (α7-nAChRs). A recent behavioral study indicates that ACh depletion from dlPFC markedly impairs working memory [Croxson PL, Kyriazis DA, Baxter MG (2011) Nat Neurosci 14(12):1510–1512]; however, little is known about how α7-nAChRs influence dlPFC cognitive circuits. Goldman-Rakic [Goldman-Rakic (1995) Neuron 14(3):477–485] discovered the circuit basis for working memory, whereby dlPFC pyramidal cells excite each other through glutamatergic NMDA receptor synapses to generate persistent network firing in the absence of sensory stimulation. Here we explore α7-nAChR localization and actions in primate dlPFC and find that they are enriched in glutamate network synapses, where they are essential for dlPFC persistent firing, with permissive effects on NMDA receptor actions. Blockade of α7-nAChRs markedly reduced, whereas low-dose stimulation selectively enhanced, neuronal representations of visual space. These findings in dlPFC contrast with the primary visual cortex, where nAChR blockade had no effect on neuronal firing [Herrero JL, et al. (2008) Nature 454(7208):1110–1114]. We additionally show that α7-nAChR stimulation is needed for NMDA actions, suggesting that it is key for the engagement of dlPFC circuits. As ACh is released in cortex during waking but not during deep sleep, these findings may explain how ACh shapes differing mental states during wakefulness vs. sleep. The results also explain why genetic insults to α7-nAChR would profoundly disrupt cognitive experience in patients with schizophrenia. PMID:23818597

A 1-year trial of repeated high-dose intravenous iron isomaltoside 1000 to maintain stable hemoglobin levels in inflammatory bowel disease

PubMed Central

Reinisch, Walter; Altorjay, Istvan; Zsigmond, Ferenc; Primas, Christian; Vogelsang, Harald; Novacek, Gottfried; Reinisch, Sieglinde; Thomsen, Lars L.

2015-01-01

Abstract Objective. Iron isomaltoside 1000 (Monofer®) is a high-dose intravenous (IV) iron, which in a recent 8 weeks trial in inflammatory bowel disease (IBD) subjects with iron deficiency anemia (IDA) demonstrated good tolerability and efficacy. The present trial is an extension to this trial, which evaluates the need for additional high IV iron doses to maintain a stable hemoglobin (Hb) ≥12.0 g/dl. Material and methods. This was a prospective, open-label, 12 months trial of European IBD subjects willing to participate after completing the lead-in trial. Subjects were allowed re-dosing with 500–2000 mg single doses of iron isomaltoside 1000 infused over ∼15 min at 3 months intervals depending on a predefined algorithm. Outcome measures included Hb, safety parameters and need for additional iron dosing. Results. A total of 39 subjects were enrolled of which 34 subjects required re-dosing with a median cumulative 1-year dose of 1.8 g (mean cumulative dose 2.2 g). The mean (SD) Hb was 12.3 (1.5) g/dl at baseline, 12.8 (1.6) g/dl at 3 months, 12.8 (1.6) g/dl at 6 months, 12.9 (1.4) g/dl at 9 months and 12.9 (1.6) g/dl at 12 months. Seventy-four percent of subjects who had an Hb ≥12.0 g/dl at baseline were able to maintain Hb ≥12.0 g/dl till the end of the trial at 12 months. Nonserious probably related hypersensitivity reactions without significant hypotension were reported at the beginning of the infusion in two subjects, who recovered without sequelae. Conclusion. Repeated treatment of iron deficiency with iron isomaltoside 1000 could avoid episodes of IDA without major safety issues. PMID:25900645

Diagnostic value of "dysphagia limit" for neurogenic dysphagia: 17 years of experience in 1278 adults.

PubMed

Aydogdu, Ibrahim; Kiylioglu, Nefati; Tarlaci, Sultan; Tanriverdi, Zeynep; Alpaydin, Sezin; Acarer, Ahmet; Baysal, Leyla; Arpaci, Esra; Yuceyar, Nur; Secil, Yaprak; Ozdemirkiran, Tolga; Ertekin, Cumhur

2015-03-01

Neurogenic dysphagia (ND) is a prevalent condition that accounts for significant mortality and morbidity worldwide. Screening and follow-up are critical for early diagnosis and management which can mitigate its complications and be cost-saving. The aims of this study are to provide a comprehensive investigation of the dysphagia limit (DL) in a large diverse cohort and to provide a longitudinal assessment of dysphagia in a subset of subjects. We developed a quantitative and noninvasive method for objective assessment of dysphagia by using laryngeal sensor and submental electromyography. DL is the volume at which second or more swallows become necessary to swallow the whole amount of bolus. This study represents 17 years experience with the DL approach in assessing ND in a cohort of 1278 adult subjects consisting of 292 healthy controls, 784 patients with dysphagia, and 202 patients without dysphagia. A total of 192 of all patients were also reevaluated longitudinally over a period of 1-19 months. DL has 92% sensitivity, 91% specificity, 94% positive predictive value, and 88% negative predictive value with an accuracy of 0.92. Patients with ALS, stroke, and movement disorders have the highest sensitivity (85-97%) and positive predictive value (90-99%). The clinical severity of dysphagia has significant negative correlation with DL (r=-0.67, p<0.0001). We propose the DL as a reliable, quick, noninvasive, quantitative test to detect and follow both clinical and subclinical dysphagia and it can be performed in an EMG laboratory. Our study provides specific quantitative features of DL test that can be readily utilized by the neurologic community and nominates DL as an objective and robust method to evaluate dysphagia in a wide range of neurologic conditions. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

[Secondary prevention of ischemic heart disease in the Cuidad Real Province, Spain. Effectiveness of lipid-lowering therapy in primary health care].

PubMed

2000-09-23

The efficacy of lipid-lowering therapy (LLT) in ischemic heart disease (IHD) is well established. But there are some doubts about its effectiveness on Primary Health Care (PHC) where we develop the long-term control of this sickness and it is difficult to reproduce the terms of the clinical trials. Multicenter cross-sectional study designed to evaluate the control of dyslipidemia achieved in patients with IHD diagnosed more than a year ago in our geographic primary health care system. The total cholesterol (tC), LDL, triglyceride, HDL levels and tC/HDL were determined to analyze the impact of LLT. 205 patients were collected by 14 general practitioners in several PHC centers. The average lipid profiles recorded (tC: 218 mg/dl; LDL: 151 mg/dl; triglyceride: 136 mg/dl; HDL: 49 mg/dl, and tC/HDL: 4,8) were far to the recommended by the international guidelines. The ideal (LDL < 100 mg/dl) and the acceptable targets (LDL < 130) were achieved by 9 and 30%. The HDL was not assess in 26.4% of the patients. It had had slight improvement of the women profile risk by more elevated values of HDLc than men (54.4 mg/dl vs. 46.9 mg/dl; p = 0.0002). Only 98 patients (45.85%) receive LLT, while 70% presented LDL > 130 mg/dl. The average dose of hypolipidemiants was small and the combination therapy had been scanty used (2.7%). The hypolipidemic secondary prevention was incorrect, with a big gap between the efficacy of the LLT and the actual effectiveness. In the majority of cases (75-80%) the values exceeded the secondary prevention targets. In a quarter of patients had never existed a clearly defined therapeutic target because the levels of HDL and LDL were not assessed. It was not prescribed neither fitting drug doses nor combinations to reach lipidemic preventive levels.

The silent burden of anaemia in Tanzanian children: a community-based study.

PubMed Central

Schellenberg, D.; Schellenberg, J. R. M. Armstrong; Mushi, A.; Savigny, D. de; Mgalula, L.; Mbuya, C.; Victora, C. G.

2003-01-01

OBJECTIVE: To document the prevalence, age-distribution, and risk factors for anaemia in Tanzanian children less than 5 years old, thereby assisting in the development of effective strategies for controlling anaemia. METHODS: Cluster sampling was used to identify 2417 households at random from four contiguous districts in south-eastern United Republic of Tanzania in mid-1999. Data on various social and medical parameters were collected and analysed. FINDINGS: Blood haemoglobin concentrations (Hb) were available for 1979 of the 2131 (93%) children identified and ranged from 1.7 to 18.6 g/dl. Overall, 87% (1722) of children had an Hb <11 g/dl, 39% (775) had an Hb <8 g/dl and 3% (65) had an Hb <5 g/dl. The highest prevalence of anaemia of all three levels was in children aged 6-11 months, of whom 10% (22/226) had an Hb <5 g/dl. However, the prevalence of anaemia was already high in children aged 1-5 months (85% had an Hb <11 g/dl, 42% had an Hb <8 g/dl, and 6% had an Hb <5 g/dl). Anaemia was usually asymptomatic and when symptoms arose they were nonspecific and rarely identified as a serious illness by the care provider. A recent history of treatment with antimalarials and iron was rare. Compliance with vaccinations delivered through the Expanded Programme of Immunization (EPI) was 82% and was not associated with risk of anaemia. CONCLUSION: Anaemia is extremely common in south-eastern United Republic of Tanzania, even in very young infants. Further implementation of the Integrated Management of Childhood Illness algorithm should improve the case management of anaemia. However, the asymptomatic nature of most episodes of anaemia highlights the need for preventive strategies. The EPI has good coverage of the target population and it may be an appropriate channel for delivering tools for controlling anaemia and malaria. PMID:14576890

Delayed peak response of cortisol to insulin tolerance test in patients with Prader-Willi syndrome.

PubMed

Oto, Yuji; Matsubara, Keiko; Ayabe, Tadayuki; Shiraishi, Masahisa; Murakami, Nobuyuki; Ihara, Hiroshi; Matsubara, Tomoyo; Nagai, Toshiro

2018-06-01

Deaths among children with Prader-Willi syndrome (PWS) are often related to only mild or moderate upper respiratory tract infections, and many causes of death remain unexplained. Several reports have hypothesized that patients with PWS may experience latent central adrenal insufficiency. However, whether PWS subjects suffer from alteration of the hypothalamus-pituitary-adrenal (HPA) axis remains unclear. This study aimed to explore the HPA axis on PWS. We evaluated the HPA axis in 36 PWS patients (24 males, 12 females; age range, 7 months to 12 years; median age 2.0 years; interquartile range [IQR], 1.5-3.4 years) using an insulin tolerance test (ITT) in the morning between 08:00 and 11:00. For comparison, ITT results in 37 age-matched healthy children evaluated for short stature were used as controls. In PWS patients, basal levels of adrenocorticotropic hormone (ACTH) were 13.5 pg/ml (IQR, 8.3-27.5 pg/ml) and basal levels of cortisol were 18.0 μg/dl (IQR, 14.2-23.7 μg/dl). For all patients, cortisol levels at 60 min after stimulation were within the reference range (>18.1 μg/dl), with a median peak of 41.5 μg/dl (IQR, 32.3-48.6 μg/dl). Among control children, basal level of ACTH and basal and peak levels of cortisol were 10.9 (IQR, 8.5-22.0 pg/ml), 15.6 (IQR, 11.9-21.6 μg/dl), and 27.8 μg/dl (IQR, 23.7-30.5 μg/dl), respectively. Basal and peak levels of cortisol were all within normal ranges, but peak response of cortisol to ITT was delayed in the majority of PWS patients (64%). Although the mechanism remains unclear, this delay may signify the existence of central obstacle in adjustment of the HPA axis. © 2018 Wiley Periodicals, Inc.

Genetic Interaction of OsMADS3, DROOPING LEAF, and OsMADS13 in Specifying Rice Floral Organ Identities and Meristem Determinacy1[W][OA

PubMed Central

Li, Haifeng; Liang, Wanqi; Yin, Changsong; Zhu, Lu; Zhang, Dabing

2011-01-01

Grass plants develop unique floral patterns that determine grain production. However, the molecular mechanism underlying the specification of floral organ identities and meristem determinacy, including the interaction among floral homeotic genes, remains largely unknown in grasses. Here, we report the interactions of rice (Oryza sativa) floral homeotic genes, OsMADS3 (a C-class gene), OsMADS13 (a D-class gene), and DROOPING LEAF (DL), in specifying floral organ identities and floral meristem determinacy. The interaction among these genes was revealed through the analysis of double mutants. osmads13-3 osmads3-4 displayed a loss of floral meristem determinacy and generated abundant carpelloid structures containing severe defective ovules in the flower center, which were not detectable in the single mutant. In addition, in situ hybridization and yeast two-hybrid analyses revealed that OsMADS13 and OsMADS3 did not regulate each other’s transcription or interact at the protein level. This indicates that OsMADS3 plays a synergistic role with OsMADS13 in both ovule development and floral meristem termination. Strikingly, osmads3-4 dl-sup6 displayed a severe loss of floral meristem determinacy and produced supernumerary whorls of lodicule-like organs at the forth whorl, suggesting that OsMADS3 and DL synergistically terminate the floral meristem. Furthermore, the defects of osmads13-3 dl-sup6 flowers appeared identical to those of dl-sup6, and the OsMADS13 expression was undetectable in dl-sup6 flowers. These observations suggest that DL and OsMADS13 may function in the same pathway specifying the identity of carpel/ovule and floral meristem. Collectively, we propose a model to illustrate the role of OsMADS3, DL, and OsMADS13 in the specification of flower organ identity and meristem determinacy in rice. PMID:21444646

Aerobic Exercise and Lipids and Lipoproteins in Women: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Kelley, George A.; Kelley, Kristi S.; Tran, Zung VU

2007-01-01

Background Cardiovascular disease (CVD) in women is the leading cause of mortality in the United States, and less than optimal lipid and lipoprotein levels are major risk factors for CVD. The purpose of this study was to use the meta-analytic approach to examine the effects of aerobic exercise on lipids and lipoproteins in women. Methods Studies were retrieved via computerized literature searches, review of reference lists, hand searching selected journals, and expert review of our reference list. The inclusion of studies was limited to randomized controlled trials published in the English language literature between January 1955 and January 2003 in which aerobic exercise was used as the primary intervention in adult women aged ≥18 years. One or more of the following lipids and lipoproteins were assessed: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Results Using a random effects model, statistically significant improvements were observed for all lipids and lipoproteins (TC, X̄ ± SEM, −4.3 ± 1.3 mg/dl, 95% CI −6.9 to −1.7 mg/dl; HDL-C, X̄± SEM, 1.8 ± 0.9 mg/dl, 95% CI 0.1 to 3.5 mg/dl; LDL-C, X̄ ± SEM, −4.4 ± 1.1 mg/dl, 95% CI −6.5 to −2.2 mg/dl; TG, X̄ ± SEM, −4.2 ± 2.1 mg/dl, 95% CI −8.4 to −0.1 mg/dl). Reductions of approximately 2%, 3%, and 5%, respectively, were observed for TC, LDL-C, and TG, whereas an increase of 3% was observed for HDL-C. Conclusions Aerobic exercise is efficacious for increasing HDL-C and decreasing TC, LDL-C, and TG in women. PMID:15650348

Suppression of a Natural Killer Cell Response by Simian Immunodeficiency Virus Peptides

PubMed Central

Schafer, Jamie L.; Ries, Moritz; Guha, Natasha; Connole, Michelle; Colantonio, Arnaud D.; Wiertz, Emmanuel J.; Wilson, Nancy A.; Kaur, Amitinder; Evans, David T.

