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Sample records for susceptibility protein elac2

  1. A survey of green plant tRNA 3'-end processing enzyme tRNase Zs, homologs of the candidate prostate cancer susceptibility protein ELAC2

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    Wang Zhikang

    2011-07-01

    Full Text Available Abstract Background tRNase Z removes the 3'-trailer sequences from precursor tRNAs, which is an essential step preceding the addition of the CCA sequence. tRNase Z exists in the short (tRNase ZS and long (tRNase ZL forms. Based on the sequence characteristics, they can be divided into two major types: bacterial-type tRNase ZS and eukaryotic-type tRNase ZL, and one minor type, Thermotoga maritima (TM-type tRNase ZS. The number of tRNase Zs is highly variable, with the largest number being identified experimentally in the flowering plant Arabidopsis thaliana. It is unknown whether multiple tRNase Zs found in A. thaliana is common to the plant kingdom. Also unknown is the extent of sequence and structural conservation among tRNase Zs from the plant kingdom. Results We report the identification and analysis of candidate tRNase Zs in 27 fully sequenced genomes of green plants, the great majority of which are flowering plants. It appears that green plants contain multiple distinct tRNase Zs predicted to reside in different subcellular compartments. Furthermore, while the bacterial-type tRNase ZSs are present only in basal land plants and green algae, the TM-type tRNase ZSs are widespread in green plants. The protein sequences of the TM-type tRNase ZSs identified in green plants are similar to those of the bacterial-type tRNase ZSs but have distinct features, including the TM-type flexible arm, the variant catalytic HEAT and HST motifs, and a lack of the PxKxRN motif involved in CCA anti-determination (inhibition of tRNase Z activity by CCA, which prevents tRNase Z cleavage of mature tRNAs. Examination of flowering plant chloroplast tRNA genes reveals that many of these genes encode partial CCA sequences. Based on our results and previous studies, we predict that the plant TM-type tRNase ZSs may not recognize the CCA sequence as an anti-determinant. Conclusions Our findings substantially expand the current repertoire of the TM-type tRNase ZSs and hint

  2. Localization of human RNase Z isoforms: dual nuclear/mitochondrial targeting of the ELAC2 gene product by alternative translation initiation.

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    Walter Rossmanith

    Full Text Available RNase Z is an endonuclease responsible for the removal of 3' extensions from tRNA precursors, an essential step in tRNA biogenesis. Human cells contain a long form (RNase Z(L encoded by ELAC2, and a short form (RNase Z(S; ELAC1. We studied their subcellular localization by expression of proteins fused to green fluorescent protein. RNase Z(S was found in the cytosol, whereas RNase Z(L localized to the nucleus and mitochondria. We show that alternative translation initiation is responsible for the dual targeting of RNase Z(L. Due to the unfavorable context of the first AUG of ELAC2, translation apparently also starts from the second AUG, whereby the mitochondrial targeting sequence is lost and the protein is instead routed to the nucleus. Our data suggest that RNase Z(L is the enzyme involved in both, nuclear and mitochondrial tRNA 3' end maturation.

  3. The Phenotype and Outcome of Infantile Cardiomyopathy Caused by a Homozygous ELAC2 Mutation.

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    Shinwari, Zarghuna M A; Almesned, Abdulrahman; Alakhfash, Ali; Al-Rashdan, Ahmad M; Faqeih, Eissa; Al-Humaidi, Zainab; Alomrani, Ahmed; Alghamdi, Malak; Colak, Dilek; Alwadai, Abdullah; Rababh, Monther; Al-Fayyadh, Majid; Al-Hassnan, Zuhair N

    2017-01-01

    Cardiomyopathy (CMP) in children is a clinically and genetically heterogeneous group of disorders. Disease-associated mutations have been identified in more than 50 genes. Recently, mutations in the mitochondrial tRNA processing gene, ELAC2, were reported to be associated with the recessively inherited form of hypertrophic CMP (HCM). This study is aimed at describing the cardiac phenotype and outcome of ELAC2 mutation. We performed whole exome sequencing followed by targeted mutation screening to identify the genetic etiology of severe infantile-onset CMP in 64 consanguineous Saudi families. A previously reported mutation (p.Phe154Leu) in ELAC2 gene was detected in 16 families. The index cases presented between 2 and 7 months of age with HCM in 13 infants and dilated CMP (DCM) in 3. Pericardial effusion was observed in 7 infants (44%). All infants died with a median age of death of 4 months. Almost 1/3 of them died during the initial presentation. Our study suggests screening the ELAC2 gene in severe infantile-onset HCM or DCM of unknown etiology, especially in the presence of pericardial effusion. Our work demonstrates a universally poor outcome of the (p.Phe154Leu) variant in ELAC2 gene; a correlation that helps in counseling parents and in planning appropriate medical intervention. © 2017 S. Karger AG, Basel.

  4. Susceptibility of sweetpotato (Ipomoea batatas) peel proteins to digestive enzymes

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    Sweet potato proteins have been shown to possess antioxidant and antidiabetic properties in vivo. The ability of a protein to exhibit systemic effects is somewhat unusual as proteins are typically susceptible to digestive enzymes. This study was undertaken to better understand how digestive enzymes ...

  5. Genetic variance is associated with susceptibility for cigarette smoke-induced DAMP release in mice.

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    Pouwels, Simon D; Faiz, Alen; den Boef, Lisette E; Gras, Reneé; van den Berge, Maarten; Boezen, H Marike; Korstanje, Ron; Ten Hacken, Nick H T; van Oosterhout, Antoon J M; Heijink, Irene H; Nawijn, Martijn C

    2017-09-01

    Chronic obstructive pulmonary disease (COPD) is characterized by unresolved neutrophilic airway inflammation and is caused by chronic exposure to toxic gases, such as cigarette smoke (CS), in genetically susceptible individuals. Recent data indicate a role for damage-associated molecular patterns (DAMPs) in COPD. Here, we investigated the genetics of CS-induced DAMP release in 28 inbred mouse strains. Subsequently, in lung tissue from a subset of strains, the expression of the identified candidate genes was analyzed. We tested whether small interfering RNA-dependent knockdown of candidate genes altered the susceptibility of the human A549 cell line to CS-induced cell death and DAMP release. Furthermore, we tested whether these genes were differentially regulated by CS exposure in bronchial brushings obtained from individuals with a family history indicative of either the presence or absence of susceptibility for COPD. We observed that, of the four DAMPs tested, double-stranded DNA (dsDNA) showed the highest correlation with neutrophilic airway inflammation. Genetic analyses identified 11 candidate genes governing either CS-induced or basal dsDNA release in mice. Two candidate genes ( Elac2 and Ppt1 ) showed differential expression in lung tissue on CS exposure between susceptible and nonsusceptible mouse strains. Knockdown of ELAC2 and PPT1 in A549 cells altered susceptibility to CS extract-induced cell death and DAMP release. In bronchial brushings, CS-induced expression of ENOX1 and ARGHGEF11 was significantly different between individuals susceptible or nonsusceptible for COPD. Our study shows that genetic variance in a mouse model is associated with CS-induced DAMP release, and that this might contribute to susceptibility for COPD. Copyright © 2017 the American Physiological Society.

  6. Differential protein expression in the susceptible and resistant Myzus persicae (Sulzer) to imidacloprid.

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    Meng, JianYu; Zhang, ChangYu; Chen, XingJiang; Cao, Yi; Shang, ShengHua

    2014-10-01

    Myzus persicae, a serious economic agricultural pest, has developed resistance to imidacloprid (IMI), which was widely used to control this aphid worldwide. To gain a better understanding of the mechanisms of IMI resistance in M. persicae, we carried out a comparative proteomic analysis. Total proteins of the IMI-susceptible and resistant strains were extracted and separated by two-dimensional gel electrophoresis. More than 1300 protein spots were reproducibly detected, including 14 that were more abundant and 14 less abundant. Mass spectrometry analysis and database searching helped us to identify 25 differentially abundant proteins. The identified proteins were categorized into several functional groups including signal transduction, RNA processing, protein processing, transport processing, stress response, metabolisms, and cytoskeleton structure, etc. This study is the first analysis of differentially expressed proteins in IMI-susceptible and resistant M. Persicae, and gives new insights into the mechanisms of IMI resistance in M. persicae. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Differentially expressed proteins in fluconazole-susceptible and fluconazole-resistant isolates of Candida glabrata.

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    Shen, Yinzhong; Zhang, Lijun; Jia, Xiaofang; Zhang, Yongxin; Lu, Hongzhou

    2015-06-01

    The current study aimed to identify the differences presented in the proteome of fluconazole-susceptible isolates of Candida glabrata compared to those with fluconazole-resistant ones. Two-dimensional differential gel electrophoresis was applied to identify proteins that were differentially expressed in fluconazole-susceptible and fluconazole-resistant isolates of C. glabrata. Eight proteins including aspartyl-tRNA synthetase, translation elongation factor 3, 3-phosphoglycerate kinase, ribosomal protein L5, coproporphyrinogen III oxidase, pyruvate kinase, G-beta like protein, and F1F0-ATPase alpha subunit were found to be more abundantly represented, while four proteins including vitamin B12-(cobalamin)-independent isozyme of methionine synthase, microtubule-associated protein, adenylosuccinate synthetase, and aldose reductase were found to be less abundantly represented in fluconazole-resistant strains versus those with fluconazole-susceptible ones. These differentially expressed proteins were primarily associated with energy metabolism, stress response, and macromolecule synthesis. Proteins associated with energy metabolism, stress response, and macromolecule synthesis may play a role in the development of fluconazole resistance in the clinical isolates of C. glabrata. Multiple different mechanisms are involved in the development of fluconazole resistance in C. glabrata. These findings provide a scientific basis for discovering new genes and mechanisms associated with fluconazole resistance in C. glabrata.

  8. Computing the Diamagnetic Susceptibility and Diamagnetic Anisotropy of Membrane Proteins from Structural Subunits.

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    Babaei, Mahnoush; Jones, Isaac C; Dayal, Kaushik; Mauter, Meagan S

    2017-06-13

    The behavior of large, complex molecules in the presence of magnetic fields is experimentally challenging to measure and computationally intensive to predict. This work proposes a novel, mixed-methods approach for efficiently computing the principal magnetic susceptibilities and diamagnetic anisotropy of membrane proteins. The hierarchical primary (amino acid), secondary (α helical and β sheet), and tertiary (α helix and β barrel) structure of transmembrane proteins enables analysis of a complex molecule using discrete subunits of varying size and resolution. The proposed method converts the magnetic susceptibility tensor for all protein subunits to a unit coordinate system and sums them to build the magnetic susceptibility tensor for the membrane protein. Using this approach, we calculate the diamagnetic anisotropy for all transmembrane proteins of known structure and investigate the effect of different subunit resolutions on the resulting predictions of diamagnetic anisotropy. We demonstrate that amino acid residues with aromatic side groups exhibit higher diamagnetic anisotropies. On average, high percentages of aromatic amino acid subunits, a β barrel tertiary structure, and a small volume are correlated with high volumetric diamagnetic anisotropy. Finally, we demonstrate that accounting for the spatial position of the residues with respect to one another is critical to accurately computing the magnetic properties of the complex protein molecule.

  9. Alzheimer Disease Susceptibility Loci: Evidence for a Protein Network under Natural Selection

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    Raj, Towfique; Shulman, Joshua M.; Keenan, Brendan T.; Chibnik, Lori B.; Evans, Denis A.; Bennett, David A.; Stranger, Barbara E.; De Jager, Philip L.

    2012-01-01

    Recent genome-wide association studies have identified a number of susceptibility loci for Alzheimer disease (AD). To understand the functional consequences and potential interactions of the associated loci, we explored large-scale data sets interrogating the human genome for evidence of positive natural selection. Our findings provide significant evidence for signatures of recent positive selection acting on several haplotypes carrying AD susceptibility alleles; interestingly, the genes found in these selected haplotypes can be assembled, independently, into a molecular complex via a protein-protein interaction (PPI) network approach. These results suggest a possible coevolution of genes encoding physically-interacting proteins that underlie AD susceptibility and are coexpressed in different tissues. In particular, PICALM, BIN1, CD2AP, and EPHA1 are interconnected through multiple interacting proteins and appear to have coordinated evidence of selection in the same human population, suggesting that they may be involved in the execution of a shared molecular function. This observation may be AD-specific, as the 12 loci associated with Parkinson disease do not demonstrate excess evidence of natural selection. The context for selection is probably unrelated to AD itself; it is likely that these genes interact in another context, such as in immune cells, where we observe cis-regulatory effects at several of the selected AD loci. PMID:22482808

  10. Protein tyrosine phosphatase variants in human hereditary disorders and disease susceptibilities.

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    Hendriks, Wiljan J A J; Pulido, Rafael

    2013-10-01

    Reversible tyrosine phosphorylation of proteins is a key regulatory mechanism to steer normal development and physiological functioning of multicellular organisms. Phosphotyrosine dephosphorylation is exerted by members of the super-family of protein tyrosine phosphatase (PTP) enzymes and many play such essential roles that a wide variety of hereditary disorders and disease susceptibilities in man are caused by PTP alleles. More than two decades of PTP research has resulted in a collection of PTP genetic variants with corresponding consequences at the molecular, cellular and physiological level. Here we present a comprehensive overview of these PTP gene variants that have been linked to disease states in man. Although the findings have direct bearing for disease diagnostics and for research on disease etiology, more work is necessary to translate this into therapies that alleviate the burden of these hereditary disorders and disease susceptibilities in man. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Susceptibility of sweet potato (Ipomoea batatas) peel proteins to digestive enzymes.

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    Maloney, Katherine P; Truong, Van-Den; Allen, Jonathan C

    2014-07-01

    Sweet potato proteins have been shown to possess antioxidant and antidiabetic properties in vivo. The ability of a protein to exhibit systemic effects is somewhat unusual as proteins are typically susceptible to digestive enzymes. This study was undertaken to better understand how digestive enzymes affect sweet potato proteins. Two fractions of industrially processed sweet potato peel, containing 6.8% and 8.5% protein and 80.5% and 83.3% carbohydrate, were used as a source of protein. Sweet potato proteins were incubated with pepsin, trypsin, and chymotrypsin and protein breakdown was visualized with SDS-PAGE. After pepsin digestion, samples were assayed for amylase inhibitory activity. Sporamin, the major storage protein in sweet potatoes, which functions as a trypsin inhibitor as well, exhibited resistance to pepsin, trypsin, and chymotrypsin. Sporamin from blanched peel of orange sweet potatoes was less resistant to pepsin digestion than sporamin from outer peel and from extract of the white-skinned Caiapo sweet potato. Trypsin inhibitory activity remained after simulated gastric digestion, with the Caiapo potato protein and peel samples exhibiting higher inhibitory activity compared to the blanched peel sample. Amylase and chymotrypsin inhibitory activity was not present in any of the samples after digestion.

  12. Association of surfactant protein B gene with chronic obstructive pulmonary disease susceptibility.

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    Yang, J; Wang, B; Zhou, H-X; Liang, B-M; Chen, H; Ma, C-L; Xiao, J; Deng, J; Yan, L; Chen, Y-P; Chen, C-L; Chen, F; Ou, X-M; Feng, Y-L

    2014-11-01

    Genetic predisposition, in addition to smoking, is known to play a key role in susceptibility to chronic obstructive pulmonary disease (COPD). Several candidate genes have been proposed for COPD, including surfactant protein B (SFTPB). However, large studies in populations with different ethnic backgrounds and environments are required to clarify the role of SFTPB in COPD. We investigated the association of SFTPB polymorphisms with COPD susceptibility and lung function in a Chinese Han population. Four single nucleotide polymorphisms (SNPs) in the SFTPB gene were genotyped in 680 COPD patients and 687 controls. Allele frequencies and genotype distributions were compared between cases and controls and the potential relationships between these SNPs and lung function were investigated. Associations between haplotypes and COPD susceptibility were also assessed. The SFTPB exon polymorphism rs1130866 significantly protected subjects from COPD (adjusted P = 0.004) and was associated with an increase in forced expiratory volume in 1 s (FEV(1)) (adjusted P = 0.014). SFTPB variants are associated with COPD susceptibility and lung function in the Chinese Han population.

  13. Wheat Mds-1 encodes a heat-shock protein and governs susceptibility towards the Hessian fly gall midge

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    Plant pests including insects must manipulate plants in order to utilize the nutrition and environment of the host. Here, we show that the heat-shock protein gene Mayetiola destructor susceptibility gene-1 (Mds-1) is a major susceptibility gene in wheat that allows the gall midge M. destructor, com...

  14. Comparison of protein profiles of beech bark disease-resistant or beech bark disease-susceptible American beech

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    Mary E. Mason; Marek Krasowski; Judy Loo; Jennifer. Koch

    2011-01-01

    Proteomic analysis of beech bark proteins from trees resistant and susceptible to beech bark disease (BBD) was conducted. Sixteen trees from eight geographically isolated stands, 10 resistant (healthy) and 6 susceptible (diseased/infested) trees, were studied. The genetic complexity of the sample unit, the sampling across a wide geographic area, and the complexity of...

  15. The Aspergillus fumigatus Damage Resistance Protein Family Coordinately Regulates Ergosterol Biosynthesis and Azole Susceptibility

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    Jinxing Song

    2016-02-01

    Full Text Available Ergosterol is a major and specific component of the fungal plasma membrane, and thus, the cytochrome P450 enzymes (Erg proteins that catalyze ergosterol synthesis have been selected as valuable targets of azole antifungals. However, the opportunistic pathogen Aspergillus fumigatus has developed worldwide resistance to azoles largely through mutations in the cytochrome P450 enzyme Cyp51 (Erg11. In this study, we demonstrate that a cytochrome b5-like heme-binding damage resistance protein (Dap family, comprised of DapA, DapB, and DapC, coordinately regulates the functionality of cytochrome P450 enzymes Erg5 and Erg11 and oppositely affects susceptibility to azoles. The expression of all three genes is induced in an azole concentration-dependent way, and the decreased susceptibility to azoles requires DapA stabilization of cytochrome P450 protein activity. In contrast, overexpression of DapB and DapC causes dysfunction of Erg5 and Erg11, resulting in abnormal accumulation of sterol intermediates and further accentuating the sensitivity of ΔdapA strains to azoles. The results of exogenous-hemin rescue and heme-binding-site mutagenesis experiments demonstrate that the heme binding of DapA contributes the decreased azole susceptibility, while DapB and -C are capable of reducing the activities of Erg5 and Erg11 through depletion of heme. In vivo data demonstrate that inactivated DapA combined with activated DapB yields an A. fumigatus mutant that is easily treatable with azoles in an immunocompromised mouse model of invasive pulmonary aspergillosis. Compared to the single Dap proteins found in Saccharomyces cerevisiae and Schizosaccharomyces pombe, we suggest that this complex Dap family regulatory system emerged during the evolution of fungi as an adaptive means to regulate ergosterol synthesis in response to environmental stimuli.

  16. Susceptibility of whey protein isolate to oxidation and changes in physicochemical, structural, and digestibility characteristics.

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    Feng, Xianchao; Li, Chenyi; Ullah, Niamat; Cao, Jiqianrui; Lan, Yongli; Ge, Wupeng; Hackman, Robert M; Li, Zhixi; Chen, Lin

    2015-11-01

    Oxidation is an important factor for denaturing of whey protein isolate (WPI) during food processing. We studied the effects of chemical oxidation on physicochemical and structural changes along with in vitro digestibility of WPI in this work. Evaluation of physicochemical changes showed that carbonyl level and dityrosine content increased, whereas total and free thiol group levels decreased for oxidized WPI samples. For the structural changes, protein aggregation was measured by surface hydrophobicity, turbidity, and particle diameter, which was increased for oxidized WPI samples. The increase of the secondary structure β-sheets and antiparallel β-sheet also supported the aggregation of oxidized WPI. A direct quantitative relationship between physicochemical and structural changes and protein digestibility indicated that oxidation-related damage restricts the susceptibility of WPI to proteases. In conclusion, WPI had high susceptibility to oxidative stress, and both physicochemical and structural changes caused by severe oxidative stress could decrease the rate of in vitro digestibility of WPI. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  17. Screening preeclamptic cord plasma for proteins associated with decreased breast cancer susceptibility.

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    Low, Hoi Pang; Tiwari, Ashutosh; Janjanam, Jagadeesh; Qiu, Li; Chang, Chien-I; Strohsnitter, William C; Norwitz, Errol R; Tam, Sun W; Evans, James E; Green, Karin M; Paulo, Joao A; Lambe, Mats; Hsieh, Chung-Cheng

    2013-12-01

    Preeclampsia, a complication of pregnancy characterized by hypertension and proteinuria, has been found to reduce the subsequent risk for breast cancer in female offspring. As this protective effect could be due to exposure to preeclampsia-specific proteins during intrauterine life, the proteomic profiles of umbilical cord blood plasma between preeclamptic and normotensive pregnancies were compared. Umbilical cord plasma samples, depleted of 14 abundant proteins, were subjected to proteomic analysis using the quantitative method of nanoACQUITY ultra performance liquid chromatography-mass spectrometry with elevated energy mode of acquisition(E) (NanoUPLC-MS(E)). Sixty-nine differentially expressed proteins were identified, of which 15 and 6 proteins were only detected in preeclamptic and normotensive pregnancies, respectively. Additionally, expression of 8 proteins (gelsolin, complement C5, keratin type I cytoskeletal 10, pigment epithelium-derived factor, complement factor B, complement component C7, hemoglobin subunit gamma-2 and alpha-fetoprotein) were up-regulated in preeclampsia with a fold change of ≥2.0 when compared to normotensive pregnancies. The identification of alpha-fetoprotein in preeclamptic umbilical cord blood plasma supported the validity of this screen as alpha-fetoprotein has anti-estrogenic properties and has previously been linked to preeclampsia as well as a reduced breast cancer risk. The findings of this pilot study may provide new insights into the mechanistic link between preeclampsia and potentially reduced breast cancer susceptibility in adult life. Copyright © 2013. Production and hosting by Elsevier Ltd.

  18. Vitamin D binding protein variants associate with asthma susceptibility in the Chinese Han population.

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    Li, Fei; Jiang, Lei; Willis-Owen, Saffron A; Zhang, Youming; Gao, Jinming

    2011-08-03

    Asthma is a genetically heterogeneous disease. Polymorphisms of genes encoding components of the vitamin D pathway have been reported to associate with the risk of asthma. We have previously demonstrated that vitamin D status was associated with lung function in Chinese asthma patients. In this study, we tested whether polymorphisms of genes encoding for vitamin D receptor (VDR), vitamin D 25-hydroxylase (CYP2R1) and vitamin D binding protein (GC) were associated with asthma in the Chinese Han population. We sequenced all 8 exons of VDR and all 5 exons of CYP2R1 in a Chinese case-control cohort of asthma consisting of 467 cases and 288 unrelated healthy controls. Two mutations were identified in these regions. These variants were specified as rs2228570 in exon 2 of VDR and rs12794714 in exon 1 of CYP2R1. We also genotyped two common polymorphisms in GC gene (rs4588 and rs7041) by a PCR-restriction fragment length polymorphism (RFLP) method. We analyzed the association between these 4 polymorphisms and asthma susceptibility and asthma-related traits. Polymorphic markers in VDR and CYP2R1 were not associated with asthma in the Chinese Han cohort. Importantly, variants in GC gene, which give rise to the two most common electrophoretic isoforms of the vitamin D binding protein, were associated with asthma susceptibility. Compared with isoform Gc1, Gc2 was significantly associated with the risk of asthma (OR = 1.35, 95% CI = 1.01-1.78 p = 0.006). The results provide supporting evidence for association between GC variants and asthma susceptibility in the Chinese Han population.

  19. Vitamin D binding protein variants associate with asthma susceptibility in the Chinese han population

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    Zhang Youming

    2011-08-01

    Full Text Available Abstract Background Asthma is a genetically heterogeneous disease. Polymorphisms of genes encoding components of the vitamin D pathway have been reported to associate with the risk of asthma. We have previously demonstrated that vitamin D status was associated with lung function in Chinese asthma patients. In this study, we tested whether polymorphisms of genes encoding for vitamin D receptor (VDR, vitamin D 25-hydroxylase (CYP2R1 and vitamin D binding protein (GC were associated with asthma in the Chinese Han population. Methods We sequenced all 8 exons of VDR and all 5 exons of CYP2R1 in a Chinese case-control cohort of asthma consisting of 467 cases and 288 unrelated healthy controls. Two mutations were identified in these regions. These variants were specified as rs2228570 in exon 2 of VDR and rs12794714 in exon 1 of CYP2R1. We also genotyped two common polymorphisms in GC gene (rs4588 and rs7041 by a PCR-restriction fragment length polymorphism (RFLP method. We analyzed the association between these 4 polymorphisms and asthma susceptibility and asthma-related traits. Results Polymorphic markers in VDR and CYP2R1 were not associated with asthma in the Chinese Han cohort. Importantly, variants in GC gene, which give rise to the two most common electrophoretic isoforms of the vitamin D binding protein, were associated with asthma susceptibility. Compared with isoform Gc1, Gc2 was significantly associated with the risk of asthma (OR = 1.35, 95% CI = 1.01-1.78 p = 0.006. Conclusions The results provide supporting evidence for association between GC variants and asthma susceptibility in the Chinese Han population.

  20. Annotated differentially expressed salivary proteins of susceptible and insecticide-resistant mosquitoes of Anopheles stephensi.

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    Sonam Vijay

    Full Text Available Vector control is one of the major global strategies for control of malaria. However, the major obstacle for vector control is the development of multiple resistances to organochlorine, organophosphorus insecticides and pyrethroids that are currently being used in public health for spraying and in bednets. Salivary glands of vectors are the first target organ for human-vector contact during biting and parasite-vector contact prior to parasite development in the mosquito midguts. The salivary glands secrete anti-haemostatic, anti-inflammatory biologically active molecules to facilitate blood feeding from the host and also inadvertently inject malaria parasites into the vertebrate host. The Anopheles stephensi mosquito, an urban vector of malaria to both human and rodent species has been identified as a reference laboratory model to study mosquito-parasite interactions. In this study, we adopted a conventional proteomic approach of 2D-electrophoresis coupled with MALDI-TOF mass spectrometry and bioinformatics to identify putative differentially expressed annotated functional salivary proteins between An. stephensi susceptible and multiresistant strains with same genetic background. Our results show 2D gel profile and MALDI-TOF comparisons that identified 31 differentially expressed putative modulated proteins in deltamethrin/DDT resistant strains of An. stephensi. Among these 15 proteins were found to be upregulated and 16 proteins were downregulated. Our studies interpret that An. stephensi (multiresistant caused an upregulated expression of proteins and enzymes like cytochrome 450, short chain dehyrdogenase reductase, phosphodiesterase etc that may have an impact in insecticide resistance and xenobiotic detoxification. Our study elucidates a proteomic response of salivary glands differentially regulated proteins in response to insecticide resistance development which include structural, redox and regulatory enzymes of several pathways. These

  1. Annotated differentially expressed salivary proteins of susceptible and insecticide-resistant mosquitoes of Anopheles stephensi.

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    Vijay, Sonam; Rawal, Ritu; Kadian, Kavita; Raghavendra, Kamaraju; Sharma, Arun

    2015-01-01

    Vector control is one of the major global strategies for control of malaria. However, the major obstacle for vector control is the development of multiple resistances to organochlorine, organophosphorus insecticides and pyrethroids that are currently being used in public health for spraying and in bednets. Salivary glands of vectors are the first target organ for human-vector contact during biting and parasite-vector contact prior to parasite development in the mosquito midguts. The salivary glands secrete anti-haemostatic, anti-inflammatory biologically active molecules to facilitate blood feeding from the host and also inadvertently inject malaria parasites into the vertebrate host. The Anopheles stephensi mosquito, an urban vector of malaria to both human and rodent species has been identified as a reference laboratory model to study mosquito-parasite interactions. In this study, we adopted a conventional proteomic approach of 2D-electrophoresis coupled with MALDI-TOF mass spectrometry and bioinformatics to identify putative differentially expressed annotated functional salivary proteins between An. stephensi susceptible and multiresistant strains with same genetic background. Our results show 2D gel profile and MALDI-TOF comparisons that identified 31 differentially expressed putative modulated proteins in deltamethrin/DDT resistant strains of An. stephensi. Among these 15 proteins were found to be upregulated and 16 proteins were downregulated. Our studies interpret that An. stephensi (multiresistant) caused an upregulated expression of proteins and enzymes like cytochrome 450, short chain dehyrdogenase reductase, phosphodiesterase etc that may have an impact in insecticide resistance and xenobiotic detoxification. Our study elucidates a proteomic response of salivary glands differentially regulated proteins in response to insecticide resistance development which include structural, redox and regulatory enzymes of several pathways. These identified proteins

  2. Epitope-Specific Tolerance Modes Differentially Specify Susceptibility to Proteolipid Protein-Induced Experimental Autoimmune Encephalomyelitis

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    Lei Wang

    2017-11-01

    Full Text Available Immunization with myelin components can elicit experimental autoimmune encephalomyelitis (EAE. EAE susceptibility varies between mouse strains, depending on the antigen employed. BL/6 mice are largely resistant to EAE induction with proteolipid protein (PLP, probably a reflection of antigen-specific tolerance. However, the extent and mechanism(s of tolerance to PLP remain unclear. Here, we identified three PLP epitopes in PLP-deficient BL/6 mice. PLP-sufficient mice did not respond against two of these, whereas tolerance was “leaky” for an epitope with weak predicted MHCII binding, and only this epitope was encephalitogenic. In TCR transgenic mice, the “EAE-susceptibility-associated” epitope was “ignored” by specific CD4 T cells, whereas the “resistance-associated” epitope induced clonal deletion and Treg induction in the thymus. Central tolerance was autoimmune regulator dependent and required expression and presentation of PLP by thymic epithelial cells (TECs. TEC-specific ablation of PLP revealed that peripheral tolerance, mediated by dendritic cells through recessive tolerance mechanisms (deletion and anergy, could largely compensate for a lack of central tolerance. However, adoptive EAE was exacerbated in mice lacking PLP in TECs, pointing toward a non-redundant role of the thymus in dominant tolerance to PLP. Our findings reveal multiple layers of tolerance to a central nervous system autoantigen that vary among epitopes and thereby specify disease susceptibility. Understanding how different modalities of tolerance apply to distinct T cell epitopes of a target in autoimmunity has implications for antigen-specific strategies to therapeutically interfere with unwanted immune reactions against self.

  3. Generic amyloidogenicity of mammalian prion proteins from species susceptible and resistant to prions.

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    Nyström, Sofie; Hammarström, Per

    2015-05-11

    Prion diseases are lethal, infectious diseases associated with prion protein (PrP) misfolding. A large number of mammals are susceptible to both sporadic and acquired prion diseases. Although PrP is highly conserved and ubiquitously expressed in all mammals, not all species exhibit prion disease. By employing full length recombinant PrP from five known prion susceptible species (human, cattle, cat, mouse and hamster) and two species considered to be prion resistant (pig and dog) the amyloidogenicity of these PrPs has been delineated. All the mammalian PrPs, even from resistant species, were swiftly converted from the native state to amyloid-like structure when subjected to a native condition conversion assay. The PrPs displayed amyloidotypic tinctorial and ultrastructural hallmarks. Self-seeded conversion of the PrPs displayed significantly decreased lag phases demonstrating that nucleation dependent polymerization is a dominating mechanism in the fibrillation process. Fibrils from Aβ1-40, Aβ1-42, Lysozyme, Insulin and Transthyretin did not accelerate conversion of HuPrP whereas fibrils from HuPrP90-231 and HuPrP121-231 as well as full length PrPs of all PrPs efficiently seeded conversion showing specificity of the assay requiring the C-terminal PrP sequence. Our findings have implications for PrP misfolding and could have ramifications in the context of prion resistant species and silent carriers.

  4. The tomato xylem sap protein XSP10 is required for full susceptibility to Fusarium wilt disease.

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    Krasikov, Vladimir; Dekker, Henk L; Rep, Martijn; Takken, Frank L W

    2011-01-01

    XSP10 is an abundant 10 kDa protein found in the xylem sap of tomato. The protein displays structural similarity to plant lipid transfer proteins (LTPs). LTPs are involved in various physiological processes, including disease resistance, and some are able to bind and transfer diverse lipid molecules. XSP10 abundance in xylem sap declines upon infection with Fusarium oxysporum f. sp. lycopersici (Fol), implying involvement of XSP10 in the plant-pathogen interaction. Here, the biochemical characterization of XSP10 with respect to fatty acid-binding properties is reported; a weak but significant binding to saturated fatty acids was found. Furthermore, XSP10-silenced tomato plants were engineered and it was found that these plants exhibited reduced disease symptom development upon infection with a virulent strain of Fol. Interestingly, the reduced symptoms observed did not correlate with an altered expression profile for known reporter genes of plant defence (PR-1 and WIPI). This work demonstrates that XSP10 has lipid-binding properties and is required for full susceptibility of tomato to Fusarium wilt.

  5. Susceptibility to Dental Caries and the Salivary Proline-Rich Proteins

    Directory of Open Access Journals (Sweden)

    Martin Levine

    2011-01-01

    Full Text Available Early childhood caries affects 28% of children aged 2–6 in the US and is not decreasing. There is a well-recognized need to identify susceptible children at birth. Caries-free adults neutralize bacterial acids in dental biofilms better than adults with severe caries. Saliva contains acidic and basic proline-rich proteins (PRPs which attach to oral streptococci. The PRPs are encoded within a small region of chromosome 12. An acidic PRP allele (Db protects Caucasian children from caries but is more common in African Americans. Some basic PRP allelic phenotypes have a three-fold greater frequency in caries-free adults than in those with severe caries. Early childhood caries may associate with an absence of certain basic PRP alleles which bind oral streptococci, neutralize biofilm acids, and are in linkage disequilibrium with Db in Caucasians. The encoding of basic PRP alleles is updated and a new technology for genotyping them is described.

  6. Susceptibility of Snails to Infection with Schistosomes is influenced by Temperature and Expression of Heat Shock Proteins

    Science.gov (United States)

    Knight, Matty; Elhelu, O; Smith, M; Haugen, B; Miller, A; Raghavan, N; Wellman, C; Cousin, C; Dixon, F; Mann, V; Rinaldi, G; Ittiprasert, W; Brindley, PJ

    2015-01-01

    The freshwater snail, Biomphalaria glabrata is the obligate intermediate host for the transmission of the parasitic trematode, Schistosoma mansoni the causative agent of the chronic debilitating neglected tropical disease, schistosomiasis. We showed previously that in juvenile snails, early and significant induction of stress manifested by the expression of stress proteins, Hsp 70, Hsp 90 and reverse transcriptase (RT) of the non- LTR retrotransposon, nimbus, is a characteristic feature of juvenile susceptible NMRI but not resistant BS-90 snails. These latter, however, could be rendered susceptible after mild heat shock at 32°C, revealing that resistance in the BS-90 resistant snail to schistosomes is a temperature dependent trait. Here we tested the hypothesis that maintenance of BS-90 resistant snails at the permissive temperature for several generations affects the resistance phenotype displayed at the non-permissive temperature of 25°C. The progeny of BS-90 snails bred and maintained through several generations (F1 to F4) at 32°C were susceptible to the schistosome infection when returned to room temperature, shedding cercariae at four weeks post-infection. Moreover, the study of expression levels of the heat shock protein (Hsp) 70 protein by ELISA and western blot analysis, showed that this protein is also differentially expressed between susceptible and resistant snails, with susceptible snails expressing more protein than their resistant counterparts after early exposure to wild-type but not to radiation-attenuated miracidia. These data suggested that in the face of global warming, the ability to sustain a reduction in schistosomiasis by using refractory snails as a strategy to block transmission of the disease might prove challenging since non-lethal elevation in temperature, affects snail susceptibility to S. mansoni. PMID:26504668

  7. Correlation of neonatal pulmonary surfactant protein A gene polymorphism with pneumonia susceptibility and inflammatory response

    Directory of Open Access Journals (Sweden)

    Yi He

    2017-06-01

    Full Text Available Objective: To study the correlation of neonatal pulmonary surfactant protein A gene polymorphism with pneumonia susceptibility and inflammatory response. Methods: Neonates who were born and diagnosed with pneumonia in Zigong Maternity and Child Healthcare Hospital between September 2015 and February 2017 were selected as pneumonia group, and neonates without infection were selected as control group. SP-A gene rs1059054 and rs1136454 loci polymorphism, the contents of inflammatory cytokines in serum as well as the expression of inflammatory transcription factors in peripheral blood were determined. Results: The constituent ratio of rs1059054 loci CC genotype of pneumonia group was significantly higher than that of control group while the constituent ratio of CT and TT genotypes were significantly lower than those of control group; the constituent ratio of rs1136454 loci AA genotype was significantly lower than that of control group while the constituent ratio of AG and GG genotypes were significantly higher than those of control group. PCT, sTREM1, TNF-α and IL-6 levels in serum as well as RORγt mRNA expression in peripheral blood of pneumonia children with SP-A gene rs1059054 loci CC genotype were significantly higher than those of pneumonia children with CT genotype and TT genotype while SOCS1 and Foxp3 mRNA expression in peripheral blood were significantly lower than those of pneumonia children with CT genotype and TT genotype; PCT, sTREM1, TNF-α and IL-6 levels in serum as well as RORγt mRNA expression in peripheral blood of pneumonia children with SP-A gene rs1136454 loci AA genotype were significantly lower than those of pneumonia children with AG genotype and GG genotype while SOCS1 and Foxp3 mRNA expression in peripheral blood were significantly higher than those of pneumonia children with AG genotype and GG genotype. Conclusion: Neonatal SP-A gene rs1059054 loci CC genotype can increase the pneumonia susceptibility and aggravate

  8. Deficiency in macrophage-stimulating protein results in spontaneous intestinal inflammation and increased susceptibility toward epithelial damage in zebrafish

    NARCIS (Netherlands)

    Witte, Merlijn; Huitema, Leonie F. A.; Nieuwenhuis, Edward E. S.; Brugman, Sylvia

    2014-01-01

    Abstract Several genome-wide association studies have identified the genes encoding for macrophage-stimulating protein (MSP) and its receptor RON (Recepteur d'Origine Nantais) as possible susceptibility factors in inflammatory bowel disease. While it has been shown that the MSP-RON signaling pathway

  9. Identification of the tyrosine-protein phosphatase non-receptor type 2 as a rheumatoid arthritis susceptibility locus in europeans.

    Directory of Open Access Journals (Sweden)

    Joanna E Cobb

    Full Text Available OBJECTIVES: Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA. However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA. METHODS: A cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data. RESULTS: Significant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4×10(-9. CONCLUSIONS: This study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene.

  10. Identification of the Tyrosine-Protein Phosphatase Non-Receptor Type 2 as a Rheumatoid Arthritis Susceptibility Locus in Europeans

    Science.gov (United States)

    Cobb, Joanna E.; Plant, Darren; Flynn, Edward; Tadjeddine, Meriem; Dieudé, Philippe; Cornélis, François; Ärlestig, Lisbeth; Dahlqvist, Solbritt Rantapää; Goulielmos, George; Boumpas, Dimitrios T.; Sidiropoulos, Prodromos; Krintel, Sophine B.; Ørnbjerg, Lykke M.; Hetland, Merete L.; Klareskog, Lars; Haeupl, Thomas; Filer, Andrew; Buckley, Christopher D.; Raza, Karim; Witte, Torsten; Schmidt, Reinhold E.; FitzGerald, Oliver; Veale, Douglas; Eyre, Stephen; Worthington, Jane

    2013-01-01

    Objectives Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA. Methods A cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data. Results Significant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4×10−9). Conclusions This study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase) with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene. PMID:23840476

  11. Susceptibility of domestic animals to a pseudotype virus bearing RD-114 virus envelope protein.

    Science.gov (United States)

    Miyaho, Rie Nakaoka; Nakagawa, So; Hashimoto-Gotoh, Akira; Nakaya, Yuki; Shimode, Sayumi; Sakaguchi, Shoichi; Yoshikawa, Rokusuke; Takahashi, Mahoko Ueda; Miyazawa, Takayuki

    2015-08-10

    Retroviral vectors are used for gene transduction into cells and have been applied to gene therapy. Retroviral vectors using envelope protein (Env) of RD-114 virus, a feline endogenous retrovirus, have been used for gene transduction. In this study, we investigated the susceptibility to RD-114 Env-pseudotyped virus in twelve domestic animals including cattle, sheep, horse, pig, dog, cat, ferret, mink, rabbit, rat, mouse, and quail. Comparison of nucleotide sequences of ASCT2 (SLC1A5), a receptor of RD-114 virus, in 10 mammalian and 2 avian species revealed that insertion and deletion events at the region C of ASCT2 where RD-114 viral Env interacts occurred independently in the mouse and rat lineage and in the chicken and quail lineage. By the pseudotype virus infection assay, we found that RD-114 Env-pseudotyped virus could efficiently infect all cell lines except those from mouse and rat. Furthermore, we confirmed that bovine ASCT2 (bASCT2) functions as a receptor for RD-114 virus infection. We also investigated bASCT2 mRNA expression in cattle tissues and found that it is expressed in various tissues including lung, spleen and kidney. These results indicate that retrovirus vectors with RD-114 virus Env can be used for gene therapy in large domestic animals in addition to companion animals such as cat and dog. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Differential roles of the hemerythrin-like proteins of Mycobacterium smegmatis in hydrogen peroxide and erythromycin susceptibility

    Science.gov (United States)

    Li, Xiaojing; Li, Jingjing; Hu, Xinling; Huang, Lige; Xiao, Jing; Chan, John; Mi, Kaixia

    2015-01-01

    Hemerythrin-like proteins are oxygen-carrying non-heme di-iron binding proteins and their functions have effect on oxidation-reduction regulation and antibiotic resistance. Recent studies using bioinformatic analyses suggest that multiple hemerythrin-like protein coding sequences might have been acquired by lateral gene transfer and the number of hemerythrin-like proteins varies amongst different species. Mycobacterium smegmatis contains three hemerythrin-like proteins, MSMEG_3312, MSMEG_2415 and MSMEG_6212. In this study, we have systematically analyzed all three hemerythrin-like proteins in M. smegmatis and our results identified and characterized two functional classes: MSMEG_2415 plays an important role in H2O2 susceptibility, and MSMEG_3312 and MSMEG_6212 are associated with erythromycin susceptibility. Phylogenetic analysis indicated that these three proteins have different evolutionary origins, possibly explaining their different physiological functions. Here, combined with biological and phylogenetic analyses, our results provide new insights into the evolutionary divergence of the hemerythrin-like proteins in M. smegmatis. PMID:26607739

  13. A role for the unfolded protein response (UPR in virulence and antifungal susceptibility in Aspergillus fumigatus.

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    Daryl L Richie

    2009-01-01

    Full Text Available Filamentous fungi rely heavily on the secretory pathway, both for the delivery of cell wall components to the hyphal tip and the production and secretion of extracellular hydrolytic enzymes needed to support growth on polymeric substrates. Increased demand on the secretory system exerts stress on the endoplasmic reticulum (ER, which is countered by the activation of a coordinated stress response pathway termed the unfolded protein response (UPR. To determine the contribution of the UPR to the growth and virulence of the filamentous fungal pathogen Aspergillus fumigatus, we disrupted the hacA gene, encoding the major transcriptional regulator of the UPR. The DeltahacA mutant was unable to activate the UPR in response to ER stress and was hypersensitive to agents that disrupt ER homeostasis or the cell wall. Failure to induce the UPR did not affect radial growth on rich medium at 37 degrees C, but cell wall integrity was disrupted at 45 degrees C, resulting in a dramatic loss in viability. The DeltahacA mutant displayed a reduced capacity for protease secretion and was growth-impaired when challenged to assimilate nutrients from complex substrates. In addition, the DeltahacA mutant exhibited increased susceptibility to current antifungal agents that disrupt the membrane or cell wall and had attenuated virulence in multiple mouse models of invasive aspergillosis. These results demonstrate the importance of ER homeostasis to the growth and virulence of A. fumigatus and suggest that targeting the UPR, either alone or in combination with other antifungal drugs, would be an effective antifungal strategy.

  14. The Nuclear Death Domain Protein p84N5; a Candidate Breast Cancer Susceptibility Gene

    National Research Council Canada - National Science Library

    Godwin, Andrew

    2004-01-01

    ...% of all cases of breast cancer exhibit a familial pattern of incidence. Efforts to identify the genetic basis of familial breast cancer reached fruition some years ago, when the breast-cancer susceptibility genes, BRCAl and BRCA2 were identified...

  15. The Nuclear Death Domain Protein p84N5; a Candidate Breast Cancer Susceptibility Gene

    National Research Council Canada - National Science Library

    Godwin, Andrew

    2005-01-01

    ...% of all cases of breast cancer exhibit a familial pattern of incidence. Efforts to identify the genetic basis of familial breast cancer reached fruition some years ago, when the breast cancer susceptibility genes, BRCA1 and BRCA2 were identified...

  16. Why mammals more susceptible to the hepatotoxic microcystins than fish: evidences from plasma and albumin protein binding through equilibrium dialysis.

    Science.gov (United States)

    Zhang, Wei; Liang, Gaodao; Wu, Laiyan; Tuo, Xun; Wang, Wenjing; Chen, Jun; Xie, Ping

    2013-08-01

    To elucidate the interspecies variation of susceptibility to microcystins (MCs), fresh plasma and purified albumin from six kinds of mammals and fish were used in toxins-substances binding test. Protein contents in the test plasma were analyzed and the binding characteristics to MCs were compared. Two kinds of widely observed MCs, microcystin-LR (MC-LR) and microcystin-RR (MC-RR) were tested and data were collected through the method of equilibrium dialysis. It was found that total plasma protein and albumin content in mammals were nearly two times and four times higher than that in fish, respectively. In the test range of 0-100 μg/mL, binding rates of fish plasma to MCs were considered significant lower (p mammals. And human plasma demonstrated the highest binding rate in mammals. In all the test species, plasma protein binding rates of MC-RR were significantly higher than MC-LR (p 0.05). From the view of protein binding, it is concluded that both the variation of plasma protein composition and albumin binding characteristic could influence the existing form of MCs in circulation, change MCs utilization, alter MCs half-life and further contribute to the difference of susceptibility between mammals and fish.

  17. cDNAs of aminopeptidase-like protein genes from Plodia interpunctella strains with different susceptibilities to Bacillus thuringiensis toxins.

    Science.gov (United States)

    Zhu, Y C; Kramer, K J; Oppert, B; Dowdy, A K

    2000-03-01

    Aminopeptidase N has been reported to be a Bacillus thuringiensis (Bt) Cry1A toxin-binding protein in several lepidopteran insects. cDNAs of aminopeptidase-like proteins from both Bt-susceptible RC688s and Bt-resistant HD198r strains of the Indianmeal moth, Plodia interpunctella, were cloned and sequenced. They contain 3345 and 3358 nucleotides, respectively, and each has a 3048 bp open reading frame that encodes 1016 amino acids. Putative protein sequences include 10 potential glycosylation sites and a zinc metal binding site motif of HEXXH, which is typical of the active site of zinc-dependent metallopeptidases. Sequence analysis indicated that the deduced protein sequences are most similar to an aminopeptidase from Heliothis virescens with 62% sequence identity and highly similar to three other lepidopteran aminopeptidases from Plutella xylostella, Manduca sexta, Bombyx mori with sequence identities of 51-52%. Four nucleotide differences were observed in the open reading frames that translated into two amino acid differences in the putative protein sequences. Polymerase chain reaction (PCR) confirmed an aminopeptidase gene coding difference between RC688s and HD198r strains of P. interpunctella in the PCR amplification of a specific allele (PASA) using preferential primers designed from a single base substitution. The gene mutation for Asp185-->Glu185 was also confirmed in two additional Bt-resistant P. interpunctella strains. This mutation is located within a region homologous to the conserved Cry1Aa toxin binding regions from Bombyx mori and Plutella xylostella. The aminopeptidase-like mRNA expression levels in the Bt-resistant strain were slightly higher than those in the Bt-susceptible strain. The sequences reported in this paper have been deposited in the GenBank database (accession numbers AF034483 for susceptible strain RC688s and AF034484 for resistant strain HD198r).

  18. Analyzing pepsin degradation assay conditions used for allergenicity assessments to ensure that pepsin susceptible and pepsin resistant dietary proteins are distinguishable.

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    Rong Wang

    Full Text Available The susceptibility of a dietary protein to proteolytic degradation by digestive enzymes, such as gastric pepsin, provides information on the likelihood of systemic exposure to a structurally intact and biologically active macromolecule, thus informing on the safety of proteins for human and animal consumption. Therefore, the purpose of standardized in vitro degradation studies that are performed during protein safety assessments is to distinguish whether proteins of interest are susceptible or resistant to pepsin degradation via a study design that enables study-to-study comparison. Attempting to assess pepsin degradation under a wide-range of possible physiological conditions poses a problem because of the lack of robust and consistent data collected under a large-range of sub-optimal conditions, which undermines the needs to harmonize in vitro degradation conditions. This report systematically compares the effects of pH, incubation time, and pepsin-to-substrate protein ratio on the relative degradation of five dietary proteins: three pepsin susceptible proteins [ribulose 1,5-bisphosphate carboxylase-oxygenase (Rubisco, horseradish peroxidase (HRP, hemoglobin (Hb], and two pepsin resistant proteins [lipid transfer protein (LTP and soybean trypsin inhibitor (STI]. The results indicate that proteins susceptible to pepsin degradation are readily distinguishable from pepsin-resistant proteins when the reaction conditions are within the well-characterized optima for pepsin. The current standardized in vitro pepsin resistant assay with low pH and high pepsin-to-substrate ratio fits this purpose. Using non-optimal pH and/or pepsin-to-substrate protein ratios resulted in susceptible proteins no longer being reliably degraded by this stomach enzyme, which compromises the ability of this in vitro assay to distinguish between resistant and susceptible proteins and, therefore, no longer providing useful data to an overall weight-of-evidence approach to

  19. Proteins purified from Mycobacterium tuberculosis MDR and Susceptible clinical isolates: Identification by proteomics approach

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    A R. Hadizadeh Tasbiti

    2015-01-01

    Conclusion: Such information could be helpful for the development of newer therapeutic agents or of diagnostic markers for better treatment or diagnosis of TB. This study extends the list of the potential determinants of differences in virulence between the two isolates (MDR and susceptible TB and adds to the current understanding of MTB pathogenesis.

  20. The Nuclear Death Domain Protein p84N5; a Candidate Breast Cancer Susceptibility Gene

    National Research Council Canada - National Science Library

    Godwin, Andrew

    2006-01-01

    ...% of all cases of breast cancer exhibit a familial pattern of incidence. Efforts to identify the genetic basis of familial breast cancer reached fruition some years ago, when the breast-cancer susceptibility genes BRCA1 and BRCA2 were identified...

  1. The tomato xylem sap protein XSP10 is required for full susceptibility to Fusarium wilt disease

    NARCIS (Netherlands)

    Krasikov, V.; Dekker, H.L.; Rep, M.; Takken, F.L.W.

    2011-01-01

    XSP10 is an abundant 10 kDa protein found in the xylem sap of tomato. The protein displays structural similarity to plant lipid transfer proteins (LTPs). LTPs are involved in various physiological processes, including disease resistance, and some are able to bind and transfer diverse lipid

  2. Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability

    Directory of Open Access Journals (Sweden)

    Kong Sun-Young

    2008-10-01

    Full Text Available Abstract Background Elucidating the molecular mechanisms by which tumors become resistant to Herceptin is critical for the treatment of Her2-overexpressed metastatic breast cancer. Methods To further understand Herceptin resistance mechanisms at the molecular level, we used comparative proteome approaches to analyze two human breast cancer cell lines; Her2-positive SK-BR-3 cells and its Herceptin-resistant SK-BR-3 (SK-BR-3 HR cells. Results Heat-shock protein 27 (HSP27 expression was shown to be upregulated in SK-BR-3 HR cells. Suppression of HSP27 by specific siRNA transfection increased the susceptibility of SK-BR-3 HR cells to Herceptin. In the presence of Herceptin, Her2 was downregulated in both cell lines. However, Her2 expression was reduced by a greater amount in SK-BR-3 parent cells than in SK-BR-3 HR cells. Interestingly, co-immunoprecipitation analysis showed that HSP27 can bind to Her2. In the absence of Herceptin, HSP27 expression is suppressed and Her2 expression is reduced, indicating that downregulation of Her2 by Herceptin can be obstructed by the formation of a Her2-HSP27 complex. Conclusion Our present study demonstrates that upregulated HSP27 in human breast cancer cells can reduce Herceptin susceptibility by increasing Her2 protein stability.

  3. Simulated microgravity increases myocardial susceptibility to ischemia-reperfusion injury via a deficiency of AMP-activated protein kinase.

    Science.gov (United States)

    Lu, Yuan-Ming; Jiao, Bo; Lee, Jun; Zhang, Lin; Yu, Zhi-Bin

    2017-01-01

    Gravitation is an important factor in maintaining cardiac contractility. Our study investigated whether simulated microgravity increases myocardial susceptibility to ischemia-reperfusion (IR) injury. Using the Langendorff-perfused heart model with 300 beats/min pacing, 4-week tail suspension (SUS) and control (CON) male Sprague-Dawley rats (n = 10 rats/group) were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 120 min of reperfusion. Left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, and infarct size were assessed. Data demonstrated that there were significantly increased LVEDP, CK, LDH, and infarct size in SUS compared with CON (P < 0.05), accompanied by decreased LVESP (P < 0.05). Furthermore, TUNEL-positive cardiomyocytes were higher in SUS than that in CON (P < 0.01), and AMP-activated protein kinase (AMPK) phosphorylation and Bcl-2/Bax in SUS were less compared with CON (P < 0.05). Similarly, isolated hearts pre-treated with A-769662 exhibited better recovery of cardiac function, increased AMPK phosphorylation, and reduced necrosis and apoptosis. Furthermore, AMPKα protein showed a significant suppression in 4-week hindlimb unweighting rats. These results suggest that AMPK deficiency increases myocardial susceptibility to IR injury in rats subjected to simulated microgravity.

  4. Association of lysosomal protein transmembrane 4 beta gene polymorphism with pancreatic carcinoma susceptibility in the Chinese population.

    Science.gov (United States)

    Wang, Bing; Wang, Shan; Liang, Guowei; Xu, Jianjun; Zhou, Rouli; Zhang, Qingyun

    2017-06-01

    Pancreatic carcinoma is an aggressive malignancy with particularly low 5-year survival rate. In order to improve the dismal survival rate, identification of new potential susceptibility risk factors for the prevention and early detection of pancreatic carcinoma is of utmost importance. Lysosomal protein transmembrane 4 beta has two alleles designated as LAPTM4B*1 and LAPTM4B*2. The aim of this study was to investigate the association between lysosomal protein transmembrane 4 beta gene polymorphism and the risk of pancreatic carcinoma in China. A population-based case-control analysis was performed in 233 patients with pancreatic carcinoma and 842 control subjects. The genotypes of lysosomal protein transmembrane 4 beta were determined by utilizing polymerase chain reaction based on specific primers. The χ2 test was used to analyze the differences of categorical variables and Hardy-Weinberg equilibrium. Odds ratio and 95% confidence intervals were computed using an unconditional logistic regression model. A significant difference in the frequency of LAPTM4B*2 was observed between the patients and the controls (33.05% vs 27.55%, p = 0.03). LAPTM4B*2 had a 1.33-fold (95% confidence interval: 1.04-1.71) higher risk for developing pancreatic carcinoma when compared with LAPTM4B*1 carriers. We found that the frequency of LAPTM4B*1/2 + *2/2 in pancreatic carcinoma group was higher than that in the control group (57.94% vs 48.34%, p = 0.01). However, no significant association was observed between lysosomal protein transmembrane 4 beta genotypes and gender, age, family history of cancer, smoking/alcohol status, histopathological differentiation, lymph node metastasis, clinical stage, or serum cancer antigen 19-9 level. These findings indicate that the LAPTM4B*2 allele is associated with the high risk of pancreatic carcinoma and carrying LAPTM4B*2 may be a susceptible factor to Chinese pancreatic carcinoma patients.

  5. [Association of surfactant protein D gene polymorphisms at rs3088308 and rs721917 with susceptibility to silicosis].

    Science.gov (United States)

    Wu, Chuan-Wen; Zhang, Xiu-Feng; Liu, Wei; Wang, Hong-Li; Hao, Xiao-Hui; Guo, Zhi-Yi; Guo, Ling-Li; Liu, He-Liang

    2016-06-20

    To investigate the relationship between polymorphisms of surfactant protein D (rs3088308 and rs721917) and the susceptibility to silicosis. This case-control study included 125 silicosis patients and 125 individuals exposed to industrial dust but without silicosis (control group), who were strictly matched with the case group for age, gender, work type and cumulative length of dust exposure. The rs3088308 and rs721917 polymorphisms of surfactant protein-D were detected in all the participants using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of T/T, T/A and A/A genotypes of surfactant protein-D rs3088308 locus were 22.2%, 71.2% and 5.6% in the case group, significantly different from the frequencies of 17.6%, 58.4% and 24.0% in the control group, respectively (P0.05). Surfactant protein-D rs3088308 polymorphism is significantly associated with silicosis, and the T allele may be a risk factor for silicosis in individuals exposed to industrial dust.

  6. Tumor susceptibility gene 101 regulates predisposition to apoptosis via ESCRT machinery accessory proteins

    Science.gov (United States)

    Kaul, Zenia; Chakrabarti, Oishee

    2017-01-01

    ESCRT proteins are implicated in myriad cellular processes, including endosome formation, fusion of autophagosomes/amphisomes with lysosomes, and apoptosis. The role played by these proteins in either facilitating or protecting against apoptosis is unclear. In this study, while trying to understand how deficiency of Mahogunin RING finger 1 (MGRN1) affects cell viability, we uncovered a novel role for its interactor, the ESCRT-I protein TSG101: it directly participates in mitigating ER stress–mediated apoptosis. The association of TSG101 with ALIX prevents predisposition to apoptosis, whereas ALIX–ALG-2 interaction favors a death phenotype. Altered Ca2+ homeostasis in cells and a simultaneous increase in the protein levels of ALIX and ALG-2 are required to elicit apoptosis by activating ER stress–associated caspase 4/12. We further demonstrate that in the presence of membrane-associated, disease-causing prion protein CtmPrP, increased ALIX and ALG-2 levels are detected along with ER stress markers and associated caspases in transgenic brain lysates and cells. These effects were rescued by overexpression of TSG101. This is significant because MGRN1 deficiency is closely associated with neurodegeneration and prenatal and neonatal mortality, which could be due to excess cell death in selected brain regions or myocardial apoptosis during embryonic development. PMID:28539405

  7. Colonization of resistant and susceptible lettuce cultivars by a green fluorescent protein-tagged isolate of Verticillium dahliae.

    Science.gov (United States)

    Vallad, G E; Subbarao, K V

    2008-08-01

    Interactions between lettuce and a green fluorescent protein (GFP)-expressing, race 1 isolate of Verticillium dahliae, were studied to determine infection and colonization of lettuce cultivars resistant and susceptible to Verticillium wilt. The roots of lettuce seedlings were inoculated with a conidial suspension of the GFP-expressing isolate. Colonization was studied with the aid of laser scanning confocal and epi-fluorescence microscopes. Few differences in the initial infection and colonization of lateral roots were observed between resistant and susceptible cultivars. Hyphal colonies formed on root tips and within the root elongation zones by 5 days, leading to the colonization of cortical tissues and penetration of vascular elements regardless of the lettuce cultivar by 2 weeks. By 8 to 10 weeks after inoculation, vascular discoloration developed within the taproot and crown regions of susceptible cultivars well in advance of V. dahliae colonization. Actual foliar wilt coincided with the colonization of the taproot and crown areas and the eruption of mycelia into surrounding cortical tissues. Advance colonization of stems, pedicels, and inflorescence, including developing capitula and mature achenes was observed. Seedborne infection was limited to the maternal tissues of the achene, including the pappus, pericarp, integument, and endosperm; but the embryo was never compromised. Resistant lettuce cultivars remained free of disease symptoms. Furthermore, V. dahliae colonization never progressed beyond infected lateral roots of resistant cultivars. Results indicated that resistance in lettuce may lie with the plant's ability to shed infected lateral roots or to inhibit the systemic progress of the fungus through vascular tissues into the taproot.

  8. Comparison of optomagnetic and AC susceptibility readouts in a magnetic nanoparticle agglutination assay for detection of C-reactive protein.

    Science.gov (United States)

    Fock, Jeppe; Parmvi, Mattias; Strömberg, Mattias; Svedlindh, Peter; Donolato, Marco; Hansen, Mikkel Fougt

    2017-02-15

    There is an increasing need to develop biosensor methods that are highly sensitive and that can be combined with low-cost consumables. The use of magnetic nanoparticles (MNPs) is attractive because their detection is compatible with low-cost disposables and because application of a magnetic field can be used to accelerate assay kinetics. We present the first study and comparison of the performance of magnetic susceptibility measurements and a newly proposed optomagnetic method. For the comparison we use the C-reactive protein (CRP) induced agglutination of identical samples of 100nm MNPs conjugated with CRP antibodies. Both methods detect agglutination as a shift to lower frequencies in measurements of the dynamics in response to an applied oscillating magnetic field. The magnetic susceptibility method probes the magnetic response whereas the optomagnetic technique probes the modulation of laser light transmitted through the sample. The two techniques provided highly correlated results upon agglutination when they measure the decrease of the signal from the individual MNPs (turn-off detection strategy), whereas the techniques provided different results, strongly depending on the read-out frequency, when detecting the signal due to MNP agglomerates (turn-on detection strategy). These observations are considered to be caused by differences in the volume-dependence of the magnetic and optical signals from agglomerates. The highest signal from agglomerates was found in the optomagnetic signal at low frequencies. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Determining the relative susceptibility of four prion protein genotypes to atypical scrapie

    Science.gov (United States)

    Atypical scrapie is a sheep prion (PrPSc) disease whose epidemiology is consistent with a sporadic origin and is associated with specific polymorphisms of the normal cellular prion protein (PrPC). We describe a mass spectrometry-based method of detecting and quantifying the polymorphisms of sheep P...