2015-01-01

Natural killer (NK) cell responses in primates are regulated in part through interactions between two highly polymorphic molecules, the killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their major histocompatibility complex (MHC) class I ligands on target cells. We previously reported that the binding of a common MHC class I molecule in the rhesus macaque, Mamu-A1*002, to the inhibitory receptor Mamu-KIR3DL05 is stabilized by certain simian immunodeficiency virus (SIV) peptides, but not by others. Here we investigated the functional implications of these interactions by testing SIV peptides bound by Mamu-A1*002 for the ability to modulate Mamu-KIR3DL05+ NK cell responses. Twenty-eight of 75 SIV peptides bound by Mamu-A1*002 suppressed the cytolytic activity of primary Mamu-KIR3DL05+ NK cells, including three immunodominant CD8+ T cell epitopes previously shown to stabilize Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. Substitutions at C-terminal positions changed inhibitory peptides into disinhibitory peptides, and vice versa, without altering binding to Mamu-A1*002. The functional effects of these peptide variants on NK cell responses also corresponded to their effects on Mamu-A1*002 tetramer binding to Mamu-KIR3DL05. In assays with mixtures of inhibitory and disinhibitory peptides, low concentrations of inhibitory peptides dominated to suppress NK cell responses. Consistent with the inhibition of Mamu-KIR3DL05+ NK cells by viral epitopes presented by Mamu-A1*002, SIV replication was significantly higher in Mamu-A1*002+ CD4+ lymphocytes co-cultured with Mamu-KIR3DL05+ NK cells than with Mamu-KIR3DL05- NK cells. These results demonstrate that viral peptides can differentially affect NK cell responses by modulating MHC class I interactions with inhibitory KIRs, and provide a mechanism by which immunodeficiency viruses may evade NK cell responses. PMID:26333068

Feeding Behaviour on Host Plants May Influence Potential Exposure to Bt Maize Pollen of Aglais Urticae Larvae (Lepidoptera, Nymphalidae).

PubMed

Lang, Andreas; Otto, Mathias

2015-08-31

Non-target butterfly larvae may be harmed by feeding on host plants dusted with Bt maize pollen. Feeding patterns of larvae and their utilization of host plants can affect the adverse Bt impact because the maize pollen is distributed unequally on the plant. In a field study, we investigated the feeding of larvae of the Small Tortoiseshell, Aglais urticae, on nettles, Urtica dioica. Young larvae used smaller host plants than older larvae. In general, the position of the larvae was in the top part of the host plant, but older larvae showed a broader vertical distribution on the nettles. Leaf blades and leaf tips were the plant parts most often consumed. Leaf veins were consumed but midribs were fed on to a lesser extent than other plant veins, particularly by young larvae. The feeding behavior of the larvae may increase possible exposure to Bt maize pollen because pollen densities are expected to be higher on the top parts and along leaf veins of nettles.

New Aspects of the Pathogenesis of Canine Distemper Leukoencephalitis

PubMed Central

Lempp, Charlotte; Spitzbarth, Ingo; Puff, Christina; Cana, Armend; Kegler, Kristel; Techangamsuwan, Somporn; Baumgärtner, Wolfgang; Seehusen, Frauke

2014-01-01

Canine distemper virus (CDV) is a member of the genus morbillivirus, which is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis (CDV-DL). In recent years, substantial progress in understanding the pathogenetic mechanisms of CDV-DL has been made. In vivo and in vitro investigations provided new insights into its pathogenesis with special emphasis on axon-myelin-glia interaction, potential endogenous mechanisms of regeneration, and astroglial plasticity. CDV-DL is characterized by lesions with a variable degree of demyelination and mononuclear inflammation accompanied by a dysregulated orchestration of cytokines as well as matrix metalloproteinases and their inhibitors. Despite decades of research, several new aspects of the neuropathogenesis of CDV-DL have been described only recently. Early axonal damage seems to represent an initial and progressive lesion in CDV-DL, which interestingly precedes demyelination. Axonopathy may, thus, function as a potential trigger for subsequent disturbed axon-myelin-glia interactions. In particular, the detection of early axonal damage suggests that demyelination is at least in part a secondary event in CDV-DL, thus challenging the dogma of CDV as a purely primary demyelinating disease. Another unexpected finding refers to the appearance of p75 neurotrophin (NTR)-positive bipolar cells during CDV-DL. As p75NTR is a prototype marker for immature Schwann cells, this finding suggests that Schwann cell remyelination might represent a so far underestimated endogenous mechanism of regeneration, though this hypothesis still remains to be proven. Although it is well known that astrocytes represent the major target of CDV infection in CDV-DL, the detection of infected vimentin-positive astrocytes in chronic lesions indicates a crucial role of this cell population in nervous distemper. While glial fibrillary acidic protein represents the characteristic intermediate filament of mature astrocytes, expression of vimentin is generally restricted to immature or reactive astrocytes. Thus, vimentin-positive astrocytes might constitute an important cell population for CDV persistence and spread, as well as lesion progression. In vitro models, such as dissociated glial cell cultures, as well as organotypic brain slice cultures have contributed to a better insight into mechanisms of infection and certain morphological and molecular aspects of CDV-DL. Summarized, recent in vivo and in vitro studies revealed remarkable new aspects of nervous distemper. These new perceptions substantially improved our understanding of the pathogenesis of CDV-DL and might represent new starting points to develop novel treatment strategies. PMID:24992230

Interaction between the predator Toxorhynchites brevipalpis and its prey Aedes aegypti1

PubMed Central

Trpis, Milan

1973-01-01

In a circumscribed area in Tanzania where the predacious larvae of Toxorhynchites brevipalpis were particularly abundant, it was found that water-filled tires and tins containing Toxorhynchites larvae had fewer larvae of Aedes aegypti than those without the predator larvae. The peaks of infestation with Toxorhynchites larvae occurred almost a month later than the peaks of A. aegypti infestation. Cannibalism was observed among the predator larvae in these containers. PMID:4152925

Parachuting behavior and predation by ants in the nettle caterpillar, Scopelodes contracta.

PubMed

Yamazaki, Kazuo

2010-01-01

This paper documents the bizarre descending behavior from the tree crown to the ground of the larvae of the moth, Scopelodes contracta Walker (Lepidoptera: Limacodidae) and the interaction of the larva with predatory ants. S. contracta larvae infest leaves of many tree species in urban areas and orchards in Japan. Mature larvae and leaves without basal leaf parts were found under trees of four species infested with S. contracta larvae in Osaka, Japan. Individual larvae riding on leaves were observed falling from tree crowns to the ground. Many S. contracta cocoons were found in the soil below the trees two weeks after the observed parachuting. These observations indicate that S. contracta larvae parachuted to the ground where they spin their cocoons in the soil. When a larva that had just parachuted down was returned to an arboreal twig, the larva repeated the parachuting behavior. This parachuting behavior appears to be adaptive, because larvae can descend to the ground safely and with low energy cost. Worker ants of Tetramorium tsushimae Emery (Hymenoptera: Formicidae) and Pristomyrmex punctatus Mayr (Hymenoptera: Formicidae) occasionally attacked larvae on the ground before they had a chance to burrow in the soil.

PREVALENCE OF ANISAKID NEMATODE LARVAE INFECTING SOME MARINE FISHES FROM THE LIBYAN COAST.

PubMed

Kassem, Hamed H; Bowashi, Salem Mohamed

2015-12-01

This study examined eight hundred ninety six marine fishes belonging to nine different fish species; Synodus saurus; Merluccius merluccius; Trachurus mediterraneus; Serranus cabrilla; Mullus surmuletus; Diplodus annularis; Spicara maena; Siganus rirulatus and Liza ramada. The fishes were bought from fish markets at five different sites on Libyan coast, from January to December 2013, for study the anisakids larvae among them. The results showed that 344/896 fishes (38.4%) were infected with Anisakids larvae. S. saurus was the highly infected (80.9%), followed by T mediterraneus (77.5%) but, S. cabrilla, S. maena, M merluccius, M surmuletus, and D. annularis were least anisakid infected showed rates of 58.2%, 53.8%, 43.7%, 36.7% & 3.6%, respectively. No parasites were in S. rirulatus and L, ramada. Ten species of Anisakids larvae was detected during the present study. Two Pseudoterranova sp. Larvae, two types of Anisakis larvae, Anisakis simplex larva and Anisakis sp. Larva, two types of Contracaecum sp. Larvae and four Hysterothylacium larvae. Females showed higher prevalence than males. The number of anisakid larvae varied according to body length and weight of infected fish, without significant difference between prevalence and seasons, but, a significant difference was between prevalence and regions.

Analysis of Cost Growth and Cost Composition in the Defense Aerospace Industry

DTIC Science & Technology

1988-09-01

Making. New York: Harcourt Brace Jovanovich, Inc., 1977. 16. Horngren , Charles T. Cost Accounting , A Managerial Emphasis. Englewood Cliffs NJ: Prentice...58 7. Scatter Plot of Cost /DL Hour Ratio, Data Set C ................ .................. 59 8. Scatter Plot of Cost /DL S Ratio, Data Set...C 62 9. Scatter Plot of Cost /DL S Ratio, Then-Year Dollars ................... .................... 63 10. Scatter Plot of OH/TC Ratio, Data Set C

The Identification of Congeners and Aliens by Drosophila Larvae.

PubMed

Del Pino, Francisco; Jara, Claudia; Pino, Luis; Medina-Muñoz, María Cristina; Alvarez, Eduardo; Godoy-Herrera, Raúl

2015-01-01

We investigated the role of Drosophila larva olfactory system in identification of congeners and aliens. We discuss the importance of these activities in larva navigation across substrates, and the implications for allocation of space and food among species of similar ecologies. Wild type larvae of cosmopolitan D. melanogaster and endemic D. pavani, which cohabit the same breeding sites, used species-specific volatiles to identify conspecifics and aliens moving toward larvae of their species. D. gaucha larvae, a sibling species of D. pavani that is ecologically isolated from D. melanogaster, did not respond to melanogaster odor cues. Similar to D. pavani larvae, the navigation of pavani female x gaucha male hybrids was influenced by conspecific and alien odors, whereas gaucha female x pavani male hybrid larvae exhibited behavior similar to the D. gaucha parent. The two sibling species exhibited substantial evolutionary divergence in processing the odor inputs necessary to identify conspecifics. Orco (Or83b) mutant larvae of D. melanogaster, which exhibit a loss of sense of smell, did not distinguish conspecific from alien larvae, instead moving across the substrate. Syn97CS and rut larvae of D. melanogaster, which are unable to learn but can smell, moved across the substrate as well. The Orco (Or83b), Syn97CS and rut loci are necessary to orient navigation by D. melanogaster larvae. Individuals of the Trana strain of D. melanogaster did not respond to conspecific and alien larval volatiles and therefore navigated randomly across the substrate. By contrast, larvae of the Til-Til strain used larval volatiles to orient their movement. Natural populations of D. melanogaster may exhibit differences in identification of conspecific and alien larvae. Larval locomotion was not affected by the volatiles.

Survival and energetic costs of repeated cold exposure in the Antarctic midge, Belgica antarctica: a comparison between frozen and supercooled larvae.

PubMed

Teets, Nicholas M; Kawarasaki, Yuta; Lee, Richard E; Denlinger, David L

2011-03-01

In this study, we examined the effects of repeated cold exposure (RCE) on the survival, energy content and stress protein expression of larvae of the Antarctic midge, Belgica antarctica (Diptera: Chironomidae). Additionally, we compared results between larvae that were frozen at -5°C in the presence of water during RCE and those that were supercooled at -5°C in a dry environment. Although >95% of larvae survived a single 12 h bout of freezing at -5°C, after five cycles of RCE survival of frozen larvae dropped below 70%. Meanwhile, the survival of control and supercooled larvae was unchanged, remaining around 90% for the duration of the study. At the tissue level, frozen larvae had higher rates of cell mortality in the midgut than control and supercooled larvae. Furthermore, larvae that were frozen during RCE experienced a dramatic reduction in energy reserves; after five cycles, frozen larvae had 25% less lipid, 30% less glycogen and nearly 40% less trehalose than supercooled larvae. Finally, larvae that were frozen during RCE had higher expression of hsp70 than those that were supercooled, indicating a higher degree of protein damage in the frozen group. Results were similar between larvae that had accumulated 60 h of freezing at -5°C over five cycles of RCE and those that were frozen continuously for 60 h, suggesting that the total time spent frozen determines the physiological response. Our results suggest that it is preferable, both from a survival and energetic standpoint, for larvae to seek dry microhabitats where they can avoid inoculative freezing and remain unfrozen during RCE.