  10. Thermodynamic analysis of unusually thermostable CutA1 protein from human brain and its protease susceptibility.

    Science.gov (United States)

    Bagautdinov, Bagautdin; Matsuura, Yoshinori; Yamamoto, Hitoshi; Sawano, Masahide; Ogasahara, Kyoko; Takehira, Michiyo; Kunishima, Naoki; Katoh, Etsuko; Yutani, Katsuhide

    2015-03-01

    Unusually stable proteins are a disadvantage for the metabolic turnover of proteins in cells. The CutA1 proteins from Pyrococcus horikoshii and from Oryza sativa (OsCutA1) have unusually high denaturation temperatures (Td) of nearly 150 and 100 °C, respectively, at pH 7.0. It seemed that the CutA1 protein from the human brain (HsCutA1) also has a remarkably high stability. Therefore, the thermodynamic stabilities of HsCutA1 and its protease susceptibility were examined. The Td was remarkably high, being over 95 °C at pH 7.0. The unfolding Gibbs energy (ΔG(0)H2O) was 174 kJ/mol at 37 °C from the denaturant denaturation. The thermodynamic analysis showed that the unfolding enthalpy and entropy values of HsCutA1 were considerably lower than those of OsCutA1 with a similar stability to HsCutA1, which should be related to flexibility of the unstructured properties in both N- and C-terminals of HsCutA1. HsCutA1 was almost completely digested after 1-day incubation at 37 °C by subtilisin, although OsCutA1 was hardly digested at the same conditions. These results indicate that easily available fragmentation of HsCutA1 with remarkably high thermodynamic stability at the body temperature should be important for its protein catabolism in the human cells. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  11. Molecular characterization of a long range haplotype affecting protein yield and mastitis susceptibility in Norwegian Red cattle

    Directory of Open Access Journals (Sweden)

    Hayes Ben J

    2011-08-01

    Full Text Available Abstract Background Previous fine mapping studies in Norwegian Red cattle (NRC in the region 86-90.4 Mb on Bos taurus chromosome 6 (BTA6 has revealed a quantitative trait locus (QTL for protein yield (PY around 88 Mb and a QTL for clinical mastitis (CM around 90 Mb. The close proximity of these QTLs may partly explain the unfavorable genetic correlation between these two traits in NRC. A long range haplotype covering this region was introduced into the NRC population through the importation of a Holstein-Friesian bull (1606 Frasse from Sweden in the 1970s. It has been suggested that this haplotype has a favorable effect on milk protein content but an unfavorable effect on mastitis susceptibility. Selective breeding for milk production traits is likely to have increased the frequency of this haplotype in the NRC population. Results Association mapping for PY and CM in NRC was performed using genotypes from 556 SNPs throughout the region 86-97 Mb on BTA6 and daughter-yield-deviations (DYDs from 2601 bulls made available from the Norwegian dairy herd recording system. Highest test scores for PY were found for single-nucleotide polymorphisms (SNPs within and surrounding the genes CSN2 and CSN1S2, coding for the β-casein and αS2-casein proteins. High coverage re-sequencing by high throughput sequencing technology enabled molecular characterization of a long range haplotype from 1606 Frasse encompassing these two genes. Haplotype analysis of a large number of descendants from this bull indicated that the haplotype was not markedly disrupted by recombination in this region. The haplotype was associated with both increased milk protein content and increased susceptibility to mastitis, which might explain parts of the observed genetic correlation between PY and CM in NRC. Plausible causal polymorphisms affecting PY were detected in the promoter region and in the 5'-flanking UTR of CSN1S2. These polymorphisms could affect transcription or translation of

  12. Molecular characterization of a long range haplotype affecting protein yield and mastitis susceptibility in Norwegian Red cattle.

    Science.gov (United States)

    Sodeland, Marte; Grove, Harald; Kent, Matthew; Taylor, Simon; Svendsen, Morten; Hayes, Ben J; Lien, Sigbjørn

    2011-08-11

    Previous fine mapping studies in Norwegian Red cattle (NRC) in the region 86-90.4 Mb on Bos taurus chromosome 6 (BTA6) has revealed a quantitative trait locus (QTL) for protein yield (PY) around 88 Mb and a QTL for clinical mastitis (CM) around 90 Mb. The close proximity of these QTLs may partly explain the unfavorable genetic correlation between these two traits in NRC. A long range haplotype covering this region was introduced into the NRC population through the importation of a Holstein-Friesian bull (1606 Frasse) from Sweden in the 1970s. It has been suggested that this haplotype has a favorable effect on milk protein content but an unfavorable effect on mastitis susceptibility. Selective breeding for milk production traits is likely to have increased the frequency of this haplotype in the NRC population. Association mapping for PY and CM in NRC was performed using genotypes from 556 SNPs throughout the region 86-97 Mb on BTA6 and daughter-yield-deviations (DYDs) from 2601 bulls made available from the Norwegian dairy herd recording system. Highest test scores for PY were found for single-nucleotide polymorphisms (SNPs) within and surrounding the genes CSN2 and CSN1S2, coding for the β-casein and α(S2)-casein proteins. High coverage re-sequencing by high throughput sequencing technology enabled molecular characterization of a long range haplotype from 1606 Frasse encompassing these two genes. Haplotype analysis of a large number of descendants from this bull indicated that the haplotype was not markedly disrupted by recombination in this region. The haplotype was associated with both increased milk protein content and increased susceptibility to mastitis, which might explain parts of the observed genetic correlation between PY and CM in NRC. Plausible causal polymorphisms affecting PY were detected in the promoter region and in the 5'-flanking UTR of CSN1S2. These polymorphisms could affect transcription or translation of CSN1S2 and thereby affect the amount

  13. The Nuclear Death Domain Protein p84N5; a Candidate Breast Cancer Susceptibility Gene

    Science.gov (United States)

    2005-05-01

    DATES COVERED ( Leave blank) May 2005 Annual (1 May 04 - 30 Apr 05) 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS The Nuclear Death Domain Protein p84N5; a...p84N5. Cell proliferation and apoptosis (data not shown) was examined using Guava ViaCount and Nexin assays, respectively. Plotted is the number of...sequence results identical to those of breast cancer cell lines. Based on these data, we concluded that there are no somatic mutations in p84N5 in these

  14. A Single Amino Acid Dictates Protein Kinase R Susceptibility to Unrelated Viral Antagonists.

    Directory of Open Access Journals (Sweden)

    Kathryn S Carpentier

    2016-10-01

    Full Text Available During millions of years of coevolution with their hosts, cytomegaloviruses (CMVs have succeeded in adapting to overcome host-specific immune defenses, including the protein kinase R (PKR pathway. Consequently, these adaptations may also contribute to the inability of CMVs to cross species barriers. Here, we provide evidence that the evolutionary arms race between the antiviral factor PKR and its CMV antagonist TRS1 has led to extensive differences in the species-specificity of primate CMV TRS1 proteins. Moreover, we identify a single residue in human PKR that when mutated to the amino acid present in African green monkey (Agm PKR (F489S is sufficient to confer resistance to HCMVTRS1. Notably, this precise molecular determinant of PKR resistance has evolved under strong positive selection among primate PKR alleles and is positioned within the αG helix, which mediates the direct interaction of PKR with its substrate eIF2α. Remarkably, this same residue also impacts sensitivity to K3L, a poxvirus-encoded pseudosubstrate that structurally mimics eIF2α. Unlike K3L, TRS1 has no homology to eIF2α, suggesting that unrelated viral genes have convergently evolved to target this critical region of PKR. Despite its functional importance, the αG helix exhibits extraordinary plasticity, enabling adaptations that allow PKR to evade diverse viral antagonists while still maintaining its critical interaction with eIF2α.

  15. A component of the Sec61 ER protein transporting pore is required for plant susceptibility to powdery mildew

    Directory of Open Access Journals (Sweden)

    Wen-Jing eZhang

    2013-05-01

    Full Text Available Biotrophic pathogens, like the powdery mildew fungi, require living plant cells for their growth and reproduction. During infection, a specialized structure called the haustorium is formed by the fungus. The haustorium is surrounded by a plant cell-derived extrahaustorial membrane (EHM. Over the EHM, the fungus obtains nutrients from and secretes effectors into the plant cell. In the plant cell these effectors interfere with cellular processes such as pathogen defense and membrane trafficking. However, the mechanisms behind effector delivery are largely unknown. This paper provides a model for and new insights into a putative transfer mechanism of effectors into the plant cell. We show that silencing of the barley Sec61βa protein results in decreased susceptibility to the powdery mildew fungus. HvSec61βa is a component of both the endoplasmic reticulum (ER translocon and retrotranslocon pores, the latter being part of the ER-associated protein degradation machinery (ERAD. We provide support for a model suggesting that the retrotranslocon function of HvSec61βa is required for successful powdery mildew fungal infection. HvSec61βa-GFP and a luminal ER marker were co-localized to the ER, which was found to be in close proximity to the EHM around the haustorial body, but not the haustorial fingers. This differential EHM proximity suggests that the ER, including HvSec61βa, may be actively recruited by the haustorium, potentially to provide efficient effector transfer to the cytosol. Effector transport across this EHM-ER interface may occur by a vesicle-mediated process, while the Sec61 retrotranslocon pore potentially provides an escape route for these proteins to reach the cytosol.

  16. Susceptibility of northern corn rootworm Diabrotica barberi Smith & Lawrence (Coleoptera: Chrysomelidae) to mCry3A and eCry3.1Ab Bacillus thuringiensis proteins

    Science.gov (United States)

    Susceptibility of the northern corn rootworm (NCR), to mCry3A and eCry3.1Ab proteins derived from Bacillus thuringiensis (Bt) was determined using a diet bioassay. Northern corn rootworm neonates were exposed to different concentrations of mCry3A and eCry3.1Ab, incorporated into artificial diet. Lar...

  17. HLA complex-linked heat shock protein genes and childhood acute lymphoblastic leukemia susceptibility.

    Science.gov (United States)

    Ucisik-Akkaya, Esma; Davis, Charronne F; Gorodezky, Clara; Alaez, Carmen; Dorak, M Tevfik

    2010-09-01

    Three heat shock protein 70 (HSP70) genes, HSPA1L, HSPA1A, and HSPA1B, are located within the human leukocyte antigen (HLA) class III region. HSPs act as stress signals and regulate natural killer cell response to cancer. HSP70 gene polymorphisms show disease associations partly due to their linkage disequilibrium with HLA alleles. To systematically evaluate their associations with childhood acute lymphoblastic leukemia (ALL), we examined the three functional single nucleotide polymorphisms (SNPs) rs2227956 (T493M) in HSPA1L, rs1043618 in HSPA1A 5'UTR, and rs1061581 (Q351Q) in HSPA1B by TaqMan assays or polymerase chain reaction-restriction fragment length polymorphism in 114 ALL cases and 414 controls from Wales (UK), in 100 Mexican Mestizo ALL cases and 253 controls belonging to the same ethnic group, and in a panel of 82 HLA-typed reference cell line samples. Homozygosity for HSPA1B rs1061581 minor allele G was associated with protection (odds ratio (OR) = 0.37, 95% confidence interval (CI) = 0.16-0.78; P = 0.007) with gene-dosage effect (additive model) reaching significance (P = 0.0001) in the Welsh case-control group. This association was replicated in the second case-control group from Mexico (OR (recessive model) = 0.49, 95% CI = 0.24-0.96; P = 0.03), and the pooled analysis yielded a strong association (Mantel-Haenszel OR = 0.43, 95% CI = 0.27-0.69, P = 0.0004). The association was stronger in males in each group and in the pooled analysis. A three-SNP haplotype including the major allele A of rs1061581 showed a highly significant increase in Welsh cases compared with respective controls (6.7% vs 1.8%; P = 0.0003) due to the difference between male cases and controls. The protective allele of rs1061581 occurred more frequently on the HLA-DRB3 haplotypes (especially DRB1*03) in the cell line panel, but the HSPA1B association was independent from the HLA-DRB4 association previously detected in the same case-control group from Wales (adjusted P = 0

  18. C-reactive protein +1444CT (rs1130864) genetic polymorphism is associated with the susceptibility to systemic lupus erythematosus and C-reactive protein levels.

    Science.gov (United States)

    Delongui, Francieli; Lozovoy, Marcell Allyson Batisti; Iriyoda, Tatiana Mayiumi Veiga; Costa, Neide Tomimura; Stadtlober, Nicole Perugini; Alfieri, Daniela Frizon; Flauzino, Tamires; Dichi, Isaias; Simão, Andréa Name Colado; Reiche, Edna Maria Vissoci

    2017-08-01

    The T rare allele of +1444CT (rs1130864) polymorphism of C-reactive protein (CRP) has been associated with increased CRP levels in some inflammatory conditions, but its role on systemic lupus erythematosus (SLE) susceptibility and on CRP levels in SLE patients remains uncertain. The objective of the study was to evaluate the association between the rs1130864 CRP polymorphism with SLE susceptibility, disease activity, and CRP levels in SLE Brazilian patients. The study enrolled 176 SLE patients and 137 controls. SLE disease activity was assessed using the SLE Disease Activity Index (SLEDAI). The rs1130864 CRP polymorphism was determined using polymerase chain reaction and restriction fragment length polymorphism. SLE patients presented higher body mass index (p = 0.046) and CRP levels (p = 0.017) than controls. The genotype and allele frequencies of patients differed from controls [CC vs. CT = odds ratio (OR) 1.730, 95% confidence interval (CI) 1.068-2.803, p = 0.035; CC vs. TT = OR 3.667, 95% CI 1.410-9.533, p = 0.009; C vs. T = OR 1.883, 95% CI 1.299-2.728, p = 0.001)]. Patients carrying the T allele presented higher CRP levels (p = 0.009), were more frequent Caucasians (p = 0.018), and with no use of immunosuppressive treatment (p = 0.004) than those carrying the C allele. However, the SLEDAI and anti-double-stranded DNA positivity did not differ from those carrying T vs. C allele (p = 0.595 and p = 0.243, respectively). The rs1130864 CRP polymorphism was associated with SLE susceptibility and CRP levels, but not with disease activity, suggesting that this polymorphism may play a role in the pathophysiology of SLE through increasing the CRP that, probably, plays an inflammatory role in SLE pathophysiology.

  19. Differential Effects of Penicillin Binding Protein Deletion on the Susceptibility of Enterococcus faecium to Cationic Peptide Antibiotics.

    Science.gov (United States)

    Sakoulas, George; Kumaraswamy, Monika; Nonejuie, Poochit; Werth, Brian J; Rybak, Micahel J; Pogliano, Joseph; Rice, Louis B; Nizet, Victor

    2015-10-01

    Beta-lactam antibiotics sensitize Enterococcus faecium to killing by endogenous antimicrobial peptides (AMPs) of the innate immune system and daptomycin through mechanisms yet to be elucidated. It has been speculated that beta-lactam inactivation of select E. faecium penicillin binding proteins (PBPs) may play a pivotal role in this sensitization process. To characterize the specific PBP inactivation that may be responsible for these phenotypes, we utilized a previously characterized set of E. faecium PBP knockout mutants to determine the effects of such mutations on the activity of daptomycin and the AMP human cathelicidin (LL-37). Enhanced susceptibility to daptomycin was dependent more on a cumulative effect of multiple PBP deletions than on inactivation of any single specific PBP. Selective knockout of PBPZ rendered E. faecium more vulnerable to killing by both recombinant LL-37 and human neutrophils, which produce the antimicrobial peptide in high quantities. Pharmacotherapy targeting multiple PBPs may be used as adjunctive therapy with daptomycin to treat difficult E. faecium infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. CSE1L/CAS, the cellular apoptosis susceptibility protein, enhances invasion and metastasis but not proliferation of cancer cells

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    Chen Ying-Chun

    2008-07-01

    Full Text Available Abstract Background The cellular apoptosis susceptibility (CAS protein is regarded as a proliferation-associated protein that associates with tumour proliferation as it associates with microtubule and functions in the mitotic spindle checkpoint. However, there is no any actual experimental study showing CAS (or CSE1 and CSE1L can increase the proliferation of cancer cells. Previous pathological study has reported that CAS was strongly positive stained in all of the metastasis melanoma that be examined. Thus, CAS may regulate the invasion and metastasis of cancers. CAS is highly expressed in cancers; if CAS is associated with cancer proliferation, then increased CAS expression should be able to increase the proliferation of cancer cells. We studied whether increased CAS expression can increase cancer cell proliferation and whether CAS regulates the invasion of cancer cells. Methods We enhanced or reduced CAS expression by transfecting CAS or anti-CAS expression vectors into human MCF-7 breast cancer cells. The proliferations of cells were determined by trypan blue exclusion assay and flow cytometry analysis. Invasion of cancer cells were determined by matrigel-based invasion assay. Results Our studies showed that increased CAS expression was unable to enhance cancer cell proliferation. Immunofluorescence showed CAS was distributed in cytoplasm areas near cell membrane and cell protrusions. CAS was localized in cytoplasmic vesicle and immunogold electronmicroscopy showed CAS was located in vesicle membrane. CAS overexpression enhanced matrix metalloproteinase-2 (MMP-2 secretion and cancer cell invasion. Animal experiments showed CAS reduction inhibited the metastasis of B16-F10 melanoma cells by 56% in C57BL/6 mice. Conclusion Our results indicate that CAS increases the invasion but not the proliferation of cancer cells. Thus, CAS plus ECM-degradation proteinases may be used as the markers for predicting the advance of tumour metastasis.

  1. Mutations in lipopolysaccharide-binding protein (LBP) gene change the susceptibility to clinical mastitis in Chinese Holstein.

    Science.gov (United States)

    Cheng, Jienan; Li, Jun; Zhang, Wenxin; Cai, Yafei; Wang, Genlin

    2012-10-01

    Mastitis is an unsolved human challenge all dairy farms facing with, which leads to immeasurable economic loss to the farmers. LBP gene plays a vital role in the innate immune recognition of Gram-negative bacterium that is a major cause of bovine clinical mastitis, but little is known about LBP mutations and their effects on cows' susceptibility to clinical mastitis. In this study, PCR-SSCP method was adopted to analyze SNPs of LBP gene in Chinese Holstein for the first time. 17 SNPs were found in the promoter core region, exon1, exon2, exon3, exon4 and exon8. The mutation g.-81C → T in promoter leads to an AP-2 binding site lost. Two mutations, g.11T → C (4 Leu → Ser) and g.68G → C (23Gly → Ala) in signal peptide brought about molecular secondary structural change, meanwhile, g.11T → C made a Big-1 domain lost, and there was an N-myristoylation site at the g.68G/C locus. The three mutations above were in complete linkage disequilibrium in allele A. In mature LBP protein, five mutations were found: g.3034G → A(36Asp → Asn), g.3040A → G(38Asn → Asp), g.3056T → C(43Ile → Thr) in allele D; g.4619G → A(67Ala → Thr) in allele F; 19975G → A (282Val → Met) in allele J. And SNPs in allele D and F were in complete linkage disequilibrium, also in which 38Asn → Asp and 67Ala → Thr influenced the protein secondary structure. Prediction of the 3-D structure shows mutations 36Asp → Asn, 38Asn → Asp and 43 Ile → Thr were on the concave surface of LBP protein at barrel-N, 67Ala → Thr was in the apolar pocket at barrel-N. Motif analysis shows 36Asp → Asn causes loss of a CK2 phosphorylation site, 67 Ala → Thr forms a new PKC phosphorylation site. And 43Ile → Thr, 67Ala → Thr made hydrophobic amino acids to be hydrophilic amino acids. Interestingly, the morbidity of AB (mixed type g.-81C/T, g.11T/C, g.68G/C), CD (mixed type g.3034G/A, g.3040A/G, g.3056T/C) and EF (mixed type g.4619G/A) genotype cows are significant higher than

  2. Identification of the tyrosine-protein phosphatase non-receptor type 2 as a rheumatoid arthritis susceptibility locus in europeans

    DEFF Research Database (Denmark)

    Cobb, Joanna E; Plant, Darren; Flynn, Edward

    2013-01-01

    Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA....

  3. Amino Acid Substitutions in Mosaic Penicillin-Binding Protein 2 Associated with Reduced Susceptibility to Cefixime in Clinical Isolates of Neisseria gonorrhoeae▿

    Science.gov (United States)

    Takahata, Sho; Senju, Nami; Osaki, Yumi; Yoshida, Takuji; Ida, Takashi

    2006-01-01

    The molecular mechanisms of reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae, particularly amino acid substitutions in mosaic penicillin-binding protein 2 (PBP2), were examined. The complete sequence of ponA, penA, and por genes, encoding, respectively, PBP1, PBP2, and porin, were determined for 58 strains isolated in 2002 from Japan. Replacement of leucine 421 by proline in PBP1 and the mosaic-like structure of PBP2 were detected in 48 strains (82.8%) and 28 strains (48.3%), respectively. The presence of mosaic PBP2 was the main cause of the elevated cefixime MIC (4- to 64-fold). In order to identify the mutations responsible for the reduced susceptibility to cefixime in isolates with mosaic PBP2, penA genes with various mutations were transferred to a susceptible strain by genetic transformation. The susceptibility of partial recombinants and site-directed mutants revealed that the replacement of glycine 545 by serine (G545S) was the primary mutation, which led to a two- to fourfold increase in resistance to cephems. Replacement of isoleucine 312 by methionine (I312M) and valine 316 by threonine (V316T), in the presence of the G545S mutation, reduced susceptibility to cefixime, ceftibuten, and cefpodoxime by an additional fourfold. Therefore, three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae. PMID:16940068

  4. Proteomic and biochemical assays of glutathione-related proteins in susceptible and multiple herbicide resistant Avena fatua L.

    Science.gov (United States)

    Burns, Erin E; Keith, Barbara K; Refai, Mohammed Y; Bothner, Brian; Dyer, William E

    2017-08-01

    Extensive herbicide usage has led to the evolution of resistant weed populations that cause substantial crop yield losses and increase production costs. The multiple herbicide resistant (MHR) Avena fatua L. populations utilized in this study are resistant to members of all selective herbicide families, across five modes of action, available for A. fatua control in U.S. small grain production, and thus pose significant agronomic and economic threats. Resistance to ALS and ACCase inhibitors is not conferred by target site mutations, indicating that non-target site resistance mechanisms are involved. To investigate the potential involvement of glutathione-related enzymes in the MHR phenotype, we used a combination of proteomic, biochemical, and immunological approaches to compare their constitutive activities in herbicide susceptible (HS1 and HS2) and MHR (MHR3 and MHR4) A. fatua plants. Proteomic analysis identified three tau and one phi glutathione S-transferases (GSTs) present at higher levels in MHR compared to HS plants, while immunoassays revealed elevated levels of lambda, phi, and tau GSTs. GST specific activity towards 1-chloro-2,4-dinitrobenzene was 1.2-fold higher in MHR4 than in HS1 plants and 1.3- and 1.2-fold higher in MHR3 than in HS1 and HS2 plants, respectively. However, GST specific activities towards fenoxaprop-P-ethyl and imazamethabenz-methyl were not different between untreated MHR and HS plants. Dehydroascorbate reductase specific activity was 1.4-fold higher in MHR than HS plants. Pretreatment with the GST inhibitor NBD-Cl did not affect MHR sensitivity to fenoxaprop-P-ethyl application, while the herbicide safener and GST inducer mefenpyr reduced the efficacy of low doses of fenoxaprop-P-ethyl on MHR4 but not MHR3 plants. Mefenpyr treatment also partially reduced the efficacy of thiencarbazone-methyl or mesosulfuron-methyl on MHR3 or MHR4 plants, respectively. Overall, the GSTs described here are not directly involved in enhanced rates of

  5. Differentially expressed proteins and associated histological and disease progression changes in cotyledon tissue of a resistant and susceptible genotype of brassica napus infected with Sclerotinia sclerotiorum.

    Science.gov (United States)

    Garg, Harsh; Li, Hua; Sivasithamparam, Krishnapillai; Barbetti, Martin J

    2013-01-01

    Sclerotinia rot caused by Sclerotinia sclerotiorum is one of the most serious diseases of oilseed rape. To understand the resistance mechanisms in the Brassica napus to S. sclerotiorum, comparative disease progression, histological and proteomic studies were conducted of two B. napus genotypes (resistant cv. Charlton, susceptible cv. RQ001-02M2). At 72 and 96 h post inoculation (hpi), lesion size on cotyledons was significantly (P≤0.001) smaller in the resistant Charlton. Anatomical investigations revealed impeded fungal growth (at 24 hpi and onwards) and hyphal disintegration only on resistant Charlton. Temporal changes (12, 24, 48 and 72 hpi) in protein profile showed certain enzymes up-regulated only in resistant Charlton, such as those related to primary metabolic pathways, antioxidant defence, ethylene biosynthesis, pathogenesis related proteins, protein synthesis and protein folding, play a role in mediating defence responses against S. sclerotiorum. Similarly a eukaryotic translation initiation factor 5A enzyme with increased abundance in susceptible RQ001-02M2 and decreased levels in resistant Charlton has a role in increased susceptibility to this pathogen. This is the first time that the expression of these enzymes has been shown to be associated with mediating the defence response against S. sclerotinia in cotyledon tissue of a resistant cultivar of B. napus at a proteomics level. This study not only provides important new insights into the resistance mechanisms within B. napus against S. sclerotiorum, but opens the way for novel engineering of new B. napus varieties that over-express these key enzymes as a strategy to enhance resistance and better manage this devastating pathogen.

  6. Crystallographic Studies of Prion Protein (PrP) Segments Suggest How Structural Changes Encoded by Polymorphism at Residue 129 Modulate Susceptibility to Human Prion Disease

    Energy Technology Data Exchange (ETDEWEB)

    Apostol, Marcin I.; Sawaya, Michael R.; Cascio, Duilio; Eisenberg, David (UCLA)

    2010-09-23

    A single nucleotide polymorphism (SNP) in codon 129 of the human prion gene, leading to a change from methionine to valine at residue 129 of prion protein (PrP), has been shown to be a determinant in the susceptibility to prion disease. However, the molecular basis of this effect remains unexplained. In the current study, we determined crystal structures of prion segments having either Met or Val at residue 129. These 6-residue segments of PrP centered on residue 129 are 'steric zippers,' pairs of interacting {beta}-sheets. Both structures of these 'homozygous steric zippers' reveal direct intermolecular interactions between Met or Val in one sheet and the identical residue in the mating sheet. These two structures, plus a structure-based model of the heterozygous Met-Val steric zipper, suggest an explanation for the previously observed effects of this locus on prion disease susceptibility and progression.

  7. Association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and susceptibility to vitiligo: Systematic review and meta-analysis.

    Science.gov (United States)

    Agarwal, Silky; Changotra, Harish

    2017-01-01

    Protein tyrosine phosphatase, non-receptor type 22 gene, which translates to lymphoid tyrosine phosphatase, is considered to be a susceptibility gene marker associated with several autoimmune diseases. Several studies have demonstrated the association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism with vitiligo. However, these studies showed conflicting results. Meta-analysis of the same was conducted earlier that included fewer number of publications in their study. We performed a meta-analysis of a total of seven studies consisting of 2094 cases and 3613 controls to evaluate the possible association of protein tyrosine phosphatase, non-receptor type 22 +1858C>T polymorphism with vitiligo susceptibility. We conducted a literature search in PubMed, Google Scholar and Dogpile for all published paper on protein tyrosine phosphatase, non-receptor type 22 +1858C→T polymorphism and vitiligo risk till June 2016. Data analysis was performed by RevMan 5.3 and comprehensive meta-analysis v3.0 software. Meta-analysis showed an overall significant association of protein tyrosine phosphatase, non- receptor type 22 +1858C→T polymorphism with vitiligo in all models (allelic model [T vs. C]: odds ratio = 1.50, 95% confidence interval [1.32-1.71], Pvitiligo-type are some limitations of the present meta-analysis. Stratifying data by ethnicity showed an association of protein tyrosine phosphatase, non-receptor type 22 +1858C→T with vitiligo in European population (odds ratio = 1.53, 95% confidence interval [1.34-1.75], Pvitiligo.

  8. Effect of genetic variation in microRNA binding site in WNT1-inducible signaling pathway protein 1 gene on oral squamous cell carcinoma susceptibility.

    Directory of Open Access Journals (Sweden)

    Hon-Kit Lau

    Full Text Available Oral squamous cell carcinoma (OSCC, which is the most common head and neck cancer, accounts for 1%-2% of all human malignancies and is characterized by poor prognosis and reduced survival rates. WNT1-inducible signaling pathway protein 1 (WISP1, a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN family of matricellular proteins, has many developmental functions and may be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms (SNPs to elucidate OSCC susceptibility and clinicopathologic characteristics.Real-time polymerase chain reaction was used to analyze 6 SNPs of WISP1 in 900 OSCC patients and 1200 cancer-free controls. The results showed that WISP1 rs2929970 polymorphism carriers with at least one G allele were susceptible to OSCC. Moreover, compared with smokers, non-smoker patients with higher frequencies of WISP1 rs2929970 (AG + GG variants had a late stage (stages III and IV and a large tumor size. In addition, OSCC patients who were betel quid chewers and carried WISP1 rs16893344 (CT + TT variants had a low risk of lymph node metastasis.Our results demonstrate that a joint effect of WISP1 rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing causally contributes to the occurrence of OSCC. WISP1 polymorphism may serve as a marker or a therapeutic target in OSCC.

  9. Studies on the Accumulation of Drought-Induced Boiling Soluble Proteins (Hydrophilins at Vegetative and Reproductive Phases of Drought Tolerant and Susceptible Cultivars of Triticum aestivum

    Directory of Open Access Journals (Sweden)

    Gurmeen RAKHRA

    2014-06-01

    Full Text Available Drought is one of the major environmental constraints affecting the crops worldwide. Expression of boiling soluble proteins (BSPs is of paramount importance, because they play important roles in the water stress responses and also in plant metabolism. In this study, the effect of drought on BSPs at vegetative (shoots and reproductive (seeds phases of drought tolerant (cv. ‘PBW 527’ and drought susceptible (cv. ‘PBW 343’ cultivars of Triticumaestivum were carried at three different developmental stages. The boiling soluble protein profiles of shoots and seeds were outlined via SDS-PAGE followed by immune-blot analysis using anti-HSP, anti-APase, anti-LEA, anti-SOD, anti-AQUA and anti-CAT antibodies. Western blot analysis revealed that expression of BSPs was modulated differentially in a stress, tissue, developmental stage and cultivar dependent manner. For instance, enhanced expression of seeds BSPs (APase, LEA, CAT, AQUA was observed in the tolerant cv. ‘PBW 527’ after drought stress. However, no such enhancement was observed in the susceptible cultivar. Similarly, in shoots of cv. ‘PBW 527’, a substantial increase of BSP (SOD expression was established after drought stress treatment, indicating their role in drought stress adaptation. Further, to gain an insight into the role of BSPs, a time course pre- and post-stress kinetic studies were also conducted in the seeds of tolerant and susceptible wheat cultivars. Based upon the observations, the possible role of boiling soluble proteins (hydrophilins in water stress tolerance is discussed.

  10. Conserved retinoblastoma protein-binding motif in human cytomegalovirus UL97 kinase minimally impacts viral replication but affects susceptibility to maribavir

    Directory of Open Access Journals (Sweden)

    Chou Sunwen

    2009-01-01

    Full Text Available Abstract The UL97 kinase has been shown to phosphorylate and inactivate the retinoblastoma protein (Rb and has three consensus Rb-binding motifs that might contribute to this activity. Recombinant viruses containing mutations in the Rb-binding motifs generally replicated well in human foreskin fibroblasts with only a slight delay in replication kinetics. Their susceptibility to the specific UL97 kinase inhibitor, maribavir, was also examined. Mutation of the amino terminal motif, which is involved in the inactivation of Rb, also renders the virus hypersensitive to the drug and suggests that the motif may play a role in its mechanism of action.

  11. Re-evaluation of the significance of penicillin binding protein 3 in the susceptibility of Listeria monocytogenes to β-lactam antibiotics

    Directory of Open Access Journals (Sweden)

    Krawczyk-Balska Agata

    2012-04-01

    Full Text Available Abstract Background Penicillin binding protein 3 (PBP3 of L. monocytogenes has long been thought of as the primary lethal target for β-lactam antibiotics due to the excellent correlation between the MICs of different β-lactams and their affinity for this protein. The gene encoding PBP3 has not yet been directly identified in this gram-positive bacterium, but based on in silico analysis, this protein is likely to be encoded by lmo1438. However, studies examining the effects of mutations in genes encoding known and putative L. monocytogenes PBPs have demonstrated that inactivation of lmo1438 does not affect sensitivity to β-lactams. Results In this study, overexpression of lmo1438 was achieved using an inducible (nisin-controlled expression system. This permitted the direct demonstration that lmo1438 encodes PBP3. PBP3 overexpression was accompanied by slightly elevated PBP4 expression. The recombinant strain overexpressing PBP3 displayed significant growth retardation and greatly reduced cell length in the stationary phase of growth in culture. In antibiotic susceptibility assays, the strain overexpressing PBP3 displayed increased sensitivity to subinhibitory concentrations of several β-lactams and decreased survival in the presence of a lethal dose of penicillin G. However, the MIC values of the tested β-lactams for this recombinant strain were unchanged compared to the parent strain. Conclusions The present study allows a reevaluation of the importance of PBP3 in the susceptibility of L. monocytogenes to β-lactams. It is clear that PBP3 is not the primary lethal target for β-lactams, since neither the absence nor an excess of this protein affect the susceptibility of L. monocytogenes to these antibiotics. The elevated level of PBP4 expression observed in the recombinant strain overexpressing PBP3 demonstrates that the composition of the L. monocytogenes cell wall is subject to tight regulation. The observed changes in the morphology of

  12. Effect of activation of canonical Wnt signaling by the Wnt-3a protein on the susceptibility of PC12 cells to oxidative and apoptotic insults

    Directory of Open Access Journals (Sweden)

    E.M. Kawamoto

    2012-01-01

    Full Text Available Wnt proteins are involved in tissue development and their signaling pathways play an important role during embryogenesis. Wnt signaling can promote cell survival, which is beneficial for neurons, but could also lead to tumor development in different tissues. The present study investigated the effects of a Wnt protein on the susceptibility of a neural tumor cell line (PC12 cells to the cytotoxic compounds ferrous sulfate (10 mM, staurosporine (100 and 500 nM, 3-nitropropionic acid (5 mM, and amyloid β-peptide (Aβ25-35; 50 µM. Cells (1 x 10(6 cells/mL were treated with the Wnt-3a recombinant peptide (200 ng/mL for 24 h before exposure to toxic insults. The Wnt-3a protein partially protected PC12 cells, with a 6-15% increase in cell viability in the presence of toxic agents, similar to the effect measured using the MTT and lactate dehydrogenase cell viability assays. The Wnt-3a protein increased protein expression of β-catenin by 52% compared to control. These findings suggest that Wnt signaling can protect neural cells against apoptosis induced by toxic agents, which are relevant to the pathogenesis of Alzheimer’s and Huntington’s diseases.

  13. Effect of activation of canonical Wnt signaling by the Wnt-3a protein on the susceptibility of PC12 cells to oxidative and apoptotic insults

    Energy Technology Data Exchange (ETDEWEB)

    Kawamoto, E.M. [Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD (United States); Gleichmann, M. [Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD (United States); Yshii, L.M.; Sá Lima, L. de [Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Mattson, M.P. [Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD (United States); Scavone, C. [Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2011-11-25

    Wnt proteins are involved in tissue development and their signaling pathways play an important role during embryogenesis. Wnt signaling can promote cell survival, which is beneficial for neurons, but could also lead to tumor development in different tissues. The present study investigated the effects of a Wnt protein on the susceptibility of a neural tumor cell line (PC12 cells) to the cytotoxic compounds ferrous sulfate (10 mM), staurosporine (100 and 500 nM), 3-nitropropionic acid (5 mM), and amyloid β-peptide (Aβ{sub 25-35}; 50 µM). Cells (1 × 10{sup 6} cells/mL) were treated with the Wnt-3a recombinant peptide (200 ng/mL) for 24 h before exposure to toxic insults. The Wnt-3a protein partially protected PC12 cells, with a 6-15% increase in cell viability in the presence of toxic agents, similar to the effect measured using the MTT and lactate dehydrogenase cell viability assays. The Wnt-3a protein increased protein expression of β-catenin by 52% compared to control. These findings suggest that Wnt signaling can protect neural cells against apoptosis induced by toxic agents, which are relevant to the pathogenesis of Alzheimer's and Huntington's diseases.

  14. The highly conserved serine threonine kinase StkP of Streptococcus pneumoniae contributes to penicillin susceptibility independently from genes encoding penicillin-binding proteins

    Directory of Open Access Journals (Sweden)

    Dias Ricardo

    2009-06-01

    Full Text Available Abstract Background The serine/threonine kinase StkP of Streptococcus pneumoniae is a major virulence factor in the mouse model of infection. StkP is a modular protein with a N-terminal kinase domain a C-terminal PASTA domain carrying the signature of penicillin-binding protein (PBP and prokaryotic serine threonine kinase. In laboratory cultures, one target of StkP is the phosphoglucosamine mutase GlmM involved in the first steps of peptidoglycan biosynthesis. In order to further elucidate the importance of StkP in S. pneumoniae, its role in resistance to β-lactams has been assessed by mutational analysis in laboratory cultures and its genetic conservation has been investigated in isolates from infected sites (virulent, asymptomatic carriers, susceptible and non-susceptible to β-lactams. Results Deletion replacement mutation in stkP conferred hypersensitivity to penicillin G and was epistatic on mutations in PBP2X, PBP2B and PBP1A from the resistant 9V clinical isolate URA1258. Genetic analysis of 55 clinical isolates identified 11 StkP alleles differing from the reference R6 allele. None relevant mutation in the kinase or the PASTA domains were found to account for susceptibility of the isolates. Rather the minimal inhibitory concentration (MIC values of the strains appeared to be determined by their PBP alleles. Conclusion The results of genetic dissection analysis in lab strain Cp1015 reveal that StkP is involved in the bacterial response to penicillin and is epistatic on mutations PBP 2B, 2X and 1A. However analysis of the clinical isolates did not allow us to find the StkP alleles putatively involved in determining the virulence or the resistance level of a given strain, suggesting a strong conservation of StkP in clinical isolates.

  15. Expressions of tight junction proteins Occludin and Claudin-1 are under the circadian control in the mouse large intestine: implications in intestinal permeability and susceptibility to colitis.

    Science.gov (United States)

    Kyoko, Oh-oka; Kono, Hiroshi; Ishimaru, Kayoko; Miyake, Kunio; Kubota, Takeo; Ogawa, Hideoki; Okumura, Ko; Shibata, Shigenobu; Nakao, Atsuhito

    2014-01-01

    The circadian clock drives daily rhythms in behavior and physiology. A recent study suggests that intestinal permeability is also under control of the circadian clock. However, the precise mechanisms remain largely unknown. Because intestinal permeability depends on tight junction (TJ) that regulates the epithelial paracellular pathway, this study investigated whether the circadian clock regulates the expression levels of TJ proteins in the intestine. The expression levels of TJ proteins in the large intestinal epithelium and colonic permeability were analyzed every 4, 6, or 12 hours between wild-type mice and mice with a mutation of a key clock gene Period2 (Per2; mPer2(m/m). In addition, the susceptibility to dextran sodium sulfate (DSS)-induced colitis was compared between wild-type mice and mPer2(m/m) mice. The mRNA and protein expression levels of Occludin and Claudin-1 exhibited daily variations in the colonic epithelium in wild-type mice, whereas they were constitutively high in mPer2(m/m) mice. Colonic permeability in wild-type mice exhibited daily variations, which was inversely associated with the expression levels of Occludin and Claudin-1 proteins, whereas it was constitutively low in mPer2(m/m) mice. mPer2(m/m) mice were more resistant to the colonic injury induced by DSS than wild-type mice. Occludin and Claudin-1 expressions in the large intestine are under the circadian control, which is associated with temporal regulation of colonic permeability and also susceptibility to colitis.

  16. Expressions of tight junction proteins Occludin and Claudin-1 are under the circadian control in the mouse large intestine: implications in intestinal permeability and susceptibility to colitis.

    Directory of Open Access Journals (Sweden)

    Oh-oka Kyoko

    Full Text Available BACKGROUND & AIMS: The circadian clock drives daily rhythms in behavior and physiology. A recent study suggests that intestinal permeability is also under control of the circadian clock. However, the precise mechanisms remain largely unknown. Because intestinal permeability depends on tight junction (TJ that regulates the epithelial paracellular pathway, this study investigated whether the circadian clock regulates the expression levels of TJ proteins in the intestine. METHODS: The expression levels of TJ proteins in the large intestinal epithelium and colonic permeability were analyzed every 4, 6, or 12 hours between wild-type mice and mice with a mutation of a key clock gene Period2 (Per2; mPer2(m/m. In addition, the susceptibility to dextran sodium sulfate (DSS-induced colitis was compared between wild-type mice and mPer2(m/m mice. RESULTS: The mRNA and protein expression levels of Occludin and Claudin-1 exhibited daily variations in the colonic epithelium in wild-type mice, whereas they were constitutively high in mPer2(m/m mice. Colonic permeability in wild-type mice exhibited daily variations, which was inversely associated with the expression levels of Occludin and Claudin-1 proteins, whereas it was constitutively low in mPer2(m/m mice. mPer2(m/m mice were more resistant to the colonic injury induced by DSS than wild-type mice. CONCLUSIONS: Occludin and Claudin-1 expressions in the large intestine are under the circadian control, which is associated with temporal regulation of colonic permeability and also susceptibility to colitis.

  17. Influence of the amino acid residues at 70 in M protein of porcine reproductive and respiratory syndrome virus on viral neutralization susceptibility to the serum antibody.

    Science.gov (United States)

    Fan, Baochao; Liu, Xing; Bai, Juan; Zhang, Tingjie; Zhang, Qiaoya; Jiang, Ping

    2016-03-22

    Porcine reproductive and respiratory syndrome virus (PRRSV) is mainly responsible for the significant economic losses in pig industry in the world. The adaptive immune responses of the host act as an important source of selective pressure in the evolutionary process of the virus. In the previous study, we confirmed that the amino acid (aa) residues at 102 and 104 sites in GP5 played an important role in escaping from the neutralizing antibodies (NAbs) against highly pathogenic PRRSV (HP-PRRSV). In this study, we further analyzed the aa mutants affecting neutralization susceptibility of NAbs in other structure proteins in NAbs resistant variants. Based on the different aa residues of the structural proteins between the resistant virus BB20s and the parent virus BB, 12 recombinant PRRSV strains containing these aa residue substitutions were constructed using reverse genetic techniques. The neutralizing antibody (NA) titers of the recombinant strains were tested on MARC-145 and porcine alveolar macrophages (PAMs). And the NAbs binding abilities of parent and rescued viruses were tested by using ELISA method. By using the neutralization assay, it was revealed that the NA titer of N4 serum with rBB/Ms was significantly lower than that with rBB. Meanwhile, NA titer of the serum with rBB20s/M was significantly higher than that with rBB20s. The ELISA binding results showed that rBB/Ms had higher binding inability to N4 than did rBB. And alignment of M protein revealed that the variant aa residue lysine (K) at 70 was also existed in field type 2 and vaccine PRRSV strains. The aa residue at 70 in M protein of PRRSV played an important role in regulating neutralization susceptibility to the porcine serum NAbs. It may be helpful for monitoring the antigen variant strains in the field and developing new vaccine against PRRSV in the future.

  18. Comparison of optomagnetic and AC susceptibility readouts in a magnetic nanoparticle agglutination assay for detection of C-reactive protein

    DEFF Research Database (Denmark)

    Fock, Jeppe; Parmvi, Mattias; Strömberg, Mattias

    2017-01-01

    of laser light transmitted through the sample. The two techniques provided highly correlated results upon agglutination when they measure the decrease of the signal from the individual MNPs (turn-off detection strategy), whereas the techniques provided different results, strongly depending on the read...... conjugated with CRP antibodies. Both methods detect agglutination as a shift to lower frequencies in measurements of the dynamics in response to an applied oscillating magnetic field. The magnetic susceptibility method probes the magnetic response whereas the optomagnetic technique probes the modulation...

  19. Scrapie susceptibility-linked polymorphisms modulate the in vitro conversion of sheep prion protein to protease-resistant forms

    NARCIS (Netherlands)

    Bossers, A.; Belt, P.B.G.M.; Raymond, G.J.; Caughey, B.; Vries, de R.; Smits, M.

    1997-01-01

    Prion diseases are natural transmissible neurodegenerative disorders in humans and animals. They are characterized by the accumulation of a protease-resistant scrapie-associated prion protein (PrPSc) of the host-encoded cellular prion protein (PrPC) mainly in the central nervous system.

  20. A Chronic Obstructive Pulmonary Disease Susceptibility Gene, FAM13A, Regulates Protein Stability of β-Catenin

    National Research Council Canada - National Science Library

    Jiang, Zhiqiang; Lao, Taotao; Qiu, Weiliang; Polverino, Francesca; Gupta, Kushagra; Guo, Feng; Mancini, John D; Naing, Zun Zar Chi; Cho, Michael H; Castaldi, Peter J; Sun, Yang; Yu, Jane; Laucho-Contreras, Maria E; Kobzik, Lester; Raby, Benjamin A; Choi, Augustine M K; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-01-01

    ...(+/+) littermate control mice. Cellular localization of FAM13A protein and mRNA levels of FAM13A in COPD lungs were assessed using immunofluorescence, Western blotting, and reverse transcriptase-polymerase chain reaction, respectively...

  1. [Physical arrangement of membrane lipids susceptible to being used in the process of cell sorting of proteins].

    Science.gov (United States)

    Wolf, C; Quinn, P; Koumanov, K; Chachaty, C; Tenchov, B

    1999-01-01

    Detection of immiscible lipid domains in biological membranes offers an alternative support to protein sorting. Liquid ordered domains ("rafts") comprising cholesterol and saturated sphingolipids incorporate saturated glycosyl-phosphatidylinositol (GPI)-anchored or acylated (palmitoyl- and myristoyl-) proteins or particular transmembrane protein sequences. These lipid domains can be isolated in the form of Detergent resistant membranes (DRM) from biological plasma membrane preparations. Caveolae appear to be a differentiated fraction of plasma membranes comprising such numerous cross-linked microdomains associated with caveolin in different cell types. While the biological relevance of such membrane domains is evidenced in vivo by co-patching of proteins sharing the identical affinity for sphingolipids and by the disruption of co-patching following cell cholesterol depletion, only a few physical studies confort the principle of membrane heterogeneity. Results are now presented where cholesterol addition in a tertiary lipid mixture forces outphase-separation, as a realistic model where the lipid segregation can promote protein sorting to the segregated Lo phase. A lipid mixture comprising phosphatidylserine, phosphatidylethanolamine and sphingomyelin of natural origin in the ratio (1/4/3: mole/mole) has been rendered neatly heterogeneous after the addition of cholesterol (27 mole%). Xray diffraction (Small angle Xray scattering) showed the splitting of two neatly resolved lamellar diffractions in the presence of cholesterol. Above 37 degrees C the heterogeneity was traceable by a broadened diffraction spot up to the complete get-to-liquid transition of sphingomyelin at temperatures > 40 degrees C where the spot became again symmetrical and narrow. The large temperature range where the immiscible lamellar phases are detected, the specific requirement for cholesterol association with sphingomyelin, the positive influence of calcium and the reversibility of domain

  2. Specific mutations of penicillin-binding protein 1A in 77 clinically acquired amoxicillin-resistant Helicobacter pylori strains in comparison with 77 amoxicillin-susceptible strains.

    Science.gov (United States)

    Kwon, Yong Hwan; Kim, Ji Yeon; Kim, Nayoung; Park, Ji Hyun; Nam, Ryoung Hee; Lee, Sun Min; Kim, Jin-Wook; Kim, Jung Mogg; Park, Jong Youn; Lee, Dong Ho

    2017-08-25

    Amoxicillin (Amx) is one of the most important antibiotics for eradication of Helicobacter pylori (H. pylori). Main determinants of genetically stable Amx resistance are mutations in the C-terminus of penicillin-binding protein 1A (pbp1A). However, contribution of individual mutation remains unclear. 77 Amx-resistant (Amx(R) ) and 77 Amx-susceptible (Amx(S) ) H. pylori strains were isolated from gastric tissues, and DNA sequencing was performed to compare C-terminus sequences of pbp1A gene between Amx(R) and Amx(S) strains. Natural transformation of these mutated genes into amoxicillin-susceptible strains was performed. Among many mutations in pbp1A, D479E (OR: 37.4, 95% CI: 5.53-252.49, P < .001), and T593 mutation (OR: 32.0, 95% CI: 4.04-252.86, P < .001) independently contributed to Amx resistance in H. pylori strains. In the transformation experiment, T593 mutations were identified in their transformants showing Amx resistance. However, PCR product of D479E was not inserted into recipient (ATCC 43504) resulting in transformation failure. Amx resistance is associated with various substitutions in pbp1A and T593 mutation contributes to Amx resistance of H. pylori. © 2017 John Wiley & Sons Ltd.

  3. Identification of plasma proteins that are susceptible to thiol oxidation by hypochlorous acid and N-chloramines.

    Science.gov (United States)

    Summers, Fiona A; Morgan, Philip E; Davies, Michael J; Hawkins, Clare L

    2008-09-01

    Hypochlorous acid (HOCl), the major strong oxidant produced by myeloperoxidase, reacts readily with free amino groups to form N-chloramines. Although HOCl and N-chloramines play an important role in the human immune system by killing bacteria and invading pathogens, they have also been shown to cause damage to tissues, which is believed to contribute to a number of diseases. It has been shown previously that N-chloramines react more readily with protein thiols than with other targets in plasma, but the nature of the plasma thiol-containing proteins oxidized is unknown. In this study, the ability of N-chloramines to selectively oxidize thiol-containing plasma proteins was determined using the thiol-specific probe, 5-iodoacetamidofluorescein, combined with two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Experiments were performed with N-chloramines formed on Nalpha-acetyl-lysine, Nalpha-acetyl-histidine (HisCA), glycine, taurine, and ammonia. With the exception of HisCA, the N-chloramines were more efficient than HOCl at oxidizing plasma thiols. The thiol-containing plasma proteins alpha1-antitrypsin and transthyretin were found to be oxidized in addition to albumin, with this treatment resulting in the inactivation of alpha1-antitrypsin. A similar selectivity of reaction and extent of thiol oxidation were also observed with myeloperoxidase in the presence of hydrogen peroxide and chloride ions.

  4. Effects of light and the regulatory Beta subunit composition of protein phosphatase 2A on the susceptibility of Arabidopsis thaliana to aphid (Myzus persicae infestation

    Directory of Open Access Journals (Sweden)

    Brwa eRasool

    2014-08-01

    Full Text Available The interactions between biotic and abiotic stress signalling pathways are complex and poorly understood but protein kinase/phosphatase cascades are potentially important components. Aphid fecundity and susceptibility to Pseudomonas syringae infection were determined in the low light-grown Arabidopsis thaliana wild type and in mutant lines defective in either the protein phosphatase (PP2A regulatory subunit B’γ (gamma; pp2a-b’γ or B’ζ (zeta; pp2a-b’ζ1-1 and pp2a-b’ζ1-2 and in gamma zeta double mutants (pp2a-b’γζ lacking both subunits. All the mutants except for pp2a-b’ζ1-1 had significantly lower leaf areas than the wild type. Susceptibility to P. syringae was similar in all genotypes. In contrast, aphid fecundity was significantly decreased in the pp2a-b’γ mutant relative to the wild type but not in the pp2a-b’γζ double mutant. A high light pre-treatment, which led to a significant increase in rosette growth in all mutant lines but not in the wild type, led to a significant decrease in aphid fecundity in all genotypes. The high light pre-treatment abolished the differences in aphid resistance observed in the pp2a-b’γ mutant relative to the wild type. The light and CO2 response curves for photosynthesis were changed in response to the high light pre-treatment, but the high light effects were similar in all genotypes. These data demonstrate that a pre-exposure to high light and the composition of subunits on the trimeric PP2A holoenzymes are important in regulating plant resistance to aphids. The functional specificity for the individual regulatory B-subunits may therefore limit aphid colonisation, depending on the prevailing abiotic stress environment.

  5. A consistent and potentially exploitable response during chondrogenesis of mesenchymal stem cells from osteoarthritis patients to the protein encoded by the susceptibility gene GDF5.

    Science.gov (United States)

    Ratnayake, Madhushika; Tselepi, Maria; Bloxham, Robert; Plöger, Frank; Reynard, Louise N; Loughlin, John

    2017-01-01

    Osteoarthritis (OA) is a common joint disease characterised by the focal loss of the protective cartilage layer at the ends of the bones. It is painful, disabling, multifactorial and polygenic. The growth differentiation factor 5 gene GDF5 was one of the first reported OA susceptibility signals that showed consistent association to OA, with the transcript single nucleotide polymorphism (SNP) rs143383 demonstrating association in Asians and Europeans. The functional effect of the signal is reduced expression of the gene. The GDF5 protein is an extracellular matrix signalling molecule that is active during chondrogenesis and in mature chondrocytes. Due to the functional impact of the susceptibility, we previously assessed the effect of supplementing chondrocytes from OA patients with exogenous GDF5. Their response was highly discordant, precluding the application of GDF5 as a simple means of attenuating the genetic deficit. Since GDF5 is also active during development, we have now assessed the effect of exogenous GDF5 on bone marrow derived mesenchymal stem cells (MSCs) that are undergoing chondrogenesis during cartilage disc formation. MSCs from healthy donors and OA patients were studied and the effect of GDF5 was assessed by measuring the wet mass of the discs, by histological staining, and by monitoring the change in expression of anabolic, catabolic and hypertrophic protein-coding genes. The MSCs expressed the three principal GDF5 receptor genes and responded in a significantly anabolic manner (increase in wet mass, p = 0.0022; Bonferroni corrected p = 0.018) to a variant form of GDF5 that targets the most abundantly expressed receptor, BMPR-IA. GDF5 elicited significant (p < 0.05) changes in the expression of anabolic, catabolic and hypertrophic genes with several consistent effects in healthy donors and in OA patients. Our data implies that, unlike OA chondrocytes, OA MSCs do respond in a predictable, anabolic manner to GDF5, which could therefore provide a

  6. Identification of proteins susceptible to thiol oxidation in endothelial cells exposed to hypochlorous acid and N-chloramines.

    Science.gov (United States)

    Summers, Fiona A; Forsman Quigley, Anna; Hawkins, Clare L

    2012-08-24

    Hypochlorous acid (HOCl) is a potent oxidant produced by the enzyme myeloperoxidase, which is released by neutrophils under inflammatory conditions. Although important in the immune system, HOCl can also damage host tissue, which contributes to the development of disease. HOCl reacts readily with free amino groups to form N-chloramines, which also cause damage in vivo, owing to the extracellular release of myeloperoxidase and production of HOCl. HOCl and N-chloramines react readily with cellular thiols, which causes dysfunction via enzyme inactivation and modulation of redox signaling processes. In this study, the ability of HOCl and model N-chloramines produced on histamine and ammonia at inflammatory sites, to oxidize specific thiol-containing proteins in human coronary artery endothelial cells was investigated. Using a proteomics approach with the thiol-specific probe, 5-iodoacetamidofluorescein, we show that several proteins including peptidylprolyl isomerase A (cyclophilin A), protein disulfide isomerase, glyceraldehyde-3-phosphate dehydrogenase and galectin-1 are particularly sensitive to oxidation by HOCl and N-chloramines formed at inflammatory sites. This will contribute to cellular dysfunction and may play a role in inflammatory disease pathogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. A component of the Sec61 ER protein transporting pore is required for plant susceptibility to powdery mildew

    DEFF Research Database (Denmark)

    Zhang, Wen-Jing; Hanisch, Susanne; Kwaaitaal, Mark Adrianus Cornelis J

    2013-01-01

    Biotrophic pathogens, like the powdery mildew fungi, require living plant cells for their growth and reproduction. During infection, a specialized structure called the haustorium is formed by the fungus. The haustorium is surrounded by a plant cell-derived extrahaustorial membrane (EHM). Over the....... Effector transport across this EHM-ER interface may occur by a vesicle-mediated process, while the Sec61 retrotranslocon pore potentially provides an escape route for these proteins to reach the cytosol....... the EHM, the fungus obtains nutrients from and secretes effector proteins into the plant cell. In the plant cell these effectors interfere with cellular processes such as pathogen defense and membrane trafficking. However, the mechanisms behind effector delivery are largely unknown. This paper provides...... and retrotranslocon pores, the latter being part of the ER-associated protein degradation machinery. We provide support for a model suggesting that the retrotranslocon function of HvSec61βa is required for successful powdery mildew fungal infection. HvSec61βa-GFP and a luminal ER marker were co-localized to the ER...

  8. Sulfhydryl reagent susceptibility in proteins with high sequence similarity--triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi and Leishmania mexicana.

    Science.gov (United States)

    Garza-Ramos, G; Cabrera, N; Saavedra-Lira, E; Tuena de Gómez-Puyou, M; Ostoa-Saloma, P; Pérez-Montfort, R; Gómez-Puyou, A

    1998-05-01

    The amino acid sequence of triosephosphate isomerase from Trypanosoma brucei, Trypanosoma cruzi, and Leishmania mexicana have an identity of 68%. Using the numbering system for the T. brucei enzyme, in their aligned sequences, the T. cruzi and leishmanial enzymes have cysteine residues at positions 14, 40, 117 and 126. T. brucei triosephosphate isomerase has cysteine residues at positions 14, 40 and 126, and a valine residue at position 117. Dithionitrobenzoic acid and methylmethane thiosulfonate inhibited the three enzymes, but T. cruzi triosephosphate isomerase was more than 100-fold more sensitive. The sensitivity of wild type triosephosphate isomerase from T. cruzi and T. brucei to the reagents was equal to that of the Cys117Val and Val117Cys mutant enzymes, respectively. Triosephosphate isomerases that have cysteine residues at positions 40 and 126, but lack a cysteine residue at position 14 are insensitive to methylmethane thiosulfonate. Thus, sulfhydryl reagents act on Cys14. At stoichiometric concentrations, the reagents inhibited the three enzymes as a consequence of structural alterations as measured by binding of 8-anilino-1-napthalenesulfonic acid to previously buried hydrophobic regions. However, the times for half-maximal alterations were 10 min, 15 hours and over 30 hours for T. cruzi, T. brucei and L. mexicana triosephosphate isomerase, respectively. The effect of pH on the action of the sulfhydryl reagents and molecular modeling showed no differences in the solvent accessibility of Cys14. As Cys14 forms part of the dimer interface, the data indicate that, in the three enzymes, barriers of different magnitude hinder the interaction between the sulfhydryl reagents and Cys14. The barrier is lower in T. cruzi triosephosphate isomerase which makes its dimer interface more susceptible for perturbation.

  9. Contrasting Roles of the Apoplastic Aspartyl Protease APOPLASTIC, ENHANCED DISEASE SUSCEPTIBILITY1-DEPENDENT1 and LEGUME LECTIN-LIKE PROTEIN1 in Arabidopsis Systemic Acquired Resistance.

    Science.gov (United States)

    Breitenbach, Heiko H; Wenig, Marion; Wittek, Finni; Jordá, Lucia; Maldonado-Alconada, Ana M; Sarioglu, Hakan; Colby, Thomas; Knappe, Claudia; Bichlmeier, Marlies; Pabst, Elisabeth; Mackey, David; Parker, Jane E; Vlot, A Corina

    2014-06-01

    Systemic acquired resistance (SAR) is an inducible immune response that depends on ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Here, we show that Arabidopsis (Arabidopsis thaliana) EDS1 is required for both SAR signal generation in primary infected leaves and SAR signal perception in systemic uninfected tissues. In contrast to SAR signal generation, local resistance remains intact in eds1 mutant plants in response to Pseudomonas syringae delivering the effector protein AvrRpm1. We utilized the SAR-specific phenotype of the eds1 mutant to identify new SAR regulatory proteins in plants conditionally expressing AvrRpm1. Comparative proteomic analysis of apoplast-enriched extracts from AvrRpm1-expressing wild-type and eds1 mutant plants led to the identification of 12 APOPLASTIC, EDS1-DEPENDENT (AED) proteins. The genes encoding AED1, a predicted aspartyl protease, and another AED, LEGUME LECTIN-LIKE PROTEIN1 (LLP1), were induced locally and systemically during SAR signaling and locally by salicylic acid (SA) or its functional analog, benzo 1,2,3-thiadiazole-7-carbothioic acid S-methyl ester. Because conditional overaccumulation of AED1-hemagglutinin inhibited SA-induced resistance and SAR but not local resistance, the data suggest that AED1 is part of a homeostatic feedback mechanism regulating systemic immunity. In llp1 mutant plants, SAR was compromised, whereas the local resistance that is normally associated with EDS1 and SA as well as responses to exogenous SA appeared largely unaffected. Together, these data indicate that LLP1 promotes systemic rather than local immunity, possibly in parallel with SA. Our analysis reveals new positive and negative components of SAR and reinforces the notion that SAR represents a distinct phase of plant immunity beyond local resistance. © 2014 American Society of Plant Biologists. All Rights Reserved.