Effects of Geostrophic Kinetic Energy on the Distribution of Mesopelagic Fish Larvae in the Southern Gulf of California in Summer/Fall Stratified Seasons.

PubMed

Contreras-Catala, Fernando; Sánchez-Velasco, Laura; Beier, Emilio; Godínez, Victor M; Barton, Eric D; Santamaría-Del-Angel, Eduardo

2016-01-01

Effects of geostrophic kinetic energy flux on the three-dimensional distribution of fish larvae of mesopelagic species (Vinciguerria lucetia, Diogenichthys laternatus, Benthosema panamense and Triphoturus mexicanus) in the southern Gulf of California during summer and fall seasons of stronger stratification were analyzed. The greatest larval abundance was found at sampling stations in geostrophic kinetic energy-poor areas (<7.5 J/m3), where the distribution of the dominant species tended to be stratified. Larvae of V. lucetia (average abundance of 318 larvae/10m2) and B. panamense (174 larvae/10m2) were mostly located in and above the pycnocline (typically ~ 40 m depth). In contrast, larvae of D. laternatus (60 larvae/10m2) were mainly located in and below the pycnocline. On the other hand, in sampling stations from geostrophic kinetic energy-rich areas (> 21 J/m3), where mesoscale eddies were present, the larvae of the dominant species had low abundance and were spread more evenly through the water column, in spite of the water column stratification. For example, in a cyclonic eddy, V. lucetia larvae (34 larvae/10m2) extended their distribution to, at least, the limit of sampling 200 m depth below the pycnocline, while D. laternatus larvae (29 larvae/10m2) were found right up to the surface, both probably as a consequence mixing and secondary circulation in the eddy. Results showed that the level of the geostrophic kinetic energy flux affects the abundance and the three-dimensional distribution of mesopelagic fish larvae during the seasons of stronger stratification, indicating that areas with low geostrophic kinetic energy may be advantageous for feeding and development of mesopelagic fish larvae because of greater water column stability.

Effects of Geostrophic Kinetic Energy on the Distribution of Mesopelagic Fish Larvae in the Southern Gulf of California in Summer/Fall Stratified Seasons

PubMed Central

Contreras-Catala, Fernando; Beier, Emilio; Godínez, Victor M.; Barton, Eric D.; Santamaría-del-Angel, Eduardo

2016-01-01

Effects of geostrophic kinetic energy flux on the three-dimensional distribution of fish larvae of mesopelagic species (Vinciguerria lucetia, Diogenichthys laternatus, Benthosema panamense and Triphoturus mexicanus) in the southern Gulf of California during summer and fall seasons of stronger stratification were analyzed. The greatest larval abundance was found at sampling stations in geostrophic kinetic energy-poor areas (<7.5 J/m3), where the distribution of the dominant species tended to be stratified. Larvae of V. lucetia (average abundance of 318 larvae/10m2) and B. panamense (174 larvae/10m2) were mostly located in and above the pycnocline (typically ~ 40 m depth). In contrast, larvae of D. laternatus (60 larvae/10m2) were mainly located in and below the pycnocline. On the other hand, in sampling stations from geostrophic kinetic energy-rich areas (> 21 J/m3), where mesoscale eddies were present, the larvae of the dominant species had low abundance and were spread more evenly through the water column, in spite of the water column stratification. For example, in a cyclonic eddy, V. lucetia larvae (34 larvae/10m2) extended their distribution to, at least, the limit of sampling 200 m depth below the pycnocline, while D. laternatus larvae (29 larvae/10m2) were found right up to the surface, both probably as a consequence mixing and secondary circulation in the eddy. Results showed that the level of the geostrophic kinetic energy flux affects the abundance and the three-dimensional distribution of mesopelagic fish larvae during the seasons of stronger stratification, indicating that areas with low geostrophic kinetic energy may be advantageous for feeding and development of mesopelagic fish larvae because of greater water column stability. PMID:27760185

Modulation of nutrient composition of black soldier fly (Hermetia illucens) larvae by feeding seaweed-enriched media

PubMed Central

Liland, Nina S.; Biancarosa, Irene; Araujo, Pedro; Biemans, Daan; Bruckner, Christian G.; Waagbø, Rune; Torstensen, Bente E.

2017-01-01

Black soldier fly (Hermetia illucens) larvae are a promising source of protein and lipid for animal feeds. The nutritional composition of the BSF larvae depend partly on the composition of the feeding medium. The BSF lipid profile in part mimics the feeding media lipid profile, and micronutrients, like minerals and vitamins, can readily accumulate in black soldier fly larvae. However, investigative studies on bioconversion and accumulation of nutrients from media to black soldier fly larvae are scarce. Here we show that inclusion of the brown algae Ascophyllum nodosum in the substrate for black soldier fly larvae can introduce valuable nutrients, commonly associated with the marine environment, into the larvae. The omega-3 fatty acid eicosapentaenoic acid (20:5n-3), iodine and vitamin E concentrations increased in the larvae when more seaweed was included in the diet. When the feeding media consisted of more than 50% seaweed, the larvae experienced poorer growth, lower nutrient retention and lower lipid levels, compared to a pure plant based feeding medium. Our results confirm the plasticity of the nutritional make-up of black soldier fly larvae, allowing it to accumulate both lipid- and water-soluble compounds. A broader understanding of the effect of the composition of the feeding media on the larvae composition can help to tailor black soldier fly larvae into a nutrient profile more suited for specific feed or food purposes. PMID:28837591

Modulation of nutrient composition of black soldier fly (Hermetia illucens) larvae by feeding seaweed-enriched media.

PubMed

Liland, Nina S; Biancarosa, Irene; Araujo, Pedro; Biemans, Daan; Bruckner, Christian G; Waagbø, Rune; Torstensen, Bente E; Lock, Erik-Jan

2017-01-01

Black soldier fly (Hermetia illucens) larvae are a promising source of protein and lipid for animal feeds. The nutritional composition of the BSF larvae depend partly on the composition of the feeding medium. The BSF lipid profile in part mimics the feeding media lipid profile, and micronutrients, like minerals and vitamins, can readily accumulate in black soldier fly larvae. However, investigative studies on bioconversion and accumulation of nutrients from media to black soldier fly larvae are scarce. Here we show that inclusion of the brown algae Ascophyllum nodosum in the substrate for black soldier fly larvae can introduce valuable nutrients, commonly associated with the marine environment, into the larvae. The omega-3 fatty acid eicosapentaenoic acid (20:5n-3), iodine and vitamin E concentrations increased in the larvae when more seaweed was included in the diet. When the feeding media consisted of more than 50% seaweed, the larvae experienced poorer growth, lower nutrient retention and lower lipid levels, compared to a pure plant based feeding medium. Our results confirm the plasticity of the nutritional make-up of black soldier fly larvae, allowing it to accumulate both lipid- and water-soluble compounds. A broader understanding of the effect of the composition of the feeding media on the larvae composition can help to tailor black soldier fly larvae into a nutrient profile more suited for specific feed or food purposes.

Feeding Behaviour on Host Plants May Influence Potential Exposure to Bt Maize Pollen of Aglais Urticae Larvae (Lepidoptera, Nymphalidae)

PubMed Central

Lang, Andreas; Otto, Mathias

2015-01-01

Non-target butterfly larvae may be harmed by feeding on host plants dusted with Bt maize pollen. Feeding patterns of larvae and their utilization of host plants can affect the adverse Bt impact because the maize pollen is distributed unequally on the plant. In a field study, we investigated the feeding of larvae of the Small Tortoiseshell, Aglais urticae, on nettles, Urtica dioica. Young larvae used smaller host plants than older larvae. In general, the position of the larvae was in the top part of the host plant, but older larvae showed a broader vertical distribution on the nettles. Leaf blades and leaf tips were the plant parts most often consumed. Leaf veins were consumed but midribs were fed on to a lesser extent than other plant veins, particularly by young larvae. The feeding behavior of the larvae may increase possible exposure to Bt maize pollen because pollen densities are expected to be higher on the top parts and along leaf veins of nettles. PMID:26463415

[Morphology of III stage larvae of Angiostrongylus cantonensis in Pomacea canaliculata].

PubMed

Zhang, Chao-Wei; Zhou, Xiao-Nong; Lv, Shan; Zhang, Yi; Liu, He-Xiang

2008-06-30

To observe the morphologic characteristics of III stage larvae of Angiostrongylus cantonensis from Pomacea canaliculata. P. canaliculata, the intermediate host snail of A. cantonensis, was infected with I stage larvae of A. cantonensis in laboratory. After 61 days, III stage larvae of A. cantonensis were harvested from snail's lungs and muscle of head-foot, followed by HE stain to observe morphological characteristics. The whole body of III stage larva was curling with obtuse head. Its pharyngeal canal extends from the buccal hole on the top of the head to the intestines at the pharyngeal intestine joint place, with apex cauda and clear anal tube. The tegument of the III stage larva was eosin-stained, with a transparent sheath outside of tegument. Some of the larvae cauda showed in circular cylinder, and some larvae presented ventral gland with two very short uterine which used to be the feature only showed in early IV stage larva. Morphologically characteristics of the III stage larvae is helpful to better understand the life-cycle and the control of A. cantonensis.

Inhibitory effect of indole analogs against Paenibacillus larvae, the causal agent of American foulbrood disease.

PubMed

Alvarado, Israel; Margotta, Joseph W; Aoki, Mai M; Flores, Fernando; Agudelo, Fresia; Michel, Guillermo; Elekonich, Michelle M; Abel-Santos, Ernesto

2017-09-01

Paenibacillus larvae, a Gram-positive bacterium, causes American foulbrood (AFB) in honey bee larvae (Apis mellifera Linnaeus [Hymenoptera: Apidae]). P. larvae spores exit dormancy in the gut of bee larvae, the germinated cells proliferate, and ultimately bacteremia kills the host. Hence, spore germination is a required step for establishing AFB disease. We previously found that P. larvae spores germinate in response to l-tyrosine plus uric acid in vitro. Additionally, we determined that indole and phenol blocked spore germination. In this work, we evaluated the antagonistic effect of 35 indole and phenol analogs and identified strong inhibitors of P. larvae spore germination in vitro. We further tested the most promising candidate, 5-chloroindole, and found that it significantly reduced bacterial proliferation. Finally, feeding artificial worker jelly containing anti-germination compounds to AFB-exposed larvae significantly decreased AFB infection in laboratory-reared honey bee larvae. Together, these results suggest that inhibitors of P. larvae spore germination could provide another method to control AFB. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America.

Experimental bacteriophage treatment of honeybees (Apis mellifera) infected with Paenibacillus larvae, the causative agent of American Foulbrood Disease

PubMed Central

Yost, Diane G.; Tsourkas, Philippos; Amy, Penny S.

2016-01-01

ABSTRACT American Foulbrood Disease (AFB) is an infection of honeybees caused by the bacterium Paenibacillus larvae. One potential remedy involves using biocontrol, such as bacteriophages (phages) to lyse P. larvae. Therefore, bacteriophages specific for P. larvae were isolated to determine their efficacy in lysing P. larvae cells. Samples from soil, beehive materials, cosmetics, and lysogenized P. larvae strains were screened; of 157 total samples, 28 were positive for at least one P. larvae bacteriophage, with a total of 30. Newly isolated bacteriophages were tested for the ability to lyse each of 11 P. larvae strains. Electron microscopy demonstrated that the phage isolates were from the family Siphoviridae. Seven phages with the broadest host ranges were combined into a cocktail for use in experimental treatments of infected bee larvae; both prophylactic and post-infection treatments were conducted. Results indicated that although both pre- and post-treatments were effective, prophylactic administration of the phages increased the survival of larvae more than post-treatment experiments. These preliminary experiments demonstrate the likelihood that phage therapy could be an effective method to control AFB. PMID:27144085

Gender difference in components of metabolic syndrome among patients of type 2 diabetes

PubMed Central

Alamgir, Muhammad Ahmad; Javid, Riaz Ahmad; Hameed, Abdul; Mustafa, Irum

2015-01-01

Background and Objectives: Diabetes mellitus, hypertension, obesity and dyslipidemia are the integral components that constitute metabolic syndrome. It has emerged as cause of substantial mortality with gender difference. To compare the gender characteristics of metabolic syndrome in subjects of type 2 diabetes mellitus. Methods: This observational comparative prospective study was conducted in medical ward of BVH Bahawalpur over period of 6 month from January 2014 to June 2014. Sample size of 100 diagnosed cases of type 2 diabetics (comprising equal number of males and females) were collected. As defined by WHO and IDF, variables of metabolic syndrome studied were BMI, hypertension, hyperglycemia and hyperlipidemia. The lipid values were interpreted in normal or high risk category by applying NCEP ATPIII criterion. Fasting sample were collected for sugar and lipid profile. Anthropometric, demographic and biochemical data was tabulated. Continuous and categorical variables were displayed as mean ± standard deviation and percentage respectively. Student ‘t’ test was use to assess the difference for the lipid profile at 5% significance level. Results: Female patients were found to be overweight, hypertensive and had uncontrolled hyperglycemia as compared to male subjects. Their systolic blood pressure was 150±25.75 and diastolic was 90±17mm/hg. The mean blood glucose concentration was 246.64±105mg/dl. In age group 35-44 years, the mean triglycerides and cholesterol levels in females were 184.54±42.05 and 192.5±34mg/dl respectively. HDL-C was 33.2±5.19mg/dl. In females with age group of 45-54 years, the mean concentration of triglycerides, total cholesterol and HDL-C were 217.75±77.6mg/dl, 190.95±14.4mg/dl and 31.75±3.8mg/dl respectively, and all were in high risk category when compared to cut off values determined by NCEP/ADA. While in females of age group 55-64 years, the values of TGs, total cholesterol and HDL-C were 204±154.11mg/dl, 200.09± 47.8 mg/dl and 33.4±4.6mg/dl respectively and again all these values were significantly raised. Conclusion: Female genders were affected in all respects. They had higher BMI, hypertension, hyperglycemia and hyperlipidemia as compared to male counterparts. PMID:26430423

Gender difference in components of metabolic syndrome among patients of type 2 diabetes.

PubMed

Alamgir, Muhammad Ahmad; Javid, Riaz Ahmad; Hameed, Abdul; Mustafa, Irum

2015-01-01

Diabetes mellitus, hypertension, obesity and dyslipidemia are the integral components that constitute metabolic syndrome. It has emerged as cause of substantial mortality with gender difference. To compare the gender characteristics of metabolic syndrome in subjects of type 2 diabetes mellitus. This observational comparative prospective study was conducted in medical ward of BVH Bahawalpur over period of 6 month from January 2014 to June 2014. Sample size of 100 diagnosed cases of type 2 diabetics (comprising equal number of males and females) were collected. As defined by WHO and IDF, variables of metabolic syndrome studied were BMI, hypertension, hyperglycemia and hyperlipidemia. The lipid values were interpreted in normal or high risk category by applying NCEP ATPIII criterion. Fasting sample were collected for sugar and lipid profile. Anthropometric, demographic and biochemical data was tabulated. Continuous and categorical variables were displayed as mean ± standard deviation and percentage respectively. Student 't' test was use to assess the difference for the lipid profile at 5% significance level. Female patients were found to be overweight, hypertensive and had uncontrolled hyperglycemia as compared to male subjects. Their systolic blood pressure was 150±25.75 and diastolic was 90±17mm/hg. The mean blood glucose concentration was 246.64±105mg/dl. In age group 35-44 years, the mean triglycerides and cholesterol levels in females were 184.54±42.05 and 192.5±34mg/dl respectively. HDL-C was 33.2±5.19mg/dl. In females with age group of 45-54 years, the mean concentration of triglycerides, total cholesterol and HDL-C were 217.75±77.6mg/dl, 190.95±14.4mg/dl and 31.75±3.8mg/dl respectively, and all were in high risk category when compared to cut off values determined by NCEP/ADA. While in females of age group 55-64 years, the values of TGs, total cholesterol and HDL-C were 204±154.11mg/dl, 200.09± 47.8 mg/dl and 33.4±4.6mg/dl respectively and again all these values were significantly raised. Female genders were affected in all respects. They had higher BMI, hypertension, hyperglycemia and hyperlipidemia as compared to male counterparts.

Maternal nutritional status during pregnancy and surma use determine cord lead levels in Karachi, Pakistan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janjua, Naveed Zafar; Department of Community Health Sciences, Aga Khan University, Karachi; Delzell, Elizabeth

Objectives: To estimate the umbilical cord blood lead levels (BLLs) of Pakistani neonates and to identify determinants for umbilical BLLs. Methods: We conducted a cross-sectional study of mothers and infants at one of the two obstetric units of two tertiary care hospitals in Karachi during January-August 2005. Information from 540 mothers selected randomly from those registered for delivery was obtained about their pregnancy, diet, and current and past lead exposures. We collected umbilical cord blood for lead levels analyzed using graphite furnace atomic absorption spectrophotometry. We computed geometric and arithmetic means. We performed multiple linear regression analysis to identify factorsmore » associated with log-transformed umbilical cord BLLs. We also performed logistic regression analysis to identify determinants of high lead cord BLLs ({>=}10 {mu}g/dl). Results: The geometric mean cord BLL of the neonates was 9.6 {mu}g/dl; arithmetic mean (S.D.) was 10.8 {mu}g/dl (5.7) with a median of 9.7 {mu}g/dl and a range of 1.8-48.9 {mu}g/dl. Women who reported intake of less than 58.5 mg of elemental iron supplement per day during pregnancy had cord BLL of 10.0 {mu}g/dl; in comparison those women who had higher iron intake had lower cord BLL (8.4 {mu}g/dl). Those who used surma (an eye cosmetic) daily had higher cord BLL (11.5 {mu}g/dl) as compared to those who used it less frequently (9.4 {mu}g/dl). In multivariable linear regression model, higher iron intake, owning a car, and being in 2nd quartile of mid-arm circumference were associated with low lead levels while father's occupation in lead-based industry was associated with significantly higher umbilical cord BLLs. There was interaction of daily surma use and ethnicity. Geometric mean BLLs were varied among surma users by ethnicity. Conclusions: Umbilical cord BLLs are high in Karachi, Pakistan, in comparison to those in developed countries such as United States. Measures are needed to reduce fetal lead exposure to prevent adverse affect on neurocognitive development. Association of low iron (below RDA of 60 mg per day) with high umbilical cord has implications for strengthening iron supplement intake during pregnancy. Umbilical cord BLLs differed among surma users by ethnicity.« less

Anaemia in pregnancy and associated factors: a cross sectional study of antenatal attendants at the Sunyani Municipal Hospital, Ghana.

PubMed

Anlaakuu, Peter; Anto, Francis

2017-08-11

Anaemia in pregnancy is an important health issue resulting in high maternal morbidity and mortality. The purpose of the current study was to identify factors associated with anaemia among pregnant women receiving antenatal care at the Sunyani Municipal Hospital in Ghana. A cross-sectional study involving pregnant women seeking antenatal care at the Sunyani Municipal Hospital was conducted between May and June, 2015. It involved the collection of data on socio demographic and obstetric variables, medical interventions and malaria infection, consumption of iron containing foods and supplements using a case record form and a structured questionnaire. Also, data on haemoglobin concentrations at first and current antenatal visit were collected. Bivariate and multivariate statistical analysis were done to determine factors associated with anaemia. Out of the 316 participants, 129 (40.8%) were found to be anaemic (Hb <11.0 g/dl) at the time of their first ANC visit (mean Hb: 11.21 g/dl, range 6.8-15.1 g/dl). Seventy-nine (61.2%) of them had mild anemia (Hb 9.0-10.9 g/dl), 48 (37.2%) had moderate anemia (Hb 7.0-8.9 g/dl) whilst 2 (1.6%) had severe anemia (Hb <7.0 g/dl). During their most recent ANC visit, the prevalence of anaemia was found to be similar to that of the first visit with 131 (41.5%) of them being anaemic [mean Hb: 11.24 g/dl, range 8.10-14.5 g/dl]. The haemoglobin levels however improved significantly during the most recent visit compared to the first with none of the women being severely anaemic (Hb <7.0 g/dl). The prevalence of moderate anaemia reduced from 37.2% (CI 28.9-46.2) during the first visit to 19.1% (12.7-26.9) during the most recent visit, a reduction of 48.7%. Malaria infection, frequency at which one consumed fish/snails and gestational age at first ANC visit were the main factors found to be associated with anaemia among the pregnant women. Malaria infection, fish/snails intake and gestational age at first ANC visit were significantly associated with anaemia. Addressing these factors can reduce the incidence of anaemia in pregnancy.

Multicentre studies of insecticide-treated durable wall lining in Africa and South-East Asia: entomological efficacy and household acceptability during one year of field use

PubMed Central

2012-01-01

Background Indoor residual spraying (IRS) is a primary method of malaria vector control, but its potential impact is constrained by several inherent limitations: spraying must be repeated when insecticide residues decay, householders can tire of the annual imposition and campaign costs are recurrent. Durable lining (DL) can be considered an advanced form of long-lasting IRS where insecticide is gradually released from an aesthetically attractive wall lining material to provide vector control for several years. A multicentre trial was carried out in Equatorial Guinea, Ghana, Mali, South Africa and Vietnam to assess the feasibility, durability, bioefficacy and household acceptability of DL, compared to conventional IRS or insecticide-treated curtains (LLITCs), in a variety of operational settings. Methods This study was conducted in 220 households in traditional rural villages over 12-15 months. In all sites, rolls of DL were cut to fit house dimensions and fixed to interior wall surfaces (usually with nails and caps) by trained teams. Acceptability was assessed using a standardized questionnaire covering such topics as installation, exposure reactions, entomology, indoor environment, aesthetics and durability. Bioefficacy of interventions was evaluated using WHO cone bioassay tests at regular intervals throughout the year. Results The deltamethrin DL demonstrated little to no decline in bioefficacy over 12-15 months, supported by minimal loss of insecticide content. By contrast, IRS displayed a significant decrease in bioactivity by 6 months and full loss after 12 months. The majority of participants in DL households perceived reductions in mosquito density (93%) and biting (82%), but no changes in indoor temperature (83%). Among those households that wanted to retain the DL, 73% cited protective reasons, 20% expressed a desire to keep theirs for decoration and 7% valued both qualities equally. In Equatorial Guinea, when offered a choice of vector control product at the end of the trial (DL, IRS or LLITCs), DL consistently emerged as the most popular intervention regardless of the earlier household allocation. Conclusions Just as long-lasting insecticidal nets overcame several of the technical and logistical constraints associated with conventionally treated nets and then went to scale, this study demonstrates the potential of DL to sustain user compliance and overcome the operational challenges associated with IRS. PMID:23107112

Performance and Injury Characteristics of Pitchers Entering the Major League Baseball Draft After Ulnar Collateral Ligament Reconstruction.

PubMed

Wymore, Lucas; Chin, Paul; Geary, Christopher; Carolan, Gregory; Keefe, Daniel; Hoenecke, Heinz; Fronek, Jan

2016-12-01

Ulnar collateral ligament (UCL) reconstruction (UCLR) has been studied and shown to be a successful procedure for returning overhead athletes to sport. Many studies of Major League Baseball (MLB) players have shown high levels of return to play with successful statistical performance. No study has followed professional advancement of drafted pitchers who underwent UCLR as amateurs when compared with drafted pitchers who did not undergo the procedure before selection in the MLB draft. There would be no difference in professional advancement, statistical performance, or injury rate between the UCLR and control groups. Cohort study; Level of evidence, 3. Thirty-eight pitchers with a UCLR as an amateur and 114 controls were identified in the MLB draft between 2006 and 2010. Highest level of professional baseball achieved was collected from all players, as well as statistical performance metrics including velocity, wins, earned run average (ERA), and walks and hits per inning pitched (WHIP). Additional data on future injuries were analyzed for days on the disabled list (DL), risk of being placed on the DL, and DL assignment for elbow injury. Thirteen of 38 UCLR pitchers reached the major league level (34.2%) compared with 29 of 114 (25.4%) control pitchers, which was not statically significant (P = .295). The UCLR and control groups were similar for average velocity, peak velocity, innings pitched, games, games started, innings per game, ERA, WHIP, wins, losses, saves, batters faced, and innings pitched per year, as well as hits, runs, home runs allowed, strikeouts, batters walked, and batters struck per inning. The UCLR group had a significantly increased rate of DL assignment when compared with controls (86.8% vs 64.0%; P = .008); however, days on DL (152.8 vs 135.6; P = .723) and DL assignment for elbow injury (45.5% vs 43.8%; P = .877) were similar. There was no difference in the rate of professional advancement among pitchers drafted by the MLB who had undergone UCLR as amateurs compared with controls. Both groups had similar statistical performance. Pitchers in the UCLR group had an increased risk of DL assignment but no increase in the number of days on DL or risk of DL placement for elbow injury. © 2016 The Author(s).

Existence of consistent hypo- and hyperresponders to dietary cholesterol in man.

PubMed

Katan, M B; Beynen, A C; de Vries, J H; Nobels, A

1986-02-01

Hyper- and hyporesponsiveness of serum cholesterol to dietary cholesterol is an established concept in animals but not in man. The authors studied the stability of the individual response of serum cholesterol to dietary cholesterol in three controlled experiments in 1982. The subjects were volunteers from the general population living in or near Wageningen, the Netherlands. Each experiment had a low-cholesterol baseline period (121, 106, and 129 mg/day in experiments 1, 2, and 3, respectively) and a high-cholesterol test period (625, 673, and 989 mg/day). Duplicate portion analysis showed that dietary cholesterol was the only variable. The 94 healthy men and women who completed experiment 1 showed an increase (mean +/- standard deviation (SD] in serum cholesterol of 0.50 +/- 0.39 mmol/liter (19 +/- 15 mg/dl). Seventeen putative hyperresponders, defined by their response in experiment 1, were retested in experiments 2 and 3; they showed responses of 0.28 +/- 0.38 mmol/liter (11 +/- 15 mg/dl) and 0.82 +/- 0.35 mmol/liter (32 +/- 14 mg/dl), respectively. Fifteen hyporesponders, selected in experiment 1, showed responses in experiments 2 and 3 of 0.06 +/- 0.35 mmol/liter (2 +/- 14 mg/dl) and 0.47 +/- 0.26 mmol/liter (18 +/- 10 mg/dl), significantly lower than the corresponding values for hyperresponders. The standardized regression coefficient for individual responses in experiment 2 on those in experiment 1 was beta = 0.34 (p = 0.03, n = 32); the corresponding regression coefficient for experiment 3 and experiment 1 was 0.53 (p less than 0.01). After correction for intraindividual fluctuations the true responsiveness distribution was found to have a between-subject standard deviation of about 0.29 mmol/liter (11 mg/dl). This implies that if the mean response to a certain dietary cholesterol load amounts to e.g., 0.58 mmol/liter (22 mg/dl), then the 16% of subjects least susceptible to diet will experience a rise of only 0.29 mmol/liter (11 mg/dl) or less, while in the 16% of subjects most susceptible to diet, serum cholesterol will rise by 0.87 mmol/liter (34 mg/dl) or more. The authors conclude that modest differences in responsiveness of serum cholesterol to dietary cholesterol do exist in man, and that the wide scatter of responses observed in single experiments is largely due to chance fluctuations.