  10. Molecular Investigation of the Mechanism of Non-Enzymatic Hydrolysis of Proteins and the Predictive Algorithm for Susceptibility.

    Science.gov (United States)

    Lauer, Timothy M; Wood, Geoffrey P F; Farkas, David; Sathish, Hasige A; Samra, Hardeep S; Trout, Bernhardt L

    2016-06-14

    A number of potential degradation routes can limit the shelf life of a biotherapeutic. While these are experimentally measurable, the tests to do so require a substantial investment in both time and material, resources rarely available early in the drug development process. To address the potential degradation route of non-enzymatic hydrolysis, we performed a molecular modeling analysis, together with an experimental study, to gain detailed insight into the reaction. On the basis of the mechanism, an algorithm for predicting the likely cleavage sites of a protein has been created. This algorithm measures four key properties during a molecular dynamics simulation, which relate to the key steps of the hydrolysis mechanism, in particular the rate-determining step (which can vary depending on the local environment). The first two properties include the secondary structure and the surface exposure of the amide bond, both of which help detect if the addition of the proton to the amide bond is possible. The second two properties relate to whether the side chain can cyclize and form a furane ring. These two properties are the orientation of the side chain relative to the amide bond and the number of hydrogen bonds between the side chain and the surrounding protein. Overall, the algorithm performs well at identifying reactive versus nonreactive bonds. The algorithm correctly classifies nearly 90% of all amide bonds following an aspartic or glutamic acid residue as reactive or nonreactive.

  11. Overexpression of the Bacillus thuringiensis (Bt) Cry2Aa2 protein in chloroplasts confers resistance to plants against susceptible and Bt-resistant insects.

    Science.gov (United States)

    Kota, M; Daniell, H; Varma, S; Garczynski, S F; Gould, F; Moar, W J

    1999-03-02

    Evolving levels of resistance in insects to the bioinsecticide Bacillus thuringiensis (Bt) can be dramatically reduced through the genetic engineering of chloroplasts in plants. When transgenic tobacco leaves expressing Cry2Aa2 protoxin in chloroplasts were fed to susceptible, Cry1A-resistant (20,000- to 40,000-fold) and Cry2Aa2-resistant (330- to 393-fold) tobacco budworm Heliothis virescens, cotton bollworm Helicoverpa zea, and the beet armyworm Spodoptera exigua, 100% mortality was observed against all insect species and strains. Cry2Aa2 was chosen for this study because of its toxicity to many economically important insect pests, relatively low levels of cross-resistance against Cry1A-resistant insects, and its expression as a protoxin instead of a toxin because of its relatively small size (65 kDa). Southern blot analysis confirmed stable integration of cry2Aa2 into all of the chloroplast genomes (5, 000-10,000 copies per cell) of transgenic plants. Transformed tobacco leaves expressed Cry2Aa2 protoxin at levels between 2% and 3% of total soluble protein, 20- to 30-fold higher levels than current commercial nuclear transgenic plants. These results suggest that plants expressing high levels of a nonhomologous Bt protein should be able to overcome or at the very least, significantly delay, broad spectrum Bt-resistance development in the field.

  12. Identification of T1D susceptibility genes within the MHC region by combining protein interaction networks and SNP genotyping data

    DEFF Research Database (Denmark)

    Brorsson, C.; Hansen, Niclas Tue; Hansen, Kasper Lage

    2009-01-01

    region were analysed in 1000 affected offspring trios generated by the Type 1 Diabetes Genetics Consortium (T1DGC). The most associated SNP in each gene was chosen and genes were mapped to ppi networks for identification of interaction partners. The association testing and resulting interacting protein...... are well known in the pathogenesis of T1D, but the modules also contain additional candidates that have been implicated in beta-cell development and diabetic complications. The extensive LD within the MHC region makes it important to develop new methods for analysing genotyping data for identification...... of additional risk genes for T1D. Combining genetic data with knowledge about functional pathways provides new insight into mechanisms underlying T1D....

  13. Crystal Structures of Penicillin-Binding Protein 2 From Penicillin-Susceptible And -Resistant Strains of Neisseria Gonorrhoeae Reveal An Unexpectedly Subtle Mechanism for Antibiotic Resistance

    Energy Technology Data Exchange (ETDEWEB)

    Powell, A.J.; Tomberg, J.; Deacon, A.M.; Nicholas, R.A.; Davies, C.

    2009-05-21

    Penicillin-binding protein 2 (PBP2) from N. gonorrhoeae is the major molecular target for {beta}-lactam antibiotics used to treat gonococcal infections. PBP2 from penicillin-resistant strains of N. gonorrhoeae harbors an aspartate insertion after position 345 (Asp-345a) and 4-8 additional mutations, but how these alter the architecture of the protein is unknown. We have determined the crystal structure of PBP2 derived from the penicillin-susceptible strain FA19, which shows that the likely effect of Asp-345a is to alter a hydrogen-bonding network involving Asp-346 and the SXN triad at the active site. We have also solved the crystal structure of PBP2 derived from the penicillin-resistant strain FA6140 that contains four mutations near the C terminus of the protein. Although these mutations lower the second order rate of acylation for penicillin by 5-fold relative to wild type, comparison of the two structures shows only minor structural differences, with the positions of the conserved residues in the active site essentially the same in both. Kinetic analyses indicate that two mutations, P551S and F504L, are mainly responsible for the decrease in acylation rate. Melting curves show that the four mutations lower the thermal stability of the enzyme. Overall, these data suggest that the molecular mechanism underlying antibiotic resistance contributed by the four mutations is subtle and involves a small but measurable disordering of residues in the active site region that either restricts the binding of antibiotic or impedes conformational changes that are required for acylation by {beta}-lactam antibiotics.

  14. Fatty acid-and retinol-binding protein, Mj-FAR-1 induces tomato host susceptibility to root-knot nematodes.

    Directory of Open Access Journals (Sweden)

    Ionit Iberkleid

    Full Text Available Plant-parasitic nematodes produce at least one structurally unique class of small helix-rich retinol- and fatty-acid-binding proteins that have no counterparts in their plant hosts. Herein we describe a protein of the plant-parasitic root-knot nematode Meloidogyne javanica, which is a member of the nematode-specific fatty-acid- and retinol-binding (Mj-FAR-1 family of proteins. The mj-far-1 mRNA was detected through M. javanica pre-parasitic J2s, migratory and sedentary parasitic stages by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Immunolocalization assays demonstrate that the FAR protein of Meloidogyne is secreted during sedentary stages, as evidenced by the accumulation of FAR at the nematode cuticle surface and along the adjacent host root tissues. Tomato roots constitutively expressing mj-far-1 demonstrated an increased susceptibility to root-knot nematodes infection as observed by accelerated gall induction and expansion, accompanied by a higher percentage of nematodes developing into mature females compared to control roots. RNA interference assays that expressed double-stranded RNA complementary to mj-far-1 in transgenic tomato lines specifically reduced nematode infection levels. Histological analysis of nematode-infested roots indicated that in roots overexpressing mj-far-1, galls contained larger feeding cells and might support a faster nematode development and maturation. Roots overexpressing mj-far-1 suppressed jasmonic acid responsive genes such as the proteinase inhibitor (Pin2 and γ-thionin, illustrating the possible role of Mj-FAR-1 in manipulating the lipid based signaling in planta. This data, suggests that Meloidogyne FAR might have a strategic function during the interaction of the nematode with its plant host. Our study present the first demonstration of an in planta functional characterization and localization of FAR proteins secreted by plant-parasitic nematodes. It provides evidence that Mj

  15. Remodelling of myocardial intercalated disc protein connexin 43 causes increased susceptibility to malignant arrhythmias in ARVC/D patients.

    Science.gov (United States)

    Chen, Xiao; Chen, Liang; Chen, Zhenglian; Chen, Xinshan; Song, Jiangping

    2017-06-01

    Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a primary cardiomyopathy characterised by fibrofatty replacement and ventricular arrhythmias. The occurrence of malignant arrhythmias may be associated with fatty infiltration and intercalated disk remodelling, but the specific pathological remodelling pattern is not yet clear. Twelve explanted hearts from patients diagnosed with ARVC/D according to the 2010 Task Force Criteria and pathology examination were divided into two groups with (SVT, n=6) or without (non-SVT, n=6) recurrent sustained ventricular tachycardia (SVT) before heart transplantation. Six ARVC autopsy hearts and six normal donor hearts were also collected. We evaluated the fibrofatty infiltration by Masson staining and the expression of intercalated disc proteins through immunohistochemistry staining combined with western blot using the ventricular tissue of ARVC as well as normal hearts. There was significant fatty replacement in the right ventricles of both the SVT and the non-SVT groups compared to normal hearts, but no significant differences were found in fibre, fatty and residual myocardium components between these two groups. Immunohistochemistry and western blot further showed disturbed distribution and significantly reduced expression of Connexin 43 (Cx43) in the SVT group (SVT vs. Normal P=0.010, SVT vs. non-SVT P=0.012). No significantly diminished expression was found in the non-SVT group. The cardiac histology of ARVC/D patients with sudden death verified by forensic pathology confirmed a similar phenomenon. Our pathology study on explanted and autopsied hearts indicates that the expression of Cx43 was significantly reduced and disturbed in distribution in ARVC/D myocardium with sustained ventricular tachycardia, but not in patients without malignant ventricular arrhythmias. This implies a correlation between Cx43 remodelling and malignant arrhythmias in ARVC/D patients. Copyright © 2017 Elsevier B.V. All rights

  16. Susceptibility to obesity and gallbladder stasis produced by a protein- and fat-enriched diet in male mice compared with female mice

    Directory of Open Access Journals (Sweden)

    Takiguchi Soichi

    2007-06-01

    Full Text Available Abstract Background The frequency of Japanese subjects over 20 years old with metabolic syndrome is 45.6% in men but just 16.7% in women. The reason why Japanese male subjects are more susceptible to metabolic syndrome than women is unknown. One possibility is the higher frequency of Japanese male subjects (40–70 years old who had a drinking habit (67%, while that of female subjects was only 25%. In addition, daily fat intake was markedly increased in Japanese subjects (from 9% to 25%, and cholesterol cholelithiasis is one of the most rapidly increasing digestive diseases during the past 50 years. The object of this study is to examine whether a potential sex-related risk factor exists in the manifestation of metabolic syndrome as well as gallstone formation. Methods Gallbladder dysmotility accerelates gallstone formation and gallbladder contraction depends on cholecystokinin (CCK and its receptor (CCK-1R. We developed CCK-1R gene knockout (-/- mice. The effects of the fat- and protein- enriched diet OA-2 on body weight, hyperlipidemia, and frequencies of sludge and gallstone formation were examined, and compared between wild-type and CCK-1R(-/- male and female mice. The OA-2 diet contains slightly higher protein and fat (7.9 % fat and 27.6 % protein compared with a standard diet (CRF-1 (5.6 % fat and 22.6 % protein, but their total energies are similar. After weaning, CRF-1 was provided until 3 months of age in all animals. Administration of an OA-2 diet was started when age-matched CCK-1R(-/- and wild-type male and female mice reached maturity, at 3 months of age. Administration of CRF-1 was continued in the rest of the animals. Mice were sacrificed by guillotine at 6 and 12 months of age and the blood was collected to measure plasma levels of triglyceride and cholesterol. The gallbladder was removed and classified as normal (clear gallbladder, clouded (sludge formation, and/or containing gallstone formations. Results As long as CRF-1 was

  17. Susceptibility to invasive meningococcal disease: polymorphism of complement system genes and Neisseria meningitidis factor H binding protein.

    Directory of Open Access Journals (Sweden)

    Declan T Bradley

    Full Text Available Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH is associated with altered risk of invasive meningococcal disease (IMD. We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP affected the risk association.We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.Rs12085435 A in C8B was associated with odds ratio (OR of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction. A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10⁻⁴. There was no bacterial load (CtrA cycle threshold difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025.The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become

  18. Increased susceptibility to fundus camera-delivered light-induced retinal degeneration in mice deficient in oxidative stress response proteins.

    Science.gov (United States)

    Ding, Yi; Aredo, Bogale; Zhong, Xin; Zhao, Cynthia X; Ufret-Vincenty, Rafael L

    2017-06-01

    Oxidative stress is an important contributor to the pathogenesis of many retinal diseases including age-related macular degeneration and retinal dystrophies. Light-induced retinal degeneration (LIRD) can serve as a model in which to study the response of the retina to stress. Of note, many genetic mutant mice are in a C57BL/6 J background and are thus resistant to the usual LIRD models. We recently developed a new model of fundus camera-delivered light-induced retinal degeneration (FCD-LIRD) which is effective in strains of mice expressing the light-resistant variant of RPE65 (450Met), including C57BL/6 J. In this work we investigated whether FCD-LIRD would be useful as a model in which to test the effect of genetic mutations on the response of the retina to stress. Furthermore, we tested whether oxidative stress plays an important role in the setting of this new FCD-LIRD model. FCD-LIRD was applied to C57BL/6 J mice and to mice simultaneously deficient in three proteins that are important in the response of the retina to oxidative stress (SOD1, DJ-1 and Parkin). Using fundus photography, we found that retinal damage was dramatically increased in the SOD1/DJ-1/Parkin deficient mice compared to C57BL/6 J. Outer retinal OCT volume and RPE cell morphology analysis in ZO-1-stained flat mounts added support to these findings. Gene expression analysis confirmed a strong oxidative stress response after FCD-LIRD, which was differentially altered in the SOD1/DJ1/Parkin deficient mice. We conclude that FCD-LIRD is useful to study the effect of genetic mutations on the response of the retina to light stress in light-resistant strains of mice. Furthermore, oxidative stress seems to be an important component of FCD-LIRD. Finally, we have established protocols to quantify the effect of FCD-LIRD on the retina and RPE which will be useful for future studies. Further dissection of the mechanisms by which the retina responds to light-induced oxidative stress may result in new

  19. Inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of Cryptococcus neoformans/Cryptococcus gattii species complex.

    Science.gov (United States)

    Cordeiro, Rossana de Aguiar; Evangelista, Antonio José de Jesus; Serpa, Rosana; Marques, Francisca Jakelyne de Farias; de Melo, Charlline Vládia Silva; de Oliveira, Jonathas Sales; Franco, Jônatas da Silva; de Alencar, Lucas Pereira; Bandeira, Tereza de Jesus Pinheiro Gomes; Brilhante, Raimunda Sâmia Nogueira; Sidrim, José Júlio Costa; Rocha, Marcos Fébio Gadelha

    2016-02-01

    Heat-shock proteins (Hsps) are chaperones required for the maintenance of cellular homeostasis in different fungal pathogens, playing an important role in the infectious process. This study investigated the effect of pharmacological inhibition of Hsp90 by radicicol on the Cryptococcus neoformans/Cryptococcus gattii species complex--agents of the most common life-threatening fungal infection amongst immunocompromised patients. The influence of Hsp90 inhibition was investigated regarding in vitro susceptibility to antifungal agents of planktonic and sessile cells, ergosterol concentration, cell membrane integrity, growth at 37 °C, production of virulence factors in vitro, and experimental infection in Caenorhabditis elegans. Hsp90 inhibition inhibited the in vitro growth of planktonic cells of Cryptococcus spp. at concentrations ranging from 0.5 to 2 μg ml(-1) and increased the in vitro inhibitory effect of azoles, especially fluconazole (FLC) (P < 0.05). Inhibition of Hsp90 also increased the antifungal activity of azoles against biofilm formation and mature biofilms of Cryptococcus spp., notably for Cryptococcus gattii. Furthermore, Hsp90 inhibition compromised the permeability of the cell membrane, and reduced planktonic growth at 37 °C and the capsular size of Cryptococcus spp. In addition, Hsp90 inhibition enhanced the antifungal activity of FLC during experimental infection using Caenorhabditis elegans. Therefore, our results indicate that Hsp90 inhibition can be an important strategy in the development of new antifungal drugs.

  20. Prion protein gene variability in Spanish goats. Inference through susceptibility to classical scrapie strains and pathogenic distribution of peripheral PrP(sc..

    Directory of Open Access Journals (Sweden)

    Cristina Acín

    Full Text Available Classical scrapie is a neurological disorder of the central nervous system (CNS characterized by the accumulation of an abnormal, partially protease resistant prion protein (PrP(sc in the CNS and in some peripheral tissues in domestic small ruminants. Whereas the pathological changes and genetic susceptibility of ovine scrapie are well known, caprine scrapie has been less well studied. We report here a pathological study of 13 scrapie-affected goats diagnosed in Spain during the last 9 years. We used immunohistochemical and biochemical techniques to discriminate between classical and atypical scrapie and bovine spongiform encephalopathy (BSE. All the animals displayed PrP(sc distribution patterns and western blot characteristics compatible with classical scrapie. In addition, we determined the complete open reading frame sequence of the PRNP in these scrapie-affected animals. The polymorphisms observed were compared with those of the herd mates (n = 665 and with the frequencies of healthy herds (n = 581 of native Spanish goats (Retinta, Pirenaica and Moncaina and other worldwide breeds reared in Spain (Saanen, Alpine and crossbreed. In total, sixteen polymorphic sites were identified, including the known amino acid substitutions at codons G37V, G127S, M137I, I142M, H143R, R151H, R154H, R211Q, Q222K, G232W, and P240S, and new polymorphisms at codons G74D, M112T, R139S, L141F and Q215R. In addition, the known 42, 138 and 179 silent mutations were detected, and one new one is reported at codon 122. The genetic differences observed in the population studied have been attributed to breed and most of the novel polymorphic codons show frequencies lower than 5%. This work provides the first basis of polymorphic distribution of PRNP in native and worldwide goat breeds reared in Spain.

  1. Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons.

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    He Li

    2017-06-01

    Full Text Available Sjögren's syndrome (SS is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1 peaking at rs10774671 (PeQTL = 6.05 × 10-14. Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta = 2.59 × 10-9; odds ratio = 0.75; 95% confidence interval = 0.66-0.86. The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.

  2. The block of adipocyte differentiation by a C-terminally truncated, but not by full-length, simian virus 40 large tumor antigen is dependent on an intact retinoblastoma susceptibility protein family binding domain.

    OpenAIRE

    Higgins, C; Chatterjee, S.; Cherington, V

    1996-01-01

    Simian virus 40 (SV40) can promote cell transformation and suppress differentiation. It does this partly by targeting tumor suppressors such as p53 and members of the retinoblastoma susceptibility protein (Rb) family. This work concentrates on mechanisms by which SV40 large tumor antigen (SVLT) suppresses adipocyte differentiation. We created cell lines derived from murine 3T3-L1 preadipocytes expressing different versions of SV40 early-region sequences. SVLT-expressing cells failed to exhibi...

  3. A Case of Decreased Susceptibility to Ceftriaxone in Neisseria gonorrhoeae in the Absence of a Mosaic Penicillin-Binding Protein 2 (penA) Allele.

    Science.gov (United States)

    Abrams, A Jeanine; Kirkcaldy, Robert D; Pettus, Kevin; Fox, Jan L; Kubin, Grace; Trees, David L

    2017-08-01

    We report a case of Neisseria gonorrhoeae with a non-mosaic penA allele that exhibited decreased susceptibility to extended-spectrum cephalosporins, including a ceftriaxone minimum inhibitory concentration of 0.5 μg/mL. An analysis of resistance determinants suggested that the observed phenotype might have resulted from the combined effects of mutations in multiple genes.

  4. Association of polymorphisms in heat shock protein 70 genes with the susceptibility to noise-induced hearing loss: A meta-analysis.

    Science.gov (United States)

    Zong, Shimin; Zeng, Xue; Liu, Tianyi; Wan, Fangmin; Luo, Pan; Xiao, Hongjun

    2017-01-01

    Several case-control studies reported the relationship between single nucleotide polymorphisms (SNPs) in HSP70 genes and noise-induced hearing loss (NIHL). However, their conclusions are conflicting. This meta-analysis aims to identify the association of HSP70 variants and NIHL susceptibility. A systematical literature search was performed in PubMed, Web of Science, EMBASE, and Wanfang Chinese database. The pooled odds radio (OR), 95% confidence interval (CI) and p value were calculated in fixed- or random-effects model according to the I2 value in the heterogeneity test. Four articles containing five studies, including 633 cases and 926 controls, were included. Under the allele, homozygote and dominant model, the pooled ORs (95%CI, p-value) of rs1061581 were 1.32 (1.06-1.67, p = 0.019), 1.93 (1.10-3.36, p = 0.021) and 1.455 (1.408-2.019, p = 0.025), respectively. In addition, a significant association was found between rs2227956 in Caucasians and the NIHL susceptibility under all five genetic models. We did not discover evidence sufficient to prove the associations between the other three SNPs (rs1043618, rs2763979 and rs2075800) and the NIHL susceptibility. This meta-analysis indicated that the two HSP70 variants, rs1061581 and rs2227956, may serve as genetic susceptibility factors for NIHL. Larger scale studies are required to further update the results.

  5. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON PROTEIN CARBONYL CONTENT IN FRONTAL CORTEX AND CEREBELLUM OF BROWN NORWAY RATS.

    Science.gov (United States)

    The influence of aging on susceptibility to environmental contaminants is poorly understood, largely due to a lack of data on exposures in older adults and adequate animal models. We examined the acute effects of the volatile organic compound, toluene, in a study investigating m...

  6. Studies on the Accumulation of Drought-Induced Boiling Soluble Proteins (Hydrophilins at Vegetative and Reproductive Phases of Drought Tolerant and Susceptible Cultivars of Triticum aestivum

    Directory of Open Access Journals (Sweden)

    Gurmeen RAKHRA

    2014-06-01

    Full Text Available Drought is one of the major environmental constraints affecting the crops worldwide. Expression of boiling soluble proteins (BSPs is of paramount importance, because they play important roles in the water stress responses and also in plant metabolism. In this study, the effect of drought on BSPs at vegetative (shoots and reproductive (seeds phases of drought tolerant (cv. ‘PBW 527’ and drought susceptible (cv. ‘PBW 343’ cultivars of Triticumaestivum were carried at three different developmental stages. The boiling soluble protein profiles of shoots and seeds were outlined via SDS-PAGE followed by immune-blot analysis using anti-HSP, anti-APase, anti-LEA, anti-SOD, anti-AQUA and anti-CAT antibodies. Western blot analysis revealed that expression of BSPs was modulated differentially in a stress, tissue, developmental stage and cultivar dependent manner. For instance, enhanced expression of seeds BSPs (APase, LEA, CAT, AQUA was observed in the tolerant cv. ‘PBW 527’ after drought stress. However, no such enhancement was observed in the susceptible cultivar. Similarly, in shoots of cv. ‘PBW 527’, a substantial increase of BSP (SOD expression was established after drought stress treatment, indicating their role in drought stress adaptation. Further, to gain an insight into the role of BSPs, a time course pre- and post-stress kinetic studies were also conducted in the seeds of tolerant and susceptible wheat cultivars. Based upon the observations, the possible role of boiling soluble proteins (hydrophilins in water stress tolerance is discussed.

  7. Susceptibility to HLA-DM Protein Is Determined by a Dynamic Conformation of Major Histocompatibility Complex Class II Molecule Bound with Peptide*

    Science.gov (United States)

    Yin, Liusong; Trenh, Peter; Guce, Abigail; Wieczorek, Marek; Lange, Sascha; Sticht, Jana; Jiang, Wei; Bylsma, Marissa; Mellins, Elizabeth D.; Freund, Christian; Stern, Lawrence J.

    2014-01-01

    HLA-DM mediates the exchange of peptides loaded onto MHCII molecules during antigen presentation by a mechanism that remains unclear and controversial. Here, we investigated the sequence and structural determinants of HLA-DM interaction. Peptides interacting nonoptimally in the P1 pocket exhibited low MHCII binding affinity and kinetic instability and were highly susceptible to HLA-DM-mediated peptide exchange. These changes were accompanied by conformational alterations detected by surface plasmon resonance, SDS resistance assay, antibody binding assay, gel filtration, dynamic light scattering, small angle x-ray scattering, and NMR spectroscopy. Surprisingly, all of those changes could be reversed by substitution of the P9 pocket anchor residue. Moreover, MHCII mutations outside the P1 pocket and the HLA-DM interaction site increased HLA-DM susceptibility. These results indicate that a dynamic MHCII conformational determinant rather than P1 pocket occupancy is the key factor determining susceptibility to HLA-DM-mediated peptide exchange and provide a molecular mechanism for HLA-DM to efficiently target unstable MHCII-peptide complexes for editing and exchange those for more stable ones. PMID:25002586

  8. Susceptibility to HLA-DM protein is determined by a dynamic conformation of major histocompatibility complex class II molecule bound with peptide.

    Science.gov (United States)

    Yin, Liusong; Trenh, Peter; Guce, Abigail; Wieczorek, Marek; Lange, Sascha; Sticht, Jana; Jiang, Wei; Bylsma, Marissa; Mellins, Elizabeth D; Freund, Christian; Stern, Lawrence J

    2014-08-22

    HLA-DM mediates the exchange of peptides loaded onto MHCII molecules during antigen presentation by a mechanism that remains unclear and controversial. Here, we investigated the sequence and structural determinants of HLA-DM interaction. Peptides interacting nonoptimally in the P1 pocket exhibited low MHCII binding affinity and kinetic instability and were highly susceptible to HLA-DM-mediated peptide exchange. These changes were accompanied by conformational alterations detected by surface plasmon resonance, SDS resistance assay, antibody binding assay, gel filtration, dynamic light scattering, small angle x-ray scattering, and NMR spectroscopy. Surprisingly, all of those changes could be reversed by substitution of the P9 pocket anchor residue. Moreover, MHCII mutations outside the P1 pocket and the HLA-DM interaction site increased HLA-DM susceptibility. These results indicate that a dynamic MHCII conformational determinant rather than P1 pocket occupancy is the key factor determining susceptibility to HLA-DM-mediated peptide exchange and provide a molecular mechanism for HLA-DM to efficiently target unstable MHCII-peptide complexes for editing and exchange those for more stable ones. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Polymorphisms of heat shock protein 70 genes (HSPA1A, HSPA1B and HSPA1L and susceptibility of noise-induced hearing loss in a Chinese population: A case-control study.

    Directory of Open Access Journals (Sweden)

    Yanhong Li

    Full Text Available Noise-induced hearing loss (NIHL is the second-most frequent form of sensorineural hearing loss. When exposed to the same noise, some workers develop NIHL while others do not, suggesting that NIHL may be associated with genetic factors. To explore the relationship between single nucleotide polymorphisms (SNPs in heat shock protein 70 (HSP70 genes (HSPA1A, HSPA1B and HSPA1L and susceptibility to NIHL in Han Chinese workers exposed to noise, a case-control association study was carried out with 286 hearing loss cases and 286 matched with gender, age, type of work, and exposure time, drawn from a population of 3790 noise-exposed workers. Four SNPs were selected and genotyped. Subsequently, the effects of the alleles and genotypes of the three HSP70 genes (HSPA1A, HSPA1B and HSPA1L on NIHL were analyzed by using a conditional logistic regression. A generalized multiple dimensionality reduction (GMDR was applied to further detect an interaction between the four SNPs. Compared with the combined genotypes CC/TC, carriers of the TT genotype of rs2763979 appeared to show greater susceptibility to NIHL (P = 0.042, adjusted OR = 1.731, 95% CI 1.021-2.935. A significant interaction between rs2763979 and CNE was found (P = 0.029, and a significant association was found between TT of s2763979 and NIHL (P = 0.024, adjusted OR = 5.694, 95%CI 1.256-25.817 in the 96 dB (A≤CNE<101 dB (A group. The results suggest that the rs2763979 locus of the HSP70 genes may be associated with susceptibility to NIHL in Chinese individuals, and other HSP70 genes may also be susceptibility genes for NIHL, but the results must be further replicated in additional independent sample sets.

  10. Sheep scrapie susceptibility-linked polymorphisms do not modulate the initial binding of cellular to disease-associated prion protein prior to conversion

    NARCIS (Netherlands)

    Rigter, A.; Bossers, A.

    2005-01-01

    Conversion of the host-encoded protease-sensitive cellular prion protein (PrPC) into the scrapie-associated protease-resistant isoform (PrPSc) of prion protein (PrP) is the central event in transmissible spongiform encephalopathies or prion diseases. Differences in transmissibility and

  11. GLIS3, a susceptibility gene for type 1 and type 2 diabetes, modulates pancreatic beta cell apoptosis via regulation of a splice variant of the BH3-only protein Bim.

    Directory of Open Access Journals (Sweden)

    Tatiane C Nogueira

    2013-05-01

    Full Text Available Mutations in human Gli-similar (GLIS 3 protein cause neonatal diabetes. The GLIS3 gene region has also been identified as a susceptibility risk locus for both type 1 and type 2 diabetes. GLIS3 plays a role in the generation of pancreatic beta cells and in insulin gene expression, but there is no information on the role of this gene on beta cell viability and/or susceptibility to immune- and metabolic-induced stress. GLIS3 knockdown (KD in INS-1E cells, primary FACS-purified rat beta cells, and human islet cells decreased expression of MafA, Ins2, and Glut2 and inhibited glucose oxidation and insulin secretion, confirming the role of this transcription factor for the beta cell differentiated phenotype. GLIS3 KD increased beta cell apoptosis basally and sensitized the cells to death induced by pro-inflammatory cytokines (interleukin 1β + interferon-γ or palmitate, agents that may contribute to beta cell loss in respectively type 1 and 2 diabetes. The increased cell death was due to activation of the intrinsic (mitochondrial pathway of apoptosis, as indicated by cytochrome c release to the cytosol, Bax translocation to the mitochondria and activation of caspases 9 and 3. Analysis of the pathways implicated in beta cell apoptosis following GLIS3 KD indicated modulation of alternative splicing of the pro-apoptotic BH3-only protein Bim, favouring expression of the pro-death variant BimS via inhibition of the splicing factor SRp55. KD of Bim abrogated the pro-apoptotic effect of GLIS3 loss of function alone or in combination with cytokines or palmitate. The present data suggest that altered expression of the candidate gene GLIS3 may contribute to both type 1 and 2 type diabetes by favouring beta cell apoptosis. This is mediated by alternative splicing of the pro-apoptotic protein Bim and exacerbated formation of the most pro-apoptotic variant BimS.

  12. Exhaustive genotyping of the interferon alpha receptor 1 (IFNAR1) gene and association of an IFNAR1 protein variant with AIDS progression or susceptibility to HIV-1 infection in a French AIDS cohort.

    Science.gov (United States)

    Diop, G; Hirtzig, T; Do, H; Coulonges, C; Vasilescu, A; Labib, T; Spadoni, J-L; Therwath, A; Lathrop, M; Matsuda, F; Zagury, J-F

    2006-11-01

    We have undertaken a systematic genomic approach in order to explore the role of the interferon alpha (IFN-alpha) pathway in AIDS disease development. As it is very difficult to genotype the IFN-alpha gene itself since it has many pseudo-genes, we have focused our interest on the genetic polymorphisms of the IFN-alpha receptor 1 (IFNAR1). We genotyped the Genetics of Resistance to Immunodeficiency Virus (GRIV) cohort composed of patients with extreme profiles of progression to AIDS, slow progressors (SP) and rapid progressors (RP), as well as seronegative controls (CTR). We identified 19 single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) greater than 1% among which two were newly characterized by our study. We found putative associations with AIDS disease development for four SNP alleles and for three haplotypes. The most interesting signals were found for two SNPs in linkage disequilibrium, the SNP IFNAR1_18339 corresponding to a Val168Leu mutation in the extracellular domain of the protein and the intronic SNP, IFNAR1_30127. The intronic SNP IFNAR1_30127 yielded a strong signal both when comparing SP with CTR (P=0.002) and RP with CTR (P=0.005) while IFNAR1_18339 yielded a smaller signal because less patients were analyzed; these SNPs could thus be involved in AIDS progression or in susceptibility to human immunodeficiency virus 1 (HIV-1) infection. Interestingly, two independent studies have previously pointed out the SNP IFNAR1_18339 in susceptibility to multiple sclerosis and to malaria. This is the first work investigating the polymorphisms of the IFNAR1 gene in AIDS. Our results which point out a possible role for the IFN-alpha pathway in susceptibility to HIV-1 infection or progression to AIDS need a necessary confirmation by genomic studies in other AIDS cohorts.

  13. Silencing of a Germin-Like Protein Gene (CchGLP in Geminivirus-Resistant Pepper (Capsicum chinense Jacq. BG-3821 Increases Susceptibility to Single and Mixed Infections by Geminiviruses PHYVV and PepGMV

    Directory of Open Access Journals (Sweden)

    Laura Mejía-Teniente

    2015-11-01

    Full Text Available Germin-like proteins (GLPs are encoded by a family of genes found in all plants, and in terms of function, the GLPs are implicated in the response of plants to biotic and abiotic stresses. CchGLP is a gene encoding a GLP identified in a geminivirus-resistant Capsicum chinense Jacq accession named BG-3821, and it is important in geminivirus resistance when transferred to susceptible tobacco in transgenic experiments. To characterize the role of this GLP in geminivirus resistance in the original accession from which this gene was identified, this work aimed at demonstrating the possible role of CchGLP in resistance to geminiviruses in Capsicum chinense Jacq. BG-3821. Virus-induced gene silencing studies using a geminiviral vector based in PHYVV component A, displaying that silencing of CchGLP in accession BG-3821, increased susceptibility to geminivirus single and mixed infections. These results suggested that CchGLP is an important factor for geminivirus resistance in C. chinense BG-3821 accession.

  14. The block of adipocyte differentiation by a C-terminally truncated, but not by full-length, simian virus 40 large tumor antigen is dependent on an intact retinoblastoma susceptibility protein family binding domain.

    Science.gov (United States)

    Higgins, C; Chatterjee, S; Cherington, V

    1996-02-01

    Simian virus 40 (SV40) can promote cell transformation and suppress differentiation. It does this partly by targeting tumor suppressors such as p53 and members of the retinoblastoma susceptibility protein (Rb) family. This work concentrates on mechanisms by which SV40 large tumor antigen (SVLT) suppresses adipocyte differentiation. We created cell lines derived from murine 3T3-L1 preadipocytes expressing different versions of SV40 early-region sequences. SVLT-expressing cells failed to exhibit adipocyte morphology, to induce glycerophosphate dehydrogenase activity, and to induce differentiation-dependent mRNA for adipocyte P2. SVLT alone was sufficient, in the absence of SV40 small tumor antigen, to inhibit differentiation. A truncated SVLT containing only the N-terminal 121 amino acids (SVLT1-121) blocked differentiation, thus mapping at least one differentiation blocking function to the N-terminal region. K1 (Glu-107-->Lys) point mutants of SVLT, which are unable to bind to the Rb protein family or induce neoplastic transformation, are defective for blocking differentiation in the case of SVLT1-121 but retain the ability to block differentiation in the case of full-length SVLT. This finding demonstrates that Rb family proteins are important in regulating adipocyte differentiation but that other functions of full-length SVLT can block adipocyte differentiation independently of RB family binding and transformation.

  15. Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis

    Science.gov (United States)

    Geyfman, Mikhail; Kumar, Vivek; Liu, Qiang; Ruiz, Rolando; Gordon, William; Espitia, Francisco; Cam, Eric; Millar, Sarah E.; Smyth, Padhraic; Ihler, Alexander; Takahashi, Joseph S.; Andersen, Bogi

    2012-01-01

    The role of the circadian clock in skin and the identity of genes participating in its chronobiology remain largely unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle-related genes, the former peaking during the day and the latter at night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes, because keratinocyte-specific deletion of Bmal1 obliterates time-of-day–dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. In agreement with higher cellular susceptibility to UV-induced DNA damage during S-phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. Because in the human epidermis maximum numbers of keratinocytes go through S-phase in the late afternoon, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation so that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers. PMID:22753467

  16. C4BPB/C4BPA is a new susceptibility locus for venous thrombosis with unknown protein S-independent mechanism: results from genome-wide association and gene expression analyses followed by case-control studies.

    Science.gov (United States)

    Buil, Alfonso; Trégouët, David-Alexandre; Souto, Juan Carlos; Saut, Noémie; Germain, Marine; Rotival, Maxime; Tiret, Laurence; Cambien, Françcois; Lathrop, Mark; Zeller, Tanja; Alessi, Marie-Christine; Rodriguez de Cordoba, Santiago; Münzel, Thomas; Wild, Philipp; Fontcuberta, Jordi; Gagnon, France; Emmerich, Joseph; Almasy, Laura; Blankenberg, Stefan; Soria, José-Manuel; Morange, Pierre-Emmanuel

    2010-06-10

    Through its binding with protein S (PS), a key element of the coagulation/fibrinolysis cascade, the C4b-binding protein (C4BP) has been hypothesized to be involved in the susceptibility to venous thrombosis (VT). To identify genetic factors that may influence the plasma levels of the 3 C4BP existing isoforms, alpha(7)beta(1), alpha(6)beta(1), and alpha(7)beta(0), we conducted a genome-wide association study by analyzing 283 437 single nucleotide polymorphisms (SNPs) in the Genetic Analysis of Idiopathic Thrombophilia (GAIT) study composed of 352 persons. Three SNPs at the C4BPB/C4BPA locus were found genome-wide significantly associated with alpha(7)beta(0) levels. One of these SNPs was further found to explain approximately 11% of the variability of mRNA C4BPA expression in the Gutenberg Heart Study composed of 1490 persons, with no effect on C4BPB mRNA expression. The allele associated with increased alpha(7)beta(0) plasma levels and increased C4BPA expression was further found associated with increased risk of VT (odds ratio [OR] = 1.24 [1.03-1.53]) in 2 independent case-control studies (MARseille THrombosis Association study [MARTHA] and FActeurs de RIsque et de récidives de la maladie thromboembolique VEineuse [FARIVE]) gathering 1706 cases and 1379 controls. This SNP was not associated with free PS or total PS. In conclusion, we observed strong evidence that the C4BPB/C4BPA locus is a new susceptibility locus for VT through a PS-independent mechanism that remains to be elucidated.

  17. Silencing of latent membrane protein 2B reduces susceptibility to activation of lytic Epstein-Barr virus in Burkitt's lymphoma Akata cells.

    Science.gov (United States)

    Rechsteiner, Markus P; Berger, Christoph; Weber, Matthias; Sigrist, Jürg A; Nadal, David; Bernasconi, Michele

    2007-05-01

    Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) blocks B-cell receptor (BCR) signalling after BCR cross-linking to inhibit activation of lytic EBV, and ectopically expressed LMP2B negatively regulates LMP2A. Here, it is demonstrated that silencing of LMP2B in EBV-harbouring Burkitt's lymphoma Akata cells results in reduced expression of EBV immediate-early lytic BZLF1 gene mRNA and late lytic gp350/220 protein upon BCR cross-linking. Similarly, reduction of lytic EBV activation was observed in Akata cells overexpressing LMP2A. In contrast, silencing of LMP2A expression resulted in higher lytic EBV mRNA and protein expression in BCR cross-linked Akata cells. These observations indicate a role for LMP2B distinct from that of LMP2A in regulation of lytic EBV activation in the host cell and support the hypothesis that LMP2B exhibits a negative-regulatory effect on the ability of LMP2A to maintain EBV latency by preventing the switch to lytic replication.

  18. Early-life sodium exposure unmasks susceptibility to stroke in hyperlipidemic, hypertensive heterozygous Tg25 rats transgenic for human cholesteryl ester transfer protein.

    Science.gov (United States)

    Decano, Julius L; Viereck, Jason C; McKee, Ann C; Hamilton, James A; Ruiz-Opazo, Nelson; Herrera, Victoria L M

    2009-03-24

    Early-life risk factor exposure increases aortic atherosclerosis and blood pressure in humans and animal models; however, limited insight has been gained as to end-organ complications. We investigated the effects of early-life Na exposure (0.23% versus 0.4% NaCl regular rat chow) on vascular disease outcomes using the inbred, transgenic [hCETP](25) Dahl salt-sensitive hypertensive rat model of male-predominant coronary atherosclerosis, Tg25. Rather than the expected increase in coronary heart disease, fetal 0.4% Na exposure (cerebral cortical hemorrhagic infarctions, microhemorrhages, neuronal ischemia, and microvascular injury. Ex vivo MRI of stroke-positive rat brains detected cerebral hemorrhages, microhemorrhages, and ischemia with middle cerebral artery distribution and cerebellar noninvolvement. Ultrasound microimaging detected carotid artery disease. Prestroke analysis detected neuronal ischemia and decreased mass of isolated cerebral but not cerebellar microvessels. Early-life Na exposure exacerbated hypertension and unmasked stroke susceptibility, with greater female vulnerability in hypertensive, hyperlipidemic Tg25 rats. The reproducible modeling in stroke-prone Tg25 rats of carotid artery disease, cerebral hemorrhagic infarctions, neuronal ischemia, microhemorrhages, and microvascular alterations suggests a pathogenic spectrum with causal interrelationships. This "mixed-stroke" spectrum could represent paradigms of ischemic-hemorrhagic transformation and/or a microangiopathic basis for the association of ischemic lesions, microhemorrhages, and strokes in humans. Together, the data reveal early-life Na exposure to be a significant modifier of hypertension and stroke disease course and hence a potentially modifiable prevention target that deserves systematic study.

  19. Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer

    DEFF Research Database (Denmark)

    Zuber, Verena; Bettella, Francesco; Witoelar, Aree

    2017-01-01

    ) and applied to other diseases such as schizophrenia. Conclusions: This is the first study to evaluate the enrichment of epigenetic readers in genome-wide associations studies for SNPs within enhancers, and provides a powerful tool for enriching and prioritizing PC and BC genetic risk loci. Our study......Background: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor...... progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding...

  20. Structure of HLA-A*0301 in complex with a peptide of proteolipid protein: insights into the role of HLA-A alleles in susceptibility to multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    McMahon, Róisín M. [University of Oxford, Oxford OX3 9DS (United Kingdom); University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Friis, Lone [University of Oxford, Oxford OX3 9DS (United Kingdom); Siebold, Christian [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Friese, Manuel A. [University of Oxford, Oxford OX3 9DS (United Kingdom); University of Oxford, Oxford OX3 9DU (United Kingdom); Universitätsklinikum Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg (Germany); Fugger, Lars, E-mail: lars.fugger@imm.ox.ac.uk [University of Oxford, Oxford OX3 9DS (United Kingdom); University of Oxford, Oxford OX3 9DU (United Kingdom); Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardsvej 100, 8200 N Aarhus (Denmark); Jones, E. Yvonne, E-mail: lars.fugger@imm.ox.ac.uk [University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); University of Oxford, Oxford OX3 9DS (United Kingdom)

    2011-05-01

    The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. The structure of the human major histocompatability (MHC) class I molecule HLA-A*0301 (HLA-A3) in complex with a nonameric peptide (KLIETYFSK) has been determined by X-ray crystallography to 2.7 Å resolution. HLA-A3 is a predisposing allele for multiple sclerosis (MS), an autoimmune disease of the central nervous system. The KLIETYFSK peptide is a naturally processed epitope of proteolipid protein, a myelin protein and candidate target for immune-mediated myelin destruction in MS. Comparison of the structure of HLA-A3 with that of HLA-A2, an MHC class I molecule which is protective against MS, indicates that both MHC class I molecules present very similar faces for T-cell receptor recognition whilst differing in the specificity of their peptide-binding grooves. These characteristics may underlie the opposing (predisposing versus protective) associations that they exhibit both in humans and in mouse models of MS-like disease. Furthermore, subtle alterations within the peptide-binding groove of HLA-A3 and other A3-like MHC class I molecules, members of the so-called A3 superfamily, may be sufficient to alter their presentation of autoantigen peptides such as KLIETYFSK. This in turn may modulate their contribution to the associated risk of autoimmune disease.

  1. Role of Penicillin-Binding Protein 2 (PBP2) in the Antibiotic Susceptibility and Cell Wall Cross-Linking of Staphylococcus aureus: Evidence for the Cooperative Functioning of PBP2, PBP4, and PBP2A

    Science.gov (United States)

    Łęski, Tomasz A.; Tomasz, Alexander

    2005-01-01

    Ceftizoxime, a beta-lactam antibiotic with high selective affinity for penicillin-binding protein 2 (PBP2) of Staphylococcus aureus, was used to select a spontaneous resistant mutant of S. aureus strain 27s. The stable resistant mutant ZOX3 had an increased ceftizoxime MIC and a decreased affinity of its PBP2 for ceftizoxime and produced peptidoglycan in which the proportion of highly cross-linked muropeptides was reduced. The pbpB gene of ZOX3 carried a single C-to-T nucleotide substitution at nucleotide 1373, causing replacement of a proline with a leucine at amino acid residue 458 of the transpeptidase domain of the protein, close to the SFN conserved motif. Experimental proof that this point mutation was responsible for the drug-resistant phenotype, and also for the decreased PBP2 affinity and reduced cell wall cross-linking, was provided by allelic replacement experiments and site-directed mutagenesis. Disruption of pbpD, the structural gene of PBP4, in either the parental strain or the mutant caused a large decrease in the highly cross-linked muropeptide components of the cell wall and in the mutant caused a massive accumulation of muropeptide monomers as well. Disruption of pbpD also caused increased sensitivity to ceftizoxime in both the parental cells and the ZOX3 mutant, while introduction of the plasmid-borne mecA gene, the genetic determinant of the beta-lactam resistance protein PBP2A, had the opposite effects. The findings provide evidence for the cooperative functioning of two native S. aureus transpeptidases (PBP2 and PBP4) and an acquired transpeptidase (PBP2A) in staphylococcal cell wall biosynthesis and susceptibility to antimicrobial agents. PMID:15716453

  2. Susceptibility to malignant hyperthermia

    NARCIS (Netherlands)

    Snoeck, Marcus Matheus Johannes

    2004-01-01

    In this thesis the author studied the diagnostic procedures for susceptibility to malignant hyperthermia (MH), with special emphasis upon refining the biological diagnostic test and improving protocols and guidelines for investigation of MH susceptibility. MH is a pharmacogenetic disease of skeletal

  3. A mutation in the poxA gene of Salmonella enterica serovar Typhimurium alters protein production, elevates susceptibility to environmental challenges, and decreases swine colonization.

    Science.gov (United States)

    Bearson, Shawn M D; Bearson, Bradley L; Brunelle, Brian W; Sharma, Vijay K; Lee, In Soo

    2011-06-01

    Control of foodborne Salmonella within the farm-retail continuum is a complex issue since over 2500 serovars of Salmonella exist, the host range of Salmonella spp. varies greatly, and Salmonella is environmentally ubiquitous. To identify Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) genes important for pathogen survival, our research group previously screened a signature-tagged mutagenesis bank in an ex vivo swine stomach content assay. A mutation in the poxA gene, a member of the gene family encoding class-II aminoacyl-tRNA synthetases, decreased survival of Salmonella Typhimurium in the ex vivo swine stomach content assay. In the current study, complementation with a plasmid-encoded poxA gene restored survival of the poxA mutant to the level of the parental, wild-type strain. In vivo analysis of the poxA mutant in the natural porcine host revealed significantly reduced fecal shedding of Salmonella, decreased colonization of the tonsils, and decreased detection of the mutant strain in the cecal contents of the pigs at 7 days postinoculation (p < 0.05). Body temperature (fever) of the pigs inoculated with wild-type Salmonella Typhimurium was significantly higher than that of pigs inoculated with the poxA mutant (p < 0.05). Two-dimensional gel electrophoresis revealed characteristic differences in the protein profile of the poxA mutant relative to the wild-type strain, indicating that deletion of poxA in Salmonella Typhimurium exerts selective effects on translation and/or posttranslational modifications of mRNA species that are necessary for stress survival and colonization of the natural swine host.

  4. Sequence Alignment to Predict Across Species Susceptibility ...

    Science.gov (United States)

    Conservation of a molecular target across species can be used as a line-of-evidence to predict the likelihood of chemical susceptibility. The web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was developed to simplify, streamline, and quantitatively assess protein sequence/structural similarity across taxonomic groups as a means to predict relative intrinsic susceptibility. The intent of the tool is to allow for evaluation of any potential protein target, so it is amenable to variable degrees of protein characterization, depending on available information about the chemical/protein interaction and the molecular target itself. To allow for flexibility in the analysis, a layered strategy was adopted for the tool. The first level of the SeqAPASS analysis compares primary amino acid sequences to a query sequence, calculating a metric for sequence similarity (including detection of candidate orthologs), the second level evaluates sequence similarity within selected domains (e.g., ligand-binding domain, DNA binding domain), and the third level of analysis compares individual amino acid residue positions identified as being of importance for protein conformation and/or ligand binding upon chemical perturbation. Each level of the SeqAPASS analysis provides increasing evidence to apply toward rapid, screening-level assessments of probable cross species susceptibility. Such analyses can support prioritization of chemicals for further ev

  5. No association of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 or complement factor H polymorphisms with early age-related maculopathy in a Chinese cohort

    Science.gov (United States)

    Chen, Jian-Huan; Yang, Yunli; Zheng, Yuqian; Qiu, Minghui; Xie, Mingliang; Lin, Wenjie; Zhang, Mingzhi; Pang, Chi Pui

    2013-01-01

    Purpose Single nucleotide polymorphisms (SNPs) of age-related maculopathy susceptibility protein 2/HtrA serine peptidase 1 (ARMS2/HTRA1) and complement factor H (CFH) have been reported to be associated with age-related macular degeneration (AMD). The purpose of this study was to investigate the association of ARMS2/HTRA1 and CFH SNPs with early age-related maculopathy (ARM) in a Han Chinese cohort. Methods The cohort consisted of 315 unrelated subjects, including 158 patients with early ARM and 157 recruited controls. Early ARM was diagnosed and graded according to the Age-Related Eye Disease Study criteria. Four SNPs in ARMS2/HTRA1 and six SNPs in CFH previously reported to be associated with AMD were genotyped using TaqMan genotyping assays. Logistic regression implemented with the R statistical language was used for association analysis. Results None of the ARMS2/HTRA1 and CFH SNPs showed any significant association with early ARM (all p>0.453), with the odds ratios ranging from 0.88 to 1.17. None of the SNPs were associated with unilateral or bilateral early ARM or any grade of early ARM (all p>0.249). Conclusions The association of ARMS2/HTRA1 and CFH SNPs in early ARM was not detected in our cohort. The findings in the current study indicated that the effects of ARMS2/HTRA1 and CFH in early ARM could be much lower compared to those in AMD. PMID:23687431

  6. [Chinese multicenter randomized trial of customized chemotherapy based on BRCA1 (breast cancer susceptibility gene 1)-RAP80 (receptor-associated protein 80) mRNA expression in advanced non-small cell lung cancer (NSCLC) patients].

    Science.gov (United States)

    Wei, J; Qian, X P; Zou, Z Y; Wang, L F; Yu, L X; You, C W; Song, Y; Lu, H Y; Hu, W J; Yan, J; Xu, X X; Chen, X F; Li, X Y; Wu, Q F; Zhou, Y; Zhang, F L; Liu, B R

    2016-11-23

    Objective: BRCA1 (breast cancer susceptibility gene 1) and RAP80 (receptor-associated protein 80) play key roles in predicting chemosensitivity of platinum and taxanes. A randomized trial was carried out to compare non-selected cisplatin-based chemotherapy with therapy customized according to BRCA1 and RAP80 expression. Methods: Advanced stage NSCLC patients whose tumor specimen was sufficient for molecular analysis were randomized (1∶3) to the control or experimental arm. Patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin (Arm 1), those with intermediate/high RAP80 expression and low/intermediate BRCA1expression received docetaxel/cisplatin (Arm 2), and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone (Arm 3). The primary end point was progression-free survival (PFS). Results: 226 patients were screened and 124 were randomized in this trial. ORR in the four subgroups was 22.6%, 48.4%, 30.3% and 19.2%, respectively (P=0.08); PFS was 4.74, 5.59, 3.78 and 2.73 months, respectively (P=0.55); and OS was 10.82, 14.44, 10.86 and 10.86 months, respectively (P=0.84). The common adverse effects included neutropenia, nausea, anemia and fatigue. Conclusions: No statistically significant difference of ORR, PFS or OS is observed in the experimental arms compared with the control arm. Patients with low RAP80 mRNA levels have a trend of better survival and higher response rate to gemcitabine/cisplatin chemotherapy.

  7. Uterine clinical findings, fertility rate, leucocyte migration, and COX-2 protein levels in the endometrial tissue of susceptible mares treated with platelet-rich plasma before and after AI.

    Science.gov (United States)

    Segabinazzi, Lorenzo G; Friso, Aime M; Correal, Sebastian B; Crespilho, André M; Dell'Aqua, José Antonio; Miró, Jordi; Papa, Frederico O; Alvarenga, Marco Antonio

    2017-12-01

    Persistent mating-induced endometritis (PMIE) results in decreased fertility in horses, thereby causing a significant impact in the horse market. Platelet-rich plasma (PRP), a modulator of the inflammatory response, has been largely used in veterinary medicine. Here, we investigated the effects of PRP on uterine inflammation, conception rate, endometrial polymorphonuclear neutrophil (PMN) migration, and COX-2 protein levels in the endometrial tissue. Thirteen PMIE-susceptible mares were used for artificial insemination (AI). The mares were inseminated with fresh semen in three consecutive cycles in a cross-over study design. The following cycle classifications were used: control cycle, no pharmacological interference; pre-AI, 20 mL of PRP was infused 24 h before AI; and post-AI, 20 mL of PRP was infused four h after AI. Follicular dynamics were monitored daily by transrectal ultrasound. When a follicle larger than 35 mm was detected, ovulation was induced with deslorelin acetate (1 mg, im). AI was performed 24 h after ovulation induction. Intrauterine fluid (FLU) was evaluated by ultrasonography before and 24 h after AI. PMNs in uterine cytology (CYT) and biopsy (HIS) were also observed before and 24 h after AI. Pregnancy was determined within 14 days after ovulation. Number of COX-2 positive cells was evaluated by immunohistochemistry. Both PRP treatments resulted in a decrease of PMNs in the CYT after breeding when compared to controls. FLU did not differ between cycles; however, the conception rates were significantly higher in the PRP mares. Mares positive for endometritis decreased in both treatment groups, and a more intense positive COX-2 labeling was observed in the control group when compared to the two treatment groups. In conclusion, PRP beneficially reduces inflammatory response in PMIE mares independent of when treatments were administered, thus increasing chances of successful pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Nutrition affects insect susceptibility to Bt toxins

    Science.gov (United States)

    Deans, Carrie A.; Behmer, Spencer T.; Tessnow, Ashley E.; Tamez-Guerra, Patricia; Pusztai-Carey, Marianne; Sword, Gregory A.

    2017-01-01

    Pesticide resistance represents a major challenge to global food production. The spread of resistance alleles is the primary explanation for observations of reduced pesticide efficacy over time, but the potential for gene-by-environment interactions (plasticity) to mediate susceptibility has largely been overlooked. Here we show that nutrition is an environmental factor that affects susceptibility to Bt toxins. Protein and carbohydrates are two key macronutrients for insect herbivores, and the polyphagous pest Helicoverpa zea self-selects and performs best on diets that are protein-biased relative to carbohydrates. Despite this, most Bt bioassays employ carbohydrate-biased rearing diets. This study explored the effect of diet protein-carbohydrate content on H. zea susceptibility to Cry1Ac, a common Bt endotoxin. We detected a 100-fold increase in LC50 for larvae on optimal versus carbohydrate-biased diets, and significant diet-mediated variation in survival and performance when challenged with Cry1Ac. Our results suggest that Bt resistance bioassays that use ecologically- and physiologically-mismatched diets over-estimate susceptibility and under-estimate resistance.

  9. Genetic susceptibility of periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Crielaard, W.; Loos, B.G.

    2012-01-01

    In this systematic review, we explore and summarize the peer-reviewed literature on putative genetic risk factors for susceptibility to aggressive and chronic periodontitis. A comprehensive literature search on the PubMed database was performed using the keywords ‘periodontitis’ or ‘periodontal

  10. Fourie susceptible.pmd

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    a number of cultivars exhibited field resistance to halo blight and bacterial brown spot, all cultivars were more or less susceptible to .... Cerillos. Alubia. I. 91. 57. Kranskop. Red speckled sugar. II. 97. 63. OPS-RS1. Red speckled sugar. II. 96. 63. OPS-RS2. Red speckled sugar. I. 100. 61. OPS-RS3. Red speckled sugar. II. 97.

  11. Susceptibility to COPD: differential proteomic profiling after acute smoking.

    Directory of Open Access Journals (Sweden)

    Lorenza Franciosi

    Full Text Available Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease, yet only a subset of smokers develops COPD. Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as "susceptible individuals". Here we perform unbiased analyses of proteomic profiles to assess how "susceptible individuals" differ from age-matched "non-susceptible individuals" in response to cigarette smoking. Epithelial lining fluid (ELF was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD. Controls at baseline were older healthy smoking and non-smoking individuals. Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ in duplicate. Six proteins were selected and validated by ELISA or immunohistochemistry. After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment. SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1 decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures. Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking. We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD. This is the first study applying unbiased proteomic profiling to unravel the underlying

  12. Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.

    Science.gov (United States)

    Uchiyama, Keiji; Miyata, Hironori; Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

    2014-01-01

    Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc.

  13. Genetic Susceptibility to Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sanja Kovacic

    2012-01-01

    Full Text Available Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic ground significantly influences susceptibility to atherosclerotic vascular diseases. Besides further investigations of monogenetic diseases, candidate genes, genetic polymorphisms, and susceptibility loci associated with atherosclerotic diseases have been identified in recent years, and their number is rapidly increasing. This paper discusses main genetic investigations fields associated with human atherosclerotic vascular diseases. The paper concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on prospective prediction from an early age of individuals who are predisposed to develop premature atherosclerosis as well as to facilitate the discovery of novel drug targets.

  14. Marijuana Usage and Hypnotic Susceptibility

    Science.gov (United States)

    Franzini, Louis R.; McDonald, Roy D.

    1973-01-01

    Anonymous self-reported drug usage data and hypnotic susceptibility scores were obtained from 282 college students. Frequent marijuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. (Author)

  15. Loss of the interferon-γ-inducible regulatory immunity-related GTPase (IRG), Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient mice to infection

    NARCIS (Netherlands)

    Maric-Biresev, Jelena; Hunn, Julia P; Krut, Oleg; Helms, J Bernd; Martens, Sascha; Howard, Jonathan C

    2016-01-01

    BACKGROUND: The interferon-γ (IFN-γ)-inducible immunity-related GTPase (IRG), Irgm1, plays an essential role in restraining activation of the IRG pathogen resistance system. However, the loss of Irgm1 in mice also causes a dramatic but unexplained susceptibility phenotype upon infection with a

  16. Susceptibility of pathogenic and nonpathogenic Naegleria ssp

    Energy Technology Data Exchange (ETDEWEB)

    Whiteman, L.Y.

    1988-01-01

    The susceptibility of four species of Naegleria amoebae to complement-mediated lysis was determined. The amoebicidal activity of normal human serum (NHS) and normal guinea pig serum (NGPS) for Naegleria amoebae was measured by an in vitro cytotoxicity assay. Release of radioactivity from amoebae labeled with {sup 3}H-uridine and visual observation with a compound microscope were used as indices of lysis. Susceptibility or resistance to complement-mediated lysis in vitro correlated with the in vivo pathogenic potential. Nonpathogenic Naegleria amoebae were lysed at a faster rate and at higher cell concentrations than were pathogenic amoebae. Electrophoretic analysis of NHS incubated with pathogenic or nonpathogenic Naegleria spp. demonstrated that amoebae activate the complement cascade resulting in the production of C3 and C5 complement cleavage products. Treatment with papain or trypsin for 1 h, but not with sialidase, increase the susceptibility of highly pathogenic, mouse-passaged N. fowleri to lysis. Treatment with actinomycin D, cycloheximide or various protease inhibitors for 4 h did not increase susceptibility to lysis. Neither a repair process involving de novo protein synthesis nor a complement-inactivating protease appear to account for the increase resistance of N. fowleri amoebae to complement-mediated lysis. A binding study with {sup 125}I radiolabeled C9 indicated that the terminal complement component does not remain stably bound to the membrane of pathogenic amoebae.

  17. Magnetic susceptibilities of minerals

    Science.gov (United States)

    Rosenblum, Sam; Brownfield, I.K.

    2000-01-01

    Magnetic separation of minerals is a topic that is seldom reported in the literature for two reasons. First, separation data generally are byproducts of other projects; and second, this study requires a large amount of patience and is unusually tedious. Indeed, we suspect that most minerals probably are never investigated for this property. These data are timesaving for mineralogists who concentrate mono-mineralic fractions for chemical analysis, age dating, and for other purposes. The data can certainly be used in the ore-beneficiation industries. In some instances, magnetic-susceptibility data may help in mineral identification, where other information is insufficient. In past studies of magnetic separation of minerals, (Gaudin and Spedden, 1943; Tille and Kirkpatrick, 1956; Rosenblum, 1958; Rubinstein and others, 1958; Flinter, 1959; Hess, 1959; Baker, 1962; Meric and Peyre, 1963; Rojas and others, 1965; and Duchesne, 1966), the emphasis has been on the ferromagnetic and paramagnetic ranges of extraction. For readers interested in the history of magnetic separation of minerals, Krumbein and Pettijohn (1938, p. 344-346) indicated nine references back to 1848. The primary purpose of this paper is to report the magnetic-susceptibility data on as many minerals as possible, similar to tables of hardness, specific gravity, refractive indices, and other basic physical properties of minerals. A secondary purpose is to demonstrate that the total and best extraction ranges are influenced by the chemistry of the minerals. The following notes are offered to help avoid problems in separating a desired mineral concentrate from mixtures of mineral grains.

  18. Alcohol increases hypnotic susceptibility.

    Science.gov (United States)

    Semmens-Wheeler, Rebecca; Dienes, Zoltán; Duka, Theodora

    2013-09-01

    One approach to hypnosis suggests that for hypnotic experience to occur frontal lobe activity must be attenuated. For example, cold control theory posits that a lack of awareness of intentions is responsible for the experience of involuntariness and/or the subjective reality of hypnotic suggestions. The mid-dorso-lateral prefrontal cortex and the ACC are candidate regions for such awareness. Alcohol impairs frontal lobe executive function. This study examined whether alcohol affects hypnotisability. We administered 0.8 mg/kg of alcohol or a placebo to 32 medium susceptible participants. They were subsequently hypnotised and given hypnotic suggestions. All participants believed they had received some alcohol. Participants in the alcohol condition were more susceptible to hypnotic suggestions than participants in the placebo condition. Impaired frontal lobe activity facilitates hypnotic responding, which supports theories postulating that attenuation of executive function facilitates hypnotic response, and contradicts theories postulating that hypnotic response involves enhanced inhibitory, attentional or other executive function. Copyright © 2013. Published by Elsevier Inc.

  19. Graphene susceptibility in Holstein model

    Energy Technology Data Exchange (ETDEWEB)

    Mousavi, Hamze, E-mail: hamze.mousavi@gmail.co [Department of Physics, Razi University, Kermanshah (Iran, Islamic Republic of); Nano Science and Nano Technology Research Center, Razi University, Kermanshah (Iran, Islamic Republic of)

    2011-06-15

    We study the effects of the electron-phonon interaction on the temperature dependence of the orbital magnetic susceptibility of monolayer graphene. We use the linear response theory and Green's function formalism within the Holstein Hamiltonian model. The results show that the effects of the electron-phonon interaction on the susceptibility of graphene sheet have different behaviors in two temperature regions. In the low temperature region, susceptibility increases when the electron-phonon coupling strength increases. On the other hand, the susceptibility reduces with increasing the electron-phonon coupling strength in the high temperature region. - Highlights: Effect of electron-phonon interaction on the susceptibility of graphene is studied. Linear response theory and Green's function technique in Holstein model are used. Effect of electron-phonon on susceptibility has different behaviors in two temperature regions.

  20. Topological susceptibility from slabs

    Energy Technology Data Exchange (ETDEWEB)

    Bietenholz, Wolfgang [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, A.P. 70-543, Distrito Federal, C.P. 04510 (Mexico); Forcrand, Philippe de [Institute for Theoretical Physics, ETH Zürich,CH-8093 Zürich (Switzerland); CERN, Physics Department, TH Unit, CH-1211 Geneva 23 (Switzerland); Gerber, Urs [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, A.P. 70-543, Distrito Federal, C.P. 04510 (Mexico); Instituto de Física y Matemáticas, Universidad Michoacana de San Nicolás de Hidalgo,Edificio C-3, Apdo. Postal 2-82, Morelia, Michoacán, C.P. 58040 (Mexico)

    2015-12-14

    In quantum field theories with topological sectors, a non-perturbative quantity of interest is the topological susceptibility χ{sub t}. In principle it seems straightforward to measure χ{sub t} by means of Monte Carlo simulations. However, for local update algorithms and fine lattice spacings, this tends to be difficult, since the Monte Carlo history rarely changes the topological sector. Here we test a method to measure χ{sub t} even if data from only one sector are available. It is based on the topological charges in sub-volumes, which we denote as slabs. Assuming a Gaussian distribution of these charges, this method enables the evaluation of χ{sub t}, as we demonstrate with numerical results for non-linear σ-models.

  1. Topological Susceptibility from Slabs

    CERN Document Server

    Bietenholz, Wolfgang; Gerber, Urs

    2015-01-01

    In quantum field theories with topological sectors, a non-perturbative quantity of interest is the topological susceptibility chi_t. In principle it seems straightforward to measure chi_t by means of Monte Carlo simulations. However, for local update algorithms and fine lattice spacings, this tends to be difficult, since the Monte Carlo history rarely changes the topological sector. Here we test a method to measure chi_t even if data from only one sector are available. It is based on the topological charges in sub-volumes, which we denote as slabs. Assuming a Gaussian distribution of these charges, this method enables the evaluation of chi_t, as we demonstrate with numerical results for non-linear sigma-models.

  2. Candidate hippocampal biomarkers of susceptibility and resilience to stress in a rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Palmfeldt, Johan; Christiansen, Sofie

    2012-01-01

    Susceptibility to stress plays a crucial role in the development of psychiatric disorders such as unipolar depression and post-traumatic stress disorder. In the present study the chronic mild stress rat model of depression was used to reveal stress-susceptible and stress-resilient rats. Large......-scale proteomics was used to map hippocampal protein alterations in different stress states. Membrane proteins were successfully captured by two-phase separation and peptide based proteomics. Using iTRAQ labeling coupled with mass spectrometry, more than 2000 proteins were quantified and 73 proteins were found...... to be differentially expressed. Stress susceptibility was associated with increased expression of a sodium-channel protein (SCN9A) currently investigated as a potential antidepressant target. Differential protein profiling also indicated stress susceptibility to be associated with deficits in synaptic vesicle release...

  3. Microwave susceptibility experiments

    Energy Technology Data Exchange (ETDEWEB)

    McConaghy, C.

    1984-05-29

    In certain experimental environments, systems can be affected or damaged by microwave pulses. I have conducted tests at LLNL to understand the phenomenology of microwave susceptibility of system components and subsystem components. To date, my experiments have concentrated on bipolar transistors, similar to what might be used in discrete analog circuits, and on CMOS RAM chips, which might be used in a computer memory system. I observed a decrease in failure energies for both the transistor and the integrated curcuit as I shortened the microwave pulse width. An S band (2.86 GHz) transmit/receive (T/R) tube has also been tested both at S band and at X band (8.16 GHz). The S band pulse had limitations in rise-time from zero power, which had an effect on the amount of power that could be transmitted through the T/R tube, as much as 0.7% of the incident power passed through the tube. All tests were conducted in closed-waveguide or coax test-fixtures, in contrast to the anechoic chambers utilized by other experimenters. I have used both S band and X band Klystron generators. For very high power (greater than 1 MW), I used an additional pulse-compression cavity at S band. Other subsystem components such as an X band mixer and an X band T/R tube will be tested in the future. 8 references.

  4. [Antimicrobial susceptibility cumulative reports].

    Science.gov (United States)

    Canut-Blasco, Andrés; Calvo, Jorge; Rodríguez-Díaz, Juan Carlos; Martínez-Martínez, Luis

    2016-10-01

    Cumulative reports on antimicrobial susceptibility tests data are important for selecting empirical treatments, as an educational tool in programs on antimicrobial use, and for establishing breakpoints defining clinical categories. These reports should be based on data validated by clinical microbiologists using diagnostic samples (not surveillance samples). In order to avoid a bias derived from including several isolates obtained from the same patient, it is recommended that, for a defined period, only the first isolate is counted. A minimal number of isolates per species should be presented: a figure of >=30 isolates is statistically acceptable. The report is usually presented in a table format where, for each cell, information on clinically relevant microorganisms-antimicrobial agents is presented. Depending on particular needs, multiple tables showing data related to patients, samples, services or special pathogens can be prepared. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  5. Island cotton Enhanced Disease Susceptibility 1 gene encoding a lipase-like protein plays a crucial role in response to Verticillium dahliae by regulating the SA level and H2O2 accumulation

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2016-12-01

    Full Text Available Cotton is one of the most economically important crops, but most cultivated varieties lack adequate innate immunity or resistance to Verticillium wilt. This results in serious losses to both yield and fiber quality. To identify the genetic resources for innate immunity and understand the pathways for pathogen defenses in this crop, here we focus on orthologs of the central Arabidopsis thaliana defense regulator Enhanced Disease Susceptibility 1 (EDS1. The full-length cDNA of GbEDS1 was obtained by screening the full-length cDNA library of Gossypium barbadense combining with RACE strategy. Its open reading frame is 1848 bp long, encoding 615 amino acid residues. Sequence analysis showed that GbEDS1 contains a conserved N-terminal lipase domain and an EDS1-specific KNEDT motif. Expression profiling indicated that the gene is induced by Verticillium dahliae as well as salicylic acid (SA treatment. Subcellular localization assays revealed that GbEDS1 is located in the cell cytoplasm and nucleus. Overexpression of GbEDS1 in Arabidopsis dramatically up-regulated SA and H2O2 production, resulting in enhanced disease resistance to V. dahliae. Silencing of GbEDS1 in G. barbadense significantly decreased SA and H2O2 acumulation, leading to the cotton more susceptibility. Moreover, combining the gene expression results from transgenic Arabidopsis and silenced-GbEDS1 cotton, it indicated that GbEDS1 could activate GbNDR1 and GbBAK1 expression. These findings not only broaden our knowledge about the biological role of GbEDS1, but also provide new insights into the defense mechanisms of GbEDS1 against V. dahliae in cotton.

  6. [Antimicrobial susceptibility in Chile 2012].

    Science.gov (United States)

    Cifuentes-D, Marcela; Silva, Francisco; García, Patricia; Bello, Helia; Briceño, Isabel; Calvo-A, Mario; Labarca, Jaime

    2014-04-01

    Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

  7. pso.ATION AND ANTIMICROBIAL SUSCEPTIBILITY

    African Journals Online (AJOL)

    isolates vere made using standard methods, Antibiotic susceptibility tests against commonly prescribed ... Acute otitis media is rapid with short .... sensitivity tests. Antimicrobial susceptibility tests: The antimicrobial susceptibility patterns of major Gram positive and negative bacterial isolates obtained from clinical specimens.

  8. Hypnotic susceptibility and dream characteristics.

    Science.gov (United States)

    Zamore, N; Barrett, D

    1989-11-01

    This study examined the relationship of hypnotic susceptibility to a variety of dream characteristics and types of dream content. A Dream Questionnaire was constructed synthesizing Gibson's dream inventory and Hilgard's theoretical conceptions of hypnosis. Employing the Harvard Group Scale of Hypnotic Susceptibility and the Field Inventory for evaluating hypnotic response, several dream dimensions correlated significantly with hypnotizability. For subjects as a whole, the strongest correlates were the frequency of dreams which they believed to be precognitive and out-of-body dreams. Ability to dream on a chosen topic also correlated significantly with hypnotic susceptibility for both genders. For females only, there was a negative correlation of hypnotic susceptibility to flying dreams. Absorption correlated positively with dream recall, ability to dream on a chosen topic, reports of conflict resolution in dreams, creative ideas occurring in dreams, amount of color in dreams, pleasantness of dreams, bizarreness of dreams, flying dreams and precognitive dreams.

  9. Ancestral susceptibility to colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Huhn, S.; Pardini, Barbara; Naccarati, Alessio; Vodička, Pavel (ed.); Hemminki, K.; Försti, A.

    2012-01-01

    Roč. 27, č. 2 (2012), s. 197-204 ISSN 0267-8357 R&D Projects: GA ČR GA310/07/1430; GA ČR GAP304/10/1286 Grant - others:EU FP7(XE) HEALTH-F4-2007-200767 Institutional research plan: CEZ:AV0Z50390512 Keywords : cancer susceptibility * molecular epidemiology * genetic susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012

  10. Contrasting effect of dark-chilling on chloroplast structure and arrangement of chlorophyll-protein complexes in pea and tomato: plants with a different susceptibility to non-freezing temperature

    NARCIS (Netherlands)

    Garstka, M.; Venema, J.H.; Rumak, I.; Gieczewska, K.; Rosiak, M.; Koziol-Lipinska, J.; Vredenberg, W.J.; Mostowska, A.

    2007-01-01

    The effect of dark-chilling and subsequent photoactivation on chloroplast structure and arrangements of chlorophyll-protein complexes in thylakoid membranes was studied in chilling-tolerant (CT) pea and in chilling-sensitive (CS) tomato. Dark-chilling did not influence chlorophyll content and Chl

  11. Contrasting effect of dark-chilling on chloroplast structure and arrangement of chlorophyll-protein complexes in pea and tomato : Plants with a different susceptibility to non-freezing temperature

    NARCIS (Netherlands)

    Garstka, Maciej; Venema, Jan Henk; Rumak, Izabela; Gieczewska, Katarzyna; Rosiak, Malgorzata; Koziol-Lipinska, Joanna; Kierdaszuk, Borys; Vredenberg, Wim J.; Mostowska, Agnieszka

    2007-01-01

    The effect of dark-chilling and subsequent photoactivation on chloroplast structure and arrangements of chlorophyll-protein complexes in thylakoid membranes was studied in chilling-tolerant (CT) pea and in chilling-sensitive (CS) tomato. Dark-chilling did not influence chlorophyll content and Chl

  12. Individual Genetic Susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    Eric J. Hall

    2008-12-08

    Risk estimates derived from epidemiological studies of exposed populations, as well as the maximum permissible doses allowed for occupational exposure and exposure of the public to ionizing radiation are all based on the assumption that the human population is uniform in its radiosensitivity, except for a small number of individuals, such as ATM homozygotes who are easily identified by their clinical symptoms. The hypothesis upon which this proposal is based is that the human population is not homogeneous in radiosensitiviry, but that radiosensitive sub-groups exist which are not easy to identify. These individuals would suffer an increased incidence of detrimental radiation effects, and distort the shape of the dose response relationship. The radiosensitivity of these groups depend on the expression levels of specific proteins. The plan was to investigate the effect of 3 relatively rare, high penetrate genes available in mice, namely Atm, mRad9 & Brca1. The purpose of radiation protection is to prevent! deterministic effects of clinical significance and limit stochastic effects to acceptable levels. We plan, therefore to compare with wild type animals the radiosensitivity of mice heterozygous for each of the genes mentioned above, as well as double heterozygotes for pairs of genes, using two biological endpoints: a) Ocular cataracts as an important and relevant deterministic effect, and b) Oncogenic transformation in cultured embryo fibroblasts, as a surrogate for carcinogenesis, the most relevant stochastic effect.

  13. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    2005-01-01

    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  14. Penicillin-Susceptible Group B Streptococcal Clinical Isolates with Reduced Cephalosporin Susceptibility

    Science.gov (United States)

    Nagano, Noriyuki; Nagano, Yukiko; Toyama, Masami; Kimura, Kouji; Shibayama, Keigo

    2014-01-01

    We characterized penicillin-susceptible group B streptococcal (PSGBS) clinical isolates exhibiting no growth inhibition zone around a ceftibuten disk (CTBr PSGBS). The CTBr PSGBS isolates, for which augmented MICs of cefaclor and ceftizoxime were found, shared a T394A substitution in penicillin-binding protein 2X (PBP 2X) and a T567I substitution in PBP 2B, together with an additional G429S substitution in PBP 2X or a T145A substitution in PBP 1A, although the T145A substitution in the transglycosidase domain of PBP 1A would have no effect on the level of resistance to ceftibuten. PMID:24920773

  15. Inherited susceptibility and radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B. [Harvard School of Public Health, Boston, MA (United States)

    1997-03-01

    There is continuing concern that some people in the general population may have genetic makeups that place them at particularly high risk for radiation-induced cancer. The existence of such a susceptible subpopulation would have obvious implications for the estimation of risks of radiation exposure. Although it has been long known that familial aggregations of cancer do sometimes occur, recent evidence suggests that a general genetic predisposition to cancer does not exist; most cancers occur sporadically. On the other hand, nearly 10% of the known Mendelian genetic disorders are associated with cancer. A number of these involve a familial predisposition to cancer, and some are characterized by an enhanced susceptibility to the induction of cancer by various physical and chemical carcinogens, including ionizing radiation. Such increased susceptibility will depend on several factors including the frequency of the susceptibility gene in the population and its penetrance, the strength of the predisposition, and the degree to which the cancer incidence in susceptible individuals may be increased by the carcinogen. It is now known that these cancer-predisposing genes may be responsible not only for rare familial cancer syndromes, but also for a proportion of the common cancers. Although the currently known disorders can account for only a small fraction of all cancers, they serve as models for genetic predisposition to carcinogen-induced cancer in the general population. In the present report, the author describes current knowledge of those specific disorders that are associated with an enhanced predisposition to radiation-induced cancer, and discusses how this knowledge may bear on the susceptibility to radiation-induced cancer in the general population and estimates of the risk of radiation exposure.

  16. pitting corrosion susceptibility pitting corrosion susceptibility of aisi ...

    African Journals Online (AJOL)

    eobe

    Abstract. The susceptibility of austenitic (AISI 301) stainless steel to pitting corrosion was evaluated in sodium chloride. (NaCl) solutions ... AISI 301 steel suffers from pitting corrosion in all the investigated solutions. AISI 301 steel suffers from ..... [1] Ijeomah, M.N.C. Elements of Corrosion and Protection. Theory, Auto Century ...

  17. Magnetic Susceptability Measurements in Superconductors

    Science.gov (United States)

    Kim, Jason; Mallory, Kendall; Seim, Ryan

    2000-04-01

    A new undergraduate research facility in magnetic susceptability measurements on superconductors is being developed at the University of Northern Colorado. Initial data measurements of the magnetic susceptability of various superconductors will be presented. These measurements were obtained with a liquid helium/nitrogen dewar that was reassembled for use in this project. The cryostat consists of two separate dewars, the first of which contains liquid nitrogen, the second, liquid helium. The liquid nitrogen dewar is used to keep the helium bath from evaporating off too quickly. Data on the evaporation rates of the two liquids will also be presented.

  18. Topological susceptibility from the overlap

    DEFF Research Database (Denmark)

    Del Debbio, Luigi; Pica, Claudio

    2003-01-01

    The chiral symmetry at finite lattice spacing of Ginsparg-Wilson fermionic actions constrains the renormalization of the lattice operators; in particular, the topological susceptibility does not require any renormalization, when using a fermionic estimator to define the topological charge. Theref...

  19. Contrasting effect of dark-chilling on chloroplast structure and arrangement of chlorophyll-protein complexes in pea and tomato: plants with a different susceptibility to non-freezing temperature.

    Science.gov (United States)

    Garstka, Maciej; Venema, Jan Henk; Rumak, Izabela; Gieczewska, Katarzyna; Rosiak, Malgorzata; Koziol-Lipinska, Joanna; Kierdaszuk, Borys; Vredenberg, Wim J; Mostowska, Agnieszka

    2007-10-01

    The effect of dark-chilling and subsequent photoactivation on chloroplast structure and arrangements of chlorophyll-protein complexes in thylakoid membranes was studied in chilling-tolerant (CT) pea and in chilling-sensitive (CS) tomato. Dark-chilling did not influence chlorophyll content and Chl a/b ratio in thylakoids of both species. A decline of Chl a fluorescence intensity and an increase of the ratio of fluorescence intensities of PSI and PSII at 120 K was observed after dark-chilling in thylakoids isolated from tomato, but not from pea leaves. Chilling of pea leaves induced an increase of the relative contribution of LHCII and PSII fluorescence. A substantial decrease of the LHCII/PSII fluorescence accompanied by an increase of that from LHCI/PSI was observed in thylakoids from chilled tomato leaves; both were attenuated by photoactivation. Chlorophyll fluorescence of bright grana discs in chloroplasts from dark-chilled leaves, detected by confocal laser scanning microscopy, was more condensed in pea but significantly dispersed in tomato, compared with control samples. The chloroplast images from transmission-electron microscopy revealed that dark-chilling induced an increase of the degree of grana stacking only in pea chloroplasts. Analyses of O-J-D-I-P fluorescence induction curves in leaves of CS tomato before and after recovery from chilling indicate changes in electron transport rates at acceptor- and donor side of PS II and an increase in antenna size. In CT pea leaves these effects were absent, except for a small but irreversible effect on PSII activity and antenna size. Thus, the differences in chloroplast structure between CS and CT plants, induced by dark-chilling are a consequence of different thylakoid supercomplexes rearrangements.

  20. Reducing Susceptibility to Courtesy Stigma.

    Science.gov (United States)

    Bachleda, Catherine L; El Menzhi, Leila

    2017-04-19

    In light of the chronic shortage of health professionals willing to care for HIV/AIDS patients, and rising epidemics in many Muslim countries, this qualitative study examined susceptibility and resistance to courtesy stigma as experienced by nurses, doctors, and social workers in Morocco. Forty-nine in-depth interviews provided rich insights into the process of courtesy stigma and how it is managed, within the context of interactions with Islam, interactions within the workplace (patients, other health professionals), and interactions outside the workplace (the general public, friends, and family). Theoretically, the findings extend understanding of courtesy stigma and the dirty work literature. The findings also offer practical suggestions for the development of culturally appropriate strategies to reduce susceptibility to courtesy stigmatization. This study represents the first to explore courtesy stigma as a process experienced by health professionals providing HIV/AIDS care in an Islamic country.

  1. Antimycotics susceptibility testing of dermatophytes

    Directory of Open Access Journals (Sweden)

    Arsić-Arsenijević Valentina

    2010-01-01

    Full Text Available Dermatophytes are moulds that produce infections of the skin, hair and nails of humans and animals. The most common forms among these infections are onychomycosis and tinea pedis affecting 20% of world population. These infections are usually chronic. The treatment of dermatophytoses tends to be prolonged partly because available treatments are not very effective. Antifungal drug consumption and public health expenditure are high worldwide, as well as in Serbia. For adequate therapy, it is necessary to prove infection by isolation of dermatophytes and to test the antifungal susceptibility of isolates. Susceptibility testing is important for the resistance monitoring, epidemiological research and to compare in vitro activities of new antifungal agents. The diffusion and dilution methods of susceptibility tests are used, and technical issues of importance for the proper performance and interpretation of test results are published in the document E.DEF 9.1 (EUCAST and M38-A2 (CLSI. The aim of our paper is to promptly inform the public about technical achievements in this area, as well as the new organization of laboratory for medical mycology in our country. The formation of laboratory networks coordinated by the National Reference Laboratory for the cause of mycosis need to enable interlaboratory studies and further standardization of methods for antifungal susceptibility testing of dermatophytes, reproducibility of tests and clinical correlation monitoring (MIK values and clinical outcome of dermatophytosis. The importance of the new organization is expected efficient improvement in the dermatophytosis therapy at home, better quality of patient's life and the reduction of the cost of treatment.

  2. Biochemical characters and antibiotic susceptibility of Staphylococcus aureus isolates

    OpenAIRE

    Subhankari Prasad Chakraborty; Santanu Kar Mahapatra; Somenath Roy

    2011-01-01

    Objective: To observe the biochemical characters and antibiotic susceptibility of isolated Staphylococcus aureus (S. auerus) strains against some conventional and traditional antibiotics. Methods: Thirty post operative pathogenic isolated S. aureus strains were used in this study. Bacterial culture was done in Mueller-Hinton broth at 37 °C. Characters of these strains were determined by traditional biochemical tests such as hydrolysis test of gelatin, urea, galactose, starch and protein, a...

  3. Antibiotic susceptibility of Atopobium vaginae

    Directory of Open Access Journals (Sweden)

    Verschraegen Gerda

    2006-03-01

    Full Text Available Abstract Background Previous studies have indicated that a recently described anaerobic bacterium, Atopobium vaginae is associated with bacterial vaginosis (BV. Thus far the four isolates of this fastidious micro-organism were found to be highly resistant to metronidazole and susceptible for clindamycin, two antibiotics preferred for the treatment of BV. Methods Nine strains of Atopobium vaginae, four strains of Gardnerella vaginalis, two strains of Lactobacillus iners and one strain each of Bifidobacterium breve, B. longum, L. crispatus, L. gasseri and L. jensenii were tested against 15 antimicrobial agents using the Etest. Results All nine strains of A. vaginae were highly resistant to nalidixic acid and colistin while being inhibited by low concentrations of clindamycin (range: G. vaginalis strains were also susceptible for clindamycin ( 256 μg/ml but susceptible to clindamycin (0.023 – 0.125 μg/ml. Conclusion Clindamycin has higher activity against G. vaginalis and A. vaginae than metronidazole, but not all A. vaginae isolates are metronidazole resistant, as seemed to be a straightforward conclusion from previous studies on a more limited number of strains.

  4. Renal proteome in mice with different susceptibilities to fluorosis.

    Directory of Open Access Journals (Sweden)

    Juliane Guimarães Carvalho

    Full Text Available A/J and 129P3/J mouse strains have different susceptibilities to dental fluorosis due to their genetic backgrounds. They also differ with respect to several features of fluoride (F metabolism and metabolic handling of water. This study was done to determine whether differences in F metabolism could be explained by diversities in the profile of protein expression in kidneys. Weanling, male A/J mice (susceptible to dental fluorosis, n = 18 and 129P3/J mice (resistant, n = 18 were housed in pairs and assigned to three groups given low-F food and drinking water containing 0, 10 or 50 ppm [F] for 7 weeks. Renal proteome profiles were examined using 2D-PAGE and LC-MS/MS. Quantitative intensity analysis detected between A/J and 129P3/J strains 122, 126 and 134 spots differentially expressed in the groups receiving 0, 10 and 50 ppmF, respectively. From these, 25, 30 and 32, respectively, were successfully identified. Most of the proteins were related to metabolic and cellular processes, followed by response to stimuli, development and regulation of cellular processes. In F-treated groups, PDZK-1, a protein involved in the regulation of renal tubular reabsorption capacity was down-modulated in the kidney of 129P3/J mice. A/J and 129P3/J mice exhibited 11 and 3 exclusive proteins, respectively, regardless of F exposure. In conclusion, proteomic analysis was able to identify proteins potentially involved in metabolic handling of F and water that are differentially expressed or even not expressed in the strains evaluated. This can contribute to understanding the molecular mechanisms underlying genetic susceptibility to dental fluorosis, by indicating key-proteins that should be better addressed in future studies.

  5. Renal Proteome in Mice with Different Susceptibilities to Fluorosis

    Science.gov (United States)

    Peres-Buzalaf, Camila; Salvato, Fernanda; Labate, Carlos Alberto; Everett, Eric T.; Whitford, Gary Milton; Buzalaf, Marília Afonso Rabelo

    2013-01-01

    A/J and 129P3/J mouse strains have different susceptibilities to dental fluorosis due to their genetic backgrounds. They also differ with respect to several features of fluoride (F) metabolism and metabolic handling of water. This study was done to determine whether differences in F metabolism could be explained by diversities in the profile of protein expression in kidneys. Weanling, male A/J mice (susceptible to dental fluorosis, n = 18) and 129P3/J mice (resistant, n = 18) were housed in pairs and assigned to three groups given low-F food and drinking water containing 0, 10 or 50 ppm [F] for 7 weeks. Renal proteome profiles were examined using 2D-PAGE and LC-MS/MS. Quantitative intensity analysis detected between A/J and 129P3/J strains 122, 126 and 134 spots differentially expressed in the groups receiving 0, 10 and 50 ppmF, respectively. From these, 25, 30 and 32, respectively, were successfully identified. Most of the proteins were related to metabolic and cellular processes, followed by response to stimuli, development and regulation of cellular processes. In F-treated groups, PDZK-1, a protein involved in the regulation of renal tubular reabsorption capacity was down-modulated in the kidney of 129P3/J mice. A/J and 129P3/J mice exhibited 11 and 3 exclusive proteins, respectively, regardless of F exposure. In conclusion, proteomic analysis was able to identify proteins potentially involved in metabolic handling of F and water that are differentially expressed or even not expressed in the strains evaluated. This can contribute to understanding the molecular mechanisms underlying genetic susceptibility to dental fluorosis, by indicating key-proteins that should be better addressed in future studies. PMID:23308176

  6. Measurements of temperature dependence of 'localized susceptibility'

    CERN Document Server

    Shiozawa, H; Ishii, H; Takayama, Y; Obu, K; Muro, T; Saitoh, Y; Matsuda, T D; Sugawara, H; Sato, H

    2003-01-01

    The magnetic susceptibility of some rare-earth compounds is estimated by measuring magnetic circular dichroism (MCD) of rare-earth 3d-4f absorption spectra. The temperature dependence of the magnetic susceptibility obtained by the MCD measurement is remarkably different from the bulk susceptibility in most samples, which is attributed to the strong site selectivity of the core MCD measurement.

  7. Dipolar response of hydrated proteins

    OpenAIRE

    Matyushov, Dmitry V.

    2011-01-01

    The paper presents an analytical theory and numerical simulations of the dipolar response of hydrated proteins. The effective dielectric constant of the solvated protein, representing the average dipole moment induced at the protein by a uniform external field, shows a remarkable variation among the proteins studied by numerical simulations. It changes from 0.5 for ubiquitin to 640 for cytochrome c. The former value implies a negative dipolar susceptibility of ubiquitin, that is a dia-electri...

  8. Monocot and dicot MLO powdery mildew susceptibility factors are functionally conserved in spite of the evolution of class-specific molecular features

    NARCIS (Netherlands)

    Appiano, M.; Catalano, D.; Santillan Martinez, M.I.; Lotti, C.; Zheng Zheng, Zheng; Visser, R.G.F.; Ricciardi, L.; Bai, Y.; Pavan, S.N.C.

    2015-01-01

    Background Specific members of the plant Mildew Locus O (MLO) protein family act as susceptibility factors towards powdery mildew (PM), a worldwide-spread fungal disease threatening many cultivated species. Previous studies indicated that monocot and dicot MLO susceptibility proteins are

  9. Biochemical characters and antibiotic susceptibility of Staphylococcus aureus isolates.

    Science.gov (United States)

    Chakraborty, Subhankari Prasad; Mahapatra, Santanu Kar; Roy, Somenath

    2011-06-01

    To observe the biochemical characters and antibiotic susceptibility of isolated Staphylococcus aureus (S. auerus) strains against some conventional and traditional antibiotics. Thirty post operative pathogenic isolated S. aureus strains were used in this study. Bacterial culture was done in Mueller-Hinton broth at 37 °C. Characters of these strains were determined by traditional biochemical tests such as hydrolysis test of gelatin, urea, galactose, starch and protein, and fermentation of lactose and sucrose. Antibiotic susceptibility were carried out by minimum inhibitory concentration test, minium bactericidal concentration test, disc agar diffusion test and brain heart infusion oxacillin screening agar. From this study, it was observed that 100% S. aureus isolates showed positive results in gelatin, urea and galactose hydrolysis test, 50% isolates were positive in starch hydrolysis test, 35% in protein hydrolysis test, 100% isolates in lactose fermenting test, but no isolate was positive in sucrose fermenting test. Antibiotic susceptibility testing suggested that 20% of isolates were resistant to kanamycin and 46.67% were resistant to oxacillin. These findings show that all these isolates have gelatin, urea, galactose hydrolysis and lactose fermenting activity. 20% of these isolates were resistant to kanamycin and 46.67% were resistant to oxacillin.

  10. Genetic susceptibility to environmental toxicants

    DEFF Research Database (Denmark)

    2001-01-01

    The toxicological challenges to the chemical industry have in recent years been greatly affected by the rapid innovation and development of analytical, molecular and genetic technologies. ECETOC recognises the importance of developing the technical and intellectual skill bases in academia...... and industrial based laboratories to meet the rapid development of the science base of toxicology. As the technology to determine genetic susceptibility develops, so scientist will be able to describe altered gene expression provoked by chemicals long before they are able to offer valid interpretations...... of their meaning. A potential for inadvertently raising concerns over the effect of chemicals in experimental animals or man, or even the intentional misrepresentation of results to suggest chemicals are “playing” with our genes is enormous. History has shown that some individuals and groups in society are willing...

  11. Genetic susceptibility, evolution and the kuru epidemic.

    Science.gov (United States)

    Mead, Simon; Whitfield, Jerome; Poulter, Mark; Shah, Paresh; Uphill, James; Beck, Jonathan; Campbell, Tracy; Al-Dujaily, Huda; Hummerich, Holger; Alpers, Michael P; Collinge, John

    2008-11-27

    The acquired prion disease kuru was restricted to the Fore and neighbouring linguistic groups of the Papua New Guinea highlands and largely affected children and adult women. Oral history documents the onset of the epidemic in the early twentieth century, followed by a peak in the mid-twentieth century and subsequently a well-documented decline in frequency. In the context of these strong associations (gender, region and time), we have considered the genetic factors associated with susceptibility and resistance to kuru. Heterozygosity at codon 129 of the human prion protein gene (PRNP) is known to confer relative resistance to both sporadic and acquired prion diseases. In kuru, heterozygosity is associated with older patients and longer incubation times. Elderly survivors of the kuru epidemic, who had multiple exposures at mortuary feasts, are predominantly PRNP codon 129 heterozygotes and this group show marked Hardy-Weinberg disequilibrium. The deviation from Hardy-Weinberg equilibrium is most marked in elderly women, but is also significant in a slightly younger cohort of men, consistent with their exposure to kuru as boys. Young Fore and the elderly from populations with no history of kuru show Hardy-Weinberg equilibrium. An increasing cline in 129V allele frequency centres on the kuru region, consistent with the effect of selection in elevating the frequency of resistant genotypes in the exposed population. The genetic data are thus strikingly correlated with exposure. Considering the strong coding sequence conservation of primate prion protein genes, the number of global coding polymorphisms in man is surprising. By intronic resequencing in a European population, we have shown that haplotype diversity at PRNP comprises two major and divergent clades associated with 129M and 129V. Kuru may have imposed the strongest episode of recent human balancing selection, which may not have been an isolated episode in human history.

  12. Phosphorylcholine impairs susceptibility to biofilm formation of hydrogel contact lenses.

    Science.gov (United States)

    Selan, Laura; Palma, Stefano; Scoarughi, Gian Luca; Papa, Rosanna; Veeh, Richard; Di Clemente, Daniele; Artini, Marco

    2009-01-01

    To compare silicone-hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), and phosphorylcholine-coated (PC-C) contact lenses in terms of their susceptibility to biofilm formation by Staphylococcus epidermidis and Pseudomonas aeruginosa. Laboratory investigation. Biofilm formation on colonized test lenses was evaluated with confocal microscopy and in vitro antibiotic susceptibility assays. The results of the latter assays were compared with those performed on planktonic cultures of the same organism. For both microorganisms, sessile colonies on silicone-hydrogel and pHEMA lenses displayed lower antibiotic susceptibility than their planktonic counterparts. In contrast, the susceptibility of cultures growing on PC-C lenses was comparable with that for planktonic cultures. In particular, minimum inhibitory concentration for Tazocin (piperacillin plus tazobactam; Wyeth Pharmaceuticals, Aprilia, Italy; S. epidermidis) and gentamicin (P. aeruginosa) was identical, either in the presence of PC-C support or in planktonic cultures (Tazocin, lenses (0.4 mug/ml) with respect to planktonic cultures (0.2 mug/ml). Confocal microscopy of lenses colonized for 24 hours with P. aeruginosa green fluorescent protein-expressing cells revealed a sessile colonization on silicone-hydrogel lens and a few isolated bacterial cells scattered widely over the surface of the PC-C lens. An increase in antibiotic susceptibility of bacterial cultures was associated with diminished bacterial adhesion. Our results indicate that PC-C lenses seem to be more resistant than silicone-hydrogel and pHEMA lenses to bacterial adhesion and colonization. This feature may facilitate their disinfection.

  13. Assessing transport susceptibility of rapeseed meal fractionation products

    Directory of Open Access Journals (Sweden)

    Milena Bojanowska

    2016-09-01

    Full Text Available Background: Having considered increasing production of liquid and solid biofuels from rapeseed and bearing in mind its stable and unquestionable position in  the food and animal feed industries, a rational approach towards technologically and logistically efficient utilization of by-products from rapeseed processing is required. The aim of the research presented in the article is to assess the transport susceptibility of rapeseed meal fractions, varying according to particle size and chemical composition. Methods: Resistance to changes stimulating self-heating has been assumed as the main criterion of transport susceptibility. The following diagnostic variables have been experimentally determined: total protein, crude fat and crude fiber content, porosity, and water activity in the fraction of examined meal. In order to organize a set of particles and to indicate their optimal applications according to criteria chosen with regard to both  utilization and transportation, two aggregate indicators have been calculated. Results: It has been proved that medium-sized particle fractions (0.075-0.4 mm exhibit the lowest transport susceptibility, whereas the those with the largest granulations (>3 mm -have the highest. One significant relationship is the decline of feeding value and concurrent increase in the transport susceptibility of meal fractions, which in practice means that those fractions least-favoured by the animal feed industry can be least cumbersome to transport. Conclusions: It has been suggested that there should be a division of rapeseed meal into two products with different applications and different transport susceptibility. The fractioning of meal can bring numerous, measurable benefits for the meal industry and logistics processes for solid biofuels, where storage and transport properties have considerable importance, alongside commodity price and transport costs.

  14. Accuracy of magnetic resonance based susceptibility measurements

    Science.gov (United States)

    Erdevig, Hannah E.; Russek, Stephen E.; Carnicka, Slavka; Stupic, Karl F.; Keenan, Kathryn E.

    2017-05-01

    Magnetic Resonance Imaging (MRI) is increasingly used to map the magnetic susceptibility of tissue to identify cerebral microbleeds associated with traumatic brain injury and pathological iron deposits associated with neurodegenerative diseases such as Parkinson's and Alzheimer's disease. Accurate measurements of susceptibility are important for determining oxygen and iron content in blood vessels and brain tissue for use in noninvasive clinical diagnosis and treatment assessments. Induced magnetic fields with amplitude on the order of 100 nT, can be detected using MRI phase images. The induced field distributions can then be inverted to obtain quantitative susceptibility maps. The focus of this research was to determine the accuracy of MRI-based susceptibility measurements using simple phantom geometries and to compare the susceptibility measurements with magnetometry measurements where SI-traceable standards are available. The susceptibilities of paramagnetic salt solutions in cylindrical containers were measured as a function of orientation relative to the static MRI field. The observed induced fields as a function of orientation of the cylinder were in good agreement with simple models. The MRI susceptibility measurements were compared with SQUID magnetometry using NIST-traceable standards. MRI can accurately measure relative magnetic susceptibilities while SQUID magnetometry measures absolute magnetic susceptibility. Given the accuracy of moment measurements of tissue mimicking samples, and the need to look at small differences in tissue properties, the use of existing NIST standard reference materials to calibrate MRI reference structures is problematic and better reference materials are required.

  15. Proteochemometric modeling of HIV protease susceptibility

    National Research Council Canada - National Science Library

    Lapins, Maris; Eklund, Martin; Spjuth, Ola; Prusis, Peteris; Wikberg, Jarl E S

    2008-01-01

    .... Therefore, we used proteochemometrics to model the susceptibility of HIV to protease inhibitors in current use, utilizing descriptions of the physico-chemical properties of mutated HIV proteases...

  16. Extended biofilm susceptibility assay for Staphylococcus aureus bovine mastitis isolates: evidence for association between genetic makeup and biofilm susceptibility.

    Science.gov (United States)

    Melchior, M B; van Osch, M H J; Lam, T J G M; Vernooij, J C M; Gaastra, W; Fink-Gremmels, J

    2011-12-01

    Staphylococcus aureus is one of the most prevalent causes of bovine mastitis. The antimicrobial treatment of this disease is currently based on antimicrobial susceptibility tests according to Clinical and Laboratory Standards Institute standards. However, various authors have shown a discrepancy between the results of this standard susceptibility test and the actual cure rate of the applied antimicrobial treatment. Increasing evidence suggests that in vivo biofilm formation by Staph. aureus, which is not assessed in the antimicrobial susceptibility tests, is associated with this problem, resulting in disappointing cure rates, especially for infections of longer duration. Previous data obtained with a limited number of strains showed that the extended biofilm antimicrobial susceptibility (EBS) assay reveals differences between strains, which cannot be derived from a standard susceptibility test or from a 24-h biofilm susceptibility test. The objective of this study was to test a collection of Staph. aureus bovine mastitis strains in the EBS assay and to model the effect of antimicrobial exposure, duration of antimicrobial exposure, and genotype profile of the strains on antimicrobial susceptibility. With the results from a previous study with the same collection of strains, the effect of genotype represented by accessory gene regulator gene (agr-type), the presence of insertional sequence 257 (IS257), intercellular adhesion (ica), and the β-lactamase (blaZ) gene were entered as explanatory factors in a logistic regression model. The agr locus of Staph. aureus controls the expression of most of the virulence factors, represses the transcription of several cell wall-associated proteins, and activates several exoproteins during the post-exponential phase. The IS257 gene has been related to biofilm formation in vitro and was found earlier in 50% of the agr-type 2 strains. The ica gene cluster encodes for the production of an extracellular polysaccharide adhesin, termed

  17. Analysis of VSV pseudotype virus infection mediated by rubella virus envelope proteins

    National Research Council Canada - National Science Library

    Masafumi Sakata; Hideki Tani; Masaki Anraku; Michiyo Kataoka; Noriyo Nagata; Fumio Seki; Maino Tahara; Noriyuki Otsuki; Kiyoko Okamoto; Makoto Takeda; Yoshio Mori

    2017-01-01

    .... To establish an infection the host cells must be susceptible and permissible. To assess the susceptibility of individual cell lines, we generated a pseudotype vesicular stomatitis virus bearing RV envelope proteins (VSV-RV/CE2E1...

  18. Assessment of PALB2 as a candidate melanoma susceptibility gene.

    Directory of Open Access Journals (Sweden)

    Lauren G Aoude

    Full Text Available Partner and localizer of BRCA2 (PALB2 interacts with BRCA2 to enable double strand break repair through homologous recombination. Similar to BRCA2, germline mutations in PALB2 have been shown to predispose to Fanconi anaemia as well as pancreatic and breast cancer. The PALB2/BRCA2 protein interaction, as well as the increased melanoma risk observed in families harbouring BRCA2 mutations, makes PALB2 a candidate for melanoma susceptibility. In order to assess PALB2 as a melanoma predisposition gene, we sequenced the entire protein-coding sequence of PALB2 in probands from 182 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, and BAP1. In addition, we interrogated whole-genome and exome data from another 19 kindreds with a strong family history of melanoma for deleterious mutations in PALB2. Here we report a rare known deleterious PALB2 mutation (rs118203998 causing a premature truncation of the protein (p.Y1183X in an individual who had developed four different cancer types, including melanoma. Three other family members affected with melanoma did not carry the variant. Overall our data do not support a case for PALB2 being associated with melanoma predisposition.

  19. Search for new breast cancer susceptibility genes

    NARCIS (Netherlands)

    Oldenburg, Rogier Abel

    2008-01-01

    This thesis describes the search for new high-risk breast cancer susceptibility genes by linkage analysis. To date 20-25% of familial breast cancer is explained by mutations in the high-risk BRCA1 and BRCA2 breast cancer susceptibility genes. For the remaining families the genetic etiology is

  20. Mapping markers linked to porcine salmonellosis susceptibility

    NARCIS (Netherlands)

    Galina-Pantoja, L.; Siggens, K.; Schriek, van M.G.M.; Heuven, H.C.M.

    2009-01-01

    The goal of this study was to identify pig chromosomal regions associated with susceptibility to salmonellosis. Genomic DNA from pig reference populations with differences in susceptibility to Salmonella enterica serovar Choleraesuis as quantified by spleen and liver bacterial colonization at day 7

  1. Crystal morphology change by magnetic susceptibility force

    OpenAIRE

    Katsuki, Aiko; Aibara, Shigeo; Tanimoto, Yoshifumi

    2006-01-01

    We found a change in morphology when lysozyme crystals were grown in a magnetic field. The phenomenon was caused by the magnetic force derived from the magnetic susceptibility gradient. We propose that this force should be called the “magnetic susceptibility force".

  2. Genetic susceptibility to pancreatic cancer.

    Science.gov (United States)

    Klein, Alison P

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited genetic factors also play an important role, with approximately 5-10% of pancreatic cancer patients reporting family history of pancreatic cancer. While the genetic basis for the majority of the familial clustering of pancreatic cancer remains unclear, several important pancreatic cancer genes have been identified. These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus. Recent advances in genotyping and genetic sequencing have accelerated the rate at which novel pancreatic cancer susceptibility genes have been identified with several genes identified within the past few years. This review addresses our current understanding of the familial aggregation of pancreatic cancer, established pancreatic cancer susceptablity genes and how this knowledge informs risk assessment and screening for high-risk families. Copyright © 2011 Wiley Periodicals, Inc.

  3. Genetic Susceptibility to Pancreatic Cancer

    Science.gov (United States)

    Klein, Alison P.

    2013-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited genetic factors also play an important role, with approximately 5–10% of pancreatic cancer patients reporting family history of pancreatic cancer. While the genetic basis for the majority of the familial clustering of pancreatic cancer remains unclear, several important pancreatic cancer genes have been identified. These consist of high penetrance genes including BRCA2 or PALB2, to more common genetic variation associated with a modest increase risk of pancreatic cancer such as genetic variation at the ABO blood group locus. Recent advances in genotyping and genetic sequencing have accelerated the rate at which novel pancreatic cancer susceptibility genes have been identified with several genes identified within the past few years. This review addresses our current understanding of the familial aggregation of pancreatic cancer, established pancreatic cancer susceptablity genes and how this knowledge informs risk assessment and screening for high-risk families. PMID:22162228

  4. Predictive tools for stabilization of therapeutic proteins

    National Research Council Canada - National Science Library

    Voynov, Vladimir; Chennamsetty, Naresh; Kayser, Veysel; Helk, Bernhard; Trout, Bernhardt L

    2009-01-01

    Monoclonal antibodies represent the fastest growing class of pharmaceuticals.  A major problem, however, is that the proteins are susceptible to aggregation at the high concentration commonly used during manufacturing and storage...

  5. The Li-Fraumeni syndrome: an inherited susceptibility to cancer.

    Science.gov (United States)

    Evans, S C; Lozano, G

    1997-09-01

    The Li-Fraumeni syndrome is a rare autosomal-dominant disease whose hallmark is a predisposition to a wide range of cancers among members of a family. Many of these families have a germline mutation within the tumor suppressor gene TP53, which encodes the p53 protein. The inheritance of a mutant TP53 allele results in a 25-fold increase in the chance of developing cancer by 50 years of age, compared with the general population. TP53 mutations are also very common in the development of somatic tumors. This article reviews the biological and biochemical role of p53 in the susceptibility to cancer in Li-Fraumeni syndrome.

  6. Fidelity susceptibility in the quantum Rabi model

    Science.gov (United States)

    Wei, Bo-Bo; Lv, Xiao-Chen

    2018-01-01

    Quantum criticality usually occurs in many-body systems. Recently it was shown that the quantum Rabi model, which describes a two-level atom coupled to a single model cavity field, presents quantum phase transitions from a normal phase to a superradiate phase when the ratio between the frequency of the two-level atom and the frequency of the cavity field extends to infinity. In this work, we study quantum phase transitions in the quantum Rabi model from the fidelity susceptibility perspective. We found that the fidelity susceptibility and the generalized adiabatic susceptibility present universal finite-size scaling behaviors near the quantum critical point of the Rabi model if the ratio between frequency of the two-level atom and frequency of the cavity field is finite. From the finite-size scaling analysis of the fidelity susceptibility, we found that the adiabatic dimension of the fidelity susceptibility and the generalized adiabatic susceptibility of fourth order in the Rabi model are 4 /3 and 2, respectively. Meanwhile, the correlation length critical exponent and the dynamical critical exponent in the quantum critical point of the Rabi model are found to be 3 /2 and 1 /3 , respectively. Since the fidelity susceptibility and the generalized adiabatic susceptibility are the moments of the quantum noise spectrum which are directly measurable by experiments in linear response regime, the scaling behavior of the fidelity susceptibility in the Rabi model could be tested experimentally. The simple structure of the quantum Rabi model paves the way for experimentally observing the universal scaling behavior of the fidelity susceptibility at a quantum phase transition.

  7. Host glycosaminoglycan confers susceptibility to bacterial infection in Drosophila melanogaster.

    Science.gov (United States)

    Baron, Miriam J; Wong, Sandra L; Nybakken, Kent; Carey, Vincent J; Madoff, Lawrence C

    2009-02-01

    Many pathogens engage host cell surface glycosaminoglycans, but redundancy in pathogen adhesins and host glycosaminoglycan-anchoring proteins (heparan sulfate proteoglycans) has limited the understanding of the importance of glycosaminoglycan binding during infection. The alpha C protein of group B streptococcus, a virulence determinant for this neonatal human pathogen, binds to host glycosaminoglycan and mediates the entry of bacteria into human cells. We studied alpha C protein-glycosaminoglycan binding in Drosophila melanogaster, whose glycosaminoglycan repertoire resembles that of humans but whose genome includes only three characterized membrane heparan sulfate proteoglycan genes. The knockdown of glycosaminoglycan polymerases or of heparan sulfate proteoglycans reduced the cellular binding of alpha C protein. The interruption of alpha C protein-glycosaminoglycan binding was associated with longer host survival and a lower bacterial burden. These data indicate that the glycosaminoglycan-alpha C protein interaction involves multiple heparan sulfate proteoglycans and impairs bacterial killing. Host glycosaminoglycans, anchored by multiple proteoglycans, thereby determine susceptibility to infection. Because there is homology between Drosophila and human glycosaminoglycan/proteoglycan structures and many pathogens express glycosaminoglycan-binding structures, our data suggest that interfering with glycosaminoglycan binding may protect against infections in humans.

  8. Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures.

    Science.gov (United States)

    Dai, Yun-Jian; Xu, Zheng-Hao; Feng, Bo; Xu, Ceng-Lin; Zhao, Hua-Wei; Wu, Deng-Chang; Hu, Wei-Wei; Chen, Zhong

    2014-12-01

    Gender differences are involved in many neurological disorders including epilepsy. However, little is known about the effect of gender difference on the risk of epilepsy in adults with a specific early pathological state such as complex febrile seizures (FSs) in infancy. Here we used a well-established complex FS model in rats and showed that: (1) the susceptibility to seizures induced by hyperthermia, pentylenetetrazol (PTZ), and maximal electroshock (MES) was similar in male and female rat pups, while males were more susceptible to PTZ- and MES-induced seizures than age-matched females in normal adult rats; (2) adult rats with complex FSs in infancy acquired higher seizure susceptibility than normal rats; importantly, female FS rats were more susceptible to PTZ and MES than male FS rats; and (3) the protein expression of interleukin-1β, an inflammatory factor associated with seizure susceptibility, was higher in adult FS females than in males, which may reflect a gender-difference phenomenon of seizure susceptibility. Our results provide direct evidence that the acquired seizure susceptibility after complex FSs is gender-dependent.

  9. Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections.

    Directory of Open Access Journals (Sweden)

    Ettie M Lipner

    Full Text Available Tuberculosis and nontuberculous mycobacterial infections constitute a high burden of pulmonary disease in humans, resulting in over 1.5 million deaths per year. Building on the premise that genetic factors influence the instance, progression, and defense of infectious disease, we undertook a systems biology approach to investigate relationships among genetic factors that may play a role in increased susceptibility or control of mycobacterial infections. We combined literature and database mining with network analysis and pathway enrichment analysis to examine genes, pathways, and networks, involved in the human response to Mycobacterium tuberculosis and nontuberculous mycobacterial infections. This approach allowed us to examine functional relationships among reported genes, and to identify novel genes and enriched pathways that may play a role in mycobacterial susceptibility or control. Our findings suggest that the primary pathways and genes influencing mycobacterial infection control involve an interplay between innate and adaptive immune proteins and pathways. Signaling pathways involved in autoimmune disease were significantly enriched as revealed in our networks. Mycobacterial disease susceptibility networks were also examined within the context of gene-chemical relationships, in order to identify putative drugs and nutrients with potential beneficial immunomodulatory or anti-mycobacterial effects.

  10. Regulation of the tonsil cytokine milieu favors HIV susceptibility.

    Science.gov (United States)

    Moutsopoulos, Niki M; Vázquez, Nancy; Greenwell-Wild, Teresa; Ecevit, Ismail; Horn, Judith; Orenstein, Jan; Wahl, Sharon M

    2006-11-01

    Mucosal associated lymphoid tissues are major targets of HIV during early infection and disease progression but can also provide a viral safe haven during highly active antiretroviral therapy. Among these tissues, the tonsils remain enigmatic regarding their status as primary and/or secondary sites of retroviral infection. To dissect the mechanisms underlying susceptibility to HIV in this compartment, isolated tonsil cells were studied for phenotypic and functional characteristics, which may account for their permissiveness to infection. For this, tonsil cells and PBMC were infected in parallel with HIV, and viral replication was monitored by p24 ELISA. Our results demonstrate that unstimulated tonsil cells were more readily infected than PBMC with HIV. Phenotypic characterization of the tonsil cells revealed heterogeneous lymphoid populations but with increased expression of early activation markers and the viral co-receptor CXCR4, relative to PBMC, all of which may contribute to viral susceptibility. Furthermore, the cytokine microenvironment appeared to be key in facilitating HIV infection and tonsil-secreted products enhanced HIV infection in PBMC. Of the cytokines detected in the tonsil supernatants, TH2 cytokines, particularly IL-4, promoted HIV infection and replication. Interestingly, this TH2 profile appeared to dominate, even in the presence of the TH1 cytokine IFNgamma and the anti-viral factor IFNalpha, likely due to the enhanced expression of suppressor of cytokine signaling (SOCS) proteins, which may disengage IFN signaling. These and other local environmental factors may render tonsil cells increasingly susceptible to HIV infection.

  11. NRAMP1 and VDR Gene Polymorphisms in Susceptibility to Tuberculosis in Venezuelan Population

    Science.gov (United States)

    Fernández-Mestre, Mercedes; Villasmil, Ángel; Takiff, Howard; Fuentes Alcalá, Zhenia

    2015-01-01

    Natural resistance-associated macrophage protein (Nramp1) and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis, and associations between susceptibility to tuberculosis and polymorphisms in the genes NRAMP and VDR have been sought in geographically diverse populations. We investigated associations of NRAMP1 and VDR gene polymorphisms with susceptibility to TB in the Venezuelan population. The results suggest the absence of any association between VDR variants FokI, ApaI, and TaqI and susceptibility to tuberculosis. In contrast, the NRAMP1 3′UTR variants were associated with susceptibility to M. tuberculosis infection, as seen in the comparisons between TST+ and TST− controls, and also with progression to TB disease, as shown in the comparisons between TB patients and TST+ controls. This study confirms the previously described association of the NRAMP1 3′UTR polymorphism with M. tuberculosis infection and disease progression. PMID:26578819

  12. Anisotropy of the magnetic susceptibility of gallium

    Science.gov (United States)

    Pankey, T.

    1960-01-01

    The bulk magnetic susceptibilities of single gallium crystals and polycrystalline gallium spheres were measured at 25??C. The following anisotropic diamagnetic susceptibilities were found: a axis (-0.119??0. 001)??10-6 emu/g, b axis (-0.416??0.002)??10 -6 emu/g, and c axis (-0.229??0.001) emu/g. The susceptibility of the polycrystalline spheres, assumed to be the average value for the bulk susceptibility of gallium, was (-0.257??0.003)??10-6 emu/g at 25??C, and (-0.299??0.003)??10-6 emu/g at -196??C. The susceptibility of liquid gallium was (0.0031??0.001) ??10-6 emu/g at 30??C and 100??C. Rotational diagrams of the susceptibilities in the three orthogonal planes of the unit cell were not sinusoidal. The anisotropy in the single crystals was presumably caused by the partial overlap of Brillouin zone boundaries by the Fermi-energy surface. The large change in susceptibility associated with the change in state was attributed to the absence of effective mass influence in the liquid state. ?? 1960 The American Institute of Physics.

  13. Genetic susceptibility for Alzheimer disease neuritic plaque pathology.

    Science.gov (United States)

    Shulman, Joshua M; Chen, Kewei; Keenan, Brendan T; Chibnik, Lori B; Fleisher, Adam; Thiyyagura, Pradeep; Roontiva, Auttawut; McCabe, Cristin; Patsopoulos, Nikolaos A; Corneveaux, Jason J; Yu, Lei; Huentelman, Matthew J; Evans, Denis A; Schneider, Julie A; Reiman, Eric M; De Jager, Philip L; Bennett, David A

    2013-09-01

    While numerous genetic susceptibility loci have been identified for clinical Alzheimer disease (AD), it is important to establish whether these variants are risk factors for the underlying disease pathology, including neuritic plaques. To investigate whether AD susceptibility loci from genome-wide association studies affect neuritic plaque pathology and to additionally identify novel risk loci for this trait. Candidate analysis of single-nucleotide polymorphisms and genome-wide association study in a joint clinicopathologic cohort, including 725 deceased subjects from the Religious Orders Study and the Rush Memory and Aging Project (2 prospective, community-based studies), followed by targeted validation in an independent neuroimaging cohort, including 114 subjects from multiple clinical and research centers. A quantitative measure of neuritic plaque pathologic burden, based on assessments of silver-stained tissue averaged from multiple brain regions. Validation based on β-amyloid load by immunocytochemistry, and replication with fibrillar β-amyloid positron emission tomographic imaging with Pittsburgh Compound B or florbetapir. Besides the previously reported APOE and CR1 loci, we found that the ABCA7 (rs3764650; P = .02) and CD2AP (rs9349407; P = .03) AD susceptibility loci are associated with neuritic plaque burden. In addition, among the top results of our genome-wide association study, we discovered a novel variant near the amyloid precursor protein gene (APP, rs2829887) that is associated with neuritic plaques (P = 3.3 × 10-6). This polymorphism was associated with postmortem β-amyloid load as well as fibrillar β-amyloid in 2 independent cohorts of adults with normal cognition. These findings enhance understanding of AD risk factors by relating validated susceptibility alleles to increased neuritic plaque pathology and implicate common genetic variation at the APP locus in the earliest, presymptomatic stages of AD.

  14. Absolute method of measuring magnetic susceptibility

    Science.gov (United States)

    Thorpe, A.; Senftle, F.E.

    1959-01-01

    An absolute method of standardization and measurement of the magnetic susceptibility of small samples is presented which can be applied to most techniques based on the Faraday method. The fact that the susceptibility is a function of the area under the curve of sample displacement versus distance of the magnet from the sample, offers a simple method of measuring the susceptibility without recourse to a standard sample. Typical results on a few substances are compared with reported values, and an error of less than 2% can be achieved. ?? 1959 The American Institute of Physics.

  15. Prevalence and antimicrobial susceptibility of Extended Spectrum ...

    African Journals Online (AJOL)

    Lactamase (ESBL) producing gram-negative uropathogens in Sokoto, Nigeria. ... Antimicrobial susceptibility testing was determined using the modified Kirby Bauer method. Confirmation of ESBL phenotype was performed by Double-Disc Synergy Test ...

  16. antimicrobial susceptibility pattern of extended spectrum

    African Journals Online (AJOL)

    JAMILU

    ABSTRACT. The emergence of resistant strains of urogenital extended spectrum beta-lactamase producing ... antimicrobial susceptibility test using CLSI recommended, WHO modified Kirby Bauer disc diffusion method. ... Keywords: Extended Spectrum Beta-lactamases, Prevalence, Gram-negative urogenital isolates,.

  17. antimicrobial susceptibility patterns of salmonella species in ...

    African Journals Online (AJOL)

    user

    Empirical treatment for enteric fevers should, therefore, be discouraged while quinolones, cefepime, carbapenem, azithromycin and third generation cephalosporins be given preference. KEY WORDS: Susceptibility, Antimicrobial, Salmonella species, Enteric fever. INTRODUCTION. In the 21st century, enteric fever in the.

  18. Human genetic susceptibility to Candida infections

    NARCIS (Netherlands)

    Plantinga, T.S.; Johnson, M.D.; Scott, W.K.; Joosten, L.A.B.; Meer, J.W. van der; Perfect, J.R.; Kullberg, B.J.; Netea, M.G.

    2012-01-01

    Infections with Candida spp. have different manifestations in humans, ranging from mucosal to bloodstream and deep-seated disseminated infections. Immunocompromised patients have increased susceptibility to these types of infections, due to reduced capacity to elicit effective innate or adaptive

  19. Real-Time Optical Antimicrobial Susceptibility Testing

    DEFF Research Database (Denmark)

    Fredborg, Marlene; Andersen, Klaus R; Jørgensen, Erik

    2013-01-01

    Rapid antibiotic susceptibility testing is in highly demand in health-care fields as antimicrobial resistant bacterial strains emerge and spread. Here we describe an optical screening system (oCelloScope), which based on time-lapse imaging of 96 bacteria-antibiotic combinations at a time, introdu......Rapid antibiotic susceptibility testing is in highly demand in health-care fields as antimicrobial resistant bacterial strains emerge and spread. Here we describe an optical screening system (oCelloScope), which based on time-lapse imaging of 96 bacteria-antibiotic combinations at a time......, introduces real-time detection of bacterial growth and antimicrobial susceptibility, with imaging material to support the automatically generated graphs. Automated antibiotic susceptibility tests of a monoculture showed statistically significant antibiotic effect within 6 minutes and within 30 minutes...

  20. Towards consumer-friendly cisgenic strawberries which are less susceptible to Botrytis cinerea

    NARCIS (Netherlands)

    Schaart, J.G.

    2004-01-01

    This thesis describes the development of genetically modified (GM) strawberries which are less susceptible to fruit rot caused by the fungus Botrytis cinerea. To achieve Botrytis resistance, a polygalacuronase inhibiting protein (PGIP) gene has been isolation from strawberry and was characterised.