Study of the Asteroid 2009 DL46

NASA Astrophysics Data System (ADS)

Vodniza, Alberto Quijano

2017-06-01

2009 DL46 was discovered by the Catalina Sky Survey on 2009-February 28. This asteroid has a diameter of about 194 meters (119 to 268 meters) [1], and Brian Warner has obtained a rotation period of at least 10 hours [2]. The asteroid 2009 DL46 flew past Earth on May 24/2016 at a distance of about 6.2 lunar distances (0.0158293668567628 A.U) [3]. The NEOWISE mission had a great likelihood to observing this asteroid in early May. Radiotelescopes of Goldstone and Arecibo had planned to make observations of 2009 DL46. “Using the Goldstone facility, we had planned to make radar observations of 2009 DL46” said Landis, Rob R. (HQ-DG000). This asteroid is on list for possible human mission targets. From our Observatory, located in Pasto-Colombia, we captured several pictures, videos and astrometry data during several hours during three days. Our data was published by the Minor Planet Center (MPC) and also appears at the web page of NEODyS [4]. The pictures and data of the asteroid were captured with the following equipment: CGE PRO 1400 CELESTRON (f/11 Schmidt-Cassegrain Telescope) and STL-1001 SBIG camera.. Astrometry was carried out, and we calculated the orbital elements. Summary and conclusions: We obtained the following orbital parameters: eccentricity = 0.30731 +/- 0.00025, semi-major axis = 1.460279 +/- 0.000532 A.U, orbital inclination = 7.9503 +/- 0.0048 deg, longitude of the ascending node = 63.45053 +/- 0.00034 deg, argument of perihelion = 159.8804 +/- 0.0024 deg, mean motion = 0.558535 +/- 0.000305 deg/d, perihelion distance = 1.01151363 +/- 3.39e-6 A.U, aphelion distance = 1.90904 +/- 0.00106 A.U, absolute magnitude = 22.5. The parameters were calculated based on 83 observations. Dates: 2016 May: 18 to 21 with mean residual = 0.29 arcseconds. The asteroid has an orbital period of 1.76 years (644.53 days).[1] http://newton.dm.unipi.it/neodys/index.php?pc=1.1.9&n=2009DL46.[2] http://echo.jpl.nasa.gov/asteroids/2009DL46/2009DL46_planning.html[3] http://ssd.jpl.nasa.gov/sbdb.cgi?sstr=2009%20DL46orb=1old=0cov=0log=0cad=1#cad[4] http://newton.dm.unipi.it/neodys/index.php?pc=2.1.2&o=H78&ab=7

Molecular pathogenesis of American Foulbrood: how Paenibacillus larvae kills honey bee larvae.

PubMed

Poppinga, Lena; Genersch, Elke

2015-08-01

American Foulbrood caused by Paenibacillus larvae is one of the unsolved health problems honey bee colonies are suffering from. In the recent past, considerable progress has been achieved in understanding molecular details of P. larvae infections of honey bee larvae. This was facilitated by the development of molecular tools for manipulating P. larvae and by the availability of complete genome sequences of different P. larvae genotypes. We here report on several peptides and proteins that have recently been identified, biochemically analyzed, and proposed to act as virulence factors of P. larvae. For some of them, experimental proof for their role as virulence factor has been provided allowing presenting a preliminary model for the molecular pathogenesis of American Foulbrood. Copyright © 2015 Elsevier Inc. All rights reserved.

[Hypercholesterolemia reduction in children and adolescents after two years of intervention].

PubMed

Robledo, Jorge A; Siccardi, Leonardo J; Cosio, Francisco; Rodríguez, María I; Robledo, Pamela; Rojas, Natalia; Lubetkin, Alberto

2009-12-01

Hypercholesterolemia, one of the main risk factors for cardiovascular diseases, can be detected since childhood. The early detection and a suitable educational process would allow to generate changes of habits and to decrease its prevalence. In 2003, total cholesterol (TC) > 170 mg/dl was found in 39.2% school children and adolescents, aged 5-17 years, of Jovita, Córdoba. To assess cholesterol levels decrease after an educational process and to analyze the relation between hypercholesterolemia and family history for cardiovascular diseases. Formal and no formal educational intervention was developed for two years, through curricular adaptations, talks, campaigns in radio and TV, graphic press, drama, workshops and leaflets. In 2005, cholesterol level was assessed, along with a survey on changes of nutritional habits and physical activity, and family history. A group of 161 students was assesses in both opportunities. There was a significant reduction in total cholesterol (average 13 mg/dl; p< 0.0000), 51 students (31.7%) normalized their TC values (<170 mg/dl). The effect of regression to the average was 3 mg/dl. In a group of 66 students with TC > 199 mg/dl, the variations of the averages were: TC= -21 mg/dl, LDL-C= -16 mg/dl. The survey revealed improvements in the habits; family history was positive in 59%, unknown in 14%, and negative in 27%, the last ones had the best response to the intervention. A significant reduction of TC was obtained in the studied population; this may be due to the educational intervention. More than a quarter of the individuals presented negative family history for cardiovascular risk factors. Decrease in TC was proportionally better in this group than in those with positive family history.

Reduction in membrane component of diffusing capacity is associated with the extent of acute pulmonary embolism

PubMed Central

Piirilä, Päivi; Laiho, Mia; Mustonen, Pirjo; Graner, Marit; Piilonen, Anneli; Raade, Merja; Sarna, Seppo; Harjola, Veli-Pekka; Sovijärvi, Anssi

2011-01-01

Acute pulmonary embolism (PE) often decreases pulmonary diffusing capacity for carbon monoxide (DL,CO), but data on the mechanisms involved are inconsistent. We wanted to investigate whether reduction in diffusing capacity of alveolo-capillary membrane (DM) and pulmonary capillary blood volume (Vc) is associated with the extent of PE or the presence and severity of right ventricular dysfunction (RVD) induced by PE and how the possible changes are corrected after 7-month follow-up. Forty-seven patients with acute non-massive PE in spiral computed tomography (CT) were included. The extent of PE was assessed by scoring mass of embolism. DL,CO, Vc, DM and alveolar volume (VA) were measured by using a single breath method with carbon monoxide and oxygen both at the acute phase and 7 months later. RVD was evaluated with transthoracic echocardiography and electrocardiogram. Fifteen healthy subjects were included as controls. DL,CO, DL, CO/VA, DM, vital capacity (VC) and VA were significantly lower in the patients with acute PE than in healthy controls (P<0·001). DM/Vc relation was significantly lower in patients with RVD than in healthy controls (P = 0·004). DM correlated inversely with central mass of embolism (r = −0·312; P = 0·047) whereas Vc did not. DM, DL,CO, VC and VA improved significantly within 7 months. In all patients (P = 0·001, P = 0·001) and persistent RVD (P = 0·020, P = 0·012), DM and DL,CO remained significantly lower than in healthy controls in the follow-up. DM was inversely related to central mass of embolism. Reduction in DM mainly explains the sustained decrease in DL,CO in PE after 7 months despite modern treatment of PE. PMID:21143754

Video laryngoscopy vs. direct laryngoscopy: Which should be chosen for endotracheal intubation during cardiopulmonary resuscitation? A prospective randomized controlled study of experienced intubators.

PubMed

Kim, Jong Won; Park, Sang O; Lee, Kyeong Ryong; Hong, Dae Young; Baek, Kwang Je; Lee, Young Hwan; Lee, Jeong Hun; Choi, Pil Cho

2016-08-01

This study compared endotracheal intubation (ETI) performance during cardiopulmonary resuscitation (CPR) between direct laryngoscopy (DL) and video laryngoscopy (VL) (GlideScope(®)) by experienced intubators (>50 successful ETIs). This was a prospective randomized controlled study conducted in an emergency department between 2011 and 2013. Intubators who used DL or VL were randomly allocated to ETI during CPR. Data were collected from recorded video clips and rhythm sheets. The success, speed, complications, and chest compressions interruption were compared between the two devices. Total 140 ETIs by experienced intubators using DL (n=69) and VL (n=71) were analysed. There were no significant differences between DL and VL in the ETI success rate (92.8% vs. 95.8%; p=0.490), first-attempt success rate (87.0% vs. 94.4%; p=0.204), and median time to complete ETI (51 [36-67] vs. 42 [34-62]s; p=0.143). In both groups, oesophageal intubation and dental injuries seldom occurred. However, longer chest compressions interruption occurred using DL (4.0 [1.0-11.0]s) compared with VL (0.0 [0.0-1.0]s) and frequent serious no-flow (interruption>10s) occurred with DL (18/69 [26.1%]) compared with VL (0/71) (p<0.001). For highly experienced intubators (>80 successful ETIs), frequent serious no-flow occurred in DL (14/55 [25.5%] vs. 0/57 in VL). The ETI success, speed and complications during CPR did not differ significantly between the two devices for experienced intubators. However, the VL was superior in terms of completion of ETI without chest compression interruptions. Clinical Research Information Service (CRIS) in South Korea KCT0000849. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Delayed luminescence: an experimental protocol for Chinese herbal medicines.

PubMed

Sun, Mengmeng; van Wijk, Roeland; van Wijk, Eduard; Wang, Mei; van Wietmarschen, Herman; Hankemeier, Thomas; van der Greef, Jan

2016-09-01

In Chinese medicine, raw herbal materials are used in processed and unprocessed forms aiming to meet the different requirements of clinical practice. To assure the chemical quality and therapeutic properties of the herbs, fast and integrated systematic assays are required. So far, such assays have not been established. Delayed luminescence (DL) refers to a decaying long-term ultraweak photon emission after exposure to light. Its decay kinetics under certain conditions may be a sensitive indicator reflecting the internal structural and chemical/physiological state of a biological system. DL measurements have been used in many applications for quality control. However, relatively little research has been reported on dried plant material such as Chinese herbs. The objective of the present study is to establish a protocol for direct and rapid DL measurements of dried Chinese herbal materials, including the determination of the dependence on: (a) the optimal excitation time utilizing a white light source; (b) the optimal size of the grinded herbal particle; and (c) the humidity conditions before and during measurement. Results indicate that stable and reproducible curves of DL photon emission depend mainly on the water content of herbal materials. To investigate the application of the established DL measurement protocol, non-processed and processed Aconitum (Aconitum carmichaelii Debx.), wild and cultivated rhubarb (Rheum palmatum L.) and ginseng (Panax ginseng C.A.Mey) of different ages were measured using DL. The results suggest that DL technology is a potential tool for assessment of dried Chinese herb qualities. The results warrant a further exploration of this technique in relation to therapeutic properties of the herbs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Continuous glucose profiles in healthy subjects under everyday life conditions and after different meals.

PubMed

Freckmann, Guido; Hagenlocher, Sven; Baumstark, Annette; Jendrike, Nina; Gillen, Ralph C; Rössner, Katja; Haug, Cornelia

2007-09-01

This study investigated continuous glucose profiles in nondiabetic subjects. Continuous interstitial glucose measurement was performed under everyday life conditions (2 days) and after ingestion of four meals with standardized carbohydrate content (50 grams), but with different types of carbohydrates and variable protein and fat content. Twenty-four healthy volunteers (12 female, 12 male, age 27.1 +/- 3.6 years) participated in the study. Each subject wore two microdialysis devices (SCGM1, Roche Diagnostics) simultaneously. The mean 24-hour interstitial glucose concentration under everyday life conditions was 89.3 +/- 6.2 mg/dl (mean +/- SD, n = 21), and mean interstitial glucose concentrations at daytime and during the night were 93.0 +/- 7.0 and 81.8 +/- 6.3 mg/dl, respectively. The highest postprandial glucose concentrations were observed after breakfast: 132.3 +/- 16.7 mg/dl (range 101-168 mg/dl); peak concentrations after lunch and dinner were 118.2 +/- 13.4 and 123.0 +/- 16.9 mg/dl, respectively. Mean time to peak glucose concentration was between 46 and 50 minutes. After ingestion of standardized meals with fast absorption characteristics, peak interstitial glucose concentrations were 133.2 +/- 14.4 and 137.2 +/- 21.1 mg/dl, respectively. Meals with a higher fiber, protein, and fat content induced a smaller increase and a slower decrease of postprandial glucose concentrations with peak values of 99.2 +/- 10.5 and 122.1 +/- 20.4 mg/dl, respectively. This study provided continuous glucose profiles in nondiabetic subjects and demonstrated that differences in meal composition are reflected in postprandial interstitial glucose concentrations. Regarding the increasing application of continuous glucose monitoring in diabetic patients, these data suggest that detailed information about the ingested meals is important for adequate interpretation of postprandial glucose profiles.

Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies.

PubMed Central

Eldridge, J H; Staas, J K; Meulbroek, J A; Tice, T R; Gilley, R M

1991-01-01

Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 microns in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10 microns in diameter exhibited stronger adjuvant activity than those greater than 10 microns, which correlated with the delivery of the 1- to 10-microns, but not the greater than 10-microns, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic V beta 8+ T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens. PMID:1879922

Diversity of killer cell immunoglobulin-like receptor genes in the Bengali population of northern West Bengal, India.

PubMed

Guha, P; Bhattacharjee, S; Chaudhuri, T K

2014-12-01

The Indian Subcontinent exhibits extensive diversity in its culture, religion, ethnicity and linguistic heritage, which symbolizes extensive genetic variations within the populations. The highly polymorphic Killer cell Immunoglobulin-like Receptor (KIR) family plays an important role in tracing genetic differentiation in human population. In this study, we aimed to analyse the KIR gene polymorphism in the Bengali population of northern West Bengal, India. To our knowledge, this is the first report on the KIR gene polymorphism in the Bengalis of West Bengal, India. Herein, we have studied the distribution of 14 KIR genes (KIR3DL1-3DL3, KIR2DL1-2DL5, KIR2DS1-2DS5 AND KIR3DS1) and two pseudogenes (KIR3DP1 and 2DP1) in the Bengalis. Apart from the framework genes (KIR2DL4, 3DL2, 3DL3 and 3DP1), which are present in all the individuals, the gene frequencies of other KIR genes varied between 0.34 and 0.88. Moreover, upon comparing the KIR polymorphism of the Bengalis with the available published data of other world populations, it has been found that the Indo-European-speaking Bengalis from the region share both Dravidian and Indo-Aryan gene pool with considerable influences of mongoloid and European descents. Furthermore, evidences from previously published data on human leucocyte antigen and Y-chromosome haplogroup diversity support the view. Our results will help to understand the genetic background of the Bengali population, in illustrating the population migration events in the eastern and north-eastern part of India, in explaining the extensive genetic admixture amongst the different linguistic groups of the region and also in KIR-related disease researches. © 2014 John Wiley & Sons Ltd.

Just-in-Time Video Laryngoscopy Versus Direct Laryngoscopy for Neonatal Intubation.

PubMed

Grgurich, Erin; Arnemann, Cynthia; Amon, Kim; Horton, Rose; Carlson, Jestin N

As neonatal endotracheal intubation (ETI) is a low-frequency, high-consequence event, it is essential that providers have access to resources to aid in ETI. We sought to determine the impact of video laryngoscopy (VL) with just-in-time training on intubation outcomes over direct laryngoscopy (DL) when performed by neonatal nurses. We conducted a prospective, randomized, crossover study with neonatal nurses employed at a level 2 neonatal intensive care unit (NICU). Nurses performed both DL and VL on a neonatal mannequin using a CMAC (Karl Storz Corp, Tuttlingen, Germany) either with the assistance of the screen (VL) or without (DL). Before performing the intubation, providers were given a just-in-time, brief education presentation and allowed to practice with the device. Each ETI attempt was reviewed to obtain the percentage of glottic opening (POGO) score, time to intubation (TTI, time from insertion of the blade into the mouth until the first breath was delivered), and time from blade insertion until the best POGO score. We enrolled 19 participants, with a median (interquartile range) of 20 (9-26) years of experience and having a median of 2 (1-3) intubations within the past year. None had used VL in the NICU previously. Median TTI did not differ between DL and VL: 19.9 (15.3-41.5) vs 20.3 (17.9-24.4) (P = 1). POGO scores and the number of attempts also did not differ between DL and VL. In our simulated setting, just-in-time VL training provided similar intubation outcomes compared with DL in ETI performed by neonatal nurses. Just-in-time VL education may be an alternative to traditional DL for neonatal intubations.

Differential impact of continuous theta-burst stimulation over left and right DLPFC on planning.

PubMed

Kaller, Christoph P; Heinze, Katharina; Frenkel, Annekathrein; Läppchen, Claus H; Unterrainer, Josef M; Weiller, Cornelius; Lange, Rüdiger; Rahm, Benjamin

2013-01-01

Most neuroimaging studies on planning report bilateral activations of the dorsolateral prefrontal cortex (dlPFC). Recently, these concurrent activations of left and right dlPFC have been shown to double dissociate with different cognitive demands imposed by the planning task: Higher demands on the extraction of task-relevant information led to stronger activation in left dlPFC, whereas higher demands on the integration of interdependent information into a coherent action sequence entailed stronger activation of right dlPFC. Here, we used continuous theta-burst stimulation (cTBS) to investigate the supposed causal structure-function mapping underlying this double dissociation. Two groups of healthy subjects (left-lateralized stimulation, n = 26; right-lateralized stimulation, n = 26) were tested within-subject on a variant of the Tower of London task following either real cTBS over dlPFC or sham stimulation over posterior parietal cortex. Results revealed that, irrespective of specific task demands, cTBS over left and right dlPFC was associated with a global decrease and increase, respectively, in initial planning times compared to sham stimulation. Moreover, no interaction between task demands and stimulation type (real vs. sham) and/or stimulation side (left vs. right hemisphere) were found. Together, against expectations from previous neuroimaging data, lateralized cTBS did not lead to planning-parameter specific changes in performance, but instead revealed a global asymmetric pattern of faster versus slower task processing after left versus right cTBS. This global asymmetry in the absence of any task-parameter specific impact of cTBS suggests that different levels of information processing may span colocalized, but independent axes of functional lateralization in the dlPFC. Copyright © 2011 Wiley Periodicals, Inc.

Oxytocin receptor neurotransmission in the dorsolateral bed nucleus of the stria terminalis facilitates the acquisition of cued fear in the fear-potentiated startle paradigm in rats.

PubMed

Moaddab, Mahsa; Dabrowska, Joanna

2017-07-15

Oxytocin (OT) is a hypothalamic neuropeptide that modulates fear and anxiety-like behaviors. Dorsolateral bed nucleus of the stria terminalis (BNST dl ) plays a critical role in the regulation of fear and anxiety, and expresses high levels of OT receptor (OTR). However, the role of OTR neurotransmission within the BNST dl in mediating these behaviors is unknown. Here, we used adult male Sprague-Dawley rats to investigate the role of OTR neurotransmission in the BNST dl in the modulation of the acoustic startle response, as well as in the acquisition and consolidation of conditioned fear using fear potentiated startle (FPS) paradigm. Bilateral intra-BNST dl administration of OT (100 ng) did not affect the acquisition of conditioned fear response. However, intra-BNST dl administration of specific OTR antagonist (OTA), (d(CH 2 ) 5 1 , Tyr(Me) 2 , Thr 4 , Orn 8 , des-Gly-NH 2 9 )-vasotocin, (200 ng), prior to the fear conditioning session, impaired the acquisition of cued fear, without affecting a non-cued fear component of FPS. Neither OTA, nor OT affected baseline startle or shock reactivity during fear conditioning. Therefore, the observed impairment of cued fear after OTA infusion resulted from the specific effect on the formation of cued fear. In contrast to the acquisition, neither OTA nor OT affected the consolidation of FPS, when administered after the completion of fear conditioning session. Taken together, these results reveal the important role of OTR neurotransmission in the BNST dl in the formation of conditioned fear to a discrete cue. This study also highlights the role of the BNST dl in learning to discriminate between threatening and safe stimuli. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-dose CT reconstruction via L1 dictionary learning regularization using iteratively reweighted least-squares.

PubMed

Zhang, Cheng; Zhang, Tao; Li, Ming; Peng, Chengtao; Liu, Zhaobang; Zheng, Jian

2016-06-18

In order to reduce the radiation dose of CT (computed tomography), compressed sensing theory has been a hot topic since it provides the possibility of a high quality recovery from the sparse sampling data. Recently, the algorithm based on DL (dictionary learning) was developed to deal with the sparse CT reconstruction problem. However, the existing DL algorithm focuses on the minimization problem with the L2-norm regularization term, which leads to reconstruction quality deteriorating while the sampling rate declines further. Therefore, it is essential to improve the DL method to meet the demand of more dose reduction. In this paper, we replaced the L2-norm regularization term with the L1-norm one. It is expected that the proposed L1-DL method could alleviate the over-smoothing effect of the L2-minimization and reserve more image details. The proposed algorithm solves the L1-minimization problem by a weighting strategy, solving the new weighted L2-minimization problem based on IRLS (iteratively reweighted least squares). Through the numerical simulation, the proposed algorithm is compared with the existing DL method (adaptive dictionary based statistical iterative reconstruction, ADSIR) and other two typical compressed sensing algorithms. It is revealed that the proposed algorithm is more accurate than the other algorithms especially when further reducing the sampling rate or increasing the noise. The proposed L1-DL algorithm can utilize more prior information of image sparsity than ADSIR. By transforming the L2-norm regularization term of ADSIR with the L1-norm one and solving the L1-minimization problem by IRLS strategy, L1-DL could reconstruct the image more exactly.

Comparative Efficacy and Immunogenicity of Replication-Defective, Recombinant Glycoprotein, and DNA Vaccines for Herpes Simplex Virus 2 Infections in Mice and Guinea Pigs

PubMed Central

Hoshino, Yo; Dalai, Sarat K.; Wang, Kening; Pesnicak, Lesley; Lau, Tsz Y.; Knipe, David M.; Cohen, Jeffrey I.; Straus, Stephen E.

2005-01-01

Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8+-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials. PMID:15596834

Comparative efficacy and immunogenicity of replication-defective, recombinant glycoprotein, and DNA vaccines for herpes simplex virus 2 infections in mice and guinea pigs.

PubMed

Hoshino, Yo; Dalai, Sarat K; Wang, Kening; Pesnicak, Lesley; Lau, Tsz Y; Knipe, David M; Cohen, Jeffrey I; Straus, Stephen E

2005-01-01

Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8(+)-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials.

Seven-month prostate-specific antigen (PSA) is prognostic in patients with prostate cancer initially diagnosed with distant metastases.

PubMed

Nieder, Carsten; Haukland, Ellinor; Pawinski, Adam; Norum, Jan

2018-03-05

Recent research suggests that prostate-specific antigen (PSA) ≤ 0.2 ng/dl at 7 months is prognostic for better survival with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer regardless of chemotherapy with docetaxel. These results were derived from a group of clinical trial participants. Therefore, we performed a confirmatory analysis in patients treated outside of trials. Furthermore, we limited inclusion to those who presented with metastases at the initial diagnosis of prostate cancer (synchronous metastases). A retrospective analysis of a comprehensive regional database was performed. The oncology care in this region (Nordland County, Northern Norway) was provided by one center. Patients who were diagnosed between January 01, 2004 and December 31, 2016 were included. Of 101 patients, 90 were alive at 7 months and had their PSA value measured. Their median age was 68.5 years. Only six patients (7%) achieved PSA ≤ 0.2 ng/dl at 7 months. The median value was 4.05 ng/dl. Median overall survival was shortest in patients with PSA > 4.0 ng/dl (22 months). For patients with PSA between 0.3 and 4.0 ng/dl, median survival was 54 months (p = 0.0001). No further increase was seen in the small group with lower PSA. Statistical significance was also found for a cutoff of ≤ 1.0 ng/dl (55 vs. 32 months). PSA at 7 months predicts overall survival. Given that only 7% of patients achieved PSA ≤ 0.2 ng/dl, confirmation of this particular cutoff requires additional studies in other populations.

Injectable biodegradable temperature-responsive PLGA-PEG-PLGA copolymers: synthesis and effect of copolymer composition on the drug release from the copolymer-based hydrogels.

PubMed

Qiao, Mingxi; Chen, Dawei; Ma, Xichen; Liu, Yanjun

2005-04-27

Injectable biodegradable temperature-responsive poly(DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with DL-lactide/glycolide molar ratio ranging from 6/1 to 15/l were synthesized from monomers of DL-lactide, glycolide and polyethylene glycol and characterized by 1H NMR. The resulting copolymers are soluble in water to form free flowing fluid at room temperature but become hydrogels at body temperature. The hydrophobicity of the copolymer increased with the increasing of DL-lactide/glycolide molar ratio. In vitro dissolution studies with two different hydrophobic drugs (5-fluorouracil and indomethacin) were performed to study the effect of DL-lactide/glycolide molar ratio on drug release and to elucidate drug release mechanism. The release mechanism for hydrophilic 5-fluorouracil was diffusion-controlled, while hydrophobic indomethacin showed an biphasic profile comprising of an initial diffusion-controlled stage followed by the hydrogel erosion-dominated stage. The effect of DL-lactide/glycolide molar ratio on drug release seemed to be dependent on the drug release mechanism. It has less effect on the drug release during the diffusion-controlled stage, but significantly affected drug release during the hydrogel erosion-controlled stage. Compared with ReGel system, the synthesized copolymers showed a higher gelation temperature and longer period of drug release. The copolymers can solubilize the hydrophobic indomethacin and the solubility (13.7 mg/ml) was increased 3425-fold compared to that in water (4 microg/ml, 25 degrees C). Two methods of physical mixing method and solvent evaporation method were used for drug solubilization and the latter method showed higher solubilization efficiency.

High Burden of Subclinical Lead Toxicity after Phase Out of Lead from Petroleum in Pakistan.

PubMed

Majid, Hafsa; Khan, Aysha Habib; Khan, Nadeem Ullah; Siddiqui, Imran; Ghani, Farooq; Jafri, Lena

2017-12-01

To evaluate the frequency of subclinical lead toxicity. Cross-sectional study. Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2011 to December 2014. Analysis of laboratory data for blood lead levels (BLL) was performed. Lead was tested by atomic absorption spectrometer. For all subjects, only initial test results were included while the results of repeated testing were excluded. Exemption was sought from institutional ethical review committee. BLL of 2-10 ug/dl and 10-70 ug/dl in children and adults, respectively were taken as subclinical lead toxicity. Amongst the total number of subjects tested (n=524), 26.5% (n=139) were children (<16 years) while rest were adults. Overall median BLLs was 6.4 ug/dl (20.9-3.1). The median BLL was 4 ug/dl (6.7-2.6) in children and 8.3 ug/dl (27.9-3.4) in adults, respectively. The BLL increased with age; higher levels were observed in age range 21-30 years of subjects [median lead level 16.9 ug/dl (36.1-4)] and lower level [4.2 ug/dl (6.8-2.6)] in children with <10 years of age. Only 16% (n=22) children had desirable lead levels while most had either subclinical (76%, n=106) or toxic lead levels (8%, n=11). In adults, (55%, n=212) subjects had desired lead levels, and 40% (n=154) and 4.99% (n=19) had subclinical and toxic lead levels. Presence of subclinical lead poisoning even after phasing out of lead petroleum in Pakistanis is alarming, especially in children. A national population-based study to determine the lead status and targeted intervention to identify potential sources is need of the time.