  1. Landslide susceptibility map: from research to application

    Science.gov (United States)

    Fiorucci, Federica; Reichenbach, Paola; Ardizzone, Francesca; Rossi, Mauro; Felicioni, Giulia; Antonini, Guendalina

    2014-05-01

    Susceptibility map is an important and essential tool in environmental planning, to evaluate landslide hazard and risk and for a correct and responsible management of the territory. Landslide susceptibility is the likelihood of a landslide occurring in an area on the basis of local terrain conditions. Can be expressed as the probability that any given region will be affected by landslides, i.e. an estimate of "where" landslides are likely to occur. In this work we present two examples of landslide susceptibility map prepared for the Umbria Region and for the Perugia Municipality. These two maps were realized following official request from the Regional and Municipal government to the Research Institute for the Hydrogeological Protection (CNR-IRPI). The susceptibility map prepared for the Umbria Region represents the development of previous agreements focused to prepare: i) a landslide inventory map that was included in the Urban Territorial Planning (PUT) and ii) a series of maps for the Regional Plan for Multi-risk Prevention. The activities carried out for the Umbria Region were focused to define and apply methods and techniques for landslide susceptibility zonation. Susceptibility maps were prepared exploiting a multivariate statistical model (linear discriminant analysis) for the five Civil Protection Alert Zones defined in the regional territory. The five resulting maps were tested and validated using the spatial distribution of recent landslide events that occurred in the region. The susceptibility map for the Perugia Municipality was prepared to be integrated as one of the cartographic product in the Municipal development plan (PRG - Piano Regolatore Generale) as required by the existing legislation. At strategic level, one of the main objectives of the PRG, is to establish a framework of knowledge and legal aspects for the management of geo-hydrological risk. At national level most of the susceptibility maps prepared for the PRG, were and still are obtained

  2. Porcine prion protein amyloid

    OpenAIRE

    Hammarstr?m, Per; Nystr?m, Sofie

    2015-01-01

    ABSTRACT Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat...

  3. PIRIN2 stabilizes cysteine protease XCP2 and increases susceptibility to the vascular pathogen Ralstonia solanacearum in Arabidopsis

    NARCIS (Netherlands)

    Zhang, B.; Tremousaygue, D.; Denancé, N.; Esse, van H.P.; Hörger, A.C.; Dabos, P.; Goffner, D.; Thomma, B.P.H.J.; Hoorn, van der R.A.L.; Tuominen, H.

    2014-01-01

    PIRIN (PRN) is a member of the functionally diverse cupin protein superfamily. There are four members of the Arabidopsis thaliana PRN family, but the roles of these proteins are largely unknown. Here we describe a function of the Arabidopsis PIRIN2 (PRN2) that is related to susceptibility to the

  4. Characterization of Renibacterium salmoninarum with reduced susceptibility to macrolide antibiotics by a standardized antibiotic susceptibility test.

    Science.gov (United States)

    Rhodes, Linda D; Nguyen, Oanh T; Deinhard, Rebecca K; White, Teresa M; Harrell, Lee W; Roberts, Marilyn C

    2008-08-07

    Three cohorts of juvenile and subadult Chinook salmon Oncorhynchus tshawytscha received multiple treatments with macrolide antibiotics for bacterial kidney disease (BKD) during rearing in a captive broodstock program. A total of 77 mortalities among the cohorts were screened for Renibacterium salmoninarum, the etiologic agent of BKD, by agar culture from kidney, and isolates from 7 fish were suitable for growth testing in the presence of macrolide antibiotics. The minimum inhibitory concentration (MIC) of erythromycin and azithromycin was determined by a modification of the standardized broth assay using defined medium. The American Type Culture Collection (ATCC) type strain 33209 exhibited a MIC of 0.008 microg m(-1) to either erythromycin or azithromycin. Isolates from 3 fish displayed MICs identical to the MICs for the ATCC type strain 33209. In contrast, isolates from 4 fish exhibited higher MICs, ranging between 0.125 and 0.250 microg ml(-1) for erythromycin and between 0.016 and 0.031 microg ml(-1) for azithromycin. Sequence analysis of the mutational hotspots for macrolide resistance in the 23S rDNA gene and the open reading frames of ribosomal proteins L4 and L22 found identical sequences among all isolates, indicating that the phenotype was not due to mutations associated with the drug-binding site of 23S rRNA. These results are the first report of R. salmoninarum with reduced susceptibility to macrolide antibiotics isolated from fish receiving multiple antibiotic treatments.

  5. Diagnostic Value of Direct Antibiotic Susceptibility Test for Faster BacterialSusceptibility Reporting in Bacteremia

    OpenAIRE

    Rebriarina Hapsari; Vincentia Rizke Ciptaningtyas; Masfiyah Masfiyah

    2012-01-01

    Background: Rapid and accurate information on susceptibility of bacteria causing bacteraemia is very helpful in sepsis management. Blood culture is the gold standard for bacteraemia diagnosis. Standard antibiotic susceptibility testing needs at least three days for completion while direct method can give the result a day earlier. The aim of this study was to investigate the diagnostic value of direct antibiotic susceptibility testing in blood culture. Methods: Bloods from positive BACTEC b...

  6. Murine glomerular transcriptome links endothelial cell-specific molecule-1 deficiency with susceptibility to diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Xiaoyi Zheng

    Full Text Available Diabetic nephropathy (DN is the leading cause of kidney disease; however, there are no early biomarkers and no cure. Thus, there is a large unmet need to predict which individuals will develop nephropathy and to understand the molecular mechanisms that govern this susceptibility. We compared the glomerular transcriptome from mice with distinct susceptibilities to DN at four weeks after induction of diabetes, but before histologic injury, and identified differential regulation of genes that modulate inflammation. From these genes, we identified endothelial cell specific molecule-1 (Esm-1, as a glomerular-enriched determinant of resistance to DN. Glomerular Esm-1 mRNA and protein were lower in DN-susceptible, DBA/2, compared to DN-resistant, C57BL/6, mice. We demonstrated higher Esm-1 secretion from primary glomerular cultures of diabetic mice, and high glucose was sufficient to increase Esm-1 mRNA and protein secretion in both strains of mice. However, induction was significantly attenuated in DN-susceptible mice. Urine Esm-1 was also significantly higher only in DN-resistant mice. Moreover, using intravital microscopy and a biomimetic microfluidic assay, we showed that Esm-1 inhibited rolling and transmigration in a dose-dependent manner. For the first time we have uncovered glomerular-derived Esm-1 as a potential non-invasive biomarker of DN. Esm-1 inversely correlates with disease susceptibility and inhibits leukocyte infiltration, a critical factor in protecting the kidney from DN.

  7. Global association between thermophilicity and vancomycin susceptibility in bacteria

    Directory of Open Access Journals (Sweden)

    Chayan eRoy

    2016-03-01

    Full Text Available Exploration of the aquatic microbiota of several circum-neutral (6.0-8.5 pH mid-temperature (55-85 OC springs revealed rich diversities of phylogenetic relatives of mesophilic bacteria, which surpassed the diversity of the truly-thermophilic taxa. To gain insight into the potentially-thermophilic adaptations of the phylogenetic relatives of Gram-negative mesophilic bacteria detected in culture-independent investigations we attempted pure-culture isolation by supplementing the enrichment media with 50 µg ml-1 vancomycin. Surprisingly, this Gram-positive-specific antibiotic eliminated the entire culturable-diversity of chemoorganotrophic and sulfur-chemolithotrophic bacteria present in the tested hot water inocula. Moreover, it also killed all the Gram-negative hot-spring isolates that were obtained in vancomycin-free media. Concurrent literature search for the description of Gram-negative thermophilic bacteria revealed that at least 16 of them were reportedly vancomycin-susceptible. While these data suggested that vancomycin-susceptibility could be a global trait of thermophilic bacteria (irrespective of their taxonomy, biogeography and Gram-character, MALDI Mass Spectroscopy of the peptidoglycans of a few Gram-negative thermophilic bacteria revealed that tandem alanines were present in the fourth and fifth positions of their muropeptide precursors (MPPs. Subsequent phylogenetic analyses revealed a close affinity between the D-alanine-D-alanine ligases (Ddl of taxonomically-diverse Gram-negative thermophiles and the thermostable Ddl protein of Thermotoga maritima, which is well-known for its high specificity for alanine over other amino acids. The Ddl tree further illustrated a divergence between the homologs of Gram-negative thermophiles and mesophiles, which broadly coincided with vancomycin-susceptibility and vancomycin-resistance respectively. It was thus hypothesized that thermophilic Ddls have been evolutionarily selected to favor a D

  8. Protein Foods

    Science.gov (United States)

    ... Text Size: A A A Listen En Español Protein Foods Foods high in protein such as fish, ... for the vegetarian proteins, whether they have carbohydrate. Protein Choices Plant-Based Proteins Plant-based protein foods ...

  9. HIV-1 subtype influences susceptibility and response to monotherapy with the protease inhibitor lopinavir/ritonavir.

    Science.gov (United States)

    Sutherland, K A; Ghosn, J; Gregson, J; Mbisa, J L; Chaix, M L; Cohen Codar, I; Delfraissy, J F; Delaugerre, C; Gupta, R K

    2015-01-01

    PI susceptibility results from a complex interplay between protease and Gag proteins, with Gag showing wide variation across HIV-1 subtypes. We explored the impact of pre-treatment susceptibility on the outcome of lopinavir/ritonavir monotherapy. Treatment-naive individuals who experienced lopinavir/ritonavir monotherapy failure from the MONARK study were matched (by subtype, viral load and baseline CD4 count) with those who achieved virological response ('successes'). Successes were defined by viral load protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with susceptibility expressed as fold change (FC) relative to a subtype B reference strain. Baseline lopinavir susceptibility was lower in viral failures compared with viral successes, but the differences were not statistically significant (median lopinavir susceptibility: 4.4 versus 8.5, respectively, P = 0.17). Among CRF02_AG/G patients, there was a significant difference in lopinavir susceptibility between the two groups (7.1 versus 10.4, P = 0.047), while in subtype B the difference was not significant (2.7 versus 3.4, P = 0.13). Subtype CRF02_AG/G viruses had a median lopinavir FC of 8.7 compared with 3.1 for subtype B (P = 0.001). We report an association between reduced PI susceptibility (using full-length Gag-protease sequences) at baseline and subsequent virological failure on lopinavir/ritonavir monotherapy in antiretroviral-naive patients harbouring subtype CRF02_AG/G viruses. We speculate that this may be important in the context of suboptimal adherence in determining viral failure. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  10. Adolescent neurobiological susceptibility to social context

    Directory of Open Access Journals (Sweden)

    Roberta A. Schriber

    2016-06-01

    Full Text Available Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment encountered (e.g., high vs. low parental warmth. Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. Ultimately, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes.

  11. Adolescent Neurobiological Susceptibility to Social Context

    Science.gov (United States)

    Schriber, Roberta A.; Guyer, Amanda E.

    2016-01-01

    Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment they encounter (e.g., high vs. low parental warmth). Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped in part by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. As such, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes. PMID:26773514

  12. Transthyretin knockout mice display decreased susceptibility to AMPA-induced neurodegeneration

    DEFF Research Database (Denmark)

    Nunes, Ana Filipa; Montero, Maria; Franquinho, Filipa

    2009-01-01

    Transthyretin (TTR) has been regarded as a neuroprotective protein given that TTR knockout (KO) mice display increased susceptibility for amyloid beta deposition and memory deficits during aging. In parallel, TTR KO mice have increased levels of neuropeptide Y (NPY), which promotes neuroprotection...... and neuroproliferation. In this work, we aimed at evaluating TTR neuroprotective effect against an excitotoxic insult that is known to be prevented by NPY action. We show that despite a putative neuroprotective role of TTR, hippocampal slice cultures from TTR KO mice display a decreased susceptibility to AMPA...

  13. Differential GR Expression and Translocation in the Hippocampus Mediates Susceptibility vs. Resilience to Chronic Social Defeat Stress

    Directory of Open Access Journals (Sweden)

    Qiu-Qin Han

    2017-05-01

    Full Text Available While social stress exposure is a common risk factor for affective disorders, most individuals exposed to it can maintain normal physical and psychological functioning. However, factors that determine susceptibility vs. resilience to social stress remain unclear. Here, the resident-intruder model of social defeat was used as a social stressor in male C57BL/6J mice to investigate the difference between susceptibility and resilience. As depression is often characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA axis, we conducted the present study to further investigate the individual differences in the HPA axis response and glucocorticoid receptor (GR protein expression and translocation between susceptible mice and resilient mice. We found that hypercortisolemia, induced by social defeat stress occurred in susceptible mice, but not in resilient mice. Moreover, susceptible mice exhibited significantly less GR protein expression and nuclear translocation in the hippocampus than resilient mice. Treatment with escitalopram could decrease the serum corticosterone (CORT, increase GR protein expression as well as nuclear translocation in the hippocampus and ultimately reverse social withdrawal behaviors in susceptible mice. These results indicate that the up-regulation of GR and the enhancement of GR nuclear translocation in the hippocampus play an important role in resilience to chronic social defeat stress.

  14. Susceptible-infected-susceptible epidemics on the complete graph and the star graph : Exact analysis

    NARCIS (Netherlands)

    Cator, E.A.; Van Mieghem, P.

    2013-01-01

    Since mean-field approximations for susceptible-infected-susceptible (SIS) epidemics do not always predict the correct scaling of the epidemic threshold of the SIS metastable regime, we propose two novel approaches: (a) an ?-SIS generalized model and (b) a modified SIS model that prevents the

  15. Nutritional influences on cognitive function: mechanisms of susceptibility.

    Science.gov (United States)

    Leigh Gibson, E; Green, Michael W

    2002-06-01

    The impact of nutritional variation, within populations not overtly malnourished, on cognitive function and arousal is considered. The emphasis is on susceptibility to acute effects of meals and glucose loads, and chronic effects of dieting, on mental performance, and effects of cholesterol and vitamin levels on cognitive impairment. New developments in understanding dietary influences on neurohormonal systems, and their implications for cognition and affect, allow reinterpretation of both earlier and recent findings. Evidence for a detrimental effect of omitting a meal on cognitive performance remains equivocal: from the outset, idiosyncrasy has prevailed. Yet, for young and nutritionally vulnerable children, breakfast is more likely to benefit than hinder performance. For nutrient composition, despite inconsistencies, some cautious predictions can be made. Acutely, carbohydrate-rich-protein-poor meals can be sedating and anxiolytic; by comparison, protein-rich meals may be arousing, improving reaction time but also increasing unfocused vigilance. Fat-rich meals can lead to a decline in alertness, especially where they differ from habitual fat intake. These acute effects may vary with time of day and nutritional status. Chronically, protein-rich diets have been associated with decreased positive and increased negative affect relative to carbohydrate-rich diets. Probable mechanisms include diet-induced changes in monoamine, especially serotoninergic neurotransmitter activity, and functioning of the hypothalamic pituitary adrenal axis. Effects are interpreted in the context of individual traits and susceptibility to challenging, even stressful, tests of performance. Preoccupation with dieting may impair cognition by interfering with working memory capacity, independently of nutritional status. The change in cognitive performance after administration of glucose, and other foods, may depend on the level of sympathetic activation, glucocorticoid secretion, and

  16. Fidelity susceptibility as holographic PV-criticality

    Energy Technology Data Exchange (ETDEWEB)

    Momeni, Davood, E-mail: davoodmomeni78@gmail.com [Eurasian International Center for Theoretical Physics and Department of General & Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan); Faizal, Mir, E-mail: mirfaizalmir@googlemail.com [Department of Physics and Astronomy, University of Lethbridge, Lethbridge, Alberta T1K 3M4 (Canada); Irving K. Barber School of Arts and Sciences, University of British Columbia – Okanagan, 3333 University Way, Kelowna, British Columbia V1V 1V7 (Canada); Myrzakulov, Kairat, E-mail: kairatmyrzakul@gmail.com [Eurasian International Center for Theoretical Physics and Department of General & Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan); Myrzakulov, Ratbay, E-mail: rmyrzakulov@gmail.com [Eurasian International Center for Theoretical Physics and Department of General & Theoretical Physics, Eurasian National University, Astana 010008 (Kazakhstan)

    2017-02-10

    It is well known that entropy can be used to holographically establish a connection among geometry, thermodynamics and information theory. In this paper, we will use complexity to holographically establish a connection among geometry, thermodynamics and information theory. Thus, we will analyze the relation among holographic complexity, fidelity susceptibility, and thermodynamics in extended phase space. We will demonstrate that fidelity susceptibility (which is the informational complexity dual to a maximum volume in AdS) can be related to the thermodynamical volume (which is conjugate to the cosmological constant in the extended thermodynamic phase space). Thus, this letter establishes a relation among geometry, thermodynamics, and information theory, using complexity.

  17. Middle Prut plain's erosion susceptibility evaluation

    Directory of Open Access Journals (Sweden)

    Tudor CASTRAVEȚ

    2011-07-01

    Full Text Available The given article is dedicated to Middle Prut Plain’s erosion susceptibility evaluation  using factorial analysis and methodology of principal component analysis implemented byGeographical Informational System GRASS. Susceptibility evaluation is executed in a qualitative mode, and the results have preliminary character, for further quantitative andmore precise study. This type of natural hazards analysis offers information on probable localization and severity of erosion phenomena, as well as their manifestation probabilityin a given place.

  18. The Aging Kidney: Increased Susceptibility to Nephrotoxicity

    Directory of Open Access Journals (Sweden)

    Xinhui Wang

    2014-09-01

    Full Text Available Three decades have passed since a series of studies indicated that the aging kidney was characterized by increased susceptibility to nephrotoxic injury. Data from these experimental models is strengthened by clinical data demonstrating that the aging population has an increased incidence and severity of acute kidney injury (AKI. Since then a number of studies have focused on age-dependent alterations in pathways that predispose the kidney to acute insult. This review will focus on the mechanisms that are altered by aging in the kidney that may increase susceptibility to injury, including hemodynamics, oxidative stress, apoptosis, autophagy, inflammation and decreased repair.

  19. Prioritisation and network analysis of Crohn's disease susceptibility genes.

    Directory of Open Access Journals (Sweden)

    Daniele Muraro

    Full Text Available Recent Genome-Wide Association Studies (GWAS have revealed numerous Crohn's disease susceptibility genes and a key challenge now is in understanding how risk polymorphisms in associated genes might contribute to development of this disease. For a gene to contribute to disease phenotype, its risk variant will likely adversely communicate with a variety of other gene products to result in dysregulation of common signaling pathways. A vital challenge is to elucidate pathways of potentially greatest influence on pathological behaviour, in a manner recognizing how multiple relevant genes may yield integrative effect. In this work we apply mathematical analysis of networks involving the list of recently described Crohn's susceptibility genes, to prioritise pathways in relation to their potential development of this disease. Prioritisation was performed by applying a text mining and a diffusion based method (GRAIL, GPEC. Prospective biological significance of the resulting prioritised list of proteins is highlighted by changes in their gene expression levels in Crohn's patients intestinal tissue in comparison with healthy donors.

  20. Prioritisation and network analysis of Crohn's disease susceptibility genes.

    Science.gov (United States)

    Muraro, Daniele; Lauffenburger, Douglas A; Simmons, Alison

    2014-01-01

    Recent Genome-Wide Association Studies (GWAS) have revealed numerous Crohn's disease susceptibility genes and a key challenge now is in understanding how risk polymorphisms in associated genes might contribute to development of this disease. For a gene to contribute to disease phenotype, its risk variant will likely adversely communicate with a variety of other gene products to result in dysregulation of common signaling pathways. A vital challenge is to elucidate pathways of potentially greatest influence on pathological behaviour, in a manner recognizing how multiple relevant genes may yield integrative effect. In this work we apply mathematical analysis of networks involving the list of recently described Crohn's susceptibility genes, to prioritise pathways in relation to their potential development of this disease. Prioritisation was performed by applying a text mining and a diffusion based method (GRAIL, GPEC). Prospective biological significance of the resulting prioritised list of proteins is highlighted by changes in their gene expression levels in Crohn's patients intestinal tissue in comparison with healthy donors.

  1. Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

    Directory of Open Access Journals (Sweden)

    Stella Koutros

    Full Text Available Uncovering SNP (single nucleotide polymorphisms-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1 SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15 (P-interaction= 0.003. Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41 (P-interaction= 0.006. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

  2. Functional characterization of the powdery mildew susceptibility gene SmMLO1 in eggplant (Solanum melongena L.).

    Science.gov (United States)

    Bracuto, Valentina; Appiano, Michela; Ricciardi, Luigi; Göl, Deniz; Visser, Richard G F; Bai, Yuling; Pavan, Stefano

    2017-06-01

    Eggplant (Solanum melongena L.) is one of the most important vegetables among the Solanaceae and can be a host to fungal species causing powdery mildew (PM) disease. Specific homologs of the plant Mildew Locus O (MLO) gene family are PM susceptibility factors, as their loss of function results in a recessive form of resistance known as mlo resistance. In a previous work, we isolated the eggplant MLO homolog SmMLO1. SmMLO1 is closely related to MLO susceptibility genes characterized in other plant species. However, it displays a peculiar non-synonymous substitution that leads to a T → M amino acid change at protein position 422, in correspondence of the MLO calmodulin-binding domain. In this study, we performed the functional characterization of SmMLO1. Transgenic overexpression of SmMLO1 in a tomato mlo mutant compromised resistance to the tomato PM pathogen Oidium neolycopersici, thus indicating that SmMLO1 is a PM susceptibility factor in eggplant. PM susceptibility was also restored by the transgenic expression of a synthetic gene, named s-SmMLO1, encoding a protein identical to SmMLO1, except for the presence of T at position 422. This indicates that the T → M polymorphism does not affect the protein role as PM susceptibility factor. Overall, the results of this work are of interest for the functional characterization of MLO proteins and the introduction of PM resistance in eggplant using reverse genetics.

  3. Unique activity spectrum of colicin FY: all 110 characterized Yersinia enterocolitica isolates were colicin FY susceptible.

    Directory of Open Access Journals (Sweden)

    Juraj Bosák

    Full Text Available Colicin FY is a plasmid encoded toxin that recognizes a yersinia-specific outer membrane protein (YiuR as a receptor molecule. We have previously shown that the activity spectrum of colicin FY comprises strains of the genus Yersinia. In this study, we analyzed the activity of colicin FY against 110 Yersinia enterocolitica isolates differing in geographical origin and source. All isolates were characterized through analysis of 16S rRNA genes, serotyping, biotyping, restriction profiling of genomic DNA, detection of virulence markers and susceptibility to antibiotics. This confirmed the broad variability of the collection, in which all 110 Y. enterocolitica isolates, representing 77 various strains, were inhibited by colicin FY. Although isolates showed variable levels of susceptibility to colicin FY, it was not associated with any strain characteristic. The universal susceptibility of Y. enterocolitica strains to colicin FY together with the absence of activity towards strains outside the Yersinia genus suggests potential therapeutic applications for colicin FY.

  4. Genetic susceptibility to HPV infection and cervical cancer

    Directory of Open Access Journals (Sweden)

    P.C. Maciag

    1999-07-01

    Full Text Available Squamous cell carcinoma of the cervix (SCCC is one of the leading causes of death in developing countries. Infection with high-risk human papillomavirus (HPV is the major risk factor to develop malignant lesions in the cervix. Polymorphisms of the MHC and p53 genes seem to influence the outcome of HPV infection and progression to SCCC, although controversial data have been reported. MHC are highly polymorphic genes that encode molecules involved in antigen presentation, playing a key role in immune regulation, while p53 is a tumor suppressor gene that regulates cell proliferation. The HPV E6 protein from high-risk types binds p53 and mediates its degradation by the ubiquitin pathway. The role of these polymorphisms in genetic susceptibility to HPV infection and to SCCC remains under investigation.

  5. Genetics of Asthma Susceptibility and Severity

    NARCIS (Netherlands)

    Slager, Rebecca E.; Hawkins, Gregory A.; Li, Xingnan; Postma, Dirkje S.; Meyers, Deborah A.; Bleecker, Eugene R.

    This article summarizes major findings in genome-wide studies of asthma susceptibility and severity. Two large meta-analyses identified four chromosomal regions which were consistently associated with development of asthma. Genes that are associated with asthma subphenotypes such as lung function,

  6. Climate change and corn susceptibility to mycotoxins

    Science.gov (United States)

    Maize is an essential part of the world’s grain supply, but climate change has the potential to increase maize susceptibility to mycotoxigenic fungal pathogens and reduce food security and safety. While rising atmospheric [CO2] is a driving force of climate change, our understanding of how elevated ...

  7. Why do Individuals Differ in Viral Susceptibility?

    NARCIS (Netherlands)

    Sluijs, van L.; Pijlman, G.P.; Kammenga, J.E.

    2017-01-01

    Viral susceptibility and disease progression is determined by host genetic variation that underlies individual differences. Genetic polymorphisms that affect the phenotype upon infection have been well-studied for only a few viruses, such as HIV-1 and Hepatitis C virus. However, even for

  8. antimicrobial susceptibility and plasmids from escherichia coli

    African Journals Online (AJOL)

    2001-10-02

    Oct 2, 2001 ... 78 No. IO October 200]. ANTIMICROBIAL SUSCEPTIBILITY AND PLASMIDS FROM ESCHERICHIA COLI ISOLATED FROM RATS. FM. Gakuya, BVM, MSc, Field Veterinarian, Kenya Wildlife Services, M.N. Kyule, BVM, ... Request for reprints to: Dr FM. ... profile index (API) 20E strips (Bio Merieux, Marcy~l?

  9. Antimicrobial susceptibility patterns of Salmonella typhi and ...

    African Journals Online (AJOL)

    The aim of this study was to determine antimicrobial susceptibility testing patterns of Candida Albicans and Salmonella typhi isolates. Fifteen isolates of each microorganism were collected from three hospitals located in Dar es Salaam region within a 3-month period in the year 2005. Candida Albicans and Salmonella typhi ...

  10. Incidence and antibiotic susceptibility pattern of Staphylococcus ...

    African Journals Online (AJOL)

    Incidence and antibiotic susceptibility pattern of Staphylococcus aureus amongst patients with urinary tract infection (UTI) in UBTH Benin City, Nigeria. ... (4.4%), Pseudomonas aeruginosa (2.0%) and Candida albican (1.0%). No growth was recorded in 46.6% of cultures. The occurrence of S. aureus was found to be ...

  11. Short Communication Antibiotic Susceptibility Pattern and Beta ...

    African Journals Online (AJOL)

    The multiple drug resistance as evident in high MICs of the antibiotics tested could probably be due to abuse/misuse of antibiotics resulting in recurrence of furuncles in the patients. Keywords: Antibiotic susceptibility, β-lactamase, Recurrent furunculosis, Staphylococcus aureus. Received 08 August 2011/ Accepted 30 ...

  12. Prevalence and susceptibility pattern of methicillinresistant ...

    African Journals Online (AJOL)

    Also, recent reports describe methicillin-resistant S. aureus (MRSA) carriage in persons in the community. The study investigated its prevalence in urine of healthy women and its susceptibility pattern to other antibiotics. Urine samples collected from healthy women volunteers in Zaria were cultured and screened for S.

  13. Landslide susceptibility analysis using Probabilistic Certainty Factor ...

    Indian Academy of Sciences (India)

    This paper reports the use of a GIS based Probabilistic Certainty Factor method to assess the geo-environmental factors that contribute to landslide susceptibility in Tevankarai Ar sub-watershed,. Kodaikkanal. Landslide occurrences are a common phenomenon in the Tevankarai Ar sub-watershed,. Kodaikkanal owing to ...

  14. Estimation of bonding nature using diamagnetic susceptibility.

    Science.gov (United States)

    Tomiyasu, Keisuke; Sato, Toyoto; Orimo, Shin-ichi

    2015-05-21

    A chemical bond includes both covalent and ionic characteristics. We develop an experimental method to estimate the degree of each contribution based on magnetic susceptibility measurements, in which Pascal's scheme for Larmor diamagnetism is combined with electronegativity. The applicability to metal hydrides is also shown.

  15. acetyltransferases: Influence on Lung Cancer Susceptibility

    African Journals Online (AJOL)

    Lung cancer remains a major health challenge in the world. It is the commonest cause of cancer mortality in men, it has been suggested that genetic susceptibility may contribute to the major risk factor, with increasing prevalence of smoking. Lung cancer has reached epidemic proportions in India. Recently indoor air ...

  16. Susceptibility Pattern of Nasopharyngeal Isolates of Streptococcus ...

    African Journals Online (AJOL)

    Aims: To determine the rate of nasopharyngeal colonization of Streptococcus pneumoniae among nursery school children in Enugu urban and to determine their antibiotic susceptibility pattern particularly the penicillin resistant strains. Methods: Specimens were collected from the nasopharynx of 385 apparently healthy ...

  17. Surveillance and insecticide susceptibility status of Culicine ...

    African Journals Online (AJOL)

    Vector control programs in Nigeria are mostly targeted towards reducing the burden of malaria with less emphasis placed on other debilitating vector borne diseases such as dengue, yellow fever and filariasis. This study assessed the indoor resting densities and insecticide susceptibility status of Culex and Aedes ...

  18. Epidemiological and antibiotic susceptibility profiles of infectious ...

    African Journals Online (AJOL)

    2011-09-28

    Sep 28, 2011 ... isolation rates among different age groups, educational status, gender, water drank, use of chlorine, toilet use, exposure at home to .... with intermediate susceptibility to ciprofloxacin in the majority of .... Antibiotic and bacterial strain specific distribution of resistance in bacteria isolated from patients attending.

  19. Bacteriological Quality and antimicrobial susceptibility of some ...

    African Journals Online (AJOL)

    Bacteriological Quality and antimicrobial susceptibility of some isolates of Well Water used for Drinking in Jimma Town, Southwest Ethiopia. ... resistance against most of the antibiotics tested. In general, the well water samples analyzed in this study were found in unacceptable condition in terms of bacteriological quality.

  20. Susceptibility to methamphetamine dependence associated with ...

    African Journals Online (AJOL)

    Khyber Saify

    2015-09-26

    Sep 26, 2015 ... Susceptibility to methamphetamine dependence associated with high transcriptional activity alleles of VNTR polymorphism in the promoter region of monoamine oxidase A (MAOA). Khyber Saify, Mostafa Saadat*. Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran. Received ...

  1. Susceptibility of Cryptococcus neoformans and Cryptococcus gattii ...

    African Journals Online (AJOL)

    Objective: To determine anti-fungal susceptibility of Cryptococcus neoformans and. Cryptococcus gattii from environmental and clinical sources in Nairobi, Kenya. Design: Prospective study. Setting: Kenya Medical Research Institute, Mycology laboratory, Nairobi, Kenya. Subjects: A total of 123 isolates were tested for their ...

  2. Susceptibility of Some Bacterial Contaminants Recovered from ...

    African Journals Online (AJOL)

    Methods: Nine bacterial isolates recovered from various brands of commercially available cosmetics marketed in Jordan were tested for their susceptibility pattern against two paraben esters and two formaldehyde donors in addition to nine commonly used antibiotics. The biocidal effect for three preservatives was tested at ...

  3. Antimicrobial susceptibility of organisms causing community ...

    African Journals Online (AJOL)

    Demographic and clinical data were recorded and mid-stream urine (MSU) specimens were cultured. UTI pathogens were Gram-stained and identified to species level. Etest-based antimicrobial susceptibility testing was performed for amoxicillin/clavulanic acid, cefixime, cefuroxime, ciprofloxacin, fosfomycin, levofloxacin, ...

  4. Antibiotic Susceptibility Pattern of Extended Spectrum ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antibiotic susceptibility pattern of various bacterial pathogens including extended spectrum betalactamase (ESBL) producers in Kano, Nigeria. Method: A total of 604 consecutive clinical samples obtained from Aminu Kano Teaching Hospital. (AKTH), Kano between January and July 2010 were ...

  5. Antimicrobial susceptibility of staphylococci species from cow ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence of antibiotic susceptibility of Staphylococcus species isolated from foremilk samples. Setting: Milk was collected from five farms within a 70 km radius of Gaborone, Botswana. Subjects: Two hundred and twenty five staphylococci isolates from foremilk samples. Main outcome measures: ...

  6. Prevalence and antibiotic susceptibility pattern of methicillin ...

    African Journals Online (AJOL)

    Methicillin resistant Staphylococcus aureus (MRSA) is a multidrug resistant bacterium that threatens the continued effectiveness of antibiotics worldwide. The objective of this study was to investigate the prevalence of MRSA and its antibiotic susceptibility pattern in patients with burns and bedsore. This was a cross- sectional ...

  7. Assessment of antibiotic susceptibilities, genotypic characteristics ...

    African Journals Online (AJOL)

    This study was designed to evaluate the antibiotic susceptibilities, genotypic characteristics and biofilm formation abilities of antibiotic-sensitive Staphylococcus aureus KACC 13236 (SAS), multiple antibiotic-resistant S. aureus CCARM 3080 (SAR), antibiotic-sensitive Salmonella Typhimurium KCCM 40253 (STS) and ...

  8. Isolation, identifications and antimicrobial susceptibility pattern of ...

    African Journals Online (AJOL)

    A cross-sectional study was conducted from November 2013 to April 2014 to isolate coagulase positive Staphylococcus (CPS) from subclinical mastitic (SCM) lactating cows, to establishing prevalence, to identify risk factors and to determine the antimicrobial susceptibility pattern of CPS isolates in and around Haramaya.

  9. Antimicrobial susceptibility in community-acquired bacterial ...

    African Journals Online (AJOL)

    Design: Cross-sectional study. Setting: Bacterial isolates were obtained from adults suspected to have community-acquired pneumonia and who sought treatment at two city council clinics in Nairobi, Kenya. Susceptibility to antimicrobial agents was performed using a microdilution broth method, according to the criteria set ...

  10. Antibiotic Susceptibility of Potentially Probiotic Vaginal Lactobacilli

    Directory of Open Access Journals (Sweden)

    Virginia Ocaña

    2006-01-01

    Full Text Available Objective. To study the antimicrobial susceptibility of six vaginal probiotic lactobacilli. Methods. The disc diffusion method in Müeller Hinton, LAPTg and MRS agars by the NCCLS (National Committee for Clinical Laboratory Standards procedure was performed. Due to the absence of a Lactobacillus reference strains, the results were compared to those of Staphylococcus aureus ATCC29213. Minimal Inhibitory Concentration (MIC with 21 different antibiotics in LAPTg agar and broth was also determined. Results. LAPTg and MRS agars are suitable media to study antimicrobial susceptibility of lactobacilli. However, the NCCLS procedure needs to be standardized for this genus. The MICs have shown that all Lactobacillus strains grew at concentrations above 10 μg/mL of chloramphenicol, aztreonam, norfloxacin, ciprofloxacin, ceftazidime, ceftriaxone, streptomycin and kanamycin. Four lactobacilli were sensitive to 1 μg/mL vancomycin and all of them were resistant to 1000 μg/mL of metronidazole. Sensitivity to other antibiotics depended on each particular strain. Conclusions. The NCCLS method needs to be standardized in an appropriate medium to determine the antimicrobial susceptibility of Lactobacillus. Vaginal probiotic lactobacilli do not display uniform susceptibility to antibiotics. Resistance to high concentrations of metronidazole suggests that lactobacilli could be simultaneously used with a bacterial vaginosis treatment to restore the vaginal normal flora.

  11. Antibiotic Susceptibility of Potentially Probiotic Vaginal Lactobacilli

    Science.gov (United States)

    Ocaña, Virginia; Silva, Clara; Nader-Macías, María Elena

    2006-01-01

    Objective. To study the antimicrobial susceptibility of six vaginal probiotic lactobacilli. Methods. The disc diffusion method in Müeller Hinton, LAPTg and MRS agars by the NCCLS (National Committee for Clinical Laboratory Standards) procedure was performed. Due to the absence of a Lactobacillus reference strains, the results were compared to those of Staphylococcus aureus ATCC29213. Minimal Inhibitory Concentration (MIC) with 21 different antibiotics in LAPTg agar and broth was also determined. Results. LAPTg and MRS agars are suitable media to study antimicrobial susceptibility of lactobacilli. However, the NCCLS procedure needs to be standardized for this genus. The MICs have shown that all Lactobacillus strains grew at concentrations above 10 μg/mL of chloramphenicol, aztreonam, norfloxacin, ciprofloxacin, ceftazidime, ceftriaxone, streptomycin and kanamycin. Four lactobacilli were sensitive to 1 μg/mL vancomycin and all of them were resistant to 1000 μg/mL of metronidazole. Sensitivity to other antibiotics depended on each particular strain. Conclusions. The NCCLS method needs to be standardized in an appropriate medium to determine the antimicrobial susceptibility of Lactobacillus. Vaginal probiotic lactobacilli do not display uniform susceptibility to antibiotics. Resistance to high concentrations of metronidazole suggests that lactobacilli could be simultaneously used with a bacterial vaginosis treatment to restore the vaginal normal flora. PMID:17485797

  12. Sparse methods for Quantitative Susceptibility Mapping

    Science.gov (United States)

    Bilgic, Berkin; Chatnuntawech, Itthi; Langkammer, Christian; Setsompop, Kawin

    2015-09-01

    Quantitative Susceptibility Mapping (QSM) aims to estimate the tissue susceptibility distribution that gives rise to subtle changes in the main magnetic field, which are captured by the image phase in a gradient echo (GRE) experiment. The underlying susceptibility distribution is related to the acquired tissue phase through an ill-posed linear system. To facilitate its inversion, spatial regularization that imposes sparsity or smoothness assumptions can be employed. This paper focuses on efficient algorithms for regularized QSM reconstruction. Fast solvers that enforce sparsity under Total Variation (TV) and Total Generalized Variation (TGV) constraints are developed using Alternating Direction Method of Multipliers (ADMM). Through variable splitting that permits closed-form iterations, the computation efficiency of these solvers are dramatically improved. An alternative approach to improve the conditioning of the ill-posed inversion is to acquire multiple GRE volumes at different head orientations relative to the main magnetic field. The phase information from such multi-orientation acquisition can be combined to yield exquisite susceptibility maps and obviate the need for regularized reconstruction, albeit at the cost of increased data acquisition time.

  13. Compensatory and Susceptive Responses of Cowpea Genotypes...

    African Journals Online (AJOL)

    User

    turing genotypes of cowpea. Control of aphid's infestation in early maturing cowpea genotypes should not be delayed up to two weeks after infestation (28 days after planting) to avoid yield loss. Aphid infestation period for studies in susceptive response in medium to late matur- ing genotypes should go beyond 28 days after.

  14. Mapping markers linked to porcine salmonellosis susceptibility

    NARCIS (Netherlands)

    Galina-Pantoja, L.; Siggens, K.; Schriek, M.G.; Heuven, H.C.M.|info:eu-repo/dai/nl/314417818

    2009-01-01

    Anim Genet. 2009 Jun 3. [Epub ahead of print] Mapping markers linked to porcine salmonellosis susceptibility. Galina-Pantoja L, Siggens K, van Schriek MG, Heuven HC. PIC/Genus, 100 Bluegrass Commons Blvd, Hendersonville, TN 37075, USA. The goal of this study was to identify pig chromosomal regions

  15. Caspofungin Etest susceptibility testing of Candida species

    DEFF Research Database (Denmark)

    Arendrup, Maiken Cavling; Pfaller, Michael A; Schønheyder, Henrik Carl

    2012-01-01

    The purpose of this study was to evaluate the performance of caspofungin Etest and the recently revised CLSI breakpoints. A total of 497 blood isolates, of which 496 were wild-type isolates, were included. A total of 65/496 susceptible isolates (13.1%) were misclassified as intermediate (I) or re...

  16. Species identification and antifungal susceptibility pattern of ...

    African Journals Online (AJOL)

    Dalia Saad ElFeky

    2015-10-23

    Oct 23, 2015 ... Species identification and antifungal susceptibility pattern of Candida isolates in cases of vulvovaginal candidiasis. Dalia Saad ElFeky a,. *, Noha Mahmoud Gohar a. , Eman Ahmad El-Seidi a. ,. Mona Mahmoud Ezzat a. , Somaia Hassan AboElew b a Department of Medical Microbiology and Immunology, ...

  17. The current susceptibility pattern of methicillin resistant ...

    African Journals Online (AJOL)

    The antimicrobial susceptibility pattern of methicillin-resistant Staphylococcus aureus (MRSA) from in-patients and out-patients at the University of Port Harcourt Teaching Hospital (UPTH) was studied. Fifty, S. aureus organisms were isolated from routine clinical specimens such as high vaginal, wound, urethral and ear ...

  18. Prevalence And Antimicrobial Susceptibility Pattern Of Methicillin ...

    African Journals Online (AJOL)

    Methicillin resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen. We report the prevalence and antibiotic susceptibility pattern of MRSA in Amravati, Maharashtra state (India). A total of 150 healthcare-associated (HA) sources (doctors mobiles phone and wound/pus swabs), and 160 ...

  19. Distribution and antibiotic susceptibility pattern of methicillin ...

    African Journals Online (AJOL)

    Background: The rise of methicillin resistant Staphylococcus aureus (MRSA) infection has become a serious health issue. The emergence of mutidrug – resistant MRSA strains compounds chemotherapy and has raised public health concern. In this preliminary study, the distribution and antimicrobial susceptibility profile of ...

  20. Prevalence and antimicrobial susceptibility profiles of ...

    African Journals Online (AJOL)

    Prevalence and antimicrobial susceptibility profiles of Staphylococcus aureus from cow's milk, nasal and environmental swabs in selected dairy farms in Morogoro, ... 28.4% (n=27) of all isolates were resistant to Oxacillin and/or Cefoxitin, and therefore classified as Methicillin-Resistant Staphylococcus aureus (MRSA).

  1. Antimicrobial susceptibility and minimal inhibitory concentration of ...

    African Journals Online (AJOL)

    The purpose of this study was to evaluate the antibiotic susceptibility profile of Pseudomonas aeruginosa isolated from different animal species with septic ocular surface disease. Sixteen strains of P. aeruginosa were isolated from different species of animals (dog, cat, horse, penguin and brown bear) with ocular surface ...

  2. Isolation, characterization and antibiotic susceptibility pattern of ...

    African Journals Online (AJOL)

    The swab sticks were inoculated into brain-heart infusion broth, transported to the laboratory and then inoculated on mannitol salt agar. Isolates with the characteristic colonial morphology of S. aureus were then identified microscopically and characterized biochemically. The susceptibility of S. aureus isolates to seven ...

  3. Antibiotic Susceptibility Pattern of Extended Spectrum ...

    African Journals Online (AJOL)

    Antibiotics susceptibility tests including, ESBL screening and confirmation, were carried out by disc diffusion technique using Clinical Laboratory Standard Institute (CLSI) criteria. Results: Ten different types of bacteria genera were observed from nine different clinical samples. E. coli was the most frequently isolated bacteria ...

  4. Antimicrobial susceptibility profile of selected bacteraemic ...

    African Journals Online (AJOL)

    Antimicrobial susceptibility tests were performed by 12 participating laboratories according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Extended-spectrum 13-lactamase (ESBL) production was determined in selected species of Enterobacteriaceae irrespective of source. Results. The overall ...

  5. Antimicrobial susceptibility of Corynebacterium group D2.

    Science.gov (United States)

    Santamaría, M; Ponte, C; Wilhelmi, I; Soriano, F

    1985-01-01

    The in vitro susceptibility of 30 Corynebacterium group D2 strains to nine antimicrobial agents was determined. Vancomycin and norfloxacin were the most active agents tested. All strains were resistant to ampicillin and cephalothin, all except one were resistant to gentamicin, and the activity of erythromycin, novobiocin, tetracycline, and rifampin varied. PMID:4083869

  6. Helicobacter pylori : Prevalence and antibiotic susceptibility among ...

    African Journals Online (AJOL)

    E-test strips for metronidazole, amoxicillin and clarithromycin were used for susceptibility testing. Results. The prevalence of H. pylori infection in children was 73.3%, and 54.8% in adults. All the H. pylori investigated in this study were largely sensitive to clarithromycin (100%, minimum inhibiting concentration (MIC) <2 ìg/ml) ...

  7. The differential susceptibility to media effects model

    NARCIS (Netherlands)

    Valkenburg, P.M.; Peter, J.

    2013-01-01

    In this theoretical article, we introduce the Differential Susceptibility to Media Effects Model (DSMM), a new, integrative model to improve our understanding of media effects. The DSMM organizes, integrates, and extends the insights developed in earlier microlevel media-effects theories. It

  8. Enumeration, Isolation and Antibiotic Susceptibility Profile of ...

    African Journals Online (AJOL)

    A study was carried out between February and March, 2012, to enumerate, isolate and identify bacteria associated with mobile cell phones in a University environment. This was with a view to determining the bacterial load and their susceptibility pattern to some commonly-used antibiotics. Samples were collected from ...

  9. Antibiotic Susceptibility Profile and Survival of Bifidobacterium ...

    African Journals Online (AJOL)

    Bifidobacteria are categorized as health-promoting microorganisms (probiotics) in the gastrointestinal tracts of humans and animals. Antibiotic susceptibility is a key criterion for probiotic agent selection. Good survival of probiotics during storage at selected storage temperature(s) is highly desirable. Bifidobacteria isolated ...

  10. Real-Time Optical Antimicrobial Susceptibility Testing

    Science.gov (United States)

    Andersen, Klaus R.; Jørgensen, Erik; Droce, Aida; Olesen, Tom; Jensen, Bent B.; Rosenvinge, Flemming S.; Sondergaard, Teis E.

    2013-01-01

    Rapid antibiotic susceptibility testing is in high demand in health care fields as antimicrobial-resistant bacterial strains emerge and spread. Here, we describe an optical screening system (oCelloScope) which, based on time-lapse imaging of 96 bacteria-antibiotic combinations at a time, introduces real-time detection of bacterial growth and antimicrobial susceptibility with imaging material to support the automatically generated graphs. Automated antibiotic susceptibility tests of a monoculture showed statistically significant antibiotic effects within 6 min and within 30 min in complex samples from pigs suffering from catheter-associated urinary tract infections. The oCelloScope system provides a fast high-throughput screening method for detecting bacterial susceptibility that might entail an earlier diagnosis and introduction of appropriate targeted therapy and thus combat the threat from multidrug-resistant pathogenic bacteria. The oCelloScope system can be employed for a broad range of applications within bacteriology and might present new vistas as a point-of-care instrument in clinical and veterinary settings. PMID:23596243

  11. Clinical assessment of wounds and antimicrobial susceptibility ...

    African Journals Online (AJOL)

    A study was conducted at two veterinary surgeries to investigate the common aerobic bacteria associated with dog bite wounds in dogs, and to determine their antimicrobial susceptibilities. From each wound, two swabs were collected for bacterial culture and cytology. A total of 50 wounds from 50 dogs were examined, with ...

  12. Isolation, identifications and antimicrobial susceptibility pattern of ...

    African Journals Online (AJOL)

    A cross-sectional study was conducted from November 2013 to April 2014 to isolate coagulase positive Staphylococcus (CPS) from subclinical mastitic (SCM) lactating cows, to establishing prevalence, to identify risk factors and to determine the antimicrobial susceptibility pattern of CPS isolates in and around Haramaya ...

  13. Relative susceptibility of banana cultivars to Xanthomonas ...

    African Journals Online (AJOL)

    short time making the disease one of the most dreaded in banana. The disease affects almost all varieties of commonly grown banana cultivars. Some knowledge of the relative susceptibility of banana cultivars would be extremely useful and could be a basis for management strategies for BXW. Ten banana cultivars were ...

  14. Biofilm production and antibiotic susceptibility profiles of ...

    African Journals Online (AJOL)

    Staphylococcus aureus is a common pathogen associated with nosocomial as well as community acquired infections. Despite multiple reports on the severity and recurrent nature of S. aureus infection, the pathogenesis as well as antibiotic susceptibility profiles of S. aureus infecting HIV and AIDS patients has not been well ...

  15. Individual Differences in Susceptibility to Inattentional Blindness

    Science.gov (United States)

    Seegmiller, Janelle K.; Watson, Jason M.; Strayer, David L.

    2011-01-01

    Inattentional blindness refers to the finding that people do not always see what appears in their gaze. Though inattentional blindness affects large percentages of people, it is unclear if there are individual differences in susceptibility. The present study addressed whether individual differences in attentional control, as reflected by…

  16. Original Paper Multicenter study on antibiotic susceptibility ...

    African Journals Online (AJOL)

    Sampling was performed by fingerprinting on culture media and ... Further investigations and previous works alleged drug use and basic hygiene as crucial in .... Susceptibility testing. This was carried out on 24 h bacterial pure culture. Prior to the test, bacterial isolates were streaked on fresh agar and incubated at 37.

  17. antimicrobial susceptibility pattern of extended spectrum

    African Journals Online (AJOL)

    JAMILU

    Microbiology Department of Aminu Kano Teaching Hospital (AKTH), Kano. The isolates were tested against third generation cephalosporins using Clinical Laboratory Standard Institute (CLSI) recommended, WHO modified Kirby-Bauer disc diffusion method. Isolates with reduced susceptibility to cefpodoxime, cefpotaxime ...

  18. Ethernet susceptibility to electric fast transients

    NARCIS (Netherlands)

    van Leersum, B.J.A.M.; Buesink, Frederik Johannes Karel; Bergsma, J.G.; Leferink, Frank Bernardus Johannes

    2013-01-01

    The effect of Electric Fast Transients (EFT) phenomena in an Ethernet interface set-up is investigated in order to get more insight in coupling and interference mechanisms, robustness and susceptibility levels of a typical Ethernet installation on board of a naval vessel. It is shown that already a

  19. Complement susceptibility in glutamine deprived breast cancer cells

    Directory of Open Access Journals (Sweden)

    Boackle Robert J

    2007-07-01

    Full Text Available Abstract Background Membrane complement regulatory proteins (mCRPs inhibit complement-mediated killing of human cells by human complement, a property that confers protection from complement to malignant breast cancer cells and that thwarts some immunotherapies. Metabolic mechanisms may come into play in protecting cancer cells from the complement system subsequent to relatively low levels of complement deposition. Results In differentiating these mechanisms, two types of human breast cancer cell lines, MCF7 (adenocarcinoma and Bcap37 (medullary carcinoma were cell-cycle synchronized using glutamine-deprivation followed by restoration. These cells were examined for the expression of two mCRPs (CD59 and CD55, and for subsequent susceptibility to antibody-mediated complement-induced membrane damage. After glutamine restoration, MCF7 and Bcap37 cells were synchronized into the G2/M phase and an average increased expression of CD59 and CD55 occurred with a corresponding resistance to complement-mediated damage. Blocking CD59 inhibitory function with monoclonal antibody revealed that CD59 played a key role in protecting unsynchronized Bcap37 and MCF7 cancer cells from the complement membrane attack complex. Interestingly, glutamine-deprivation did not significantly affect the expression of proteins e.g., the surface level of CD59 or CD55, but did increase the susceptibility to complement-mediated killing. One possible explanation is that glutamine-deprivation may have slowed the turnover rate of mCRPs, preventing the cells from replacing pre-existing mCRPs, as they became neutralized by covalent C4b and C3b depositions. Conclusion Taken together the findings are consistent with the conclusion that future immunotherapies should aim to achieve a highly specific and profound activation and deposition of complement as well as to disrupt the synthesis and expression of CD59 and CD55 by the cancer cells.

  20. Distribution of CBP genes in Streptococcus pneumoniae isolates in relation to vaccine types, penicillin susceptibility and clinical site.

    Science.gov (United States)

    Desa, M N; Sekaran, S D; Vadivelu, J; Parasakthi, N

    2008-07-01

    Choline-binding proteins (CBP) have been associated with the pathogenesis of Streptococcus pneumoniae. We screened, using PCR, for the presence of genes (cbpA, D, E, G) encoding these proteins in 34 isolates of pneumococci of known serotypes and penicillin susceptibility from invasive and non-invasive disease. All isolates harboured cbpD and cbpE whereas cbpA and cbpG were found in 47% and 59% respectively; the latter were more frequent in vaccine-associated types and together accounted for 77% of these isolates. No association was observed with penicillin susceptibility but 85% of non-invasive isolates were positive for these genes.

  1. Exploration of deleterious single nucleotide polymorphisms in late-onset Alzheimer disease susceptibility genes.

    Science.gov (United States)

    Masoodi, Tariq Ahmad; Al Shammari, Sulaiman A; Al-Muammar, May N; Alhamdan, Adel A; Talluri, Venkateswar Rao

    2013-01-10

    Non-synonymous single nucleotide polymorphisms (nsSNPs) are considered as biomarkers to disease susceptibility. In the present study, nsSNPs in CLU, PICALM and BIN1 genes were screened for their functional impact on concerned proteins and their plausible role in Alzheimer disease (AD) susceptibility. Initially, SNPs were retrieved from dbSNP database, followed by identification of potentially deleterious nsSNPs and prediction of their effect on proteins by PolyPhen and SIFT. Protein stability and the probability of mutation occurrence were predicted using I-Mutant and PANTHER respectively. SNPs3D and FASTSNP were used for the functional analysis of nsSNPs. The functional impact on the 3D structure of proteins was evaluated by SWISSPDB viewer and NOMAD-Ref server. On analysis, 3 nsSNPs with IDs rs12800974 (T158P) of PICALM and rs11554585 (R397C) and rs11554585 (N106D) of BIN1 were predicted to be functionally significant with higher scores of I-Mutant, SIFT, PolyPhen, PANTHER, FASTSNP and SNPs3D. The mutant models of these nsSNPs also showed very high energies and RMSD values compared to their native structures. Current study proposes that the three nsSNPs identified in this study constitute a unique resource of potential genetic factors for AD susceptibility. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Effects of disruption of heat shock genes on susceptibility of Escherichia coli to fluoroquinolones

    Directory of Open Access Journals (Sweden)

    Morioka Mizue

    2003-08-01

    Full Text Available Abstract Background It is well known that expression of certain bacterial genes responds rapidly to such stimuli as exposure to toxic chemicals and physical agents. It is generally believed that the proteins encoded in these genes are important for successful survival of the organism under the hostile conditions. Analogously, the proteins induced in bacterial cells exposed to antibiotics are believed to affect the organisms' susceptibility to these agents. Results We demonstrated that Escherichia coli cells exposed to levofloxacin (LVFX, a fluoroquinolone (FQ, induce the syntheses of heat shock proteins and RecA. To examine whether the heat shock proteins affect the bactericidal action of FQs, we constructed E. coli strains with mutations in various heat shock genes and tested their susceptibility to FQs. Mutations in dnaK, groEL, and lon increased this susceptibility; the lon mutant exhibited the greatest effects. The increased susceptibility of the lon mutant was corroborated by experiments in which the gene encoding the cell division inhibitor, SulA, was subsequently disrupted. SulA is induced by the SOS response and degraded by the Lon protease. The findings suggest that the hypersusceptibility of the lon mutant to FQs could be due to abnormally high levels of SulA protein resulting from the depletion of Lon and the continuous induction of the SOS response in the presence of FQs. Conclusion The present results show that the bactericidal action of FQs is moderately affected by the DnaK and GroEL chaperones and strongly affected by the Lon protease. FQs have contributed successfully to the treatment of various bacterial infections, but their widespread use and often misuse, coupled with emerging resistance, have gradually compromised their utility. Our results suggest that agents capable of inhibiting the Lon protease have potential for combination therapy with FQs.

  3. Endurance Exercise Training Reduces Cardiac Sodium/Calcium Exchanger Expression in Animals Susceptible to Ventricular Fibrillation

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    Monica eKukielka

    2011-02-01

    Full Text Available Aim: Increased sodium/calcium exchanger activity (NCX1, an important regulator of cardiomyocyte cystolic calcium may provoke arrhythmias. Exercise training can decrease NCX1 expression in animals with heart failure improving cytosolic calcium regulation, and could thereby reduce the risk for ventricular fibrillation (VF. Methods: To test this hypothesis, a 2-min coronary occlusion was made during the last min. of exercise in dogs with healed myocardial infarctions; 23 had VF (S, susceptible and 13 did not (R, resistant. The animals were randomly assigned to either 10-wk exercise training (progressively increasing treadmill running (S n = 9; R n = 8 or 10-wk sedentary (S n = 14; R n = 5 groups. At the end of the 10-wk period, the exercise + ischemia test provoked VF in sedentary but not trained susceptible dogs. On a subsequent day, cardiac tissue was harvested and NCX1 protein expression was determined by Western blot. Results: In the sedentary group, NCX1 expression was significantly (ANOVA, P<0.05 higher in susceptible compared to resistant dogs. In contrast, NCX1 levels were similar in the exercise trained resistant and susceptible animals. Conclusion: These data suggest that exercise training can restore a more normal NCX1 level in dogs susceptible to ventricular fibrillation, improving cystolic calcium regulation and could thereby reduce the risk for sudden death following myocardial infarction.

  4. PRNP promoter polymorphisms are associated with BSE susceptibility in Swiss and German cattle

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    Ziegler Ute

    2007-04-01

    Full Text Available Abstract Background Non-synonymous polymorphisms within the prion protein gene (PRNP influence the susceptibility and incubation time for transmissible spongiform encephalopathies (TSE in some species such as sheep and humans. In cattle, none of the known polymorphisms within the PRNP coding region has a major influence on susceptibility to bovine spongiform encephalopathy (BSE. Recently, however, we demonstrated an association between susceptibility to BSE and a 23 bp insertion/deletion (indel polymorphism and a 12 bp indel polymorphism within the putative PRNP promoter region using 43 German BSE cases and 48 German control cattle. The objective of this study was to extend this work by including a larger number of BSE cases and control cattle of German and Swiss origin. Results Allele, genotype and haplotype frequencies of the two indel polymorphisms were determined in 449 BSE cattle and 431 unaffected cattle from Switzerland and Germany including all 43 German BSE and 16 German control animals from the original study. When breeds with similar allele and genotype distributions were compared, the 23 bp indel polymorphism again showed a significant association with susceptibility to BSE. However, some additional breed-specific allele and genotype distributions were identified, mainly related to the Brown breeds. Conclusion Our study corroborated earlier findings that polymorphisms in the PRNP promoter region have an influence on susceptibility to BSE. However, breed-specific differences exist that need to be accounted for when analyzing such data.

  5. Inhibition of ACCase220 and ACCase240 isozymes from sethoxydim-resistant and -susceptible maize hybrids.

    Science.gov (United States)

    Incledon, B J; Hall, J C

    1999-01-01

    Acetyl-coenzyme A carboxylase (ACCase) isozymes were separated from cyclohexanedione-resistant and -susceptible maize. ACCase240 from resistant maize was 3.7-, >77-, and 12.8-fold more resistant to inhibition by clethodim, sethoxydim, and tralkoxydim, respectively, than ACCase240 from susceptible maize. The resistant ACCase240 preparation had 3.0-fold more protein and 14.5-fold lower specific activity than susceptible ACCase240. Resistant ACCase240 has a V(max) 5.5-fold lower than that of susceptible ACCase240, whereas apparent K(m) values were similar. ACCase220 from resistant maize was >25- and 7.2-fold more resistant to inhibition by sethoxydim and tralkoxydim, respectively, than susceptible ACCase220 but was inhibited to the same extent by clethodim. In summary, sethoxydim-resistant corn has an altered herbicide-resistant ACCase220 isozyme and increased expression of a less efficient, herbicide-resistant ACCase240 isozyme. However, to what extent alteration of both isozymes contributes to sethoxydim resistance is not clear.

  6. Protein-protein interactions

    DEFF Research Database (Denmark)

    Byron, Olwyn; Vestergaard, Bente

    2015-01-01

    Responsive formation of protein:protein interaction (PPI) upon diverse stimuli is a fundament of cellular function. As a consequence, PPIs are complex, adaptive entities, and exist in structurally heterogeneous interplays defined by the energetic states of the free and complexed protomers. The bi...

  7. Thermal hysteresis proteins.

    Science.gov (United States)

    Barrett, J

    2001-02-01

    Extreme environments present a wealth of biochemical adaptations. Thermal hysteresis proteins (THPs) have been found in vertebrates, invertebrates, plants, bacteria and fungi and are able to depress the freezing point of water (in the presence of ice crystals) in a non-colligative manner by binding to the surface of nascent ice crystals. The THPs comprise a disparate group of proteins with a variety of tertiary structures and often no common sequence similarities or structural motifs. Different THPs bind to different faces of the ice crystal, and no single mechanism has been proposed to account for THP ice binding affinity and specificity. Experimentally THPs have been used in the cryopreservation of tissues and cells and to induce cold tolerance in freeze susceptible organisms. THPs represent a remarkable example of parallel and convergent evolution with different proteins being adapted for an anti-freeze role.

  8. Diagnostic Value of Direct Antibiotic Susceptibility Test for Faster BacterialSusceptibility Reporting in Bacteremia

    Directory of Open Access Journals (Sweden)

    Rebriarina Hapsari

    2012-12-01

    Methods: Bloods from positive BACTEC bottles which met inclusion and exclusion criteria were put into sterile tubes and centrifuged. The pellets were then used to make 0.5 McFarland bacterial suspensions and directly used for antibiotic susceptibility testing. Interpretations of direct method were compared to standard method to count sensitivity, specificity, sensitive predictive value, resistant predictive value, accuracy, and kappa value. Results: From 58 samples (containing 22 gram negative, 36 gram positive bacteria, there were 309 total antibiotic susceptibility tests. Direct method showed sensitivity, specificity, sensitive predictive value, resistant predictive value, accuracy, and kappa value of 89.3%, 92.9%, 93.8%, 87.8%, 86.4%, and 0.82, respectively. Conclusion: Direct antibiotic susceptibility testing has a good agreement with the standard method so it can aid faster antibiotic susceptibility reporting in bacteraemia (Sains Medika, 4(2:174-181.