Seasonal variations in atmospheric concentrations and gas-particle partitioning of PCDD/Fs and dioxin-like PCBs around industrial sites in Shanghai, China

NASA Astrophysics Data System (ADS)

Die, Qingqi; Nie, Zhiqiang; Liu, Feng; Tian, Yajun; Fang, Yanyan; Gao, Hefeng; Tian, Shulei; He, Jie; Huang, Qifei

2015-10-01

Gas and particle phase air samples were collected in summer and winter around industrial sites in Shanghai, China, to allow the concentrations, profiles, and gas-particle partitioning of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) to be determined. The total 2,3,7,8-substituted PCDD/F and dl-PCB toxic equivalent (TEQ) concentrations were 14.2-182 fg TEQ/m3 (mean 56.8 fg TEQ/m3) in summer and 21.9-479 fg TEQ/m3 (mean 145 fg TEQ/m3) in winter. The PCDD/Fs tended to be predominantly in the particulate phase, while the dl-PCBs were predominantly found in the gas phase, and the proportions of all of the PCDD/F and dl-PCB congeners in the particle phase increased as the temperature decreased. The logarithms of the gas-particle partition coefficients correlated well with the subcooled liquid vapor pressures of the PCDD/Fs and dl-PCBs for most of the samples. Gas-particle partitioning of the PCDD/Fs deviated from equilibrium either in summer or winter close to local sources, and the Junge-Pankow model and predictions made using a model based on the octanol-air partition coefficient fitted the measured particulate PCDD/F fractions well, indicating that absorption and adsorption mechanism both contributed to the partitioning process. However, gas-particle equilibrium of the dl-PCBs was reached more easily in winter than in summer. The Junge-Pankow model predictions fitted the dl-PCB data better than did the predictions made using the model based on the octanol-air partition coefficient, indicating that adsorption mechanism made dominated contribution to the partitioning process.

[The effects of simvastatin combined with different antioxidant vitamin regimens on serum lipid profile in patients with low HDL cholesterol levels].

PubMed

Pirat, Bahar; Korkmaz, Mehmet Emin; Eroğlu, Serpil; Tayfun, Egemen; Yildirir, Aylin; Uluçam, Melek; Ozin, Bülent; Müderrisoğlu, Haldun

2004-12-01

This study was designed to compare the effects of simvastatin versus a combination of simvastatin with vitamin C or E on serum lipid profile, particularly, high-density lipoprotein (HDL)-cholesterol (C) level, in patients with a low HDL-C level. Fifty-nine women and 49 men, who had a baseline HDL-C level equal to or lower than 40 mg/dl were randomized to one of the following study treatment groups: Group S (n=39) simvastatin 20 mg/day, Group S+C (n=33) simvastatin 20 mg/day + vitamin C 500 mg/day, and Group S+E (n=36) simvastatin 20 mg/day + vitamin E 400 IU/day. The groups' lipid profiles were obtained at baseline, 3rd and 6th months. Comparing with baseline values, total-C and low-density cholesterol (LDL-C) values significantly reduced (p<0.001) and HDL-C values significantly increased (Group S--33.9+/-3.9 mg/dl vs. 39.8+/-6.9 mg/dl, Group S+C--34.2+/-3.5 mg/dl vs. 38.1+/-6.1 mg/dl, Group S+E--33.1+/-3.6 mg/dl vs. 34.8+/-5.9 mg/dl, p<0.001) on therapy within the groups; however, there were no significant differences among the groups with regards to these parameters. The HDL-C levels increased from baseline by 14.0%, 11.7% and 10.2% in Group S, S+C, and S+E, respectively (p>0.05). A combination of simvastatin with antioxidant vitamins does not offer any beneficial effect over simvastatin alone. Particularly vitamin E seems to blunt the simvastatin induced HDL-C increase.

Phase I study of UCN-01 and perifosine in patients with relapsed and refractory acute leukemias and high-risk myelodysplastic syndrome

PubMed Central

Gojo, Ivana; Perl, Alexander; Luger, Selina; Baer, Maria R.; Norsworthy, Kelly J.; Bauer, Kenneth S.; Tidwell, Michael; Fleckinger, Stephanie; Carroll, Martin; Sausville, Edward A.

2013-01-01

Summary Background The PI3K-Akt pathway is frequently activated in acute leukemias and represents an important therapeutic target. UCN-01 and perifosine are known to inhibit Akt activation. Methods The primary objective of this phase I study was to determine the maximum tolerated dose (MTD) of UCN-01 given in combination with perifosine in patients with advanced acute leukemias and myelodysplastic syndrome. Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and efficacy. Perifosine 150 mg every 6 hours was given orally on day 1 followed by 100 mg once a day continuously in 28-day cycles. UCN-01 was given intravenously over 3 hours on day 4 at three dose levels (DL1=40 mg/m2; DL2=65 mg/m2; DL3=90 mg/m2). Results Thirteen patients were treated (DL1, n=6; DL2, n=4; DL3, n=3) according to a traditional “3+3” design. Two patients at the DL3 experienced dose-limiting toxicity including grade 3-4 pericardial effusion, hypotension, hyperglycemia, hyperkalemia, constitutional symptoms and grade 5 pneumonitis. Other frequent toxicities were grade 1-2 nausea, diarrhea, vomiting, fatigue and hyperglycemia. The MTD was determined to be UCN-01 65 mg/m2 with perifosine 100 mg a day. No appreciable direct Akt inhibition could be demonstrated in patients’ mononuclear cells using Western blot, however, reduced phosphorylation of the downstream target ribosomal protein S6 in leukemic blasts was noted by intracellular flow cytometry. No objective responses were observed on this study. Conclusion UCN-01 and perifosine can be safely administered, but this regimen lacked clinical efficacy. This approach may have failed because of insufficient Akt inhibition in vivo. PMID:23443507

Substance P immunoreactive nerve terminals in the dorsolateral nucleus of the tractus solitarius: roles in the baroreceptor reflex.

PubMed

Massari, V J; Shirahata, M; Johnson, T A; Lauenstein, J M; Gatti, P J

1998-03-02

Physiological and light microscopic evidence suggest that substance P (SP) may be a neurotransmitter contained in first-order sensory baroreceptor afferents; however, ultrastructural support for this hypothesis is lacking. We have traced the central projections of the carotid sinus nerve (CSN) in the cat by utilizing the transganglionic transport of horseradish peroxidase (HRP). The dorsolateral subnucleus of the nucleus tractus solitarius (dlNTS) was processed for the histochemical visualization of transganglionically labeled CSN afferents and for the immunocytochemical visualization of SP by dual labeling light and electron microscopic methods. Either HRP or SP was readily identified in single-labeled unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS. SP immunoreactivity was also identified in unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS, which were simultaneously identified as CSN primary afferents. However, only 15% of CSN terminals in the dlNTS were immunoreactive for SP. Therefore, while the ultrastructural data support the hypothesis that SP immunoreactive first-order neurons are involved in the origination of the baroreceptor reflex, they suggest that only a modest part of the total sensory input conveyed from the carotid sinus baroreceptors to the dlNTS is mediated by SP immunoreactive CSN terminals. Five types of axo-axonic synapses were observed in the dlNTS. SP immunoreactive CSN afferents were very rarely involved in these synapses. Furthermore, SP terminals were never observed to form the presynaptic element in an axo-axonic synapse with a CSN afferent. Therefore, SP does not appear to be involved in the modulation of the baroreceptor reflex in the dlNTS. Copyright 1998 Elsevier Science B.V.

Diagnostic laparoscopy should be performed before definitive resection for pancreatic cancer: a financial argument

PubMed Central

Jayakrishnan, Thejus T; Nadeem, Hasan; Groeschl, Ryan T; George, Ben; Thomas, James P; Ritch, Paul S; Christians, Kathleen K; Tsai, Susan; Evans, Douglas B; Pappas, Sam G; Gamblin, T Clark; Turaga, Kiran K

2015-01-01

Objectives Laparoscopy is recommended to detect radiographically occult metastases in patients with pancreatic cancer before curative resection. This study was conducted to test the hypothesis that diagnostic laparoscopy (DL) is cost-effective in patients undergoing curative resection with or without neoadjuvant therapy (NAT). Methods Decision tree modelling compared routine DL with exploratory laparotomy (ExLap) at the time of curative resection in resectable cancer treated with surgery first, (SF) and borderline resectable cancer treated with NAT. Costs (US$) from the payer's perspective, quality-adjusted life months (QALMs) and incremental cost-effectiveness ratios (ICERs) were calculated. Base case estimates and multi-way sensitivity analyses were performed. Willingness to pay (WtP) was US$4166/QALM (or US$50 000/quality-adjusted life year). Results Base case costs were US$34 921 for ExLap and US$33 442 for DL in SF patients, and US$39 633 for ExLap and US$39 713 for DL in NAT patients. Routine DL is the dominant (preferred) strategy in both treatment types: it allows for cost reductions of US$10 695/QALM in SF and US$4158/QALM in NAT patients. Conclusions The present analysis supports the cost-effectiveness of routine DL before curative resection in pancreatic cancer patients treated with either SF or NAT. PMID:25123702

Blood lead level and its relationship to essential elements in preschool children from Nanning, China.

PubMed

Chen, Jingwen; Li, Muyan; Lv, Qun; Chen, Guoli; Li, Yong; Li, Shaojun; Mo, Yuhuan; Ou, Shiyan; Yuan, Zongxiang; Huang, Mingli; Jiang, Yueming

2015-04-01

Our study aimed to assess the distribution of blood lead level and its relationship to essential elements in preschool children in an urban area of China. A total of 6741 children aged 0- to 6-year-old were recruited. Levels of lead, zinc, copper, iron, calcium, and magnesium in whole blood samples were determined using atomic absorption spectrometry. The mean blood lead level (BLL) and the prevalence of BLL≥10μg/dl (5.26±4.08μg/dl and 6.84%, respectively) increased with age gradually, and there was a gender-difference for blood lead, copper, zinc and iron levels. Compared with the group of children who had BLLs<5μg/dl, the groups of 5≤BLLs<10μg/dl and 10≤BLLs<15μg/dl showed higher blood zinc, iron and magnesium levels, and a lower blood calcium level. A positive correlation of lead with zinc, iron and magnesium, and a negative correlation of lead with calcium were found in the group of children with BLL<5μg/dl. Age- and gender-differences were found when assessing the BLL and intoxication prevalence in preschool children. Metabolic disorder of essential elements was found even with a low level of lead exposure. Copyright © 2014 Elsevier GmbH. All rights reserved.

Plasma electrophoretogram in feline immunodeficiency virus (FIV) and/or feline leukaemia virus (FeLV) infections.

PubMed

Miró, G; Doménech, A; Escolar, E; Collado, V M; Tejerizo, G; De Las Heras, A; Gómez-Lucía, E

2007-05-01

The electrophoretogram of 89 cats, including those infected by feline immunodeficiency virus (FIV+), feline leukaemia virus (FeLV+) and non-infected, showed statistically significant differences in several of the fractions. FIV+ cats had very high protein values (mean, 8.10 g/dl), mostly because of hypergammaglobulinemia (mean, 2.81 g/dl) as compared with non-infected animals and FeLV+. In addition, in these FIV+ animals, the albumin/globulins ratio (A/G) was very low (mean, 0.72). Statistically significant differences in A/G and alpha2-globulin fraction were observed in FeLV+ group (A/G mean, 0.88 +/- 0.08; alpha2-globulin, mean, 0.84 +/- 0.07 g/dl) when compared with non-infected group (A/G mean, 1.06 +/- 0.08; alpha2-globulin mean, 0.68 +/- 0.04 g/dl). The alpha1-globulin fraction was higher in double infected animals (FIV and FeLV positive, F-F) (3.55 g/dl), than in FeLV+ or FIV+ cats (3.10 and 3.07 g/dl respectively), but no statistical conclusions may be drawn from this fact because of the low number of F-F animals. This technique may help to assess the initial clinical status of retrovirus-infected cats, and the clinical course of these chronic diseases, specifically during and after suitable therapy.

Systematic review and meta-analysis of method comparison studies of Masimo pulse co-oximeters (Radical-7™ or Pronto-7™) and HemoCue® absorption spectrometers (B-Hemoglobin or 201+) with laboratory haemoglobin estimation.

PubMed

Hiscock, R; Kumar, D; Simmons, S W

2015-05-01

We assessed agreement in haemoglobin measurement between Masimo pulse co-oximeters (Rad-7™ and Pronto-7™) and HemoCue® photometers (201+ or B-Hemoglobin) with laboratory-based determination and identified 39 relevant studies (2915 patients in Masimo group and 3084 patients in HemoCue group). In the Masimo group, the overall mean difference was -0.03 g/dl (95% prediction interval -0.30 to 0.23) and 95% limits of agreement -3.0 to 2.9 g/dl compared to 0.08 g/dl (95% prediction interval -0.04 to 0.20) and 95% limits of agreement -1.3 to 1.4 g/dl in the HemoCue group. Only B-Hemoglobin exhibited bias (0.53, 95% prediction interval 0.27 to 0.78). The overall standard deviation of difference was larger (1.42 g/dl versus 0.64 g/dl) for Masimo pulse co-oximeters compared to HemoCue photometers. Masimo devices and HemoCue 201+ both provide an unbiased, pooled estimate of laboratory haemoglobin. However, Masimo devices have lower precision and wider 95% limits of agreement than HemoCue devices. Clinicians should carefully consider these limits of agreement before basing transfusion or other clinical decisions on these point-of-care measurements alone.