  9. Comparative Proteomic Analysis of Susceptible and Resistant Rice Plants during Early Infestation by Small Brown Planthopper.

    Science.gov (United States)

    Dong, Yan; Fang, Xianping; Yang, Yong; Xue, Gang-Ping; Chen, Xian; Zhang, Weilin; Wang, Xuming; Yu, Chulang; Zhou, Jie; Mei, Qiong; Fang, Wang; Yan, Chengqi; Chen, Jianping

    2017-01-01

    The small brown planthopper (Laodelphax striatellus Fallén, Homoptera, Delphacidae-SBPH) is one of the major destructive pests of rice (Oryza sativa L.). Understanding on how rice responds to SBPH infestation will contribute to developing strategies for SBPH control. However, the response of rice plant to SBPH is poorly understood. In this study, two contrasting rice genotypes, Pf9279-4 (SBPH-resistant) and 02428 (SBPH-susceptible), were used for comparative analysis of protein profiles in the leaf sheath of rice plants in responses to SBPH infestation. One hundred and thirty-two protein spots that were differentially expressed between the resistant and susceptible rice lines were identified with significant intensity differences (≥2-fold, P < 0.05) at 0, 6, and 12 h after SBPH infestation. Protein expression profile analysis in the leaf sheath of SBPH-resistant and SBPH-susceptible rice lines after SBPH infestation showed that proteins induced by SBPH feeding were involved mainly in stress response, photosynthesis, protein metabolic process, carbohydrate metabolic process, energy metabolism, cell wall-related proteins, amino acid metabolism and transcriptional regulation. Gene expression analysis of 24 differentially expressed proteins (DEPs) showed that more than 50% DEPs were positively correlated with their mRNA levels. Analysis of some physiological indexes mainly involved in the removal of oxygen reactive species showed that the levels of superoxide dismutase (SOD) and glutathione (GSH) were considerably higher in Pf9279-4 than 02428 during SBPH infestation. The catalase (CAT) activity and hydroxyl radical inhibition were lower in Pf9279-4 than 02428. Analysis of enzyme activities indicates that Pf9279-4 rice plants defend against SBPH through the activation of the pathway of the salicylic acid (SA)-dependent systemic acquired resistance. In conclusion, this study provides some insights into the molecular networks involved on cellular and physiological

  10. Comparative Proteomic Analysis of Susceptible and Resistant Rice Plants during Early Infestation by Small Brown Planthopper

    Directory of Open Access Journals (Sweden)

    Yan Dong

    2017-10-01

    Full Text Available The small brown planthopper (Laodelphax striatellus Fallén, Homoptera, Delphacidae-SBPH is one of the major destructive pests of rice (Oryza sativa L.. Understanding on how rice responds to SBPH infestation will contribute to developing strategies for SBPH control. However, the response of rice plant to SBPH is poorly understood. In this study, two contrasting rice genotypes, Pf9279-4 (SBPH-resistant and 02428 (SBPH-susceptible, were used for comparative analysis of protein profiles in the leaf sheath of rice plants in responses to SBPH infestation. One hundred and thirty-two protein spots that were differentially expressed between the resistant and susceptible rice lines were identified with significant intensity differences (≥2-fold, P < 0.05 at 0, 6, and 12 h after SBPH infestation. Protein expression profile analysis in the leaf sheath of SBPH-resistant and SBPH-susceptible rice lines after SBPH infestation showed that proteins induced by SBPH feeding were involved mainly in stress response, photosynthesis, protein metabolic process, carbohydrate metabolic process, energy metabolism, cell wall-related proteins, amino acid metabolism and transcriptional regulation. Gene expression analysis of 24 differentially expressed proteins (DEPs showed that more than 50% DEPs were positively correlated with their mRNA levels. Analysis of some physiological indexes mainly involved in the removal of oxygen reactive species showed that the levels of superoxide dismutase (SOD and glutathione (GSH were considerably higher in Pf9279-4 than 02428 during SBPH infestation. The catalase (CAT activity and hydroxyl radical inhibition were lower in Pf9279-4 than 02428. Analysis of enzyme activities indicates that Pf9279-4 rice plants defend against SBPH through the activation of the pathway of the salicylic acid (SA-dependent systemic acquired resistance. In conclusion, this study provides some insights into the molecular networks involved on cellular and

  11. Monocot and dicot MLO powdery mildew susceptibility factors are functionally conserved in spite of the evolution of class-specific molecular features.

    Science.gov (United States)

    Appiano, Michela; Catalano, Domenico; Santillán Martínez, Miguel; Lotti, Concetta; Zheng, Zheng; Visser, Richard G F; Ricciardi, Luigi; Bai, Yuling; Pavan, Stefano

    2015-10-26

    Specific members of the plant Mildew Locus O (MLO) protein family act as susceptibility factors towards powdery mildew (PM), a worldwide-spread fungal disease threatening many cultivated species. Previous studies indicated that monocot and dicot MLO susceptibility proteins are phylogenetically divergent. A bioinformatic approach was followed to study the type of evolution of Angiosperm MLO susceptibility proteins. Transgenic complementation tests were performed for functional analysis. Our results show that monocot and dicot MLO susceptibility proteins evolved class-specific conservation patterns. Many of them appear to be the result of negative selection and thus are likely to provide an adaptive value. We also tested whether different molecular features between monocot and dicot MLO proteins are specifically required by PM fungal species to cause pathogenesis. To this aim, we transformed a tomato mutant impaired for the endogenous SlMLO1 gene, and therefore resistant to the tomato PM species Oidium neolycopersici, with heterologous MLO susceptibility genes from the monocot barley and the dicot pea. In both cases, we observed restoration of PM symptoms. Finally, through histological observations, we demonstrate that both monocot and dicot susceptibility alleles of the MLO genes predispose to penetration of a non-adapted PM fungal species in plant epidermal cells. With this study, we provide insights on the evolution and function of MLO genes involved in the interaction with PM fungi. With respect to breeding research, we show that transgenic complementation assays involving phylogenetically distant plant species can be used for the characterization of novel MLO susceptibility genes. Moreover, we provide an overview of MLO protein molecular features predicted to play a major role in PM susceptibility. These represent ideal targets for future approaches of reverse genetics, addressed to the selection of loss-of-function resistant mutants in cultivated species.

  12. Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

    Directory of Open Access Journals (Sweden)

    C. J. Carter

    2013-01-01

    Full Text Available Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (multiple sclerosis, and autism (, but not anorexia or chronic fatigue are highly enriched in the human arm of this interactome and 18 (ADHD to 33% (MS of the susceptibility genes relate to it. The signalling pathways involved in the susceptibility gene/interactome overlaps are relatively specific and relevant to each disease suggesting a means whereby susceptibility genes could orient the attentions of a single pathogen towards disruption of the specific pathways that together contribute (positively or negatively to the endophenotypes of different diseases. Conditional protein knockdown, orchestrated by T. gondii proteins or antibodies binding to those of the host (pathogen derived autoimmunity and metabolite exchange, may contribute to this disruption. Susceptibility genes may thus be related to the causes and influencers of disease, rather than (and as well as to the disease itself.

  13. Thyroid status affects membranes susceptibility to free radicals and oxidative balance in skeletal muscle of Muscovy ducklings (Cairina moschata).

    Science.gov (United States)

    Rey, Benjamin; Romestaing, Caroline; Bodennec, Jacques; Dumet, Adeline; Fongy, Anaïs; Duchamp, Claude; Roussel, Damien

    2014-10-01

    Thyroid hormones (TH) are major contributor to oxidative stress in mammals because they (1) stimulate reactive oxygen species generation (ROS), (2) impair antioxidant defenses, and (3) increase the susceptibility to free radicals of most tissues. Unlike mammals, THs seem to diminish mitochondrial ROS while they have limited effect on the antioxidant machinery in birds. However, how THs modify the susceptibility to ROS has never been explored in an avian model, and very little is known about their effect on oxidative balance in birds. Therefore, the objective of our study was to examine the effect of chronic pharmacological hypo- and hyperthyroidism on (i) the susceptibility of mitochondrial membranes to ROS; and (ii) the level of oxidative stress assessed by measuring oxidative damage to lipids, nucleic acids and proteins in the gastrocnemius muscle of ducklings. We show that hypothyroidism had no effect on the susceptibility of mitochondrial membranes to free radicals. Hypothyroid ducklings had lower oxidized lipids (-31%) and DNA (-25%) but a similar level of protein carbonylation relative to controls. Conversely, mitochondrial membranes of hyperthyroid ducklings exhibited higher unsaturation (+12%) and peroxidation (+31%) indexes than in controls indicating a greater susceptibility to free radicals. However, hyperthyroid ducklings exhibited more oxidative damages on proteins (+67%) only, whereas lipid damages remained unchanged, and there was a slight reduction (-15%) in damages to DNA compared to euthyroid controls. Our results indicate that birds and mammals present fundamental differences in their oxidative stress response to thyroid status. © 2014 Wiley Periodicals, Inc.

  14. Novel susceptibility loci for Alzheimer's disease.

    Science.gov (United States)

    Reitz, Christiane

    2015-12-01

    Late-onset Alzheimer's disease (AD), a highly prevalent neurodegenerative disorder characterized by progressive deterioration in cognition, function and behavior terminating in incapacity and death, is a clinically and pathologically heterogeneous disease with a substantial heritable component. During the past 5 years, the technological developments in next-generation high-throughput genome technologies have led to the identification of more than 20 novel susceptibility loci for AD, and have implicated specific pathways in the disease, in particular intracellular trafficking/endocytosis, inflammation and immune response and lipid metabolism. These observations have significantly advanced our understanding of underlying pathogenic mechanisms and potential therapeutic targets. This review article summarizes these recent advances in AD genomics and discusses the value of identified susceptibility loci for diagnosis and prognosis of AD.

  15. Entanglement susceptibility: area laws and beyond

    Science.gov (United States)

    Zanardi, Paolo; Campos Venuti, Lorenzo

    2013-04-01

    Generic quantum states in the Hilbert space of a many-body system are nearly maximally entangled whereas low-energy physical states are not; the so-called area laws for quantum entanglement are widespread. In this paper we introduce the novel concept of entanglement susceptibility by expanding the 2-Rényi entropy in the boundary couplings. We show how this concept leads to the emergence of area laws for bi-partite quantum entanglement in systems ruled by local gapped Hamiltonians. Entanglement susceptibility also captures quantitatively which violations one should expect when the system becomes gapless. We also discuss an exact series expansion of the 2-Rényi entanglement entropy in terms of connected correlation functions of a boundary term. This is obtained by identifying Rényi entropy with ground state fidelity in a doubled and twisted theory.

  16. Individual differences in susceptibility to inattentional blindness.

    Science.gov (United States)

    Seegmiller, Janelle K; Watson, Jason M; Strayer, David L

    2011-05-01

    Inattentional blindness refers to the finding that people do not always see what appears in their gaze. Though inattentional blindness affects large percentages of people, it is unclear if there are individual differences in susceptibility. The present study addressed whether individual differences in attentional control, as reflected by variability in working memory capacity, modulate susceptibility to inattentional blindness. Participants watched a classic inattentional blindness video (Simons & Chabris, 1999) and were instructed to count passes among basketball players, wherein 58% noticed the unexpected: a person wearing a gorilla suit. When participants were accurate with their pass counts, individuals with higher working memory capacity were more likely to report seeing the gorilla (67%) than those with lesser working memory capacity (36%). These results suggest that variability in attentional control is a potential mechanism underlying the apparent modulation of inattentional blindness across individuals.

  17. [Rapid antibiotic susceptibility test in Clinical Microbiology].

    Science.gov (United States)

    March Rosselló, Gabriel Alberto; Bratos Pérez, Miguel Ángel

    2016-01-01

    The most widely used antibiotic susceptibility testing methods in Clinical Microbiology are based on the phenotypic detection of antibiotic resistance by measuring bacterial growth in the presence of the antibiotic being tested. These conventional methods take typically 24hours to obtain results. A review is presented here of recently developed techniques for the rapid determination of antibiotic susceptibility. Data obtained with different methods such as molecular techniques, flow cytometry, chemiluminescence, mass spectrometry, commercial methods used in routine work, colorimetric methods, nephelometry, microarrays, microfluids, and methods based on cell disruption and sequencing, are analyzed and discussed in detail. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Trained Immunity and Susceptibility to HIV.

    Science.gov (United States)

    Derrick, Steven C

    2017-01-01

    In this issue of Clinical and Vaccine Immunology, K. Jensen et al. (Clin Vaccine Immunol 24:e00360-16, 2017, https://doi.org/10.1128/CVI.00360-16) describe a dual-purpose attenuated Mycobacterium tuberculosis-simian immunodeficiency virus vaccine (AMTB-SIV). Interestingly, immunized infant macaques required fewer oral exposures to SIV to become infected relative to nonimmunized animals. The authors hypothesized that augmented susceptibility to SIV was due to activation of CD4+ T cells through trained immunity. This commentary explores the possible relationship between trained immunity, enhanced CD4 T cell responses, and increased susceptibility to human immunodeficiency virus (HIV). Copyright © 2017 American Society for Microbiology.

  19. Magnetization and magnetic susceptibility of kunzite

    Energy Technology Data Exchange (ETDEWEB)

    Bartkowska, J.A. E-mail: jobart@polsl.katowice.pl; Cisowski, J.; Voiron, J.; Heimann, J.; Czaja, M.; Mazurak, Z

    2000-11-01

    We have studied the high-field magnetization up to 14.5 T and magnetic susceptibility in the temperature range 1.6-400 K of three different samples of natural kunzite crystals, being a variety of spodumene (LiAlSi{sub 2}O{sub 6}) and containing transition metal ions. It appears that the total magnetization and susceptibility consist of the paramagnetic contribution following from the temperature-dependent Brillouin-type behavior of magnetic ions and temperature-independent diamagnetic contribution of the spodumene matrix which we have found as being equal to -3.5x10{sup -7} emu/g. We have identified the Mn{sup 2+} ions as the dominant ones in the kunzites studied and we have determined the molar concentration of these ions as lying in the range 0.2-0.4%.

  20. Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility.

    Science.gov (United States)

    Chandra, Ramesh; Francis, T Chase; Nam, Hyungwoo; Riggs, Lace M; Engeln, Michel; Rudzinskas, Sarah; Konkalmatt, Prasad; Russo, Scott J; Turecki, Gustavo; Iniguez, Sergio D; Lobo, Mary Kay

    2017-07-05

    Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression. Consistent with our preclinical data, we observed Slc6a15 mRNA reduction in NAc of individuals with major depressive disorder (MDD). The Slc6a15 reduction in NAc occurred selectively in D2-neurons. Next, we used Cre-inducible viruses combined with D2-Cre mice to reduce or overexpress Slc6a15 in NAc D2-neurons. Slc6a15 reduction in D2-neurons caused enhanced susceptibility to a subthreshold social defeat stress (SSDS) as observed by reduced social interaction, while a reduction in social interaction following CSDS was not observed when Slc6a15 expression in D2-neurons was restored. Finally, since both D2-medium spiny neurons (MSNs) and D2-expressing choline acetyltransferase (ChAT) interneurons express Slc6a15, we examined Slc6a15 protein in these interneurons after CSDS. Slc6a15 protein was unaltered in ChAT interneurons. Consistent with this, reducing Slc5a15 selectively in NAc D2-MSNs, using A2A-Cre mice that express Cre selectively in D2-MSNs, caused enhanced susceptibility to SSDS. Collectively, our data demonstrate that reduced Slc6a15 in NAc occurs in MDD individuals and that Slc6a15 reduction in NAc D2-neurons underlies stress susceptibility. SIGNIFICANCE STATEMENT Our study demonstrates a role for reduced Slc6a15, a neutral amino acid transporter, in nucleus accumbens (NAc) in depression and stress susceptibility. The

  1. In vitro susceptibility testing of Dientamoeba fragilis.

    Science.gov (United States)

    Nagata, N; Marriott, D; Harkness, J; Ellis, J T; Stark, D

    2012-01-01

    Dientamoeba fragilis is a commonly encountered trichomonad which has been implicated as a cause of gastrointestinal disease in humans. Despite the frequency of reports recording infections with this parasite, little research has been undertaken in terms of antimicrobial susceptibility. The aim of this study was to evaluate the susceptibility of D. fragilis to several commonly used antiparasitic agents: diloxanide furoate, furazolidone, iodoquinol, metronidazole, nitazoxanide, ornidazole, paromomycin, secnidazole, ronidazole, tetracycline, and tinidazole. Antibiotic susceptibility testing was performed on four clinical strains of D. fragilis, designated A, E, M, and V, respectively. Molecular testing followed, and all strains were determined to be genotype 1. The activities of antiprotozoal compounds at concentrations ranging from 2 μg/ml to 500 μg/ml were determined via cell counts of D. fragilis trophozoites grown in dixenic culture. Minimum lethal concentrations (MLCs) were as follows: ornidazole, 8 to 16 μg/ml; ronidazole, 8 to 16 μg/ml; tinidazole, 31 μg/ml; metronidazole, 31 μg/ml; secnidazole, 31 to 63 μg/ml; nitazoxanide, 63 μg/ml; tetracycline, 250 μg/ml; furazolidone, 250 to 500 μg/ml; iodoquinol, 500 μg/ml; paromomycin, 500 μg/ml; and diloxanide furoate, >500 μg/ml. This is the first study to report the profiles of susceptibility to a wide range of commonly used treatments for clinical isolates of D. fragilis. Our study indicated 5-nitroimidazole derivatives to be the most active compounds in vitro against D. fragilis.

  2. THE SUSCEPTIBILITY OF MICE TO BACTERIAL ENDOTOXINS

    Science.gov (United States)

    Schaedler, Russell W.; Dubos, Rene J.

    1961-01-01

    Albino mice (Rockefeller NCS strain) raised and maintained free of ordinary bacterial pathogens, as well as of intestinal Escherichia coli and of Proteus bacilli, were found to be highly resistant to the lethal effect of bacterial endotoxins. When newborn mice of this NCS colony were nursed by foster mothers from another colony raised under ordinary conditions (SS colony from which the NCS colony was derived), they acquired the intestinal flora of the latter animals and became susceptible to the lethal effects of endotoxins. NCS adult mice could be rendered susceptible to the lethal effect of endotoxins by vaccination with heat killed Gram-negative bacilli. The susceptibility thus induced exhibited a certain degree of specificity for the bacterial strain used in vaccination. Although untreated NCS mice were resistant to the lethal effect of endotoxins, they proved exquisitively susceptible to the infection-enhancing effect of these materials. For example, 1 µg. or less of endotoxin was found sufficient to help establish a rapidly fatal septicemia with Staphylococcus aureus. Small amounts of endotoxin (1 µg. or less), administered alone, caused a marked but transient loss of weight. Vaccination with heat-killed Gram-negative bacilli or with killed BCG increased the resistance of NCS mice to the infection-enhancing effect of small amounts of endotoxin. This protective effect exhibited a certain degree of specificity for the bacterial strain from which the toxin used in the infection-enhancing test was derived. These various findings can be explained by assuming that the pathological effects of endotoxins involve at least two unrelated mechanisms; (a) a primary toxicity illustrated in this study by the loss of weight and enhancement of infection resulting from the injection of small doses of toxin; (b) an immunological reaction with lethal consequences which became manifest only in animals sensitized to the endotoxin by prior exposure to Gram-negative bacilli. PMID

  3. Polymyxins: Antimicrobial susceptibility concerns and therapeutic options

    Directory of Open Access Journals (Sweden)

    V Balaji

    2011-01-01

    Full Text Available The increasing prevalence of multidrug-resistant nosocomial pathogens such as Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae poses a great challenge to the treating physicians. The paucity of newer effective antimicrobials has led to renewed interest in the polymyxin group of drugs, as a last resort for treatment of gram-negative bacterial infections. There is a dearth of information on the pharmacological properties of colistin, leading to difficulties in selecting the right dose, dosing interval, and route of administration for treatment, especially in critically-ill patients. The increasing use of colistin over the last few years necessitates the need for accurate and reliable in vitro susceptibility testing methods. Development of heteroresistant strains as a result of colistin monotherapy is also a growing concern. There is a compelling need from the clinicians to provide options for probable and possible colistin combination therapy for multidrug-resistant bacterial infections in the ICU setting. Newer combination drug synergy determination tests are being developed and reported. There are no standardized recommendations from antimicrobial susceptibility testing reference agencies for the testing and interpretation of these drug combinations. Comparison and analysis of these reported methodologies may help to understand and assist the microbiologist to choose the best method that produces accurate results at the earliest. This will help clinicians to select the appropriate combination therapy. In this era of multidrug resistance it is important for the microbiology laboratory to be prepared, by default, to provide timely synergistic susceptibility results in addition to routine susceptibility, if warranted. Not as a favour or at request, but as a responsibility.

  4. Nasopharyngeal carriage and susceptibility patterns of Streptococcu ...

    African Journals Online (AJOL)

    Résistance à la Pénicilline streptocoque pneumonie soulève la question croissante dans le domaine de la pédiatrie, aux pays sous développés en particulier. A l'extérieur de l'Afrique du Sud, on a connue peu de choses en ce qui concerné S. pneumonie et ses susceptibilities on Afrique sous Sahara. L'objet de cette étude ...

  5. Identification of Potential Biomarkers for Antimony Susceptibility ...

    Indian Academy of Sciences (India)

    Identification of Potential Biomarkers for Antimony Susceptibility/Resistance in L. donovani Rentala Madhubala School of Life Sciences Jawaharlal Nehru University New Delhi, India · Slide 2 · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16.

  6. Antimicrobial susceptibility of Bordetella avium and Bordetella bronchiseptica isolates.

    OpenAIRE

    Mortensen, J E; Brumbach, A; Shryock, T R

    1989-01-01

    Two veterinary pathogens, Bordetella bronchiseptica and Bordetella avium, were tested for their antimicrobial susceptibilities. Of the 20 antimicrobial agents tested, both species were consistently resistant to penicillin and cefuroxime but susceptible to mezlocillin, piperacillin, gentamicin, amikacin, and cefoperazone.

  7. Adolescent Susceptibility to Peer Influence in Sexual Situations

    National Research Council Canada - National Science Library

    Widman, Laura; Choukas-Bradley, Sophia; Helms, Sarah W; Prinstein, Mitchell J

    2016-01-01

    ...; however, not all youth are equally susceptible to these peer influence effects. Understanding individual differences in susceptibility to peer influence is critical to identifying adolescents at risk for negative health outcomes...

  8. Drug susceptibility testing of Mycobacterium tuberculosis to fluoroquinolones

    DEFF Research Database (Denmark)

    Johansen, I S; Larsen, A R; Sandven, P

    2003-01-01

    In the first attempt to establish a quality assurance programme for susceptibility testing of Mycobacterium tuberculosis to fluoroquinolones, 20 strains with different fluoroquinolone susceptibility patterns were distributed by the Supranational Reference Laboratory in Stockholm to the other...

  9. Characterization and quantification of path dependency in landslide susceptibility

    NARCIS (Netherlands)

    Samia, Jalal; Temme, Arnaud; Bregt, Arnold; Wallinga, Jakob; Guzzetti, Fausto; Ardizzone, Francesca; Rossi, Mauro

    2017-01-01

    Landslides cause major environmental damage, economic losses and casualties. Although susceptibility to landsliding is usually considered an exclusively location-specific phenomenon, indications exist that landslide history co-determines susceptibility to future landslides. In this contribution,

  10. Polaritons and retarded interactions in nonlinear optical susceptibilities

    NARCIS (Netherlands)

    Knoester, Jasper; Mukamel, Shaul

    1989-01-01

    The role of retarded intermolecular interactions (polariton effects) in the nonlinear optical susceptibilities of condensed phases is studied. A systematic method for calculating these susceptibilities is developed, based on the derivation of reduced equations of motion which couple the electronic

  11. Diamagnetic bulk susceptibility data of C4H8S

    Science.gov (United States)

    Kumar, M.; Gupta, R.

    This document is part of Subvolume B `Diamagnetic Susceptibility of Organic Compounds, Oils, Paraffins and Polyethylenes' of Volume 27 `Diamagnetic Susceptibility and Anisotropy' of Landolt-Börnstein - Group II Molecules and Radicals.

  12. fosI Is a New Integron-Associated Gene Cassette Encoding Reduced Susceptibility to Fosfomycin

    OpenAIRE

    Pelegrino,Karla de Oliveira; Campos, Juliana Coutinho; Sampaio, Suely Carlos Ferreira; Lezirovitz,Karina; Seco, Bruna Mara; Pereira, Mayne de Oliveira; Rocha, Darlan Augusto da Costa; Jové, Thomas; Nicodemo, Antonio Carlos; Sampaio, Jorge Luiz Mello

    2015-01-01

    In this work, we demonstrate that the fosI gene encodes a predicted small protein with 134 amino acids and determines reduced susceptibility to fosfomycin. It raised the MIC from 0.125 to 6 μg/ml when the pBRA100 plasmid was introduced into Escherichia coli TOP10 and to 16 μg/ml when the gene was cloned into the pBC_SK(−) vector and expressed in E. coli TOP10.

  13. Genetic architecture of intrinsic antibiotic susceptibility.

    Directory of Open Access Journals (Sweden)

    Hany S Girgis

    2009-05-01

    Full Text Available Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired.To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance.Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect.

  14. Genetic heterogeneity in breast cancer susceptibility.

    Science.gov (United States)

    Andersen, T I

    1996-01-01

    Approximately 20% of breast cancer patients have a family history of the disease, and in one-fourth of these cases breast cancer appears to be inherited as an autosomally dominant trait. Five genes and gene regions involved in breast cancer susceptibility have been uncovered. Germ-line mutations in the recently cloned BRCA1 gene at 17q21 is considered to be responsible for the disease in a majority of the breast-ovarian cancer families and in 40-45% of the site-specific breast cancer families, but appears not to be involved in families with both male and female breast cancer cases. The BRCA2 locus at 13q12-q13 appears to be involved in 40-45% of the site-specific breast cancer families, and in most of the families with affected males. The gene located in this region, however, does not seem to confer susceptibility to ovarian cancer. The TP53 gene is involved in breast cancer development in the Li-Fraumeni syndrome and Li-Fraumeni syndrom-like families, whereas germ-line mutations in the androgen receptor (AR) gene is present in a subset of male breast cancers. Furthermore, females who are obligate carriers of ataxia telangiectasia (AT) have a 4-12 times relative risk of developing breast cancer as compared with the general female population, indicating that germ-line mutations in AT also confer susceptibility to breast cancer.

  15. Penicillin-susceptible Staphylococcus aureus: susceptibility testing, resistance rates and outcome of infection.

    Science.gov (United States)

    Hagstrand Aldman, Malin; Skovby, Annette; I Påhlman, Lisa

    2017-06-01

    Staphylococcus aureus (SA) is an important human pathogen that causes both superficial and invasive infections. Penicillin is now rarely used in the treatment of SA infections due to widespread resistance and a concern about the accuracy of existing methods for penicillin susceptibility testing. The aims of the present study were to determine the frequency of penicillin-susceptible SA isolates from blood and wound cultures in Lund, Sweden, and to evaluate methods for penicillin testing in SA. We also wanted to investigate if penicillin-susceptible isolates are associated with higher mortality. Hundred blood culture isolates collected 2008/2009, 140 blood culture isolates from 2014/2015, and 141 superficial wound culture strains from 2015 were examined. Penicillin susceptibility was tested with disk diffusion according to EUCAST guidelines, and results were confirmed with a cloverleaf assay and PCR amplification of the BlaZ gene. Patient data for all bacteraemia cases were extracted from medical records. The disk diffusion method with assessment of both zone size and zone edge appearance had high accuracy in our study. About 57% of bacteraemia isolates from 2008/2009 were sensitive to penicillin compared to 29% in 2014/2015 (p penicillin susceptible. There was no difference in co-morbidity or mortality rates between patients with penicillin resistant and penicillin sensitive SA bacteraemia. Disk-diffusion is a simple and reliable method to detect penicillin resistance in SA, and susceptibility rates are significant. Penicillin has many theoretical advantages and should be considered in the treatment of SA bacteraemia when susceptible.

  16. Definition of a magnetic susceptibility of conglomerates with magnetite particles. Particularities of defining single particle susceptibility

    Science.gov (United States)

    Sandulyak, A. A.; Sandulyak, A. V.; Ershova, V.; Pamme, N.; Ngmasom, B.; Iles, A.

    2017-11-01

    Data of a magnetic susceptibility of ferro-and the ferrimagnetic particles of many technogenic, natural, special media are especially demanded for the solution of various tasks connected with purposeful magnetic impact on these particles. One of productive approaches to definition of a magnetic susceptibility χ of these particles consists in receiving experimental data of a susceptibility of disperse samples with a disperse phase of these particles. The paper expounds and analyses the results of experiments on defining (by Faraday method in a magnetic field with intensity H = 90-730 kA/m) the magnetic susceptibility of disperse samples (conglomerates) with a given volume ratio γ of magnetite particles (γ = 0.0065-0.25). The corresponding families of concentration and field dependences are provided alongside with discussing the applicability of linear and exponential functions to describe these dependences. We consider the possibility of defining single particles susceptibility χ (with simultaneous obtaining field dependence of this susceptibility) by the commonly used relation χ = /γ both at relatively small (preferable for accuracy reasons) values γ - to γ = 0.02…0.025, as well as at increased values γ - up to γ = 0.25. The data χ are provided depending on H and correlating with known data at H defined here value of constant-multiplier (0.8), it provides the grounds for obtaining valid data χ, employing the results of measuring for conglomerates with not obligatory small values of γ. It is demonstrated that being obtained by data χ, the calculated field dependence of the particle matter magnetic susceptibility χm (for the case when the particles are traditionally likened to balls with the characteristic for them demagnetising factor equalling 1/3) complies with the anticipated inverse function χm ∼ 1/H in the studied area H (where magnetization M expressed as M = χH reaches saturation M = Const).

  17. FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Leandra Fiori Lopes

    2014-01-01

    Full Text Available Triple negative breast cancer (TNBC is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2. FOXP3 (forkhead transcription factor 3 is a marker of regulatory T cells (Tregs, whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548 and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction. Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06 in relation to TNBC susceptibility. Most of the patients (83% showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026. In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples.

  18. Gene Expression Analysis of Plum pox virus (Sharka Susceptibility/Resistance in Apricot (Prunus armeniaca L..

    Directory of Open Access Journals (Sweden)

    Manuel Rubio

    Full Text Available RNA-Seq has proven to be a very powerful tool in the analysis of the Plum pox virus (PPV, sharka disease/Prunus interaction. This technique is an important complementary tool to other means of studying genomics. In this work an analysis of gene expression of resistance/susceptibility to PPV in apricot is performed. RNA-Seq has been applied to analyse the gene expression changes induced by PPV infection in leaves from two full-sib apricot genotypes, "Rojo Pasión" and "Z506-7", resistant and susceptible to PPV, respectively. Transcriptomic analyses revealed the existence of more than 2,000 genes related to the pathogen response and resistance to PPV in apricot. These results showed that the response to infection by the virus in the susceptible genotype is associated with an induction of genes involved in pathogen resistance such as the allene oxide synthase, S-adenosylmethionine synthetase 2 and the major MLP-like protein 423. Over-expression of the Dicer protein 2a may indicate the suppression of a gene silencing mechanism of the plant by PPV HCPro and P1 PPV proteins. On the other hand, there were 164 genes involved in resistance mechanisms that have been identified in apricot, 49 of which are located in the PPVres region (scaffold 1 positions from 8,050,804 to 8,244,925, which is responsible for PPV resistance in apricot. Among these genes in apricot there are several MATH domain-containing genes, although other genes inside (Pleiotropic drug resistance 9 gene or outside (CAP, Cysteine-rich secretory proteins, Antigen 5 and Pathogenesis-related 1 protein; and LEA, Late embryogenesis abundant protein PPVres region could also be involved in the resistance.

  19. Gene Expression Analysis of Plum pox virus (Sharka) Susceptibility/Resistance in Apricot (Prunus armeniaca L.).

    Science.gov (United States)

    Rubio, Manuel; Ballester, Ana Rosa; Olivares, Pedro Manuel; Castro de Moura, Manuel; Dicenta, Federico; Martínez-Gómez, Pedro

    2015-01-01

    RNA-Seq has proven to be a very powerful tool in the analysis of the Plum pox virus (PPV, sharka disease)/Prunus interaction. This technique is an important complementary tool to other means of studying genomics. In this work an analysis of gene expression of resistance/susceptibility to PPV in apricot is performed. RNA-Seq has been applied to analyse the gene expression changes induced by PPV infection in leaves from two full-sib apricot genotypes, "Rojo Pasión" and "Z506-7", resistant and susceptible to PPV, respectively. Transcriptomic analyses revealed the existence of more than 2,000 genes related to the pathogen response and resistance to PPV in apricot. These results showed that the response to infection by the virus in the susceptible genotype is associated with an induction of genes involved in pathogen resistance such as the allene oxide synthase, S-adenosylmethionine synthetase 2 and the major MLP-like protein 423. Over-expression of the Dicer protein 2a may indicate the suppression of a gene silencing mechanism of the plant by PPV HCPro and P1 PPV proteins. On the other hand, there were 164 genes involved in resistance mechanisms that have been identified in apricot, 49 of which are located in the PPVres region (scaffold 1 positions from 8,050,804 to 8,244,925), which is responsible for PPV resistance in apricot. Among these genes in apricot there are several MATH domain-containing genes, although other genes inside (Pleiotropic drug resistance 9 gene) or outside (CAP, Cysteine-rich secretory proteins, Antigen 5 and Pathogenesis-related 1 protein; and LEA, Late embryogenesis abundant protein) PPVres region could also be involved in the resistance.

  20. Etiology and antibiotic susceptibility pattern of community-acquired ...

    African Journals Online (AJOL)

    Streptomycin showed the highest susceptibility to bacteria isolates while the least susceptibility was observed with augmentin. Rational use of antibiotics with regular antibiotics susceptibility surveillance studies is recommended to maintain high antibiotic therapeutic profile. Keywords: Community-acquired urinary tract ...

  1. Susceptibility Status of Anopheles gambiae s.l. (Diptera: Culicidae ...

    African Journals Online (AJOL)

    komla

    susceptible 'Kisumu' strain, both Korle-Bu and Airport populations were highly resistant to DDT and gave resistance levels which were over nine-fold for permethrin and over 2.5-fold for deltamethrin. Both wild and susceptible populations showed full susceptibility to malathion. The S and M forms of A. gambiae s.s. were ...

  2. Susceptibility status of Anopheles gambiae s.l. (Diptera: Culicidae ...

    African Journals Online (AJOL)

    susceptible 'Kisumu' strain, both Korle-Bu and Airport populations were highly resistant to DDT and gave resistance levels which were over nine-fold for permethrin and over 2.5-fold for deltamethrin. Both wild and susceptible populations showed full susceptibility to malathion. The S and M forms of A. gambiae s.s. were ...

  3. Quark number density and susceptibility calculation under one loop ...

    Indian Academy of Sciences (India)

    S Somorendro Singh

    2017-05-30

    May 30, 2017 ... Abstract. We calculate quark number density and susceptibility under one-loop correction in the mean- field potential. The calculation shows continuous increase in the number density and susceptibility up to the temperature T = 0.4 GeV. Then the values of number density and susceptibility approach the ...

  4. Porcine prion protein amyloid.

    Science.gov (United States)

    Hammarström, Per; Nyström, Sofie

    2015-01-01

    Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions.

  5. Aquifer susceptibility in Virginia, 1998-2000

    Science.gov (United States)

    Nelms, David L.; Harlow, George E.; Plummer, L. Niel; Busenberg, Eurybiades

    2003-01-01

    The U.S. Geological Survey (USGS), in cooperation with the Virginia Department of Health, sampled water from 171 wells and springs across the Commonwealth of Virginia between 1998 and 2000 as part of the Virginia Aquifer Susceptibility study. Most of the sites sampled are public water supplies that are part of the comprehensive Source Water Assessment Program for the Commonwealth. The fundamental premise of the study was that the identification of young waters (less than 50 years) by multiple environmental tracers could be used as a guide for classifying aquifers in terms of susceptibility to contamination from near-surface sources. Environmental tracers, including chlorofluorocarbons (CFCs), sulfur hexafluoride (SF6), tritium (3H), and tritium/helium-3 (3H/3He), and carbon isotopes (14C and d13C) were used to determine the age of water discharging from wells and springs. Concentrations of CFCs greater than 5 picograms per kilogram and 3H concentrations greater than 0.6 tritium unit were used as thresholds to indicate that parts of the aquifer sampled have a component of young water and are, therefore, susceptible to near-surface contamination. Concentrations of CFCs exceeded the susceptibility threshold in 22 percent of the wells and in one spring sampled in the Coastal Plain regional aquifer systems. About 74 percent of the samples from wells with the top of the first water zone less than 100 feet below land surface exceeded the threshold values, and water supplies developed in the upper 100 feet of the Coastal Plain are considered to be susceptible to contamination from near-surface sources. The maximum depth to the top of the screened interval for wells that contained CFCs was less than 150 feet. Wells completed in the deep confined aquifers in the Coastal Plain generally contain water older than 1,000 years, as indicated by carbon-14 dating, and are not considered to be susceptible to contamination under natural conditions. All of the water samples from wells

  6. Proteomic analysis of membrane proteins of vero cells: exploration of potential proteins responsible for virus entry.

    Science.gov (United States)

    Guo, Donghua; Zhu, Qinghe; Zhang, Hong; Sun, Dongbo

    2014-01-01

    Vero cells are highly susceptible to many viruses in humans and animals, and its membrane proteins (MPs) are responsible for virus entry. In our study, the MP proteome of the Vero cells was investigated using a shotgun LC-MS/MS approach. Six hundred twenty-seven proteins, including a total of 1839 peptides, were identified in MP samples of the Vero cells. In 627 proteins, 307 proteins (48.96%) were annotated in terms of biological process of gene ontology (GO) categories; 356 proteins (56.78%) were annotated in terms of molecular function of GO categories; 414 proteins (66.03%) were annotated in terms of cellular components of GO categories. Of 627 identified proteins, seventeen proteins had been revealed to be virus receptor proteins. The resulting protein lists and highlighted proteins may provide valuable information to increase understanding of virus infection of Vero cells.

  7. Chlorine gas exposure increases susceptibility to invasive lung fungal infection.

    Science.gov (United States)

    Gessner, Melissa A; Doran, Stephen F; Yu, Zhihong; Dunaway, Chad W; Matalon, Sadis; Steele, Chad

    2013-06-01

    Chlorine (Cl₂) is a highly irritating and reactive gas with potential occupational and environmental hazards. Acute exposure to Cl₂ induces severe epithelial damage, airway hyperreactivity, impaired alveolar fluid clearance, and pulmonary edema in the presence of heightened inflammation and significant neutrophil accumulation in the lungs. Herein, we investigated whether Cl₂ exposure affected the lung antimicrobial immune response leading to increased susceptibility to opportunistic infections. Mice exposed to Cl₂ and challenged intratracheally 24 h thereafter with the opportunistic mold Aspergillus fumigatus demonstrated an >500-fold increase in A. fumigatus lung burden 72 h postchallenge compared with A. fumigatus mice exposed to room air. Cl₂-exposed A. fumigatus challenged mice also demonstrated significantly higher lung resistance following methacholine challenge and increased levels of plasma proteins (albumin and IgG) in the bronchoalveolar lavage fluid. Despite enhanced recruitment of inflammatory cells to the lungs of Cl₂-exposed A. fumigatus challenged mice, these cells (>60% of which were neutrophils) demonstrated a profound impairment in generating superoxide. Significantly higher A. fumigatus burden in the lungs of Cl₂ exposed mice correlated with enhanced production of IL-6, TNF-α, CXCL1, CCL2, and CCL3. Surprisingly, however, Cl₂-exposed A. fumigatus challenged mice had a specific impairment in the production of IL-17A and IL-22 in the lungs compared with mice exposed to room air and challenged with A. fumigatus. In summary, our results indicate that Cl₂ exposure markedly impairs the antimicrobial activity and inflammatory reactivity of myeloid cells in the lung leading to increased susceptibility to opportunistic pathogens.

  8. Post-Electrophoretic Identification of Oxidized Proteins

    Directory of Open Access Journals (Sweden)

    Conrad Craig

    2000-01-01

    Full Text Available The oxidative modification of proteins has been shown to play a major role in a number of human diseases. However, the ability to identify specific proteins that are most susceptible to oxidative modifications is difficult. Separation of proteins using polyacrylamide gel electrophoresis (PAGE offers the analytical potential for the recovery, amino acid sequencing, and identification of thousands of individual proteins from cells and tissues. We have developed a method to allow underivatized proteins to be electroblotted onto PVDF membranes before derivatization and staining. Since both the protein and oxidation proteins are quantifiable, the specific oxidation index of each protein can be determined. The optimal sequence and conditions for the staining process are (a electrophoresis, (b electroblotting onto PVDF membranes, (c derivatization of carbonyls with 2,4-DNP, (d immunostaining with anti DNP antibody, and (e protein staining with colloidal gold.

  9. [Examination of urogenital tract microorganism infection and antibiotic susceptibility test].

    Science.gov (United States)

    Li, Wen-wen; Yan, Zu-wei; Dai, Gan

    2003-06-01

    To isolate bacteria, mycoplasma and chlamydia from the urogenital tract, and to determine their antibiotic susceptibility. Bacteria, mycoplasma and chlamydia were isolated from the urogenital tract secretion by artifical culture, and their antibiotic susceptibility was detected by disk diffusion. The common microorganisms were S. epidermidis and corynebacberium, and the minority microorganisms were G- bacteria or E. coli. Bacteria were susceptible to amikacin, cephazolin V, rifampin, gentamycin, and docycyclin. S. epidermidis and corynebacterium are important pathogens of the urogenital tract infection. Disk susceptibility test can be used to screen the susceptible antibiotic.

  10. Antibiotic susceptibility of Listeria monocytogenes in Argentina.

    Science.gov (United States)

    Prieto, Mónica; Martínez, Claudia; Aguerre, Lorena; Rocca, María Florencia; Cipolla, Lucía; Callejo, Raquel

    2016-02-01

    Listeria monocytogenes is the causative agent of listeriosis, a food-borne disease that mainly affects pregnant women, the elderly, and immunocompromised patients. The primary treatment of choice of listeriosis is the combination of ampicillin or penicillin G, with an aminoglycoside, classically gentamicin. The second-choice therapy for patients allergic to β-lactams is the combination of trimethoprim with a sulfonamide (such as co-trimoxazole). The aim of this study was to analyze the antimicrobial susceptibility profile of strains isolated from human infections and food during the last two decades in Argentina. The minimal inhibitory concentration (MIC) of 8 antimicrobial agents was determined for a set of 250 strains of L. monocytogenes isolated in Argentina during the period 1992-2012. Food-borne and human isolates were included in this study. The antibiotics tested were ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, erythromycin, gentamicin, penicillin G, tetracycline and rifampicin. Breakpoints for penicillin G, ampicillin and trimethoprim-sulfamethoxazole were those given in the CLSI for L. monocytogenes. CLSI criteria for staphylococci were applied to the other antimicrobial agents tested. Strains were serotyped by PCR, and confirmed by an agglutination method. Strains recovered from human listeriosis patients showed a prevalence of serotype 4b (71%), with the remaining 29% corresponding to serotype 1/2b. Serotypes among food isolates were distributed as 62% serotype 1/2b and 38% serotype 4b. All antimicrobial agents showed good activity. The strains of L. monocytogenes isolated in Argentina over a period of 20 years remain susceptible to antimicrobial agents, and that susceptibility pattern has not changed during this period. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  11. Magnetic susceptibility as a biosignature in stromatolites

    Science.gov (United States)

    Petryshyn, Victoria A.; Corsetti, Frank A.; Frantz, Carie M.; Lund, Steve P.; Berelson, William M.

    2016-03-01

    Microbialites have long been a focus of study in geobiology because they are macroscopic sedimentary records of the activities of microscopic organisms. However, abiotic processes can result in microbialite-like morphologies. Developing robust tools for substantiating the biogenicity of putative microbialites remains an important challenge. Here, we report a new potential biosignature based on the detrital magnetic mineral component present in nearly all sedimentary rocks. Detrital grains falling onto a hard, abiogenic, chemically precipitated structure would be expected to roll off surfaces at high incline angles. Thus, the distribution of grains in an abiogenic microbialite should exhibit a dependence on the dip angle along laminae. In contrast, a microbialite formed by the active trapping and binding of detrital grains by microorganisms could exhibit a distribution of detrital grains significantly less dependent on the dip angle of the laminae. However, given that most ancient stromatolites are micritic (composed of carbonate mud), tracking detrital grains vs. precipitated carbonate is not straightforward. Recent advances in our ability to measure miniscule magnetic fields open up the possibility to map magnetic susceptibility as a tracer of detrital grains in stromatolites. In abiogenic carbonate precipitation experiments, magnetic susceptibility fell to zero when the growth surface was inclined above 30° (the angle at which grains rolled off). In cyanobacterial mat experiments, even vertically inclined mats held magnetic material. The results indicate that cyanobacterial mats trap and bind small grains more readily than abiogenic carbonate precipitates alone. A variety of stromatolites of known and unknown biogenicity were then analyzed. Tested stromatolites span many different ages (Eocene to Holocene) and depositional environments (hot springs, lakes), and compositional forms (micritic, sparry crusts, etc.). The results were consistent with the laboratory

  12. Dipolar response of hydrated proteins.

    Science.gov (United States)

    Matyushov, Dmitry V

    2012-02-28

    The paper presents an analytical theory and numerical simulations of the dipolar response of hydrated proteins in solution. We calculate the effective dielectric constant representing the average dipole moment induced at the protein by a uniform external field. The dielectric constant shows a remarkable variation among the proteins, changing from 0.5 for ubiquitin to 640 for cytochrome c. The former value implies a negative dipolar susceptibility, that is a dia-electric dipolar response and negative dielectrophoresis. It means that ubiquitin, carrying an average dipole of ≃240 D, is expected to repel from the region of a stronger electric field. This outcome is the result of a negative cross-correlation between the protein and water dipoles, compensating for the positive variance of the intrinsic protein dipole in the overall dipolar susceptibility. In contrast to the neutral ubiquitin, charged proteins studied here show para-electric dipolar response and positive dielectrophoresis. The study suggests that the dipolar response of proteins in solution is strongly affected by the coupling of the protein surface charge to the hydration water. The protein-water dipolar cross-correlations are long-ranged, extending ~2 nm from the protein surface into the bulk. A similar correlation length of about 1 nm is seen for the electrostatic potential produced by the hydration water inside the protein. The analysis of numerical simulations suggests that the polarization of the protein-water interface is highly heterogeneous and does not follow the standard dielectric results for cavities carved in dielectrics. The polarization of the water shell gains in importance, relative to the intrinsic protein dipole, at high frequencies, above the protein Debye peak. The induced interfacial dipole can be either parallel or antiparallel to the protein dipole, depending on the distribution of the protein surface charge. As a result, the high-frequency absorption of the protein solution can

  13. Interpretive criteria and quality control limits for ceftibuten disk susceptibility tests. Collaborative Antimicrobial Susceptibility Testing Group.

    Science.gov (United States)

    Barry, A L; Jones, R N

    1990-01-01

    In vitro studies were undertaken to evaluate susceptibility tests with 30-micrograms ceftibuten disks. The following interpretive criteria were proposed: less than or equal to 17 mm for resistance (MIC, greater than or equal to 32 micrograms/ml) and greater than or equal to 21 mm for susceptibility (MIC, less than or equal to 8.0 micrograms/ml). A multilaboratory quality control study led to the conclusion that Escherichia coli ATCC 25922 should provide zones 29 to 35 mm in diameter. PMID:2182675

  14. A landslide susceptibility map of Africa

    Science.gov (United States)

    Broeckx, Jente; Vanmaercke, Matthias; Duchateau, Rica; Poesen, Jean

    2017-04-01

    Studies on landslide risks and fatalities indicate that landslides are a global threat to humans, infrastructure and the environment, certainly in Africa. Nonetheless our understanding of the spatial patterns of landslides and rockfalls on this continent is very limited. Also in global landslide susceptibility maps, Africa is mostly underrepresented in the inventories used to construct these maps. As a result, predicted landslide susceptibilities remain subject to very large uncertainties. This research aims to produce a first continent-wide landslide susceptibility map for Africa, calibrated with a well-distributed landslide dataset. As a first step, we compiled all available landslide inventories for Africa. This data was supplemented by additional landslide mapping with Google Earth in underrepresented regions. This way, we compiled 60 landslide inventories from the literature (ca. 11000 landslides) and an additional 6500 landslides through mapping in Google Earth (including 1500 rockfalls). Various environmental variables such as slope, lithology, soil characteristics, land use, precipitation and seismic activity, were investigated for their significance in explaining the observed spatial patterns of landslides. To account for potential mapping biases in our dataset, we used Monte Carlo simulations that selected different subsets of mapped landslides, tested the significance of the considered environmental variables and evaluated the performance of the fitted multiple logistic regression model against another subset of mapped landslides. Based on these analyses, we constructed two landslide susceptibility maps for Africa: one for all landslide types and one excluding rockfalls. In both maps, topography, lithology and seismic activity were the most significant variables. The latter factor may be surprising, given the overall limited degree of seismicity in Africa. However, its significance indicates that frequent seismic events may serve as in important

  15. Macroeconomic susceptibility, inflation, and aggregate supply

    Science.gov (United States)

    Hawkins, Raymond J.

    2017-03-01

    We unify aggregate-supply dynamics as a time-dependent susceptibility-mediated relationship between inflation and aggregate economic output. In addition to representing well various observations of inflation-output dynamics this parsimonious formalism provides a straightforward derivation of popular representations of aggregate-supply dynamics and a natural basis for economic-agent expectations as an element of inflation formation. Our formalism also illuminates questions of causality and time-correlation that challenge central banks for whom aggregate-supply dynamics is a key constraint in their goal of achieving macroeconomic stability.

  16. ANTIBIOTIC SUSCEPTIBILITY OF POTENTIALLY PROBIOTIC LACTOBACILLUS STRAINS

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    Junhua Han

    2015-09-01

    Full Text Available Susceptibility of 29 Lactobacilli to 13 antibiotics was assayed by paper disc diffusion method. Plasmids and gastrointestinal tolerance were detected. The relationship between plasmids andantibiotic resistance was discussed. The results showed that all of the strains were resistant to bacitracin, polymyxin B, kanamycin, and nalidixic acid. Many strains were relatively sensitive tochloramphenicol and tetracycline. Six strains contained plasmids and showed good gastrointestinal tolerance. β-lactam resistance gene blr was found in the plasmid of L. plantarum CICC 23180by PCR. The study will be helpful to promote the safety evaluation and development of potentially probiotic lactic acid bacteria.

  17. Genetic Susceptibility to Triple Negative Breast Cancer

    OpenAIRE

    Stevens, Kristen N.; Vachon, Celine M.; Couch, Fergus J.

    2013-01-01

    Triple negative breast cancers (TNBC), defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 expression, account for 12-24% of all breast cancers. TNBC is associated with early recurrence of disease and poor outcome. Germline mutations in the BRCA1 and BRCA2 breast cancer susceptibility genes have been associated with up to 15% of TNBC, and TNBC accounts for 70% of breast tumors arising in BRCA1 mutation carriers and 16-23% of breast ...

  18. Tobacco use increases susceptibility to bacterial infection

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    Demuth Donald R

    2008-12-01

    Full Text Available Abstract Active smokers and those exposed to secondhand smoke are at increased risk of bacterial infection. Tobacco smoke exposure increases susceptibility to respiratory tract infections, including tuberculosis, pneumonia and Legionnaires disease; bacterial vaginosis and sexually transmitted diseases, such as chlamydia and gonorrhoea; Helicobacter pylori infection; periodontitis; meningitis; otitis media; and post-surgical and nosocomial infections. Tobacco smoke compromises the anti-bacterial function of leukocytes, including neutrophils, monocytes, T cells and B cells, providing a mechanistic explanation for increased infection risk. Further epidemiological, clinical and mechanistic research into this important area is warranted.

  19. Operator fidelity susceptibility, decoherence, and quantum criticality

    Science.gov (United States)

    Lu, Xiao-Ming; Sun, Zhe; Wang, Xiaoguang; Zanardi, Paolo

    2008-09-01

    The extension of the notion of quantum fidelity from the state-space to the operator level can be used to study environment-induced decoherence. The state-dependent operator fidelity susceptibility (OFS), the leading-order term for slightly different operator parameters, is shown to have a nontrivial behavior when the environment is at critical points. Two different contributions to the OFS are identified which have distinct physical origins and temporal dependence. Exact results are obtained for the finite-temperature decoherence caused by a bath described by the Ising model in a transverse field.

  20. Susceptibility weighted imaging of the neonatal brain

    Energy Technology Data Exchange (ETDEWEB)

    Meoded, A.; Poretti, A. [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Northington, F.J. [Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Tekes, A.; Intrapiromkul, J. [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Huisman, T.A.G.M., E-mail: thuisma1@jhmi.edu [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States)

    2012-08-15

    Susceptibility weighted imaging (SWI) is a well-established magnetic resonance technique, which is highly sensitive for blood, iron, and calcium depositions in the brain and has been implemented in the routine clinical use in both children and neonates. SWI in neonates might provide valuable additional diagnostic and prognostic information for a wide spectrum of neonatal neurological disorders. To date, there are few articles available on the application of SWI in neonatal neurological disorders. The purpose of this article is to illustrate and describe the characteristic SWI findings in various typical neonatal neurological disorders.

  1. Confirmation of five novel susceptibility loci for systemic lupus erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci.

    Science.gov (United States)

    Molineros, Julio E; Yang, Wanling; Zhou, Xu-Jie; Sun, Celi; Okada, Yukinori; Zhang, Huoru; Heng Chua, Kek; Lau, Yu-Lung; Kochi, Yuta; Suzuki, Akari; Yamamoto, Kazuhiko; Ma, Jianyang; Bang, So-Young; Lee, Hye-Soon; Kim, Kwangwoo; Bae, Sang-Cheol; Zhang, Hong; Shen, Nan; Looger, Loren L; Nath, Swapan K

    2017-03-15

    We recently identified ten novel SLE susceptibility loci in Asians and uncovered several additional suggestive loci requiring further validation. This study aimed to replicate five of these suggestive loci in a Han Chinese cohort from Hong Kong, followed by meta-analysis (11,656 cases and 23,968 controls) on previously reported Asian and European populations, and to perform bioinformatic analyses on all 82 reported SLE loci to identify shared regulatory signatures. We performed a battery of analyses for these five loci, as well as joint analyses on all 82 SLE loci. All five loci passed genome-wide significance: MYNN (rs10936599, Pmeta = 1.92 × 10-13, OR = 1.14), ATG16L2 (rs11235604, Pmeta = 8.87 × 10 -12, OR = 0.78), CCL22 (rs223881, Pmeta = 5.87 × 10-16, OR = 0.87), ANKS1A (rs2762340, Pmeta = 4.93 × 10-15, OR = 0.87) and RNASEH2C (rs1308020, Pmeta = 2.96 × 10-19, OR = 0.84) and co-located with annotated gene regulatory elements. The novel loci share genetic signatures with other reported SLE loci, including effects on gene expression, transcription factor binding, and epigenetic characteristics. Most (56%) of the correlated (r2 > 0.8) SNPs from the 82 SLE loci were implicated in differential expression (9.81 × 10-198 SLE loci, consistent with apoptosis playing a critical role in SLE. Enrichment analysis revealed common pathways, gene ontology, protein domains, and cell type-specific expression. In summary, we provide evidence of five novel SLE susceptibility loci. Integrated bioinformatics using all 82 loci revealed that SLE susceptibility loci share many gene regulatory features, suggestive of conserved mechanisms of SLE etiopathogenesis. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Genome variations associated with viral susceptibility and calcification in Emiliania huxleyi.

    Directory of Open Access Journals (Sweden)

    Jessica U Kegel

    Full Text Available Emiliania huxleyi, a key player in the global carbon cycle is one of the best studied coccolithophores with respect to biogeochemical cycles, climatology, and host-virus interactions. Strains of E. huxleyi show phenotypic plasticity regarding growth behaviour, light-response, calcification, acidification, and virus susceptibility. This phenomenon is likely a consequence of genomic differences, or transcriptomic responses, to environmental conditions or threats such as viral infections. We used an E. huxleyi genome microarray based on the sequenced strain CCMP1516 (reference strain to perform comparative genomic hybridizations (CGH of 16 E. huxleyi strains of different geographic origin. We investigated the genomic diversity and plasticity and focused on the identification of genes related to virus susceptibility and coccolith production (calcification. Among the tested 31940 gene models a core genome of 14628 genes was identified by hybridization among 16 E. huxleyi strains. 224 probes were characterized as specific for the reference strain CCMP1516. Compared to the sequenced E. huxleyi strain CCMP1516 variation in gene content of up to 30 percent among strains was observed. Comparison of core and non-core transcripts sets in terms of annotated functions reveals a broad, almost equal functional coverage over all KOG-categories of both transcript sets within the whole annotated genome. Within the variable (non-core genome we identified genes associated with virus susceptibility and calcification. Genes associated with virus susceptibility include a Bax inhibitor-1 protein, three LRR receptor-like protein kinases, and mitogen-activated protein kinase. Our list of transcripts associated with coccolith production will stimulate further research, e.g. by genetic manipulation. In particular, the V-type proton ATPase 16 kDa proteolipid subunit is proposed to be a plausible target gene for further calcification studies.

  3. Genome variations associated with viral susceptibility and calcification in Emiliania huxleyi.

    Science.gov (United States)

    Kegel, Jessica U; John, Uwe; Valentin, Klaus; Frickenhaus, Stephan

    2013-01-01

    Emiliania huxleyi, a key player in the global carbon cycle is one of the best studied coccolithophores with respect to biogeochemical cycles, climatology, and host-virus interactions. Strains of E. huxleyi show phenotypic plasticity regarding growth behaviour, light-response, calcification, acidification, and virus susceptibility. This phenomenon is likely a consequence of genomic differences, or transcriptomic responses, to environmental conditions or threats such as viral infections. We used an E. huxleyi genome microarray based on the sequenced strain CCMP1516 (reference strain) to perform comparative genomic hybridizations (CGH) of 16 E. huxleyi strains of different geographic origin. We investigated the genomic diversity and plasticity and focused on the identification of genes related to virus susceptibility and coccolith production (calcification). Among the tested 31940 gene models a core genome of 14628 genes was identified by hybridization among 16 E. huxleyi strains. 224 probes were characterized as specific for the reference strain CCMP1516. Compared to the sequenced E. huxleyi strain CCMP1516 variation in gene content of up to 30 percent among strains was observed. Comparison of core and non-core transcripts sets in terms of annotated functions reveals a broad, almost equal functional coverage over all KOG-categories of both transcript sets within the whole annotated genome. Within the variable (non-core) genome we identified genes associated with virus susceptibility and calcification. Genes associated with virus susceptibility include a Bax inhibitor-1 protein, three LRR receptor-like protein kinases, and mitogen-activated protein kinase. Our list of transcripts associated with coccolith production will stimulate further research, e.g. by genetic manipulation. In particular, the V-type proton ATPase 16 kDa proteolipid subunit is proposed to be a plausible target gene for further calcification studies.

  4. Comparative Transcriptomic Analysis of Primary Duck Hepatocytes Provides Insight into Differential Susceptibility to DHBV Infection.

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    Liang Yan

    Full Text Available Primary duck hepatocytes (PDH displays differential susceptibility to duck hepatitis B virus when maintained in the media supplemented with fetal bovine serum or dimethyl sulfoxide (DMSO which has been widely used for the maintenance of hepatocytes, and prolonging susceptibility to hepadnavirus. However the mechanism underlying maintenance of susceptibility to hepadnavirus by DMSO treatment remains unclear. In this study, a global transcriptome analysis of PDHs under different culture conditions was conducted for investigating the effects of DMSO on maintenance of susceptibility of PDH to DHBV in vitro. The 384 differential expressed genes (DEGs were identified by comparisons between each library pair (PDHs cultured with or without DMSO or fresh isolated PDH. We analyzed canonical pathways in which the DEGs were enriched in Hepatic Fibrosis / Hepatic Stellate Cell Activation, Bile Acid Biosynthesis and Tight Junction signaling. After re-annotation against human genome data, the 384 DEGs were pooled together with proteins belonging to hepatitis B pathway to construct a protein-protein interaction network. The combination of decreased expression of liver-specific genes (CYP3A4, CYP1E1, CFI, RELN and GSTA1 et al with increased expression of hepatocyte-dedifferentiation-associated genes (PLA2G4A and PLCG1 suggested that in vitro culture conditions results in the fading of hepatocyte phenotype in PDHs. The expression of seven DEGs associated with tight junction formation (JAM3, PPP2R2B, PRKAR1B, PPP2R2C, MAGI2, ACTA2 and ACTG2 was up-regulated after short-term culture in vitro, which was attenuated in the presence of DMSO. Those results could shed light on DHBV infection associated molecular events affected by DMSO.

  5. Infection susceptibility and immune senescence with advancing age replicated in accelerated aging Lmna(Dhe) mice.

    Science.gov (United States)

    Xin, Lijun; Jiang, Tony T; Kinder, Jeremy M; Ertelt, James M; Way, Sing Sing

    2015-12-01

    Aging confers increased susceptibility to common pathogens including influenza A virus. Despite shared vulnerability to infection with advancing age in humans and rodents, the relatively long time required for immune senescence to take hold practically restricts the use of naturally aged mice to investigate aging-induced immunological shifts. Here, we show accelerated aging Lmna(Dhe) mice with spontaneous mutation in the nuclear scaffolding protein, lamin A, replicate infection susceptibility, and substantial immune cell shifts that occur with advancing age. Naturally aged (≥ 20 month) and 2- to 3-month-old Lmna(Dhe) mice share near identically increased influenza A susceptibility compared with age-matched Lmna(WT) control mice. Increased mortality and higher viral burden after influenza infection in Lmna(Dhe) mice parallel reduced accumulation of lung alveolar macrophage cells, systemic expansion of immune suppressive Foxp3⁺ regulatory T cells, and skewed immune dominance among viral-specific CD8⁺T cells similar to the immunological phenotype of naturally aged mice. Thus, aging-induced infection susceptibility and immune senescence are replicated in accelerated aging Lmna(Dhe) mice. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  6. Lactobacillus species: taxonomic complexity and controversial susceptibilities.

    Science.gov (United States)

    Goldstein, Ellie J C; Tyrrell, Kerin L; Citron, Diane M

    2015-05-15

    The genus Lactobacillus is a taxonomically complex and is composed of over 170 species that cannot be easily differentiated phenotypically and often require molecular identification. Although they are part of the normal human gastrointestinal and vaginal flora, they can also be occasional human pathogens. They are extensively used in a variety of commercial products including probiotics. Their antimicrobial susceptibilities are poorly defined in part because of their taxonomic complexity and are compounded by the different methods recommended by Clinical Laboratory Standards Institute and International Dairy Foundation. Their use as probiotics for prevention of Clostridium difficile infection is prevalent among consumers worldwide but raises the question of will the use of any concurrent antibiotic effect their ability to survive. Lactobacillus species are generally acid resistant and are able to survive ingestion. They are generally resistant to metronidazole, aminoglycosides and ciprofloxacin with L. acidophilus being susceptible to penicillin and vancomycin, whereas L. rhamnosus and L. casei are resistant to metronidazole and vancomycin. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Organisms causing pyoderma and their susceptibility patterns

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    R G Baslas

    1990-01-01

    Full Text Available Five hundred and seventy cases of pyoderma were studied clinically and bacteriologically. Of these, 58.8% cases were of primary pyoderma, and the rest were secondary pyoderma. Primary pyoderma consituted impetigo contagiosa (21.4%, bullous impetigo (3.3%, ecthyma (4.4%, superficial folliculitis (12.3%, chronic folliculitis of legs (8.8%; forunculosis (3.7% carbuncle (1.8%, folliculitis decalvans (0.4%, sycosis barbae (0.4% and abscess (2.5%. Secondary pyderma cases were infected scabies (23.9%, infected wound (1.1%, infectious eczematoid dermatitis (12.6%, intertrigo (0.4% and miscellaneous (3.3%. In 85 samples, no organism was isolated. Out of 485 samples, 75.9% grew a single organism and the rest (24.1% gave multiple organisms. Among the 603 strains collected, 73.6% were staphylococcus aureus, 25.0% were beta-haemolytic streptococcus and 0.7% each were alpha-haemolytic streptococcus and Gram negative bacilli. Eighty eight per cent strains of Staphylococcus aureous were susceptible to cephaloridine and 27.4% to ampicillin while 97.4% beta haemolytic streptococcus were susceptible to cephaloridine and 23.2% to pencillin.

  8. Measuring Nematic Susceptibilities from the Elastoresistivity Tensor

    Science.gov (United States)

    Hristov, A. T.; Shapiro, M. C.; Hlobil, Patrick; Maharaj, Akash; Chu, Jiun-Haw; Fisher, Ian

    The elastoresistivity tensor mijkl relates changes in resistivity to the strain on a material. As a fourth-rank tensor, it contains considerably more information about the material than the simpler (second-rank) resistivity tensor; in particular, certain elastoresistivity coefficients can be related to thermodynamic susceptibilities and serve as a direct probe of symmetry breaking at a phase transition. The aim of this talk is twofold. First, we enumerate how symmetry both constrains the structure of the elastoresistivity tensor into an easy-to-understand form and connects tensor elements to thermodynamic susceptibilities. In the process, we generalize previous studies of elastoresistivity to include the effects of magnetic field. Second, we describe an approach to measuring quantities in the elastoresistivity tensor with a novel transverse measurement, which is immune to relative strain offsets. These techniques are then applied to BaFe2As2 in a proof of principle measurement. This work is supported by the Department of Energy, Office of Science, Basic Energy Sciences, Materials Sciences and Engineering Division, under Contract DE-AC02-76SF00515.

  9. Antimicrobial susceptibility of Brachyspira hyodysenteriae in Switzerland.

    Science.gov (United States)

    Kirchgässner, C; Schmitt, S; Borgström, A; Wittenbrink, M M

    2016-06-01

    Brachyspira (B.) hyodysenteriae is the causative agent of swine dysentery (SD), a severe mucohaemorrhagic diarrheal disease in pigs worldwide. So far, the antimicrobial susceptibility patterns of B. hyodysenteriae in Switzerland have not been investigated. Therefore, a panel of 30 porcine B. hyodysenteriae isolates were tested against 6 antimicrobial agents by using the VetMIC Brachy panel, a broth microdilution test. Tiamulin and valnemulin showed high antimicrobial activity inhibiting all isolates at low concentrations. The susceptibility testing of doxycycline revealed values from ≤0.25 μg/ ml (47%) to 2 μg/ml (10%). The MIC values of lincomycin ranged between ≤0.5 μg/ml (30%) and 32 μg/ml (43%). For tylosin, 57% of the isolates could not be inhibited at the highest concentration of ≥128 μg/ml. The MIC values for tylvalosin were between ≤0.25 μg/ml (10%) and 8 μg/ml (20%). These findings reveal Switzerland's favourable situation compared to other European countries. Above all, tiamulin and valnemulin are still effective antimicrobial agents and can be further used for the treatment of SD.

  10. Antibiotic Susceptibility Patterns of Vibrio cholerae isolates

    Directory of Open Access Journals (Sweden)

    S D Shrestha

    2010-09-01

    Full Text Available INTRODUCTION: Cholera is one of the most common diarrhoeal diseases in Nepal. Etiological agent of cholera is Vibrio cholerae which removes essential body fluids, salts and vital nutrients, which are necessary for life causing dehydration and malnutrition. Emerging antimicrobial resistant is common. The aim of the present study was to determine the antibiotic susceptibility pattern of cholera patients in Nepal. METHODS: All the laboratory works were conducted in the bacteriology section of National Public Health Laboratory, Teku from March to September 2005. During this period a total of 340 stool samples from diarrhoeal patients were collected and processed according to the standard laboratory methods. Each patient suffering from diarrhoea was directly interviewed for his or her clinical history during sample collection. RESULTS: A total of 340 stool samples were processed and studied from both sex including all ages of patients. Among the processed sample 53 Vibrio cholerae cases were found. All isolated Vibrio cholerae O1 were El Tor, Inaba. All isolated (100% Vibrio cholerae O1 were sensitive to Ampicillin, Ciprofloxacin, Erythromycin and Tetracycline whereas all were resistant to Nalidixic acid and Cotrimoxazole. Only 15.1% cases were sensitive to Furazolidone whereas 84.9% were resistant. CONCLUSION: All V. cholerae strains isolated in this study were found resistant to Multi Drug Resistant (resistant to at least two antibiotics of different group. Ampicillin, Ciprofloxacin, Erythromycin and Tetracycline were found still more potent antibiotics against Vibrio cholerae isolated during the study. Keywords: antibiotics, susceptibility, Vibrio cholera.

  11. Universal locality of quantum thermal susceptibility

    Science.gov (United States)

    De Palma, Giacomo; De Pasquale, Antonella; Giovannetti, Vittorio

    2017-05-01

    The ultimate precision of any measurement of the temperature of a quantum system is the inverse of the local quantum thermal susceptibility [A. De Pasquale et al., Nat. Commun. 7, 12782 (2016), 10.1038/ncomms12782] of the subsystem with which the thermometer interacts. If this subsystem can be described with the canonical ensemble, such quantity reduces to the variance of the local Hamiltonian, which is proportional to the heat capacity of the subsystem. However, the canonical ensemble might not apply in the presence of interactions between the subsystem and the rest of the system. In this work, we address this problem in the framework of locally interacting quantum systems. We prove that the local quantum thermal susceptibility of any subsystem is close to the variance of its local Hamiltonian, provided the volume-to-surface ratio of the subsystem is much larger than the correlation length. This result greatly simplifies the determination of the ultimate precision of any local estimate of the temperature and rigorously determines the regime where interactions can affect this precision.

  12. Hyperglycemia Increases Susceptibility to Ischemic Necrosis

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    D. Lévigne

    2013-01-01

    Full Text Available Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.. In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia.

  13. FLOOD SUSCEPTIBILITY ASSESSMENT IN THE NIRAJ BASIN

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    SANDA ROŞCA

    2012-03-01

    Full Text Available Flood susceptibility assessment in the Niraj basin. In the context of global warming and the increasing frequency of extreme weather events, it becomes evident that we have to face natural hazards, such as floods. In the area of Niraj basin this phenomenon is specific both in the spring, because of the snow melting and of the precipitations which come along with the season, and then in the summer because of the torrential precipitations but rarely in autumn and winter. The aim of this paper is to determinate the susceptibility of the zone and obtain a map which will take into consideration the possibility of a flooding. Defining vulnerability can help us understand this type of natural disasters and find the best ways to reduce it. For this purpose we use thematic layers, morphological characteristics (slope and depth fragmentation, hydrological characteristics, geology, pedology (permeability and soil texture, landuse, precipitation data, and human interventions because in this way we have the possibility to use data mining for this purpose. Data mining will allow us to extract new information based on the existing sets of data.The final result will be a thematic map that highlights the areas which are exposed to the flood. Therefore, this map can be used as a support decision for local government or business purposes.

  14. Microfluidics for Antibiotic Susceptibility and Toxicity Testing

    Directory of Open Access Journals (Sweden)

    Jing Dai

    2016-10-01

    Full Text Available The recent emergence of antimicrobial resistance has become a major concern for worldwide policy makers as very few new antibiotics have been developed in the last twenty-five years. To prevent the death of millions of people worldwide, there is an urgent need for a cheap, fast and accurate set of tools and techniques that can help to discover and develop new antimicrobial drugs. In the past decade, microfluidic platforms have emerged as potential systems for conducting pharmacological studies. Recent studies have demonstrated that microfluidic platforms can perform rapid antibiotic susceptibility tests to evaluate antimicrobial drugs’ efficacy. In addition, the development of cell-on-a-chip and organ-on-a-chip platforms have enabled the early drug testing, providing more accurate insights into conventional cell cultures on the drug pharmacokinetics and toxicity, at the early and cheaper stage of drug development, i.e., prior to animal and human testing. In this review, we focus on the recent developments of microfluidic platforms for rapid antibiotics susceptibility testing, investigating bacterial persistence and non-growing but metabolically active (NGMA bacteria, evaluating antibiotic effectiveness on biofilms and combinatorial effect of antibiotics, as well as microfluidic platforms that can be used for in vitro antibiotic toxicity testing.

  15. Multiscale/multiresolution landslides susceptibility mapping

    Science.gov (United States)

    Grozavu, Adrian; Cătălin Stanga, Iulian; Valeriu Patriche, Cristian; Toader Juravle, Doru

    2014-05-01

    Within the European strategies, landslides are considered an important threatening that requires detailed studies to identify areas where these processes could occur in the future and to design scientific and technical plans for landslide risk mitigation. In this idea, assessing and mapping the landslide susceptibility is an important preliminary step. Generally, landslide susceptibility at small scale (for large regions) can be assessed through qualitative approach (expert judgements), based on a few variables, while studies at medium and large scale requires quantitative approach (e.g. multivariate statistics), a larger set of variables and, necessarily, the landslide inventory. Obviously, the results vary more or less from a scale to another, depending on the available input data, but also on the applied methodology. Since it is almost impossible to have a complete landslide inventory on large regions (e.g. at continental level), it is very important to verify the compatibility and the validity of results obtained at different scales, identifying the differences and fixing the inherent errors. This paper aims at assessing and mapping the landslide susceptibility at regional level through a multiscale-multiresolution approach from small scale and low resolution to large scale and high resolution of data and results, comparing the compatibility of results. While the first ones could be used for studies at european and national level, the later ones allows results validation, including through fields surveys. The test area, namely the Barlad Plateau (more than 9000 sq.km) is located in Eastern Romania, covering a region where both the natural environment and the human factor create a causal context that favor these processes. The landslide predictors were initially derived from various databases available at pan-european level and progressively completed and/or enhanced together with scale and the resolution: the topography (from SRTM at 90 meters to digital

  16. Protein aggregation kinetics during Protein A chromatography. Case study for an Fc fusion protein.

    Science.gov (United States)

    Shukla, Abhinav A; Gupta, Priyanka; Han, Xuejun

    2007-11-09

    Protein A chromatography has come to be widely adopted for large-scale purification of monoclonal antibodies and Fc fusion proteins. The low pH conditions required for Protein A elution can often lead to aggregation issues for these products. A concerted study of the kinetics of aggregate formation and their relation to chromatography on Protein A media has been lacking. This paper provides a framework to describe aggregation kinetics for an Fc fusion protein that was highly susceptible to aggregate formation under low pH conditions. In contrast to what is usually expected to be a higher order reaction, first order aggregation kinetics were observed for this protein over a wide range of conditions. A comparison of the rate constants of aggregation forms an effective means of comparing various stabilizing additives to the elution buffer with one another. Inclusion of urea in the elution buffer at moderate concentrations (Protein A column were both found to be effective solutions to the aggregation issue. Elution from the Protein A resin was found to increase the aggregation rate constants over and above what would be expected from exposure to low pH conditions in solution alone. This demonstrates that Protein A-Fc interactions can destabilize product structure and increase the tendency to aggregate. The results presented here are anticipated to assist the development of Protein A process conditions for products that are prone to form high molecular weight aggregates during column elution.

  17. Comparison of susceptibility patterns using commercially available susceptibility testing methods performed on prevalent Candida spp.

    Science.gov (United States)

    Cretella, David; Barber, Katie E; King, S Travis; Stover, Kayla R

    2016-12-01

    The rising rates of invasive fungal infections caused by non-albicans Candida and the increasing emergence of antifungal resistance complicate the management of invasive candidiasis. Accurate and timely antifungal susceptibility testing is critical to targeting antifungal therapy. The purpose of this study was to compare commercially available susceptibility testing methods using prospectively collected Candida isolates. Susceptibility testing was performed on 74 Candida isolates collected from July 2014 to March 2015 using broth microdilution according to the Clinical and Laboratory Standards Institute method, Etest, Vitek 2 (YS-05) and Sensititre. Essential agreement and categorical agreement (CA) were assessed using the reference method. Of the 34 total blood isolates collected, Candida albicans comprised only 38 % (13) of the Candida spp. with Candidaglabrata being nearly as prevalent (29 %, 10). CA using Etest was 86 % for fluconazole, 72 % for caspofungin, 98 % for micafungin and 97 % for anidulafungin. Vitek 2 CA was 90 % for fluconazole and 98 % for caspofungin. Sensititre CA was 93 % for fluconazole, 98 % for caspofungin, 98 % for micafungin and 100 % for anidulafungin. Although our study tested a small population of Candida isolates, our results were variable by method. When implementing antifungal susceptibility testing, clinicians should be aware of the strengths and limitations of each testing method.

  18. Comparative assessment of antibiotic susceptibility of coagulase-negative staphylococci in biofilm versus planktonic culture as assessed by bacterial enumeration or rapid XTT colorimetry.

    Science.gov (United States)

    Cerca, Nuno; Martins, Silvia; Cerca, Filipe; Jefferson, Kimberly K; Pier, Gerald B; Oliveira, Rosário; Azeredo, Joana

    2005-08-01

    To quantitatively compare the antibiotic susceptibility of biofilms formed by the coagulase-negative staphylococci (CoNS) Staphylococcus epidermidis and Staphylococcus haemolyticus with the susceptibility of planktonic cultures. Several CoNS strains were grown planktonically or as biofilms to determine the effect of the mode of growth on the level of susceptibility to antibiotics with different mechanisms of action. The utility of a new, rapid colorimetric method that is based on the reduction of a tetrazolium salt (XTT) to measure cell viability was tested by comparison with standard bacterial enumeration techniques. A 6 h kinetic study was performed using dicloxacillin, cefazolin, vancomycin, tetracycline and rifampicin at the peak serum concentration of each antibiotic. In planktonic cells, inhibitors of cell wall synthesis were highly effective over a 3 h period. Biofilms were much less susceptible than planktonic cultures to all antibiotics tested, particularly inhibitors of cell wall synthesis. The susceptibility to inhibitors of protein and RNA synthesis was affected by the biofilm phenotype to a lesser degree. Standard bacterial enumeration techniques and the XTT method produced equivalent results both in biofilms and planktonic assays. This study provides a more accurate comparison between the antibiotic susceptibilities of planktonic versus biofilm populations, because the cell densities in the two populations were similar and because we measured the concentration required to inhibit bacterial metabolism rather than to eradicate the entire bacterial population. While the biofilm phenotype is highly resistant to antibiotics that target cell wall synthesis, it is fairly susceptible to antibiotics that target RNA and protein synthesis.

  19. Unexpected effects of azole transporter inhibitors on antifungal susceptibility in Candida glabrata and other pathogenic Candida species.

    Science.gov (United States)

    Nagayoshi, Yohsuke; Miyazaki, Taiga; Shimamura, Shintaro; Nakayama, Hironobu; Minematsu, Asuka; Yamauchi, Shunsuke; Takazono, Takahiro; Nakamura, Shigeki; Yanagihara, Katsunori; Kohno, Shigeru; Mukae, Hiroshi; Izumikawa, Koichi

    2017-01-01

    The pathogenic fungus Candida glabrata is often resistant to azole antifungal agents. Drug efflux through azole transporters, such as Cdr1 and Cdr2, is a key mechanism of azole resistance and these genes are under the control of the transcription factor Pdr1. Recently, the monoamine oxidase A (MAO-A) inhibitor clorgyline was shown to inhibit the azole efflux pumps, leading to increased azole susceptibility in C. glabrata. In the present study, we have evaluated the effects of clorgyline on susceptibility of C. glabrata to not only azoles, but also to micafungin and amphotericin B, using wild-type and several mutant strains. The addition of clorgyline to the culture media increased fluconazole susceptibility of a C. glabrata wild-type strain, whereas micafungin and amphotericin B susceptibilities were markedly decreased. These phenomena were also observed in other medically important Candida species, including Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida krusei. Expression levels of CDR1, CDR2 and PDR1 mRNAs and an amount of Cdr1 protein in the C. glabrata wild-type strain were highly increased in response to the treatment with clorgyline. However, loss of Cdr1, Cdr2, Pdr1, and a putative clorgyline target (Fms1), which is an ortholog of human MAO-A, or overexpression of CDR1 did not affect the decreased susceptibility to micafungin and amphotericin B in the presence of clorgyline. The presence of other azole efflux pump inhibitors including milbemycin A4 oxime and carbonyl cyanide 3-chlorophenylhydrazone also decreased micafungin susceptibility in C. glabrata wild-type, Δcdr1, Δcdr2, and Δpdr1 strains. These findings suggest that azole efflux pump inhibitors increase azole susceptibility but concurrently induce decreased susceptibility to other classes of antifungals independent of azole transporter functions.

  20. Trends towards Lower Antimicrobial Susceptibility and Characterization of Acquired Resistance among Clinical Isolates of Brachyspira hyodysenteriae in Spain ▿

    Science.gov (United States)

    Hidalgo, Álvaro; Carvajal, Ana; Vester, Birte; Pringle, Märit; Naharro, Germán; Rubio, Pedro

    2011-01-01

    The antimicrobial susceptibility of clinical isolates of Brachyspira hyodysenteriae in Spain was monitored, and the underlying molecular mechanisms of resistance were investigated. MICs of tylosin, tiamulin, valnemulin, lincomycin, and tylvalosin were determined for 87 B. hyodysenteriae isolates recovered from 2008 to 2009 by broth dilution. Domain V of the 23S rRNA gene and the ribosomal protein L3 gene were sequenced in 20 isolates for which the tiamulin MIC was ≥4 μg/ml, presenting decreased susceptibility, and in 18 tiamulin-susceptible isolates (MIC ≤ 0.125 μg/ml), and all isolates were typed by multiple-locus variable-number tandem repeats analysis. A comparison with antimicrobial susceptibility data from 2000 to 2007 showed an increase in pleuromutilin resistance over time, doubling the number of isolates with decreased susceptibility to tiamulin. No alteration in susceptibility was detected for lincomycin, and the MIC of tylosin remained high (MIC50 > 128 μg/ml). The decreased susceptibility to tylosin and lincomycin can be explained by mutations at position A2058 of the 23S rRNA gene (Escherichia coli numbering). A2058T was the predominant mutation, but A2058G also was found together with a change of the neighboring base pair at positions 2057 to 2611. The role of additional point mutations in the vicinity of the peptidyl transferase center and mutations in the L3 at amino acids 148 and 149 and their possible involvement in antimicrobial susceptibility are considered. An association between G2032A and high levels of tiamulin and lincomycin MICs was found, suggesting an increasing importance of this mutation in antimicrobial resistance of clinical isolates of B. hyodysenteriae. PMID:21555771

  1. Trends towards lower antimicrobial susceptibility and characterization of acquired resistance among clinical isolates of Brachyspira hyodysenteriae in Spain.

    Science.gov (United States)

    Hidalgo, Álvaro; Carvajal, Ana; Vester, Birte; Pringle, Märit; Naharro, Germán; Rubio, Pedro

    2011-07-01

    The antimicrobial susceptibility of clinical isolates of Brachyspira hyodysenteriae in Spain was monitored, and the underlying molecular mechanisms of resistance were investigated. MICs of tylosin, tiamulin, valnemulin, lincomycin, and tylvalosin were determined for 87 B. hyodysenteriae isolates recovered from 2008 to 2009 by broth dilution. Domain V of the 23S rRNA gene and the ribosomal protein L3 gene were sequenced in 20 isolates for which the tiamulin MIC was ≥ 4 μg/ml, presenting decreased susceptibility, and in 18 tiamulin-susceptible isolates (MIC ≤ 0.125 μg/ml), and all isolates were typed by multiple-locus variable-number tandem repeats analysis. A comparison with antimicrobial susceptibility data from 2000 to 2007 showed an increase in pleuromutilin resistance over time, doubling the number of isolates with decreased susceptibility to tiamulin. No alteration in susceptibility was detected for lincomycin, and the MIC of tylosin remained high (MIC(50) > 128 μg/ml). The decreased susceptibility to tylosin and lincomycin can be explained by mutations at position A2058 of the 23S rRNA gene (Escherichia coli numbering). A2058T was the predominant mutation, but A2058G also was found together with a change of the neighboring base pair at positions 2057 to 2611. The role of additional point mutations in the vicinity of the peptidyl transferase center and mutations in the L3 at amino acids 148 and 149 and their possible involvement in antimicrobial susceptibility are considered. An association between G2032A and high levels of tiamulin and lincomycin MICs was found, suggesting an increasing importance of this mutation in antimicrobial resistance of clinical isolates of B. hyodysenteriae.

  2. Susceptibility of Porphyromonas gingivalis in biofilms to amoxicillin, doxycycline and metronidazole

    DEFF Research Database (Denmark)

    Larsen, T.

    2002-01-01

    Biofilm, Porphyromonas gingivalis, susceptibility testing, amoxicillin, doxycycline, metronidazole......Biofilm, Porphyromonas gingivalis, susceptibility testing, amoxicillin, doxycycline, metronidazole...

  3. Candida and candidaemia. Susceptibility and epidemiology.

    Science.gov (United States)

    Arendrup, Maiken Cavling

    2013-11-01

    In our part of the world invasive fungal infections include invasive yeast infections with Candida as the absolutely dominating pathogen and invasive mould infections with Aspergillus as the main organism. Yeasts are part of our normal micro-flora and invasive infections arise only when barrier leakage or impaired immune function occurs. On the contrary, moulds are ubiquitous in the nature and environment and their conidia inhaled at a daily basis. Hence invasive mould infections typically arise from the airways whereas invasive yeast infections typically enter the bloodstream causing fungaemia. Candida is by far the most common fungal blood stream pathogen; hence this genus has been the main focus of this thesis. As neither the Danish epidemiology nor the susceptibility of fungal pathogens was well described when we initiated our studies we initially wanted to be able to include animal models in our work. Therefore, a comprehensive animal study was undertaken comparing the virulence in a haematogenous mouse model of eight different Candida species including the five most common ones in human infections (C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis and in addition three rarer species C. guilliermondii, C. lusitaniae and C. kefyr). We found remarkable differences in the virulence among these species and were able to group the species according to decreasing virulence in three groups I: C. albicans and C. tropicalis, II: C. glabrata, C. lusitaniae and C. kefyr, and III: C. krusei, C. parapsilosis and C. guilliermondii. Apart from being necessary for our subsequent animal experiments exploring in vivo antifungal susceptibility, these findings also helped us understand at least part of the reason for the differences in the epidemiology and the pitfalls associated with the establishment of genus rather than species specific breakpoints. In example, it was less surprising that C. albicans has been the dominant pathogen and associated with a

  4. Phase processing for quantitative susceptibility mapping of regions with large susceptibility and lack of signal.

    Science.gov (United States)

    Fortier, Véronique; Levesque, Ives R

    2017-11-11

    Phase processing impacts the accuracy of quantitative susceptibility mapping (QSM). Techniques for phase unwrapping and background removal have been proposed and demonstrated mostly in brain. In this work, phase processing was evaluated in the context of large susceptibility variations (Δχ) and negligible signal, in particular for susceptibility estimation using the iterative phase replacement (IPR) algorithm. Continuous Laplacian, region-growing, and quality-guided unwrapping were evaluated. For background removal, Laplacian boundary value (LBV), projection onto dipole fields (PDF), sophisticated harmonic artifact reduction for phase data (SHARP), variable-kernel sophisticated harmonic artifact reduction for phase data (V-SHARP), regularization enabled sophisticated harmonic artifact reduction for phase data (RESHARP), and 3D quadratic polynomial field removal were studied. Each algorithm was quantitatively evaluated in simulation and qualitatively in vivo. Additionally, IPR-QSM maps were produced to evaluate the impact of phase processing on the susceptibility in the context of large Δχ with negligible signal. Quality-guided unwrapping was the most accurate technique, whereas continuous Laplacian performed poorly in this context. All background removal algorithms tested resulted in important phase inaccuracies, suggesting that techniques used for brain do not translate well to situations where large Δχ and no or low signal are expected. LBV produced the smallest errors, followed closely by PDF. Results suggest that quality-guided unwrapping should be preferred, with PDF or LBV for background removal, for QSM in regions with large Δχ and negligible signal. This reduces the susceptibility inaccuracy introduced by phase processing. Accurate background removal remains an open question. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  5. Human Alveolar Macrophages May Not Be Susceptible to Direct Infection by a Human Influenza Virus.

    Science.gov (United States)

    Ettensohn, David B; Frampton, Mark W; Nichols, Joan E; Roberts, Norbert J

    2016-12-01

    The current studies were undertaken to determine the susceptibility of human alveolar macrophages (AMs) to influenza A virus (IAV) infection in comparison with autologous peripheral blood-derived monocytes-macrophages (PBMs). AMs and PBMs were exposed to IAV in vitro and examined for their ability to bind and internalize IAV, and synthesize viral proteins and RNA. PBMs but not AMs demonstrated binding and internalization of the virus, synthesizing viral proteins and RNA. Exposure of AMs in the presence of a sialidase inhibitor or anti-IAV antibody resulted in viral protein synthesis by the cells. Exposure of AMs to fluorescein isothiocyanate-labeled IAV in the presence of anti-fluorescein isothiocyanate antibody also resulted in viral protein synthesis. Thus, human AMs are apparently not susceptible to direct infection by a human IAV but are likely to be infected indirectly in the setting of exposure in the presence of antibody that binds the challenging strain of IAV. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  6. Resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein

    NARCIS (Netherlands)

    Meade-White, K.; Race, B.; Trifilo, M.; Bossers, A.; Favara, C.; Lacasse, R.; Miller, M.; Williams, E.; Oldstone, M.; Race, R.; Chesebro, B.

    2007-01-01

    Prion protein (PrP) is a required factor for susceptibility to transmissible spongiform encephalopathy or prion diseases. In transgenic mice, expression of prion protein (PrP) from another species often confers susceptibility to prion disease from that donor species. For example, expression of deer

  7. Inflationary susceptibilities, duality and large-scale magnetic fields generation

    CERN Document Server

    Giovannini, Massimo

    2013-01-01

    We investigate what can be said about the interaction of scalar fields with Abelian gauge fields during a quasi-de Sitter phase of expansion and under the assumption that the electric and the magnetic susceptibilities do not coincide. The duality symmetry, transforming the magnetic susceptibility into the inverse of the electric susceptibility, exchanges the magnetic and electric power spectra. The mismatch between the two susceptibilities determines an effective refractive index affecting the evolution of the canonical fields. The constraints imposed by the duration of the inflationary phase and by the magnetogenesis requirements pin down the rate of variation of the susceptibilities that is consistent with the observations of the magnetic field strength over astrophysical and cosmological scales but avoids back-reaction problems. The parameter space of this magnetogenesis scenario is wider than in the case when the susceptibilities are equal, as it happens when the inflaton or some other spectator field is ...

  8. Orientational Glasses: NMR and Electric Susceptibility Studies

    Directory of Open Access Journals (Sweden)

    Neil Sullivan

    2017-11-01

    Full Text Available We review the results of a wide range of nuclear magnetic resonance (NMRmeasurements of the local order parameters and the molecular dynamics of solid ortho-para hydrogen mixtures and solid nitrogen-argon mixtures that form novel molecular orientational glass states at low temperatures. From the NMR measurements, the distribution of the order parameters can be deduced and, in terms of simple models, used to analyze the thermodynamic measurements of the heat capacities of these systems. In addition, studies of the dielectric susceptibilities of the nitrogen-argon mixtures are reviewed in terms of replica symmetry breaking analogous to that observed for spin glass states. It is shown that this wide set of experimental results is consistent with orientation or quadrupolar glass ordering of the orientational degrees of freedom.

  9. Susceptibility of cell lines to avian viruses

    Directory of Open Access Journals (Sweden)

    Simoni Isabela Cristina

    1999-01-01

    Full Text Available The susceptibility of the five cell lines - IB-RS-2, RK-13, Vero, BHK-21, CER - to reovirus S1133 and infectious bursal disease virus (IBDV vaccine GBV-8 strain was studied to better define satisfactory and sensitive cell culture systems. Cultures were compared for presence of CPE, virus titers and detection of viral RNA. CPE and viral RNA were detected in CER and BHK-21 cells after reovirus inoculation and in RK-13 cell line after IBDV inoculation and with high virus titers. Virus replication by production of low virus titers occurred in IB-RS-2 and Vero cells with reovirus and in BHK-21 cell line with IBDV.

  10. TREATMENT EFFICIENCY OF DRUG SUSCEPTIBLE PULMONARY TUBERCULOSIS

    Directory of Open Access Journals (Sweden)

    M. V. Pavlova

    2016-01-01

    Full Text Available The article describes the study of comparative efficiency of fenazid (isonicotinoilhydrazine-О,N’ ferrous dihydrate sulphate (II and isoniazid in drug susceptible pulmonary tuberculosis patients.The high treatment efficiency namely significant improvement and improvement was observed in the patients of Group 1 – 84.1% which could be compared to the standard treatment regimen (85-7% in Group 2. The total number of adverse reactions in the main group was confidently lower – 18.6% against 33.9%, p < 0.05. Hepatotoxic reactions with 2-3 fold increase of alaninetransferase level was registered significantly less (9.3% in Group 1 compared to the Group treated with isoniazid.

  11. Evaluation of SLE Susceptibility Genes in Malaysians.

    Science.gov (United States)

    Molineros, Julio E; Chua, Kek Heng; Sun, Celi; Lian, Lay Hoong; Motghare, Prasenjeet; Kim-Howard, Xana; Nath, Swapan K

    2014-01-01

    Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous autoimmune disease with strong genetic and environmental components. Our objective was to replicate 25 recently identified SLE susceptibility genes in two distinct populations (Chinese (CH) and Malays (MA)) from Malaysia. We genotyped 347 SLE cases and 356 controls (CH and MA) using the ImmunoChip array and performed an admixture corrected case-control association analysis. Associated genes were grouped into five immune-related pathways. While CH were largely homogenous, MA had three ancestry components (average 82.3% Asian, 14.5% European, and 3.2% African). Ancestry proportions were significantly different between cases and controls in MA. We identified 22 genes with at least one associated SNP (P SLE genes are also associated in the major ethnicities of Malaysia. However, these novel SNPs showed stronger association in these Asian populations than with the SNPs reported in previous studies.

  12. Are there stress resistant and susceptible myocardia?

    Science.gov (United States)

    Knight, V A

    1988-11-01

    The satisfactory analysis of the Na/K ATPase, its pumping component and the mechanism of action of the inhibitor digitalis remains elusive; yet the controversial inotropic effect of digitalis in the clinical setting has been known for over a century. There are also conflicting reports of the effect of urea and uremia on the cardiovascular system, and the evidence as it exists, suggests that urea may have two effects on the intact heart, by virtue of its extent of action on hydrogen bonding of water molecules, determined by which type of muscle constitutes the myocardium. If different types of myocardium do exist, they could well respond differently to inotropic agents. Evidence suggests that two types of myocardia, relatively stress resistant or susceptible may exist, analagous to known skeletal muscle differences.

  13. FGF receptor genes and breast cancer susceptibility

    DEFF Research Database (Denmark)

    Agarwal, D; Pineda, S; Michailidou, K

    2014-01-01

    Background:Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying...... genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium.Methods:Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry......, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression.Results:Little evidence of association with breast cancer risk...

  14. Susceptibility of Genital Mycoplasmas to Antimicrobial Agents

    Science.gov (United States)

    Braun, Peter; Klein, Jerome O.; Kass, Edward H.

    1970-01-01

    The susceptibility of 11 T-strains, 12 strains of Mycoplasma hominis, and a single strain of M. fermentans to 15 antimicrobial agents was determined by study of inhibition of metabolic activity in a broth dilution system. All three species were inhibited by tetracycline, chloramphenicol, streptomycin, gentamicin, and kanamycin, and were relatively resistant to cephalothin, cephaloridine, polymyxin, vancomycin, and ampicillin. Three antimicrobial agents had significant differential effects on these species. Erythromycin was more active against T-strains than against M. hominis or M. fermentans. Lincomycin, clindamycin, and nitrofurantoin had greater activity against M. hominis and M. fermentans than against T-strains. The activity of the drugs tested was generally uniform over a wide range of inocula. The effect of pH and the difference between minimal inhibiting and minimal mycoplasmacidal concentrations of the drugs tested were consistent with expectations based on the effects of these drugs on bacteria. PMID:4313312

  15. Automated sliding susceptibility mapping of rock slopes

    Directory of Open Access Journals (Sweden)

    A. Günther

    2004-01-01

    Full Text Available We present a suite of extensions for ARCVIEW GIS™ (ESRI that allows to map the spatial distribution of first-order mechanical slope-properties in hard rock terrain, e.g. for large slope areas like water reservoir slopes. Besides digital elevation data, this expert-system includes regional continuous grid-based data on geological structures that might act as potential sliding or cutoff planes for rockslides. The system allows rapid automated mapping of geometrical and kinematical slope properties in hard rock, providing the basis for spatially distributed deterministic sliding-susceptibility evaluations on a pixel base. Changing hydrostatic slope conditions and rock mechanical parameters can be implemented and used for simple predictive static stability calculations. Application is demonstrated for a study area in the Harz Mts., Germany.

  16. [Oxidative stress and susceptibility of periodontal disease].

    Science.gov (United States)

    Zhang, Mei-fang; Huang, Yi-jing; Zhang, Hai-feng; Tang, Wen; Zhou, Jie

    2013-10-01

    To investigate the relationship between dietary antioxidant status and susceptibility of periodontal disease in humans. Fifty patients with moderate-to-sever periodontal disease and 50 subjects without periodontal disease were enrolled in this study. Food frequency questionnaire and 72-hour diet recall were conducted to study the dietary pattern and antioxidant nutrients intake in patients and healthy subjects. Nutritional status including vitamins, mineral substance, and antioxidant enzymes in these 2 groups were analyzed in serum and saliva samples by liquid chromatography-mass spectrometry (LC-MS). SPSS 19.0 software package was used for paired t test. Compared with the control group, the chronic periodontal group had lower levels of potatoes, aquatic product, milk, soy, fresh vegetables, fruit and vitamin supplements intake(Pperiodontal disease group than that in the control group (Pperiodontal group than in the control group (Pperiodontal disease. The antioxidant nutrients may help to protect paradentium. Supported by Research Fund from Shanghai Municipal Health Bureau (20114103).

  17. Sociability and susceptibility to the common cold.

    Science.gov (United States)

    Cohen, Sheldon; Doyle, William J; Turner, Ronald; Alper, Cuneyt M; Skoner, David P

    2003-09-01

    There is considerable evidence that social relationships can influence health, but only limited evidence on the health effects of the personality characteristics that are thought to mold people's social lives. We asked whether sociability predicts resistance to infectious disease and whether this relationship is attributable to the quality and quantity of social interactions and relationships. Three hundred thirty-four volunteers completed questionnaires assessing their sociability, social networks, and social supports, and six evening interviews assessing daily interactions. They were subsequently exposed to a virus that causes a common cold and monitored to see who developed verifiable illness. Increased sociability was associated in a linear fashion with a decreased probability of developing a cold. Although sociability was associated with more and higher-quality social interactions, it predicted disease susceptibility independently of these variables. The association between sociability and disease was also independent of baseline immunity (virus-specific antibody), demographics, emotional styles, stress hormones, and health practices.

  18. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States); Knowlton, Caitlin; Kim, Baek [Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 (United States); Sawyer, Sara L. [Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712 (United States); Diaz-Griffero, Felipe, E-mail: Felipe.Diaz-Griffero@einstein.yu.edu [Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park – Price Center 501, New York, NY 10461 (United States)

    2014-07-15

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

  19. CELSR2 is a candidate susceptibility gene in idiopathic scoliosis.

    Science.gov (United States)

    Einarsdottir, Elisabet; Grauers, Anna; Wang, Jingwen; Jiao, Hong; Escher, Stefan A; Danielsson, Aina; Simony, Ane; Andersen, Mikkel; Christensen, Steen Bach; Åkesson, Kristina; Kou, Ikuyo; Khanshour, Anas M; Ohlin, Acke; Wise, Carol; Ikegawa, Shiro; Kere, Juha; Gerdhem, Paul

    2017-01-01

    A Swedish pedigree with an autosomal dominant inheritance of idiopathic scoliosis was initially studied by genetic linkage analysis, prioritising genomic regions for further analysis. This revealed a locus on chromosome 1 with a putative risk haplotype shared by all affected individuals. Two affected individuals were subsequently exome-sequenced, identifying a rare, non-synonymous variant in the CELSR2 gene. This variant is rs141489111, a c.G6859A change in exon 21 (NM_001408), leading to a predicted p.V2287I (NP_001399.1) change. This variant was found in all affected members of the pedigree, but showed reduced penetrance. Analysis of tagging variants in CELSR1-3 in a set of 1739 Swedish-Danish scoliosis cases and 1812 controls revealed significant association (p = 0.0001) to rs2281894, a common synonymous variant in CELSR2. This association was not replicated in case-control cohorts from Japan and the US. No association was found to variants in CELSR1 or CELSR3. Our findings suggest a rare variant in CELSR2 as causative for idiopathic scoliosis in a family with dominant segregation and further highlight common variation in CELSR2 in general susceptibility to idiopathic scoliosis in the Swedish-Danish population. Both variants are located in the highly conserved GAIN protein domain, which is necessary for the auto-proteolysis of CELSR2, suggesting its functional importance.

  20. Susceptibility of laboratory rodents to Trichinella papuae.

    Science.gov (United States)

    Sadaow, Lakkhana; Intapan, Pewpan M; Boonmars, Thidarut; Morakote, Nimit; Maleewong, Wanchai

    2013-12-01

    Members of the genus Trichinella are small nematodes that can infect a wide range of animal hosts. However, their infectivity varies depending on the parasite and host species combination. In this study, we examined the susceptibility of 4 species of laboratory rodents, i.e., mice, rats, hamsters, and gerbils to Trichinella papuae, an emerging non-encapsulated Trichinella species. Trichinella spiralis and Trichinella pseudospiralis were also included in this study for comparison. Fifteen animals of each rodent species were infected orally with 100 muscle larvae of each Trichinella species. Intestinal worm burden was determined at day 6 and 10 post-inoculation (PI). The numbers of muscle larvae were examined at day 45 PI. The reproductive capacity index (RCI) of the 3 Trichinella species in different rodent hosts was determined. By day 6 PI, 33.2-69.6% of the inoculated larvae of the 3 Trichinella species became adult worms in the small intestines of the host animals. However, in rats, more than 96% of adult worms of all 3 Trichinella species were expelled from the gut by day 10 PI. In gerbils, only 4.8-18.1% of adult worms were expelled by day 10 PI. In accordance with the intestinal worm burden and the persistence of adults, the RCI was the highest in gerbils with values of 241.5±41.0 for T. papuae, 432.6±48 for T. pseudospiralis, and 528.6±20.6 for T. spiralis. Hamsters ranked second and mice ranked third in susceptibility in terms of the RCI, Rats yielded the lowest parasite RCI for all 3 Trichinella species. Gerbils may be an alternative laboratory animal for isolation and maintenance of Trichinella spp.

  1. On magnetic and vortical susceptibilities of the Cooper condensate

    Science.gov (United States)

    Gorsky, A.; Popov, F.

    2017-11-01

    We discuss the susceptibility of the Cooper condensate in the s-wave 2 + 1 superconductor in the external magnetic field and in the rotating frame. The extended holographic model involving the charged rank-two field is considered and it is argued that the susceptibility does not vanish. We interpret non-vanishing susceptibilities as the admixture of the p-wave triplet component in the Cooper condensate in the external field.

  2. Susceptibilities and Spin Gaps of Weakly Coupled Spin Ladders

    Energy Technology Data Exchange (ETDEWEB)

    Larochelle, S.

    2004-05-11

    We calculate the uniform and staggered susceptibilities of two-chain spin-1/2 Heisenberg ladders using Monte-Carlo simulations. We show that the gap extracted from the uniform susceptibility and the saturation value of the staggered susceptibility are independent of the sign of the interchain coupling J{perpendicular} in the asymptotic limit |J{perpendicular}|/J {yields} 0. Furthermore, we examine the existence of logarithmic corrections to the linear scaling of the gap with |J{perpendicular}|.

  3. Dynamical spin dependent susceptibility of graphene like structure

    Science.gov (United States)

    Moradian, Rostam; Rezania, Hamed; Marvi, Saeed

    2018-02-01

    Spin dependent susceptibility of gapped graphene is calculated using Hubbard model. We found that by increasing the electron density, energy gap and repulsive coulomb interaction the imaginary part of the susceptibility peaks will be shifted towards higher frequencies and by increasing the magnetization the imaginary part of the susceptibility peaks will be shifted towards lower frequencies. It means that plasmonic frequency depends on electrons band filling, electronic coulomb repulsion, magnetization and graphene initial energy gap.

  4. The electricity sector susceptibility of European countries to climate change

    Science.gov (United States)

    Klein, Daniel R.; Olonscheck, Mady; Walther, Carsten; Kropp, Jürgen P.

    2014-05-01

    Due to the close relationship between electricity consumption, production and temperature, the electricity systems of countries are particularly susceptible to climate change. Based on a number of quantitative influencing factors, we provide a relative index for 21 European countries. This allows relevant stakeholders to identify the main influencing factors that determine the electricity system susceptibility of their country. The index was determined using 14 influencing factors that include those that increase or decrease susceptibility. This includes information on monthly mean temperature, electricity consumption, import, export and production by energy source for the period 2000-2011. Moreover, we consider the results of nine global climate models regarding future temperature changes as well as data on air conditioner prevalence by country. A quantitative relative ranked index describing the susceptibility of each country's electricity system is provided. In both Luxembourg and Greece, which top the list, the inability to meet electricity demand with inland production as well as a heavy reliance on combustible fuel electricity production explain part of the high relative susceptibility. Summer electricity consumption (another influencing factor) is expected to increase in Greece where current relatively warm temperatures, in the context of the countries included in this study, are expected to increase in the future. Comparatively, Norway was the least susceptible country based on our index. Norway is expected to benefit from rising projected temperatures, which will decrease winter electricity consumption and limit susceptibility. Furthermore, Norway's current electricity production exceeds consumption demand and is largely based on hydro, which also decreases susceptibility. The findings of this study enable policy makers, scientists and energy managers to examine the most important influencing factors that increase susceptibility and focus their adaptation

  5. Innate immune defense defines susceptibility of sarcoma cells to measles vaccine virus-based oncolysis.

    Science.gov (United States)

    Berchtold, Susanne; Lampe, Johanna; Weiland, Timo; Smirnow, Irina; Schleicher, Sabine; Handgretinger, Rupert; Kopp, Hans-Georg; Reiser, Jeanette; Stubenrauch, Frank; Mayer, Nora; Malek, Nisar P; Bitzer, Michael; Lauer, Ulrich M

    2013-03-01

    The oncolytic potential of measles vaccine virus (MeV) has been demonstrated in several tumor entities. Here, we investigated the susceptibility of eight sarcoma cell lines to MeV-mediated oncolysis and found five to be susceptible, whereas three proved to be resistant. In the MeV-resistant cell lines, we often observed an inhibition of viral replication along with a strong upregulation of the intracellular virus-sensing molecule RIG-I and of the interferon (IFN)-stimulated gene IFIT1. Not only expression of IFIT1 but also phosphorylation of IFN-stimulated Stat1 took place rapidly and were found to be persistent over time. In contrast, susceptible cell lines showed a much weaker, delayed, or completely missing expression of IFIT1 as well as a delayed or only transient phosphorylation of Stat1, whereas exogenic stimulation with beta interferon (IFN-β) resulted in a comparable profound activation of Stat1 and expression of IFIT1 in all cell lines. Pretreatment with IFN-β rendered three of the susceptible cell lines more resistant to MeV-mediated oncolysis. These data suggest that differences in the innate immune defense often account for different degrees of susceptibility of sarcoma cell lines to MeV-mediated oncolysis. From a therapeutic perspective, we were able to overcome resistance to MeV by increasing the multiplicity of infection (MOI) and by addition of the prodrug 5-fluorocytosine (FC), thereby exploiting the suicide gene function of virotherapeutic vector MeV-SCD armed with the SCD fusion protein, which consists of yeast cytosine deaminase and yeast uracil phosphoribosyltransferase.

  6. Assessment of the process of movement of Xylella fastidiosa within susceptible and resistant grape cultivars.

    Science.gov (United States)

    Baccari, C; Lindow, S E

    2011-01-01

    To better understand the processes contributing to symptoms and resistance to Pierce's disease of grape, we examined the movement and multiplication of a green fluorescent protein-marked strain of Xylella fastidiosa in the stems and petioles of Cabernet Sauvignon, Chenin Blanc, Roucaneuf, and Tampa grape cultivars that differ in their susceptibility to this disease. X. fastidiosa achieved much lower population sizes and colonized fewer xylem vessels in the stem of resistant cultivars compared with more susceptible cultivars. In contrast, X. fastidiosa achieved similarly high population sizes and colonized a similar proportion of the vessels in petioles of susceptible and resistant cultivars, suggesting that, compared with the stem, X. fastidiosa is relatively unrestricted in its movement and growth within the petiole. There was not a direct relationship between the population size of X. fastidiosa in the stem and the proportion of vessels colonized; a much higher population size of the pathogen was observed in susceptible cultivars than expected based on the proportion of vessels colonized. The high population sizes of X. fastidiosa in stems of susceptible genotypes were associated with both a high number of infected vessels and a much higher extent of colonization of those vessels that become infested than in more resistant cultivars. The formation of large cellular aggregates in vessels is not required for X. fastidiosa to move laterally in the stem to adjacent vessels because most vessels harbored only small assemblages, especially in resistant cultivars such as Roucaneuf, in which some intervessel movement was detected. Resistance to Pierce's disease is apparently not due to inhibitory compounds that circulate in the xylem because they might be expected to operate similarly in all tissues.

  7. BSAC standardized disc susceptibility testing method (version 11).

    Science.gov (United States)

    Howe, R A; Andrews, J M

    2012-12-01

    This article highlights key amendments incorporated into version 11 of the BSAC standardized disc susceptibility testing method, available as Supplementary data at JAC Online (http://jac.oxfordjournals.org/) and on the BSAC web site (http://bsac.org.uk/susceptibility/guidelines-standardized-disc-susceptibility-testing-method/). The basic disc susceptibility testing method remains unchanged, but there have been a number of alterations to the interpretive criteria for certain organism/drug combinations due to continuing harmonization with the EUCAST MIC breakpoints and constant efforts to improve the reliability and clinical applicability of the guidance.

  8. ENU Mutagenic Screen for Susceptibility and Resistance to Streptococcus Pneumoniae

    National Research Council Canada - National Science Library

    Kindy, Mark S

    2005-01-01

    .... The genetic pathways that control susceptibility and resistance to bacterial infection have remained poorly understood, because of the lack of expertise in the development of techniques capable...

  9. Differential susceptibility to the environment: an evolutionary--neurodevelopmental theory.

    Science.gov (United States)

    Ellis, Bruce J; Boyce, W Thomas; Belsky, Jay; Bakermans-Kranenburg, Marian J; van Ijzendoorn, Marinus H

    2011-02-01

    Two extant evolutionary models, biological sensitivity to context theory (BSCT) and differential susceptibility theory (DST), converge on the hypothesis that some individuals are more susceptible than others to both negative (risk-promoting) and positive (development-enhancing) environmental conditions. These models contrast with the currently dominant perspective on personal vulnerability and environmental risk: diathesis stress/dual risk. We review challenges to this perspective based on emerging theory and data from the evolutionary, developmental, and health sciences. These challenges signify the need for a paradigm shift in conceptualizing Person x Environment interactions in development. In this context we advance an evolutionary--neurodevelopmental theory, based on DST and BSCT, of the role of neurobiological susceptibility to the environment in regulating environmental effects on adaptation, development, and health. We then outline current thinking about neurogenomic and endophenotypic mechanisms that may underpin neurobiological susceptibility, summarize extant empirical research on differential susceptibility, and evaluate the evolutionary bases and implications of BSCT and DST. Finally, we discuss applied issues including methodological and statistical considerations in conducting differential susceptibility research; issues of ecological, cultural, and racial--ethnic variation in neurobiological susceptibility; and implications of differential susceptibility for designing social programs. We conclude that the differential susceptibility paradigm has far-reaching implications for understanding whether and how much child and adult development responds, for better and for worse, to the gamut of species-typical environmental conditions.

  10. Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Susceptibility

    Science.gov (United States)

    Nilsson, Eric E.; Skinner, Michael K.

    2014-01-01

    Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed in regards to disease etiology. PMID:24657180

  11. Antimicrobial Susceptibilities of Abiotrophia defectiva, Granulicatella adiacens, and Granulicatella elegans

    National Research Council Canada - National Science Library

    Alberti, Michael O; Hindler, Janet A; Humphries, Romney M

    2016-01-01

    .... Antimicrobial susceptibility testing (AST) was performed for 14 antimicrobials using the broth microdilution MIC method described in the Clinical and Laboratory Standards Institute (CLSI) M45 guideline...

  12. Spectrum of Uropathogens and its Antibiotic Susceptibility in ...

    African Journals Online (AJOL)

    Spectrum of Uropathogens and its Antibiotic Susceptibility in Pregnant Women with Symptomatic Urinary Tract Infection in a Nigerian Teaching Hospital. Running headline: Urinary Tract Infection in Pregnancy.

  13. Differential Antimicrobial Susceptibilities of Granulicatella adiacens and Abiotrophia defectiva.

    Science.gov (United States)

    Mushtaq, Ammara; Greenwood-Quaintance, Kerryl E; Cole, Nicolynn C; Kohner, Peggy C; Ihde, Sherry M; Strand, Gregory J; Harper, Lance W; Virk, Abinash; Patel, Robin

    2016-08-01

    MICs of 25 Abiotrophia defectiva and 109 Granulicatella adiacens isolates were determined by broth microdilution. Using CLSI breakpoints, the susceptibilities of A. defectiva and G. adiacens isolates were, respectively, 24% and 34% to penicillin, 92% and 22% to ceftriaxone, 48% and 3% to cefepime, 72% and 87% to meropenem, 92% and 10% to cefotaxime, 100% and 97% to levofloxacin, 92% and 80% to clindamycin, and 24% and 50% to erythromycin. All isolates were susceptible to vancomycin. In the penicillin-susceptible subgroup, all A. defectiva isolates were susceptible to ceftriaxone; however, 62% of G. adiacens isolates were ceftriaxone nonsusceptible. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Antimicrobial susceptibility of Prototheca zopfii isolated from bovine intramammary infections.

    Science.gov (United States)

    McDonald, J S; Richard, J L; Anderson, A J

    1984-06-01

    In vitro antimicrobial susceptibility tests were carried out on 48 strains of Prototheca zopfii, an achlorophyllous algae causing refractory mastitis in dairy cows; 27 antimicrobials were evaluated. All strains were susceptible to both myxin and nystatin. In addition, 22 strains were susceptible to amphotericin B, 21 to polymyxin B, and 18 to gentamicin. Only 1 strain was susceptible to kanamycin. All strains were resistant to ampicillin, bacitracin, carbenicillin, cephalothin, chloramphenicol, clotrimazole, cloxacillin, erythromycin, flucytosine, ketoconazole, lincomycin, miconazole, neomycin, nitrofurazone, novobiocin, oleandomycin, penicillin, rifampin, streptomycin, tetracycline, and vancomycin.

  15. Specific adjustments in grapevine leaf proteome discriminating resistant and susceptible grapevine genotypes to Plasmopara viticola.

    Science.gov (United States)

    Figueiredo, Andreia; Martins, Joana; Sebastiana, Mónica; Guerreiro, Ana; Silva, Anabela; Matos, Ana Rita; Monteiro, Filipa; Pais, Maria Salomé; Roepstorff, Peter; Coelho, Ana Varela

    2017-01-30

    Grapevine downy mildew is an important disease affecting crop production leading to severe yield losses. This study aims to identify the grapevine cultivar-specific adjustments of leaf proteome that allow the discrimination between resistance and susceptibility towards P. viticola (constitutive (0h) and in after inoculation (6, 12 and 24h). Leaf proteome analysis was performed using 2D difference gel electrophoresis followed by protein identification via mass spectrometry. In addition, we analysed ROS production, antioxidant capacity, lipid peroxidation and gene expression. Proteins related to photosynthesis and metabolism allowed the discrimination of resistant and susceptible grapevine cultivars prior to P. viticola inoculation. Following inoculation increase of hydrogen peroxide levels, cellular redox regulation, establishment of ROS signalling and plant cell death seem to be key points differentiating the resistant genotype. Lipid associated signalling events, particularly related to jasmonates appear also to play a major role in the establishment of resistance. The findings from this study contribute to a better understanding of genotype-specific differences that account for a successful establishment of a defence response to the downy mildew pathogen. Here, we present for the first time grapevine cultivar-specific adjustments of leaf proteome that allow the discrimination between resistance and susceptibility towards P. viticola (constitutive (0h) and in after inoculation (6, 12 and 24h). We have highlighted that, following inoculation, the major factors differentiating the resistant from the susceptible grapevine cultivars are the establishment of effective ROS signalling together with lipid-associated signalling events, particularly related to jasmonates. It is believed that plants infected with biotrophic pathogens suppress JA-mediated responses, however recent evidences shown that jasmonic acid signalling pathway in grapevine resistance against Plasmopara

  16. Increased susceptibility of aging gastric mucosa to injury: the mechanisms and clinical implications.

    Science.gov (United States)

    Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

    2014-04-28

    This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older

  17. Comparative proteomic analysis of antimony-resistant and -susceptible Leishmania braziliensis and Leishmania infantum chagasi lines.

    Science.gov (United States)

    Matrangolo, Fabiana S V; Liarte, Daniel B; Andrade, Laila C; de Melo, Melina F; Andrade, Juvana M; Ferreira, Rafael F; Santiago, André S; Pirovani, Carlos P; Silva-Pereira, Rosiane A; Murta, Silvane M F

    2013-08-01

    The emergence of drug-resistant Leishmania species is a significant problem in several countries. A comparative proteomic analysis of antimony-susceptible and antimony-resistant Leishmania braziliensis (LbSbR) and Leishmania infantum chagasi (LcSbR) lines was carried out using two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry (LC/MS/MS) for protein identification. Out of 132 protein spots exclusive or up-regulated submitted to MS, we identified 80 proteins that corresponded to 57 distinct proteins. Comparative analysis of data showed that most of the protein spots with differential abundance in both species are involved in antioxidant defense, general stress response, glucose and amino acid metabolism, and cytoskeleton organization. Five proteins were commonly more abundant in both SbIII-resistant Leishmania lines: tryparedoxin peroxidase, alpha-tubulin, HSP70, HSP83, and HSP60. Analysis of the protein abundance by Western blotting assays confirmed our proteomic data. These assays revealed that cyclophilin-A is less expressed in both LbSbR and LcSbR lines. On the other hand, the expression of pteridine reductase is higher in the LbSbR line, whereas tryparedoxin peroxidase is overexpressed in both LbSbR and LcSbR lines. Together, these results show that the mechanism of antimony-resistance in Leishmania spp. is complex and multifactorial. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Strong ties promote the epidemic prevalence in susceptible-infected-susceptible spreading dynamics

    CERN Document Server

    Cui, Ai-Xiang; Zhou, Tao

    2013-01-01

    Understanding spreading dynamics will benefit society as a whole in better preventing and controlling diseases, as well as facilitating the socially responsible information while depressing destructive rumors. In network-based spreading dynamics, edges with different weights may play far different roles: a friend from afar usually brings novel stories, and an intimate relationship is highly risky for a flu epidemic. In this article, we propose a weighted susceptible-infected-susceptible model on complex networks, where the weight of an edge is defined by the topological proximity of the two associated nodes. Each infected individual is allowed to select limited number of neighbors to contact, and a tunable parameter is introduced to control the preference to contact through high-weight or low-weight edges. Experimental results on six real networks show that the epidemic prevalence can be largely promoted when strong ties are favored in the spreading process. By comparing with two statistical null models respe...

  19. The Accuracy of Mean-Field Approximation for Susceptible-Infected-Susceptible Epidemic Spreading

    CERN Document Server

    Qu, Bo

    2016-01-01

    The epidemic spreading has been studied for years by applying the mean-field approach in both homogeneous case, where each node may get infected by an infected neighbor with the same rate, and heterogeneous case, where the infection rates between different pairs of nodes are different. Researchers have discussed whether the mean-field approaches could accurately describe the epidemic spreading for the homogeneous cases but not for the heterogeneous cases. In this paper, we explore under what conditions the mean-field approach could perform well when the infection rates are heterogeneous. In particular, we employ the Susceptible-Infected-Susceptible (SIS) model and compare the average fraction of infected nodes in the metastable state obtained by the continuous-time simulation and the mean-field approximation. We concentrate on an individual-based mean-field approximation called the N-intertwined Mean Field Approximation (NIMFA), which is an advanced approach considered the underlying network topology. Moreove...

  20. Solving the Dynamic Correlation Problem of the Susceptible-Infected-Susceptible Model on Networks

    CERN Document Server

    Cai, Chao-Ran; Chen, Michael Z Q; Holme, Petter; Guan, Jian-Yue

    2016-01-01

    The Susceptible-Infected-Susceptible model is a canonical model for emerging disease outbreaks. Such outbreaks are naturally modeled as taking place on networks. A theoretical challenge in network epidemiology is the dynamic correlations coming from that if one node is occupied, or infected (for disease spreading models), then its neighbors are likely to be occupied. By combining two theoretical approaches---the heterogeneous mean-field theory and the effective degree method---we are able to include these correlations in an analytical solution of the SIS model. We derive accurate expressions for the average prevalence (fraction of infected) and epidemic threshold. We also discuss how to generalize the approach to a larger class of stochastic population models.

  1. Multiple phase transitions of the susceptible-infected-susceptible epidemic model on complex networks

    CERN Document Server

    Mata, Angélica S

    2014-01-01

    We show that the susceptible-infected-susceptible (SIS) epidemic dynamics running on the top of networks with a power law degree distribution can exhibit multiple phase transitions. Three main transitions involving different mechanisms responsible by sustaining the epidemics are identified: A short-term epidemics concentrated around the most connected vertex; a long-term (asymptotically stable) localized epidemics with a vanishing threshold; and an endemic phase occurring at a finite threshold. The different transitions are suited through different mean-field approaches. We finally show that the multiple transitions are due to the activations of different domains of the network that are observed in rapid (singular) variations of both stationary density of infected vertices and the participation ratio against the infection rate.

  2. Bacterial protein toxins : tools to study mammalian molecular cell biology

    NARCIS (Netherlands)

    Wüthrich, I.W.