Ethylphenidate as a selective dopaminergic agonist and methylphenidate-ethanol transesterification biomarker

PubMed Central

Patrick, Kennerly S.; Corbin, Timothy R.; Murphy, Cristina E.

2014-01-01

We review the pharmaceutical science of ethylphenidate (EPH) in the contexts of drug discovery; drug interactions; biomarker for dl-methylphenidate (MPH)-ethanol exposure; potentiation of dl-MPH abuse liability; contemporary “designer drug”; pertinence to the newer transdermal and chiral switch MPH formulations; as well as problematic internal standard. d-EPH selectively targets the dopamine transporter while d-MPH exhibits equipotent actions at dopamine and norepinephrine transporters. This selectivity carries implications for the advancement of tailored attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in the era of genome-based diagnostics. Abuse of dl-MPH often involves ethanol co-abuse. Carboxylesterase 1 enantioselectively transesterifies l-MPH with ethanol to yield l-EPH accompanied by significantly increased early exposure to d-MPH and rapid potentiation of euphoria. The pharmacokinetic component of this drug interaction can largely be avoided using dexmethylphenidate (dexMPH). This notwithstanding, maximal potentiated euphoria occurs following dexMPH-ethanol. C57BL/6 mice model dl-MPH-ethanol interactions: An otherwise depressive dose of ethanol synergistically increases dl-MPH stimulation; A sub-stimulatory dose of dl-MPH potentiates a low, stimulatory dose of ethanol; Ethanol elevates blood, brain and urinary d-MPH concentrations while forming l-EPH. Integration of EPH preclinical neuropharmacology with clinical studies of MPH-ethanol interactions provides a translational approach toward advancement of ADHD personalized medicine and management of comorbid alcohol use disorder. PMID:25303048

Ethylphenidate as a selective dopaminergic agonist and methylphenidate-ethanol transesterification biomarker.

PubMed

Patrick, Kennerly S; Corbin, Timothy R; Murphy, Cristina E

2014-12-01

We review the pharmaceutical science of ethylphenidate (EPH) in the contexts of drug discovery, drug interactions, biomarker for dl-methylphenidate (MPH)-ethanol exposure, potentiation of dl-MPH abuse liability, contemporary "designer drug," pertinence to the newer transdermal and chiral switch MPH formulations, as well as problematic internal standard. d-EPH selectively targets the dopamine transporter, whereas d-MPH exhibits equipotent actions at dopamine and norepinephrine transporters. This selectivity carries implications for the advancement of tailored attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in the era of genome-based diagnostics. Abuse of dl-MPH often involves ethanol coabuse. Carboxylesterase 1 enantioselectively transesterifies l-MPH with ethanol to yield l-EPH accompanied by significantly increased early exposure to d-MPH and rapid potentiation of euphoria. The pharmacokinetic component of this drug interaction can largely be avoided using dexmethylphenidate (dexMPH). This notwithstanding, maximal potentiated euphoria occurs following dexMPH-ethanol. C57BL/6 mice model dl-MPH-ethanol interactions: an otherwise depressive dose of ethanol synergistically increases dl-MPH stimulation; a substimulatory dose of dl-MPH potentiates a low, stimulatory dose of ethanol; ethanol elevates blood, brain, and urinary d-MPH concentrations while forming l-EPH. Integration of EPH preclinical neuropharmacology with clinical studies of MPH-ethanol interactions provides a translational approach toward advancement of ADHD personalized medicine and management of comorbid alcohol use disorder. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Honey bees consider larval nutritional status rather than genetic relatedness when selecting larvae for emergency queen rearing.

PubMed

Sagili, Ramesh R; Metz, Bradley N; Lucas, Hannah M; Chakrabarti, Priyadarshini; Breece, Carolyn R

2018-05-16

In honey bees and many other social insects, production of queens is a vital task, as colony fitness is dependent on queens. The factors considered by honey bee workers in selecting larvae to rear new queens during emergency queen rearing are poorly understood. Identifying these parameters is critical, both in an evolutionary and apicultural context. As female caste development in honey bees is dependent on larval diet (i.e. nutrition), we hypothesized that larval nutritional state is meticulously assessed and used by workers in selection of larvae for queen rearing. To test this hypothesis, we conducted a series of experiments manipulating the nutritional status of one day old larvae by depriving them of brood food for a four-hour period, and then allowing workers to choose larvae for rearing queens from nutritionally deprived and non-deprived larvae. We simultaneously investigated the role of genetic relatedness in selection of larvae for queen rearing. In all the experiments, significantly greater numbers of non-deprived larvae than deprived larvae were selected for queen rearing irrespective of genetic relatedness. Our results demonstrate that honey bees perceive the nutritional state of larvae and use that information when selecting larvae for rearing queens in the natural emergency queen replacement process.

Elucidation of sevadicin, a novel non-ribosomal peptide secondary metabolite produced by the honey bee pathogenic bacterium Paenibacillus larvae.

PubMed

Garcia-Gonzalez, Eva; Müller, Sebastian; Ensle, Paul; Süssmuth, Roderich D; Genersch, Elke

2014-05-01

American foulbrood (AFB) caused by the bee pathogenic bacterium Paenibacillus larvae is the most devastating bacterial disease of honey bees worldwide. From AFB-dead larvae, pure cultures of P. larvae can normally be cultivated indicating that P. larvae is able to defend its niche against all other bacteria present. Recently, comparative genome analysis within the species P. larvae suggested the presence of gene clusters coding for multi-enzyme complexes, such as non-ribosomal peptide synthetases (NRPSs). The products of these enzyme complexes are known to have a wide range of biological activities including antibacterial activities. We here present our results on antibacterial activity exhibited by vegetative P. larvae and the identification and analysis of a novel antibacterially active P. larvae tripeptide (called sevadicin; Sev) produced by a NRPS encoded by a gene cluster found in the genome of P. larvae. Identification of Sev was ultimately achieved by comparing the secretome of wild-type P. larvae with knockout mutants of P. larvae lacking production of Sev. Subsequent mass spectrometric studies, enantiomer analytics and chemical synthesis revealed the sequence and configuration of the tripeptide, D-Phe-D-ALa-Trp, which was shown to have antibacterial activity. The relevance of our findings is discussed in respect to host-pathogen interactions.

Effect of heavy metal layer thickness on spin-orbit torque and current-induced switching in Hf|CoFeB|MgO structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akyol, Mustafa; Jiang, Wanjun; Yu, Guoqiang

We study the heavy metal layer thickness dependence of the current-induced spin-orbit torque (SOT) in perpendicularly magnetized Hf broken vertical bar CoFeB broken vertical bar MgO multilayer structures. The damping-like (DL) current-induced SOT is determined by vector anomalous Hall effect measurements. A non-monotonic behavior in the DL-SOT is found as a function of the thickness of the heavy-metal layer. The sign of the DL-SOT changes with increasing the thickness of the Hf layer in the trilayer structure. As a result, in the current-driven magnetization switching, the preferred direction of switching for a given current direction changes when the Hf thicknessmore » is increased above similar to 7 nm. Although there might be a couple of reasons for this unexpected behavior in DL-SOT, such as the roughness in the interfaces and/or impurity based electric potential in the heavy metal, one can deduce a roughness dependence sign reversal in DL-SOT in our trilayer structure.« less

Effect of heavy metal layer thickness on spin-orbit torque and current-induced switching in Hf|CoFeB|MgO structures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akyol, Mustafa; Department of Physics, University of Çukurova, Adana 01330; Jiang, Wanjun

We study the heavy metal layer thickness dependence of the current-induced spin-orbit torque (SOT) in perpendicularly magnetized Hf|CoFeB|MgO multilayer structures. The damping-like (DL) current-induced SOT is determined by vector anomalous Hall effect measurements. A non-monotonic behavior in the DL-SOT is found as a function of the thickness of the heavy-metal layer. The sign of the DL-SOT changes with increasing the thickness of the Hf layer in the trilayer structure. As a result, in the current-driven magnetization switching, the preferred direction of switching for a given current direction changes when the Hf thickness is increased above ∼7 nm. Although there might bemore » a couple of reasons for this unexpected behavior in DL-SOT, such as the roughness in the interfaces and/or impurity based electric potential in the heavy metal, one can deduce a roughness dependence sign reversal in DL-SOT in our trilayer structure.« less

Tracheal intubation by novice staff: the direct vision laryngoscope or the lighted stylet (Trachlight)?

PubMed Central

Soh, C; Kong, C; Kong, C; Ip-Yam, P; Chin, E; Goh, M

2002-01-01

Objective: To compare the ease of use of the direct vision laryngoscope and the lighted stylet (Trachlight) by novice staff. Methods: Ten novice medical officers (MOs) performed orotracheal intubations using either the conventional direct vision laryngoscope (DL) or a lighted stylet device (Trachlight). They performed their DL intubations during the first phase of the study, followed by the Trachlight intubations in the subsequent phase. Results: 51 of 54 (94%) of the DL intubation attempts were successful compared with 36 of 54 (67%) of the Trachlight intubations (p<0.001). The mean (SEM) time for intubation was 44 (7) seconds in the DL group and 66 (13) seconds in the Trachlight group (p=0.004). In addition 45 of 54 (83%) of the DL intubations were successful at the first attempt versus 15 of 54 (28%) in the Trachlight group (p<0.001). Conclusion: The results show that the use of the conventional direct vision laryngoscope in novices is associated with significantly shorter mean intubation times and higher success rates on the first attempt compared with the Trachlight. PMID:12101133

The use of laparoscopy in the diagnosis and treatment of blunt and penetrating abdominal injuries: 10-year experience at a level 1 trauma center.

PubMed

Johnson, Jeremy J; Garwe, Tabitha; Raines, Alexander R; Thurman, Joseph B; Carter, Sandra; Bender, Jeffrey S; Albrecht, Roxie M

2013-03-01

Diagnostic laparoscopy (DL) has decreased the rate of nontherapeutic laparotomy for patients suffering from penetrating injuries. We evaluated whether DL similarly lowers the rate of nontherapeutic laparotomy for patients with blunt injuries. All patients undergoing DL over a 10-year period (ie, 2001-2010) in a single level 1 trauma center were classified by the mechanism of injury. Demographic and perioperative data were compared using the Student t and Fisher exact tests. There were 131 patients included, 22 of whom sustained blunt injuries. Patients suffering from blunt injuries were more severely injured (Injury Severity Score 18.0 vs 7.3, P = .0001). The most common indication for DL after blunt injury was a computed tomographic scan concerning for bowel injury (59.1%). The rate of nontherapeutic laparotomy for patients sustaining penetrating vs blunt injury was 1.8% and nil, respectively. DL, when coupled with computed tomographic findings, is an effective tool for the initial management of patients with blunt injuries. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of repetitive element polymerase chain reaction for surveillance of methicillin-resistant Staphylococcus aureus at a large academic medical center and community hospitals.

PubMed

Wang, Shu-Hua; Stevenson, Kurt B; Hines, Lisa; Mediavilla, José R; Khan, Yosef; Soni, Ruchi; Dutch, Wendy; Brandt, Eric; Bannerman, Tammy; Kreiswirth, Barry N; Pancholi, Preeti

2015-01-01

Repetitive element polymerase chain reaction (rep-PCR) typing has been used for methicillin-resistant Staphylococcus aureus (MRSA) strain characterization. The goal of this study was to determine if a rapid commercial rep-PCR system, DiversiLab™ (DL; bioMérieux, Durham, NC, USA), could be used for MRSA surveillance at a large medical center and community hospitals. A total of 1286 MRSA isolates genotyped by the DL system were distributed into 84 distinct rep-PCR patterns: 737/1286 (57%) were clustered into 6 major rep-PCR patterns. A subset of 220 isolates was further typed by pulsed-field gel electrophoresis (PFGE), spa typing, and SCCmec typing. The 220 isolates were distributed into 80 rep-PCR patterns, 94 PFGE pulsotypes, 27 spa, and 3 SCCmec types. The DL rep-PCR system is sufficient for surveillance, but the DL system alone cannot be used to compare data to other institutions until a standardized nomenclature is established and the DL MRSA reference library is expanded. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression, purification and preliminary X-ray characterization of dl-2-haloacid dehalogenase from Methylobacterium sp. CPA1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Omi, Rie; Department of Chemistry, Graduate School of Science, Osaka City University, Sumiyoshi-ku, Osaka 558-8585; Jitsumori, Keiji

A recombinant form of dl-2-haloacid dehalogenase from Methylobacterium sp. CPA1 has been expressed in E. coli, purified and crystallized. The crystal belongs to space group P6{sub 3}. Diffraction data have been collected to 1.75 Å resolution. dl-2-Haloacid dehalogenase from Methylobacterium sp. CPA1 (dl-DEX Mb) is a unique enzyme that catalyzes the dehalogenation reaction without the formation of an ester intermediate. A recombinant form of dl-DEX Mb has been expressed in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method. The crystal belongs to the hexagonal space group P6{sub 3}, with unit-cell parameters a = b = 186.2, c =more » 114.4 Å. The crystals are likely to contain between four and eight monomers in the asymmetric unit, with a V{sub M} value of 4.20–2.10 Å{sup 3} Da{sup −1}. A self-rotation function revealed peaks on the χ = 180° section. X-ray data have been collected to 1.75 Å resolution.« less