    2014-01-01

    Bacterial protein toxins are genetically encoded proteinaceous macromolecules that upon exposure causes perturbation of cellular metabolism in a susceptible host. A bacterial toxin can work at a distance from the site of infection, and has direct and quantifiable actions. Bacterial protein toxins

  3. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

    Science.gov (United States)

    Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

    2016-01-01

    Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wide association study (GWAS). More than 40 robust susceptible loci have been identified and confirmed to be associated with vitiligo by using GWAS. Most of these associated genes participate in important pathways involved in the pathogenesis of vitiligo. Many susceptible loci with unknown functions in the pathogenesis of vitiligo have also been identified, indicating that additional molecular mechanisms may contribute to the risk of developing vitiligo. In this review, we summarize the key loci that are of genome-wide significance, which have been shown to influence vitiligo risk. These genetic loci may help build the foundation for genetic diagnosis and personalize treatment for patients with vitiligo in the future. However, substantial additional studies, including gene-targeted and functional studies, are required to confirm the causality of the genetic variants and their biological relevance in the development of vitiligo. PMID:26870082

  4. Antimicrobial Susceptibilities of Abiotrophia defectiva, Granulicatella adiacens, and Granulicatella elegans.

    Science.gov (United States)

    Alberti, Michael O; Hindler, Janet A; Humphries, Romney M

    2015-12-14

    Nutritionally variant streptococci (NVS) are fastidious Gram-positive cocci comprised of the species Abiotrophia defectiva, Granulicatella adiacens, and Granulicatella elegans. NVS are an important cause of bacteremia and infective endocarditis (IE) associated with significant morbidity and mortality. Antimicrobial susceptibility testing (AST) was performed for 14 antimicrobials using the broth microdilution MIC method described in the Clinical and Laboratory Standards Institute (CLSI) M45 guideline. A total of 132 clinical NVS blood isolates collected from 2008 to 2014 were tested. Species level identification of NVS isolates was achieved by 16S rRNA gene sequencing and/or matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Ninety isolates were identified as G. adiacens, 37 as A. defectiva, and 5 as G. elegans. All isolates were susceptible to vancomycin (MIC90 = 1 μg/ml), and none displayed high-level resistance to aminoglycosides. G. adiacens was considerably more susceptible to penicillin than A. defectiva (38.9% versus 10.8% of isolates susceptible) but was less susceptible to cephalosporins than was A. defectiva (43.3% versus 100% of isolates susceptible to ceftriaxone). Several isolates were resistant to levofloxacin (6%), erythromycin (51%), and clindamycin (10%). The MIC90 for daptomycin was ≥ 4 μg/ml for G. adiacens and A. defectiva. G. elegans isolates were 100% susceptible to all antimicrobials tested, with the exception of erythromycin, to which only 20% were susceptible. This study provides antimicrobial susceptibility data for a recent collection of NVS and demonstrates important NVS species-related differences with respect to susceptibility to penicillin, cephalosporins, carbapenems, and daptomycin. Species-level identification of NVS organisms when susceptibility testing is not readily available may aid in treatment decisions. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. Identification of maize genes associated with host plant resistance or susceptibility to Aspergillus flavus infection and aflatoxin accumulation.

    Directory of Open Access Journals (Sweden)

    Rowena Y Kelley

    Full Text Available BACKGROUND: Aspergillus flavus infection and aflatoxin contamination of maize pose negative impacts in agriculture and health. Commercial maize hybrids are generally susceptible to this fungus. Significant levels of host plant resistance have been observed in certain maize inbred lines. This study was conducted to identify maize genes associated with host plant resistance or susceptibility to A. flavus infection and aflatoxin accumulation. RESULTS: Genome wide gene expression levels with or without A. flavus inoculation were compared in two resistant maize inbred lines (Mp313E and Mp04:86 in contrast to two susceptible maize inbred lines (Va35 and B73 by microarray analysis. Principal component analysis (PCA was used to find genes contributing to the larger variances associated with the resistant or susceptible maize inbred lines. The significance levels of gene expression were determined by using SAS and LIMMA programs. Fifty candidate genes were selected and further investigated by quantitative RT-PCR (qRT-PCR in a time-course study on Mp313E and Va35. Sixteen of the candidate genes were found to be highly expressed in Mp313E and fifteen in Va35. Out of the 31 highly expressed genes, eight were mapped to seven previously identified quantitative trait locus (QTL regions. A gene encoding glycine-rich RNA binding protein 2 was found to be associated with the host hypersensitivity and susceptibility in Va35. A nuclear pore complex protein YUP85-like gene was found to be involved in the host resistance in Mp313E. CONCLUSION: Maize genes associated with host plant resistance or susceptibility were identified by a combination of microarray analysis, qRT-PCR analysis, and QTL mapping methods. Our findings suggest that multiple mechanisms are involved in maize host plant defense systems in response to Aspergillus flavus infection and aflatoxin accumulation. These findings will be important in identification of DNA markers for breeding maize lines

  6. Assessing Degree of Susceptibility to Landslide Hazard

    Science.gov (United States)

    Sheridan, M. F.; Cordoba, G. A.; Delgado, H.; Stefanescu, R.

    2013-05-01

    The modeling of hazardous mass flows, both dry and water saturated, is currently an area of active research and several stable models have now emerged that have differing degrees of physical and mathematical fidelity. Models based on the early work of Savage and Hutter (1989) assume that very large dense granular flows could be modeled as incompressible continua governed by a Coulomb failure criterion. Based on this concept, Patra et al. (2005) developed a code for dry avalanches, which proposes a thin layer mathematical model similar to shallow-water equations. This concept was implemented in the widely-used TITAN2D program, which integrates the shock-capturing Godunov solution methodology for the equation system. We propose a method to assess the susceptibility of specific locations susceptible to landslides following heavy tephra fall using the TIATN2D code. Successful application requires that the range of several uncertainties must be framed in the selection of model input data: 1) initial conditions, like volume and location of origin of the landslide, 2) bed and internal friction parameters and 3) digital elevation model (DEM) uncertainties. Among the possible ways of coping with these uncertainties, we chose to use Latin Hypercube Sampling (LHS). This statistical technique reduces a computationally intractable problem to such an extent that is it possible to apply it, even with current personal computers. LHS requires that there is only one sample in each row and each column of the sampling matrix, where each row (multi-dimensional) corresponds to each uncertainty. LHS requires less than 10% of the sample runs needed by Monte Carlo approaches to achieve a stable solution. In our application LHS output provides model sampling for 4 input parameters: initial random volumes, UTM location (x and y), and bed friction. We developed a simple Octave script to link the output of LHS with TITAN2D. In this way, TITAN2D can run several times with successively different

  7. Transcriptomics and systems biology analysis in identification of specific pathways involved in cacao resistance and susceptibility to witches' broom disease.

    Science.gov (United States)

    da Hora Junior, Braz Tavares; Poloni, Joice de Faria; Lopes, Maíza Alves; Dias, Cristiano Villela; Gramacho, Karina Peres; Schuster, Ivan; Sabau, Xavier; Cascardo, Júlio Cézar De Mattos; Mauro, Sônia Marli Zingaretti Di; Gesteira, Abelmon da Silva; Bonatto, Diego; Micheli, Fabienne

    2012-04-01

    This study reports on expression analysis associated with molecular systems biology of cacao-Moniliophthora perniciosa interaction. Gene expression data were obtained for two cacao genotypes (TSH1188, resistant; Catongo, susceptible) challenged or not with the fungus M. perniciosa and collected at three time points through disease. Using expression analysis, we identified 154 and 227 genes that are differentially expressed in TSH1188 and Catongo, respectively. The expression of some of these genes was confirmed by RT-qPCR. Physical protein-protein interaction (PPPI) networks of Arabidopsis thaliana orthologous proteins corresponding to resistant and susceptible interactions were obtained followed by cluster and gene ontology analyses. The integrated analysis of gene expression and systems biology allowed designing a general scheme of major mechanisms associated with witches' broom disease resistance/susceptibility. In this sense, the TSH1188 cultivar shows strong production of ROS and elicitors at the beginning of the interaction with M. perniciosa followed by resistance signal propagation and ROS detoxification. On the other hand, the Catongo genotype displays defense mechanisms that include the synthesis of some defense molecules but without success in regards to elimination of the fungus. This phase is followed by the activation of protein metabolism which is achieved with the production of proteasome associated with autophagy as a precursor mechanism of PCD. This work also identifies candidate genes for further functional studies and for genetic mapping and marker assisted selection.

  8. Dystrophin-deficiency increases the susceptibility to doxorubicin-induced cardiotoxicity.

    Science.gov (United States)

    Deng, Shiwei; Kulle, Bettina; Hosseini, Mehdi; Schlüter, Gregor; Hasenfuss, Gerd; Wojnowski, Leszek; Schmidt, Albrecht

    2007-10-01

    The clinical use of doxorubicin (DOX) and other anthracyclines is limited by a dosage-dependent cardiotoxicity, which can lead to cardiomyopathy. The role of the individual genetic makeup in this disorder is poorly understood. Alterations in genes encoding cardiac cytoskeleton or sarcolemma proteins may increase the susceptibility to doxorubicin-related cardiotoxicity. Female dystrophin-deficient mice (MDX) and age-matched wild-type mice underwent chronic treatment with doxorubicin. Cardiac function and tissue damage were assessed by echocardiography and histopathology, respectively. Gene expression changes were investigated using microarrays. DOX treatment resulted in mortality, cardiac insufficiency, and cardiac interstitial fibrosis. These alterations were more pronounced in DOX-treated MDX mice than in DOX-treated wild-type mice. Changes in gene expression were more numerous in MDX mice, including genes involved in cell adhesion, oxidative stress, cytoskeleton organization, inflammatory and immune response and cell death. Dystrophin deficiency facilitates the development and progression of doxorubicin-induced cardiac injury. The underlying mechanisms may involve changes in cell adhesion, in cytoskeleton, as well as in inflammatory and immune responses. Genetic variants of cytoskeletal proteins in humans may affect the individual susceptibility to doxorubicin. Cardiotoxic drugs may accelerate the manifestation of pre-clinical cardiomyopathies caused by deficiencies in cytoskeletal or sarcolemma proteins.

  9. Genotypic and phenotypic patterns of antimicrobial susceptibility of ...

    African Journals Online (AJOL)

    ... of antibiotics' susceptibility to H. pylori strains among Egyptian patients. 60 symptomatic cases were enrolled. H. pylori infection was diagnosed by upper endoscopy as well as biopsy. Antimicrobial susceptibility to H. pylori strains was assessed in all subjects by disc diffusion and Ellipsometer testing (E-testing) methods.

  10. Usefulness of Routine Antibacterial Susceptibility Testing Results for ...

    African Journals Online (AJOL)

    The objective was to evaluate the usefulness and reliability of routine antibacterial susceptibility testing data in antibacterial resistance surveillance in Lagos Metropolis. The antibacterial susceptibility testing results of 3,961 clinical isolates of bacteria from four highly rated hospitals in Lagos metropolis were collated and ...

  11. GIS-based assessment of landslide susceptibility using certainty ...

    Indian Academy of Sciences (India)

    lions of people still live under the high-risk threat of landslides (Liu et al. 2013). The main goal of landslide susceptibility analy- sis is to identify dangerous and high risk areas. Keywords. Landslide; susceptibility mapping ...... the decision makers, managers, urban planners, engineers, and land-use developers to manage.

  12. Susceptibility for thin ideal media and eating styles

    NARCIS (Netherlands)

    Anschutz, Doeschka J; Engels, Rutger C M E; van Strien, Tatjana

    This study examined the relations between susceptibility for thin ideal media and restrained, emotional and external eating, directly and indirectly through body dissatisfaction. Thin ideal media susceptibility, body dissatisfaction and eating styles were measured in a sample of 163 female students.

  13. A genome wide linkage search for breast cancer susceptibility genes

    NARCIS (Netherlands)

    Smith, Paula; McGuffog, Lesley; Easton, Douglas F.; Mann, Graham J.; Pupo, Gulietta M.; Newman, Beth; Chenevix-Trench, Georgia; Szabo, Csilla; Southey, Melissa; Renard, Hélène; Odefrey, Fabrice; Lynch, Henry; Stoppa-Lyonnet, Dominique; Couch, Fergus; Hopper, John L.; Giles, Graham G.; McCredie, Margaret R. E.; Buys, Saundra; Andrulis, Irene; Senie, Ruby; Goldgar, David E.; Oldenburg, Rogier; Kroeze-Jansema, Karin; Kraan, Jaennelle; Meijers-Heijboer, Hanne; Klijn, Jan G. M.; van Asperen, Christi; van Leeuwen, Inge; Vasen, Hans F. A.; Cornelisse, Cees J.; Devilee, Peter; Baskcomb, Linda; Seal, Sheila; Barfoot, Rita; Mangion, Jon; Hall, Anita; Edkins, Sarah; Rapley, Elizabeth; Wooster, Richard; Chang-Claude, Jenny; Eccles, Diana; Evans, D. Gareth; Futreal, P. Andrew; Nathanson, Katherine L.; Weber, Barbara L.; Rahman, Nazneen; Stratton, Michael R.

    2006-01-01

    Mutations in known breast cancer susceptibility genes account for a minority of the familial aggregation of the disease. To search for further breast cancer susceptibility genes, we performed a combined analysis of four genome-wide linkage screens, which included a total of 149 multiple case breast

  14. Susceptibility levels of Rhododendron species and hybrids to Phytophthora ramorum

    Science.gov (United States)

    Isabelle De Dobbelaere; Kurt Heungens; Martine Maes

    2006-01-01

    Until now there has been little scientific information available about the susceptibility of different Rhododendron species and cultivars to Phytophthora ramorum. However, growers could use this knowledge as part of their control strategy. In our susceptibility screening we first optimized different inoculation methods on stem and...

  15. Antimicrobial susceptibility profile of Listeria species isolated from ...

    African Journals Online (AJOL)

    The antimicrobial susceptibility profile of L. monocytogenes and other Listeria species isolated from some ready-to-eat (RTE) foods sold in Kano metropolis, north-western Nigeria was carried out using disc-diffusion method. The results obtained showed that L. monocytogenes was moderately susceptible to all the ...

  16. Establishment of valnemulin susceptibility breakpoint against Clostridium perfringens in rabbits.

    Science.gov (United States)

    Tao, Meng-Ting; Zhou, Yu-Feng; Sun, Jian; Liu, Ya-Hong; Liao, Xiao-Ping

    2017-12-01

    Susceptibility breakpoints provide fundamental information for rational administration of antibiotics. The present investigation reports the first valnemulin susceptibility breakpoint (MICvalnemulin might be useful in resistance surveillance of pleuromutilins and development of clinical breakpoints. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. 21 CFR 866.1620 - Antimicrobial susceptibility test disc.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimicrobial susceptibility test disc. 866.1620 Section 866.1620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to...

  18. 21 CFR 866.1640 - Antimicrobial susceptibility test powder.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimicrobial susceptibility test powder. 866.1640 Section 866.1640 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic...

  19. Magnetic susceptibility of a two-channel Anderson model

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, J.V.B.; Oliveira, L.N. de; Cox, D.L.; Libero, V.L. E-mail: valter@if.sc.usp.br

    2001-05-01

    Temperature-dependent magnetic susceptibility is calculated for a two-channel Anderson model, by using the numerical renormalization group plus an interleaving procedure to recover the continuum of the conduction band. Fermi- and non-Fermi-liquid fixed points can be obtained in the low-temperature regime of the model susceptibility.

  20. Reduced fluoroquinolone susceptibility in Salmonella enterica isolates from travelers, Finland.

    Science.gov (United States)

    Lindgren, Marianne M; Kotilainen, Pirkko; Huovinen, Pentti; Hurme, Saija; Lukinmaa, Susanna; Webber, Mark A; Piddock, Laura J V; Siitonen, Anja; Hakanen, Antti J

    2009-05-01

    We tested the fluoroquinolone susceptibility of 499 Salmonella enterica isolates collected from travelers returning to Finland during 2003-2007. Among isolates from travelers to Thailand and Malaysia, reduced fluoroquinolone susceptibility decreased from 65% to 22% (p = 0.002). All isolates showing nonclassical quinolone resistance were from travelers to these 2 countries.

  1. Susceptibility and reactivity in polysensitized individuals following controlled induction

    DEFF Research Database (Denmark)

    Bangsgaard, Nannie; Carlsen, Berit C; Johansen, Jeanne Duus

    2010-01-01

    It is uncertain whether polysensitized patients acquire multiple allergies only because of a high degree of exposure to environmental allergens, or because of being highly susceptible to developing contact allergy.......It is uncertain whether polysensitized patients acquire multiple allergies only because of a high degree of exposure to environmental allergens, or because of being highly susceptible to developing contact allergy....

  2. Antimicrobial susceptibility profile of community-acquired urinary ...

    African Journals Online (AJOL)

    Introduction: With the increasing trend of antibiotic resistance, the management of urinary tract infection (UTI) is likely to become complicated, and there is a need for continuous surveillance of antibiotic susceptibility of uropathogens. Objective: This study aimed to assess the current antimicrobial susceptibility pattern in the ...

  3. Susceptibility profiles of Nocardia isolates based on current taxonomy.

    Science.gov (United States)

    Schlaberg, Robert; Fisher, Mark A; Hanson, Kimberley E

    2014-01-01

    The genus Nocardia has undergone rapid taxonomic expansion in recent years, and an increasing number of species are recognized as human pathogens. Many established species have predictable antimicrobial susceptibility profiles, but sufficient information is often not available for recently described organisms. Additionally, the effectiveness of sulfonamides as first-line drugs for Nocardia has recently been questioned. This led us to review antimicrobial susceptibility patterns for a large number of molecularly identified clinical isolates. Susceptibility results were available for 1,299 isolates representing 39 different species or complexes, including 11 that were newly described, during a 6-year study period. All tested isolates were susceptible to linezolid. Resistance to trimethoprim-sulfamethoxazole (TMP-SMX) was rare (2%) except among Nocardia pseudobrasiliensis (31%) strains and strains of the N. transvalensis complex (19%). Imipenem susceptibility varied for N. cyriacigeorgica and N. farcinica, as did ceftriaxone susceptibility of the N. nova complex. Resistance to more than one of the most commonly used drugs (amikacin, ceftriaxone, TMP-SMX, and imipenem) was highest for N. pseudobrasiliensis (100%), N. transvalensis complex (83%), N. farcinica (68%), N. puris (57%), N. brasiliensis (51%), N. aobensis (50%), and N. amikacinitolerans (43%). Thus, while antimicrobial resistance can often be predicted, susceptibility testing should still be considered when combination therapy is warranted, for less well characterized species or those with variable susceptibility profiles, and for patients with TMP-SMX intolerance.

  4. The usefulness of microscopic observation for drug susceptibility of ...

    African Journals Online (AJOL)

    transmission, and control development of drug resistance. This study was undertaken to establish microscopic observation for drug susceptibility (MODS) in clinical microbiology routine. Thirty Mycobacter um tuberculos s isolates and four smear positive sputum specimens were tested for susceptibility to isoniazid, rifampicin,.

  5. The usefulness of microscopic observation for drug susceptibility of ...

    African Journals Online (AJOL)

    This study was undertaken to establish microscopic observation for drug susceptibility (MODS) in clinical microbiology routine. Thirty Mycobacterium tuberculosis isolates and four smear positive sputum specimens were tested for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin using MODS. Results were ...

  6. Stability analysis of fractional-order generalized chaotic susceptible ...

    Indian Academy of Sciences (India)

    the spread and control of infectious diseases. In a given model, a person contracting the disease and then becoming immune to future infection after recovery is called susceptible– infected–recovered (SIR). .... of susceptible, k is the carrying capacity of susceptible, a is the saturation factor that mea- sures the inhibitory effect ...

  7. Quantitative Susceptibility Mapping in Cerebral Cavernous Malformations: Clinical Correlations.

    Science.gov (United States)

    Tan, H; Zhang, L; Mikati, A G; Girard, R; Khanna, O; Fam, M D; Liu, T; Wang, Y; Edelman, R R; Christoforidis, G; Awad, I A

    2016-07-01

    Quantitative susceptibility mapping has been shown to assess iron content in cerebral cavernous malformations. In this study, our aim was to correlate lesional iron deposition assessed by quantitative susceptibility mapping with clinical and disease features in patients with cerebral cavernous malformations. Patients underwent routine clinical scans in addition to quantitative susceptibility mapping on 3T systems. Data from 105 patients met the inclusion criteria. Cerebral cavernous malformation lesions identified on susceptibility maps were cross-verified by T2-weighted images and differentiated on the basis of prior overt hemorrhage. Mean susceptibility per cerebral cavernous malformation lesion (χ̄lesion) was measured to correlate with lesion volume, age at scanning, and hemorrhagic history. Temporal rates of change in χ̄lesion were evaluated in 33 patients. Average χ̄lesion per patient was positively correlated with patient age at scanning (P cavernous malformation lesions with prior overt hemorrhages exhibited higher χ̄lesion than those without (P cavernous malformation lesions, higher mean quantitative susceptibility mapping signal in hemorrhagic lesions, and minimum longitudinal quantitative susceptibility mapping signal change in clinically stable lesions. Quantitative susceptibility mapping has the potential to be a novel imaging biomarker supplementing conventional imaging in cerebral cavernous malformations. The clinical significance of such measures merits further study. © 2016 by American Journal of Neuroradiology.

  8. Susceptibility to air pollution in elderly males and females

    NARCIS (Netherlands)

    Boezen, H M; Vonk, J.M.; van der Zee, S C; Gerritsen, J; Hoek, G; Brunekreef, B; Schouten, Jan; Postma, D S

    It is important to know which individuals in the general population have increased susceptibility to air pollution. The aim of this study was to identify susceptible subgroups by studying airways hyperresponsiveness (AHR), high total immunoglobulin (Ig)E and sex. Diary data on lower and upper

  9. degraded forests are more susceptible to forest fires: some possible ...

    African Journals Online (AJOL)

    2006-08-02

    Aug 2, 2006 ... There is a strong belief that degraded forests are, more susceptible to forest fires than non~ degraded ... fire as well as the impact that the fire will have on the forest. When a forest is well protected and a close canopy maintained, its susceptibility to accidental ... human interference in the ecosystem. Swaine ...

  10. Antibiotic susceptibility of methicillin-resistant and methicillin-susceptible coagulase-negative staphylococci isolated from bovine mastitis.

    Science.gov (United States)

    Bochniarz, M; Wawron, W

    2011-01-01

    The aim of the present study was to evaluate the antibiotic susceptibility of methicillin-susceptible (MS) and methicillin-resistant (MR) coagulase-negative Staphylococcus (CNS) strains isolated from milk of cows with mastitis. The study was conducted on 100 CNS strains (20 MRCNS and 80 MSCNS) isolated from milk samples of 86 cows from the Lublin (Poland) region farms. Antibiotic susceptibility of microorganisms was evaluated using the disc-diffusion method on the Mueller-Hinton agar according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS). The highest efficacy against MSCNS was demonstrated for cephalosporin antibiotics, i.e. cefacetril (91.3%), ceftiofur (67.5%), cefoperazone (66.3%) and cephalexin (60.0% of susceptible MSCNS strains). Moreover, a high percentage of vancomycin-susceptible strains was demonstrated (83.8%). The activity of combination of amoxicillin with clavulanic acid and gentamicin was found weaker (63.8% and 61.3% of susceptible strains, respectively). About 50.0% of MSCNS were susceptible to erythromycin, enrofloxacine and amoxicillin. A large proportion of CNS was resistant to neomycin, penicillin, tetracycline, streptomycin, lincomycin and ampicillin (28.8%, 30.0%, 31.3%, 31.3%, 33.8% and 33.8% of susceptible strains, respectively). The highest percentage of MRCNS was susceptible to vancomycin (75.0%), erythromycin (65.0%) and streptomycin (50.0%). Their susceptibility to enrofloxacine (35.0%) as well as gentamicin and tetracycline (30.0%) was markedly lower. The lowest activity was found for lincomycin and neomycin (20.0% of susceptible MRCNS strains, each).

  11. Genetic predictions of prion disease susceptibility in carnivore species based on variability of the prion gene coding region.

    Directory of Open Access Journals (Sweden)

    Paula Stewart

    Full Text Available Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE during the bovine spongiform encephalopathy (BSE epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD remains an open question. Variation in the host-encoded prion protein (PrP(C largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrP(C protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo and pine marten (Martes martes were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus and mountain lion (Puma concolor from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter.

  12. Genetic predictions of prion disease susceptibility in carnivore species based on variability of the prion gene coding region.

    Science.gov (United States)

    Stewart, Paula; Campbell, Lauren; Skogtvedt, Susan; Griffin, Karen A; Arnemo, Jon M; Tryland, Morten; Girling, Simon; Miller, Michael W; Tranulis, Michael A; Goldmann, Wilfred

    2012-01-01

    Mammalian species vary widely in their apparent susceptibility to prion diseases. For example, several felid species developed prion disease (feline spongiform encephalopathy or FSE) during the bovine spongiform encephalopathy (BSE) epidemic in the United Kingdom, whereas no canine BSE cases were detected. Whether either of these or other groups of carnivore species can contract other prion diseases (e.g. chronic wasting disease or CWD) remains an open question. Variation in the host-encoded prion protein (PrP(C)) largely explains observed disease susceptibility patterns within ruminant species, and may explain interspecies differences in susceptibility as well. We sequenced and compared the open reading frame of the PRNP gene encoding PrP(C) protein from 609 animal samples comprising 29 species from 22 genera of the Order Carnivora; amongst these samples were 15 FSE cases. Our analysis revealed that FSE cases did not encode an identifiable disease-associated PrP polymorphism. However, all canid PrPs contained aspartic acid or glutamic acid at codon 163 which we propose provides a genetic basis for observed susceptibility differences between canids and felids. Among other carnivores studied, wolverine (Gulo gulo) and pine marten (Martes martes) were the only non-canid species to also express PrP-Asp163, which may impact on their prion diseases susceptibility. Populations of black bear (Ursus americanus) and mountain lion (Puma concolor) from Colorado showed little genetic variation in the PrP protein and no variants likely to be highly resistant to prions in general, suggesting that strain differences between BSE and CWD prions also may contribute to the limited apparent host range of the latter.

  13. Evaluation of SLE Susceptibility Genes in Malaysians

    Directory of Open Access Journals (Sweden)

    Julio E. Molineros

    2014-01-01

    Full Text Available Systemic Lupus Erythematosus (SLE is a clinically heterogeneous autoimmune disease with strong genetic and environmental components. Our objective was to replicate 25 recently identified SLE susceptibility genes in two distinct populations (Chinese (CH and Malays (MA from Malaysia. We genotyped 347 SLE cases and 356 controls (CH and MA using the ImmunoChip array and performed an admixture corrected case-control association analysis. Associated genes were grouped into five immune-related pathways. While CH were largely homogenous, MA had three ancestry components (average 82.3% Asian, 14.5% European, and 3.2% African. Ancestry proportions were significantly different between cases and controls in MA. We identified 22 genes with at least one associated SNP (P<0.05. The strongest signal was at HLA-DRA (PMeta=9.96×10-9; PCH=6.57×10-8, PMA=6.73×10-3; the strongest non-HLA signal occurred at STAT4 (PMeta=1.67×10-7; PCH=2.88×10-6, PMA=2.99×10-3. Most of these genes were associated with B- and T-cell function and signaling pathways. Our exploratory study using high-density fine-mapping suggests that most of the established SLE genes are also associated in the major ethnicities of Malaysia. However, these novel SNPs showed stronger association in these Asian populations than with the SNPs reported in previous studies.

  14. Susceptibility to chronic inflammation: an update.

    Science.gov (United States)

    Nasef, Noha Ahmed; Mehta, Sunali; Ferguson, Lynnette R

    2017-03-01

    Chronic inflammation is defined by the persistence of inflammatory processes beyond their physiological function, resulting in tissue destruction. Chronic inflammation is implicated in the progression of many chronic diseases and plays a central role in chronic inflammatory and autoimmune disease. As such, this review aims to collate some of the latest research in relation to genetic and environmental susceptibilities to chronic inflammation. In the genetic section, we discuss some of the updates in cytokine research and current treatments that are being developed. We also discuss newly identified canonical and non-canonical genes associated with chronic inflammation. In the environmental section, we highlight some of the latest updates and evidence in relation to the role that infection, diet and stress play in promoting inflammation. The aim of this review is to provide an overview of the latest research to build on our current understanding of chronic inflammation. It highlights the complexity associated with chronic inflammation, as well as provides insights into potential new targets for therapies that could be used to treat chronic inflammation and consequently prevent disease progression.

  15. Dermatophyte susceptibility varies towards antimicrobial textiles.

    Science.gov (United States)

    Hammer, Timo R; Mucha, Helmut; Hoefer, Dirk

    2012-07-01

    Dermatophytoses are a widespread problem worldwide. Textiles in contact with infected skin can serve as a carrier for fungus propagation. Hitherto, it is unknown, whether antifungal textiles could contribute in controlling dermatophytes e.g. by disrupting the chain of infection. Testing of antimicrobial fabrics for their antifungal activities therefore is a fundamental prerequisite to assess the putative clinical relevance of textiles for dermatophyte prevention. Fabrics finished with either didecyldimethylammonium chloride (DDAC), poly-hexamethylenbiguanide, copper and two silver chloride concentrations were tested for their antifungal activity against Trichophyton rubrum, Trichophyton mentagrophytes and Candida albicans. To prove dermatophyte susceptibility towards the textiles, swatches were subjected to DIN EN 14199 (Trichophyton sp.) or DIN EN ISO 20743 (C. albicans) respectively. In addition, samples were embedded, and semi-thin sections were analysed microscopically. While all samples showed a clear inhibition of C. albicans, activity against Trichophyton sp. varied significantly: For example, DDAC completely inhibited T. rubrum growth, whereas T. mentagrophytes growth remained unaffected even in direct contact to the fibres. The results favour to add T. mentagrophytes as a test organism in textile dermatophyte efficacy tests. Microscopic analysis of swatches allowed detailed evaluation of additional parameters like mycelium thickness, density and hyphae penetration depth into the fabric. © 2011 Blackwell Verlag GmbH.

  16. Pinning Susceptibility Near the Jamming Transition

    Science.gov (United States)

    Nashed, Samer; Graves, Amy; Goodrich, Carl; Padgett, Elliot; Liu, Andrea

    2014-03-01

    The study of jamming in the presence of pinned obstacles is of both practical and theoretical interest. In simulations of soft, bidisperse disks and spheres, we pin a small fraction, nf of particles prior to the equilibration process. The presence of pinned particles is known to lower the critical packing fraction, ϕJ, for jamming. Further, around this threshold there is a peak in a quantity which we have termed the ``pinning susceptibility'': χP =limnf --> 0∂PJ(ϕ/,nf) ∂nf . In the thermodynamic limit, we have posited that χP ~| Δϕ | -γP . Finite-size scaling calculations, involving careful fits of PJ to logistic sigmoidal functions, yield a value for the critical exponent, γP. This new exponent is proposed to be independent of inter-particle potential. Its dependence on dimensionality (2 vs. 3 dimensions) will be discussed. Acknowledgement is made to the Donors of the Petroleum Research Fund administered by the American Chemical Society, NSF grant DMR-1062638 and DOE grant DE-FG02-05ER46199.

  17. Susceptibility of Freesia to hydrogen fluoride

    Energy Technology Data Exchange (ETDEWEB)

    Wolting, H.G.

    1973-01-01

    Freesia's are very sensitive to hydrogen-fluoride. If they are exposed for a long period to concentrations between 0.5 and 0.9 part per billion several cultivars may show a severe damage. Differences in susceptibility between the varieties appear to exist. Some varieties that were heavily injured by HF had almost no flowers and a much lower yield of corns. After fumigation during a long period with very low concentrations of HF, besides the damage characteristic for HF (necrotic leaf tips and margins) there appeared oblong brown spots and stripes between the veins, which mimic the symptoms caused by the third freesia virus, also called bladnecrose. Some of the cultivars show this effect rather generally, in others it occurs only in a few plants. It could be demonstrated with the cultivars Rose Marie and Royal Blue that the sensitivity for HF increases by the presence of bladnecrose. This points to a synergistic action of hydrogen fluoride and the bladnecrose virus.

  18. Prophylactic stretching does not reduce cramp susceptibility.

    Science.gov (United States)

    Miller, Kevin C; Harsen, James D; Long, Blaine C

    2017-08-10

    Some clinicians advocate stretching to prevent muscle cramps. It is unknown whether static or proprioceptive neuromuscular facilitation (PNF) stretching increases cramp threshold frequency (TFc ), a quantitative measure of cramp susceptibility. Fifteen individuals completed this randomized, counterbalanced, cross-over study. We measured passive hallux range of motion (ROM) and then performed 3 minutes of either static stretching, PNF stretching (hold-relax-with agonist contraction), or no stretching. ROM was reassessed and TFc was measured. PNF stretching increased hallux extension (pre-PNF 81 ± 11°, post-PNF 90 ± 10°; P PNF 40 ± 7°, post-PNF 40 ± 7°; P > 0.05). Static stretching increased hallux extension (pre-static 80 ± 11°, post-static 88 ± 9°; P 0.05). No ROM changes occurred with no stretching (P > 0.05). TFc was unaffected by stretching (no stretching 18 ± 7 Hz, PNF 16 ± 4 Hz, static 16 ± 5 Hz; P = 0.37). Static and PNF stretching increased hallux extension, but neither increased TFc . Acute stretching may not prevent muscle cramping. Muscle Nerve, 2017. © 2017 Wiley Periodicals, Inc.

  19. Individual Susceptibility to Hypobaric Environments: An Update

    Science.gov (United States)

    Law, Jennifer; Watkins, Sharmi

    2009-01-01

    Astronauts are at risk for developing decompression sickness (DCS) while exposed to the hypobaric environment of the extravehicular suit in space, in terrestrial hypobaric chambers, and during ascent from neutral buoyancy training dives. There is increasing recognition that DCS risk is different between diving and altitude exposures, with many individual parameters and environmental factors implicated as risk factors for development of DCS in divers but are not recognized as risk factors in altitude exposures. Much of the literature to date has focused on patent foramen ovale (PFO), which has long been considered a major risk factor for DCS in diving exposures, but its link to serious DCS in altitude exposures remains unclear. Knowledge of those risk factors specific to hypobaric DCS may help identify susceptible individuals and aid in astronaut selection, crew assignment, and mission planning. This paper reviews the current literature pertaining to these risk factors, including PFO, anthropometric parameters, gender, menstrual cycle, lifetime diving experience, physical fitness, biochemical levels, complement activation, cigarette smoking, fluid balance, and ambient temperature. Further research to evaluate pertinent risk factors for DCS in altitude exposures is recommended.

  20. Plasminogen alleles influence susceptibility to invasive aspergillosis.

    Directory of Open Access Journals (Sweden)

    Aimee K Zaas

    2008-06-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

  1. Prediction of susceptibility to the porcine stress syndrome.

    Science.gov (United States)

    Mabry, J W; Christian, L L; Kuhlers, D L; Rasmusen, B A

    1983-01-01

    An experiment designed to compare different predictors of porcine stress syndrome (PSS) was conducted. Animals were exposed to the anesthetic gas, halothane, and their reactions monitored to determine susceptibility or resistance to PSS. Two blood creatine phosphokinase (CPK) traits plus their logs10 were examined as predictors of PSS susceptibility. These were Sigma CPK, Antonik CPK, log Sigma CPK, and log Antonik CPK. The accuracy of these predictors varied from 87 percent to 91 percent in agreement with halothane-determined stress susceptibility. In addition, the relationship of PSS and blood types systems (AO,H) were studied. Two blood types, (+,-/-) and (-,+/+), were consistently stress susceptible while three blood types, (+,a/a), (+,a/c), and (+,c/-), were consistently stress resistant. However, one blood type (+,a/-) contained both stress-susceptible and stress-resistant individuals.

  2. Toxoplasma gondii antigen SAG2A differentially modulates IL-1β expression in resistant and susceptible murine peritoneal cells.

    Science.gov (United States)

    Leal-Sena, Jamilly Azevedo; Dos Santos, Jane Lima; Dos Santos, Thaise Anne Rocha; de Andrade, Edson Mário; de Oliveira Mendes, Tiago Antônio; Santana, Juliano Oliveira; Mineo, Tiago Wilson Patriarca; Mineo, José Roberto; da Cunha-Júnior, Jair Pereira; Pirovani, Carlos Priminho

    2018-03-01

    The cell surface of Toxoplasma gondii is covered by antigens (SAGs) from the SRS family anchored by glycosylphosphatidylinositol (GPI) and includes antigens from the SAG2 family. Among these, the SAG2A surface antigen shows great potential in activating humoral responses and has been used in characterizing the acute phase of infection and in the serological diagnosis of toxoplasmosis. In this study, we aimed to evaluate rSAG2A-induced proteins in BALB/c and C57BL/c mice macrophages and to evaluate the phenotypic polarization induced in the process. We treated the peritoneal macrophages from mouse strains that were resistant or susceptible to T. gondii with rSAG2A to analyze their proteomic profile by mass spectrometry and systems biology. We also examined the gene expression of these cells by RT-qPCR using the phenotypic markers of M1 and M2 macrophages. Differences were observed in the expression of proteins involved in the inflammatory process in both resistant and susceptible cells, and macrophages were preferentially induced to obtain a pro-inflammatory immune response (M1) via the overexpression of IL-1β in mice susceptible to this parasite. These data suggest that the SAG2A antigen induces phenotypic and classical activation of macrophages in both resistant and susceptible strains of mice during the acute phase of the disease.

  3. Total protein

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003483.htm Total protein To use the sharing features on this page, please enable JavaScript. The total protein test measures the total amount of two classes ...

  4. fosI Is a New Integron-Associated Gene Cassette Encoding Reduced Susceptibility to Fosfomycin.

    Science.gov (United States)

    Pelegrino, Karla de Oliveira; Campos, Juliana Coutinho; Sampaio, Suely Carlos Ferreira; Lezirovitz, Karina; Seco, Bruna Mara; Pereira, Mayne de Oliveira; Rocha, Darlan Augusto da Costa; Jové, Thomas; Nicodemo, Antonio Carlos; Sampaio, Jorge Luiz Mello

    2015-11-09

    In this work, we demonstrate that the fosI gene encodes a predicted small protein with 134 amino acids and determines reduced susceptibility to fosfomycin. It raised the MIC from 0.125 to 6 μg/ml when the pBRA100 plasmid was introduced into Escherichia coli TOP10 and to 16 μg/ml when the gene was cloned into the pBC_SK(-) vector and expressed in E. coli TOP10. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. [Antibiotics susceptibility of Streptococcus and Enterococcus: data of Onerba network].

    Science.gov (United States)

    Vachée, A; Varon, E; Jouy, E; Meunier, D

    2009-05-01

    This work was aimed to analyze trends in susceptibility to antibiotics among the main species of beta-hemolytic streptococci involved in community-acquired infections in human (Streptococcus pyogenes and Streptococcus agalactiae), or in animals (Streptococcus suis and Streptococcus uberis) and also among the main enterocci species, Enterococcus faecalis and Enterococcus faecium. Data were recorded since 1996 through the Onerba networks. S. pyogenes, as the other beta-hemolytic streptococci studied remained fully susceptible to beta-lactam antibiotics. However, susceptibility to macrolides is clearly decreasing in S. pyogenes. In 2002, only 62 to 65% of the strains according to the network considered, were susceptible to erythromycin. A similar trend was observed for S. agalactiae with only 75% of erythromycin susceptibility in 2002, and for both species isolated from animals S. suis and S. uberis, with respectively 35 and 76% of strains susceptible to erythromycin. In enterococci, susceptibility to beta-lactams remained stable between 2000 and 2004. Indeed, the susceptibility to aminopenicillins remained high in E. faecalis (about 98%), whereas the proportion of E. faecium isolates susceptible to these antibiotics were lower than 60%. From 1999 to 2004, various studies conducted in French hospitals showed that the vancomycin resistance among enterococci accounted for less than 2%. However, the recent emergence of glycopeptide resistant enterococci clusters in French hospitals is a matter of concern and emphasizes the need for an ongoing surveillance. Such trend in macrolide resistance among S. pyogenes or S. agalactiae should consequently lead to propose other alternatives in case of beta-lactam allergy, and for pharyngitis, to rethink the place of the culture for susceptibility testing.

  6. Protein Structure

    Science.gov (United States)

    Asmus, Elaine Garbarino

    2007-01-01

    Individual students model specific amino acids and then, through dehydration synthesis, a class of students models a protein. The students clearly learn amino acid structure, primary, secondary, tertiary, and quaternary structure in proteins and the nature of the bonds maintaining a protein's shape. This activity is fun, concrete, inexpensive and…

  7. ATP-Sensitive K+ Channel Knockout Induces Cardiac Proteome Remodeling Predictive of Heart Disease Susceptibility

    Science.gov (United States)

    Arrell, D. Kent; Zlatkovic, Jelena; Kane, Garvan C.; Yamada, Satsuki; Terzic, Andre

    2010-01-01

    Forecasting disease susceptibility requires detection of maladaptive signatures prior to onset of overt symptoms. A case-in-point are cardiac ATP-sensitive K+ (KATP) channelopathies, for which the substrate underlying disease vulnerability remains to be identified. Resolving molecular pathobiology, even for single genetic defects, mandates a systems platform to reliably diagnose disease predisposition. High-throughput proteomic analysis was here integrated with network biology to decode consequences of Kir6.2 KATP channel pore deletion. Differential two-dimensional gel electrophoresis reproducibly resolved > 800 protein species from hearts of asymptomatic wild-type and Kir6.2-knockout counterparts. KATP channel ablation remodeled the cardiac proteome, significantly altering 71 protein spots, from which 102 unique identities were assigned following hybrid linear ion trap quadrupole-Orbitrap tandem mass spectrometry. Ontological annotation stratified the KATP channel-dependent protein cohort into a predominant bioenergetic module (63 resolved identities), with additional focused sets representing signaling molecules (6), oxidoreductases (8), chaperones (6), and proteins involved in catabolism (6), cytostructure (8), and transcription and translation (5). Protein interaction mapping, in conjunction with expression level changes, localized a KATP channel-associated subproteome within a nonstochastic scale-free network. Global assessment of the KATP channel deficient environment verified the primary impact on metabolic pathways and revealed overrepresentation of markers associated with cardiovascular disease. Experimental imposition of graded stress precipitated exaggerated structural and functional myocardial defects in the Kir6.2-knockout, decreasing survivorship and validating the forecast of disease susceptibility. Proteomic cartography thus provides an integral view of molecular remodeling in the heart induced by KATP channel deletion, establishing a systems

  8. AIRE: a missing link to explain female susceptibility to autoimmune diseases.

    Science.gov (United States)

    Berrih-Aknin, Sonia; Panse, Rozen Le; Dragin, Nadine

    2018-01-01

    Women are more susceptible to autoimmune diseases than men. Autoimmunity results from tolerance breakdown toward self-components. Recently, three transcription modulators were identified in medullary thymic epithelial cells that orchestrate immune central tolerance processes: the autoimmune regulator (AIRE), FEZ family zinc finger 2 (FEZF2 or FEZ1), and PR domain zinc finger protein 1 (PRDM1). Interestingly, these three transcription modulators regulate nonredundant tissue-specific antigen subsets and thus cover broad antigen diversity. Recent data from different groups demonstrated that sex hormones (estrogen and testosterone) are involved in the regulation of thymic AIRE expression in humans and mice through direct transcriptional modulation and epigenetic changes. As a consequence, AIRE displays gender-biased thymic expression, with females showing a lower expression compared with males, a finding that could explain the female susceptibility to autoimmune diseases. So far, FEZF2 has not been related to an increased gender bias in autoimmune disease. PRDM1 expression has not been shown to display gender-differential thymic expression, but its expression level and its gene polymorphisms are associated with female-dependent autoimmune disease risk. Altogether, various studies have demonstrated that increased female susceptibility to autoimmune diseases is in part a consequence of hormone-driven reduced thymic AIRE expression. © 2017 New York Academy of Sciences.

  9. High susceptibility of Bt maize to aphids enhances the performance of parasitoids of lepidopteran pests.

    Directory of Open Access Journals (Sweden)

    Cristina A Faria

    Full Text Available Concerns about possible undesired environmental effects of transgenic crops have prompted numerous evaluations of such crops. So-called Bt crops receive particular attention because they carry bacteria-derived genes coding for insecticidal proteins that might negatively affect non-target arthropods. Here we show a remarkable positive effect of Bt maize on the performance of the corn leaf aphid Rhopalosiphum maidis, which in turn enhanced the performance of parasitic wasps that feed on aphid honeydew. Within five out of six pairs that were evaluated, transgenic maize lines were significantly more susceptible to aphids than their near-isogenic equivalents, with the remaining pair being equally susceptible. The aphids feed from the phloem sieve element content and analyses of this sap in selected maize lines revealed marginally, but significantly higher amino acid levels in Bt maize, which might partially explain the observed increased aphid performance. Larger colony densities of aphids on Bt plants resulted in an increased production of honeydew that can be used as food by beneficial insects. Indeed, Cotesia marginiventris, a parasitoid of lepidopteran pests, lived longer and parasitized more pest caterpillars in the presence of aphid-infested Bt maize than in the presence of aphid-infested isogenic maize. Hence, depending on aphid pest thresholds, the observed increased susceptibility of Bt maize to aphids may be either a welcome or an undesirable side effect.

  10. SIRT3 is regulated by nutrient excess and modulates hepatic susceptibility to lipotoxicity

    Science.gov (United States)

    Bao, Jianjun; Scott, Iain; Lu, Zhongping; Pang, Liyan; Dimond, Christopher C.; Gius, David; Sack, Michael N.

    2010-01-01

    SIRT3 is the primary mitochondrial deacetylase that modulates mitochondrial metabolic and oxidative stress regulatory pathways. However, its role in response to nutrient excess remains unknown. Thus, we investigated SIRT3 regulation of the electron transfer chain and evaluated the role of SIRT3 in hepatic lipotoxic stress. SIRT3 depleted HepG2 cells shows diffuse disruption in mitochondrial electron transfer chain functioning, a concurrent reduction in the mitochondrial membrane potential, and excess basal reactive oxygen species levels. As this phenotype may predispose to increased lipotoxic hepatic susceptibility we evaluated the expression of SIRT3 in murine liver following chronic high-fat feeding. In this nutrient-excess model SIRT3 transcript and protein levels are downregulated in parallel with increased hepatic fat storage and oxidative stress. Palmitate was used to investigate lipotoxic susceptibility in SIRT3 knockout mouse primary hepatocytes and SIRT3 siRNA depleted HepG2 cells. Under SIRT3 deficient conditions palmitate enhances reactive oxygen species and increases hepatocyte cell death. Reconstitution of SIRT3 levels and/or treatment with N-acetylcysteine ameliorates these adverse effects. In conclusion SIRT3 functions to ameliorate hepatic lipotoxicity, although paradoxically, exposure to high-fat downregulates this adaptive program in the liver. This SIRT3-dependent lipotoxic susceptibility is possibly modulated, in part, by SIRT3 mediated control of electron transfer chain flux. PMID:20647045

  11. Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B12-Defective Mice Is Subject to Maternal Influences

    Directory of Open Access Journals (Sweden)

    Lynda Mottram

    2016-06-01

    Full Text Available Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif, a protein essential for the absorption of vitamin B12/cobalamin (Cbl, have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Giftm1a/tm1a mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1 mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2 equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility.

  12. Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease

    Science.gov (United States)

    Harold, Denise; Jones, Lesley; Holmans, Peter; Gerrish, Amy; Vedernikov, Alexey; Richards, Alexander; DeStefano, Anita L.; Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A.; Naj, Adam C.; Sims, Rebecca; Jun, Gyungah; Bis, Joshua C.; Beecham, Gary W.; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A.; Denning, Nicola; Smith, Albert V.; Chouraki, Vincent; Thomas, Charlene; Ikram, M. Arfan; Zelenika, Diana; Vardarajan, Badri N.; Kamatani, Yoichiro; Lin, Chiao-Feng; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L.; Vronskaya, Maria; Johnson, Andrew D.; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Hanon, Olivier; Fitzpatrick, Annette L.; Buxbaum, Joseph D.; Campion, Dominique; Crane, Paul K.; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L.; De Jager, Philip L.; Deramecourt, Vincent; Johnston, Janet A.; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Hernández, Isabel; Rubinsztein, David C.; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M.; Fiévet, Nathalie; Huentelman, Matthew J.; Gill, Michael; Brown, Kristelle; Kamboh, M. Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B.; Myers, Amanda J.; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; George-Hyslop, Peter St; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W.; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petra; Collinge, John; Sorbi, Sandro; Garcia, Florentino Sanchez; Fox, Nick C.; Hardy, John; Naranjo, Maria Candida Deniz; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Scarpini, Elio; Bonuccelli, Ubaldo; Mancuso, Michelangelo; Siciliano, Gabriele; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Frank-García, Ana; Panza, Francesco; Solfrizzi, Vincenzo; Caffarra, Paolo; Nacmias, Benedetta; Perry, William; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M.; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G.; Coto, Eliecer; Hamilton-Nelson, Kara L.; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J.; Faber, Kelley M.; Jonsson, Palmi V.; Combarros, Onofre; O'Donovan, Michael C.; Cantwell, Laura B.; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H.; Bennett, David A.; Harris, Tamara B.; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F. A. G.; Passmore, Peter; Montine, Thomas J.; Bettens, Karolien; Rotter, Jerome I.; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M.; Kukull, Walter A.; Hannequin, Didier; Powell, John F.; Nalls, Michael A.; Ritchie, Karen; Lunetta, Kathryn L.; Kauwe, John S. K.; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R.; Schmidt, Reinhold; Rujescu, Dan; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M.; Graff, Caroline; Psaty, Bruce M.; Haines, Jonathan L.; Lathrop, Mark; Pericak-Vance, Margaret A.; Launer, Lenore J.; Van Broeckhoven, Christine; Farrer, Lindsay A.; van Duijn, Cornelia M.; Ramirez, Alfredo

    2014-01-01

    Background Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci. Significance The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease. PMID:24922517

  13. Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Valentina Escott-Price

    Full Text Available Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10-6 and 14 (IGHV1-67 p = 7.9×10-8 which indexed novel susceptibility loci.The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.

  14. Regulatory element-based prediction identifies new susceptibility regulatory variants for osteoporosis.

    Science.gov (United States)

    Yao, Shi; Guo, Yan; Dong, Shan-Shan; Hao, Ruo-Han; Chen, Xiao-Feng; Chen, Yi-Xiao; Chen, Jia-Bin; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2017-08-01

    Despite genome-wide association studies (GWASs) have identified many susceptibility genes for osteoporosis, it still leaves a large part of missing heritability to be discovered. Integrating regulatory information and GWASs could offer new insights into the biological link between the susceptibility SNPs and osteoporosis. We generated five machine learning classifiers with osteoporosis-associated variants and regulatory features data. We gained the optimal classifier and predicted genome-wide SNPs to discover susceptibility regulatory variants. We further utilized Genetic Factors for Osteoporosis Consortium (GEFOS) and three in-house GWASs samples to validate the associations for predicted positive SNPs. The random forest classifier performed best among all machine learning methods with the F1 score of 0.8871. Using the optimized model, we predicted 37,584 candidate SNPs for osteoporosis. According to the meta-analysis results, a list of regulatory variants was significantly associated with osteoporosis after multiple testing corrections and contributed to the expression of known osteoporosis-associated protein-coding genes. In summary, combining GWASs and regulatory elements through machine learning could provide additional information for understanding the mechanism of osteoporosis. The regulatory variants we predicted will provide novel targets for etiology research and treatment of osteoporosis.

  15. Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.

    Science.gov (United States)

    Martineau, A R; Leandro, A C C S; Anderson, S T; Newton, S M; Wilkinson, K A; Nicol, M P; Pienaar, S M; Skolimowska, K H; Rocha, M A; Rolla, V C; Levin, M; Davidson, R N; Bremner, S A; Griffiths, C J; Eley, B S; Bonecini-Almeida, M G; Wilkinson, R J

    2010-05-01

    Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p = 0.009). This association was preserved if serum 25(OH)D was or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.

  16. Comparison of cellular responses to Xanthomonas perforans infection between resistant and susceptible tomato accessions.

    Science.gov (United States)

    Wang, Y Q; Zhang, X F; Li, N; Liu, X

    2017-02-01

    Bacterial spot of tomato (Solanum lycopersicum L.) caused by several Xanthomonas species is one of the most destructive diseases. Genes regulating the hypersensitive resistance and field resistance to X. perforans race T3 have been intensively investigated over the last decade. However, a comparative analysis of cellular responses to the pathogen in susceptible and resistant hosts has not been completed, which prevents the detailed understanding of the interactions between the pathogen and tomato plants. In this study, the characteristics of lesions, stomata, and pathogen colonization in hypersensitive response (HR) PI 128216, field-resistant PI 114490, and susceptible OH 88119 tomato plants after inoculation with green fluorescent protein-labeled X. perforans race T3 bacteria were investigated. Significant differences in developmental processes and the micromorphology of spot lesions among three tomato lines were observed. Our results suggested that the faster lesion development in OH 88119 plants compared with that of the other two lines was associated with a greater increase in the stomatal apertures over a longer period following bacterial inoculation. The depth of bacterial colonization and pathogen density inside infected leaves in OH 88119 were also significantly different from that of resistant tomato plants. Determination of the ultrastructural responses to X. perforans among three tomato lines revealed that cell wall defense response was the main difference between resistant and susceptible tomato lines. These results may provide fundamental information for understanding the cellular and molecular mechanisms regulating tomato responses to X. perforans race T3. Copyright © 2016 Elsevier GmbH. All rights reserved.

  17. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.

    Directory of Open Access Journals (Sweden)

    Fuu-Jen Tsai

    2010-02-01

    Full Text Available To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D in a Han Chinese population. A two-stage genome-wide association (GWA study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD (P = 8.54x10(-10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82, and serine racemase (SRR (P = 3.06x10(-9; OR = 1.28; 95% CI = 1.18-1.39. We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10; OR = 1.29, 95% CI = 1.19-1.40. By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.

  18. [Spectrum and susceptibility of preoperative conjunctival bacteria].

    Science.gov (United States)

    Fernández-Rubio, M E; Cuesta-Rodríguez, T; Urcelay-Segura, J L; Cortés-Valdés, C

    2013-12-01

    To describe the conjunctival bacterial spectrum of our patients undergoing intraocular surgery and their antibiotic sensitivity during the study period. A retrospective study of preoperative conjunctival culture of patients consecutively scheduled for intraocular surgery from 21 February 2011 to 1 April 2013. Specimens were directly seeded onto blood-agar and MacConkey-agar (aerobiosis incubation, 2 days), and on chocolate-agar (6% CO2 incubation, 7 days). The identified bacteria were divided into 3 groups according to their origin; the bacteria susceptibility tests were performed on those more pathogenic and on some of the less pathogenic when more than 5 colonies were isolated. The sensitivity of the exigent growing bacteria was obtained with disk diffusion technique, and for of the non-exigent bacteria by determining their minimum inhibitory concentration. The Epidat 3.1 program was used for statistical calculations. A total of 13,203 bacteria were identified in 6,051 cultures, with 88.7% being typical colonizers of conjunctiva (group 1), 8.8% typical of airways (group 2), and the remaining 2.5% of undetermined origin (group 3). 530 cultures (8.8%) were sterile. The sensitivity of group 1 was: 99% vancomycin, 95% rifampicin, 87% chloramphenicol, 76% tetracycline. Levels of co-trimoxazole, aminoglycosides, quinolones, β-lactams and macrolides decreased since 2007. The group 2 was very sensitive to chloramphenicol, cefuroxime, rifampicin, ciprofloxacin and amoxicillin/clavulanate. In group 3, to levofloxacin 93%, ciprofloxacin 89%, tobramycin 76%, but ceftazidime 53% and cefuroxime 29% decreased. None of the tested antibiotics could eradicate all possible conjunctival bacteria. Bacteria living permanently on the conjunctiva (group 1) have achieved higher resistance than the eventual colonizers. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  19. Peramivir susceptibilities of recombinant influenza A and B variants selected with various neuraminidase inhibitors.

    Science.gov (United States)

    Fage, Clément; Tu, Véronique; Carbonneau, Julie; Abed, Yacine; Boivin, Guy

    2017-03-22

    Peramivir is a parenteral neuraminidase inhibitor (NAI) approved for treating influenza infections in a few countries. We determined peramivir susceptibilities of several uncharacterized influenza A and B neuraminidase (NA) and haemagglutinin (HA) mutants selected with different NAIs. Recombinant wild-type (WT) and mutant NA proteins were expressed in 293T cells and susceptibility to peramivir, oseltamivir and zanamivir was determined by NA inhibition assay using the MUNANA substrate. Recombinant/reassortant influenza A(H1N1), A(H3N2) and B HA mutants were rescued by reverse genetics and assessed by plaque size or viral yield assays for drug susceptibility. Recombinant R152K, I222K/T, G248R+I266V, Q312R+I427T and R371K (A[H1N1]pdm09); E41G, 1222L/V, Q226H and S247P (A[H3N2]) and D198Y, A246D/S/T and G402S (B) mutant NA proteins (N2 numbering) were analysed. Peramivir exhibited the lowest IC50 values against both influenza A and B WT NAs. Peramivir and oseltamivir generally shared similar phenotypes. Of note, peramivir retained activity against I222K/T (A[H1N1]pdm09), I222L/V (A[H3N2]) and A246T (B) mutants, which had reduced inhibition (RI) or highly RI (HRI) against oseltamivir. Cross-RI/HRI against the three NAIs was observed for R152K, R371K and Q312R+I427T (A[H1N1]pdm09); S247P (A[H3N2]) and D198Y (B) mutants. All tested recombinant/reassortant R208K (A/Puerto Rico/8/34 [H1N1]); A28T, R124M and K189E (A/Victoria/3/75 [H3N2]) and T139N (B/Phuket/3073/13) HA mutants were susceptible to peramivir in cell culture experiments. Peramivir is highly active against seasonal influenza subtypes. Although peramivir and oseltamivir generally share similar phenotypes, peramivir still possesses activity against some variants with RI/HRI against oseltamivir. Finally, NAI-induced HA substitutions alone did not significantly impact NAI susceptibility.

  20. Genetic Factors Affecting Late-Onset Alzheimer's Disease Susceptibility.

    Science.gov (United States)

    Rezazadeh, Maryam; Khorrami, Aziz; Yeghaneh, Tarlan; Talebi, Mahnaz; Kiani, Seyed Jalal; Heshmati, Yaser; Gharesouran, Jalal

    2016-03-01

    Alzheimer's disease is considered a progressive brain disease in the older population. Late-onset Alzheimer's disease (LOAD) as a multifactorial dementia has a polygenic inheritance. Age, environment, and lifestyle along with a growing number of genetic factors have been reported as risk factors for LOAD. Our aim was to present results of LOAD association studies that have been done in northwestern Iran, and we also explored possible interactions with apolipoprotein E (APOE) status. We re-evaluated the association of these markers in dominant, recessive, and additive models. In all, 160 LOAD and 163 healthy control subjects of Azeri Turkish ethnicity were studied. The Chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. A Bonferroni-corrected p value, based on the number of statistical tests, was considered significant. Our results confirmed that chemokine receptor type 2 (CCR2), estrogen receptor 1 (ESR1), toll-like receptor 2 (TLR2), tumor necrosis factor alpha (TNF α), APOE, bridging integrator 1 (BIN1), and phosphatidylinositol-binding clathrin assembly protein (PICALM) are LOAD susceptibility loci in Azeri Turk ancestry populations. Among them, variants of CCR2, ESR1, TNF α, and APOE revealed associations in three different genetic models. After adjusting for APOE, the association (both allelic and genotypic) with CCR2, BIN1, and ESRα (PvuII) was evident only among subjects without the APOE ε4, whereas the association with CCR5, without Bonferroni correction, was significant only among subjects carrying the APOE ε4 allele. This result is an evidence of a synergistic and antagonistic effect of APOE on variant associations with LOAD.

  1. Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations

    Science.gov (United States)

    Heaton, Michael P.; Clawson, Michael L.; Chitko-Mckown, Carol G.; Leymaster, Kreg A.; Smith, Timothy P. L.; Harhay, Gregory P.; White, Stephen N.; Herrmann-Hoesing, Lynn M.; Mousel, Michelle R.; Lewis, Gregory S.; Kalbfleisch, Theodore S.; Keen, James E.; Laegreid, William W.

    2012-01-01

    Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3×10−9). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-valuesheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-valuesheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection. PMID:22291605

  2. Ozone increases susceptibility to antigen inhalation in allergic dogs

    Energy Technology Data Exchange (ETDEWEB)

    Yanai, M.; Ohrui, T.; Aikawa, T.; Okayama, H.; Sekizawa, K.; Maeyama, K.; Sasaki, H.; Takishima, T. (Tohoku Univ., Sendai (Japan))

    1990-06-01

    To determine whether O3 exposure increased airway responsiveness to antigen inhalation, we studied airway responsiveness to acetylcholine (ACh) and Ascaris suum antigen (AA) before and after O3 in dogs both sensitive and insensitive to AA. Airway responsiveness was assessed by determining the provocative concentration of ACh and AA aerosols that increased respiratory resistance (Rrs) to twice the base-line value. O3 (3 parts per million) increased airway responsiveness to ACh in dogs both sensitive and insensitive to AA, and it significantly decreased the ACh provocation concentration from 0.541 +/- 0.095 to 0.102 +/- 0.047 (SE) mg/ml (P less than 0.01; n = 10). AA aerosols, even at the highest concentration in combination with O3, did not increase Rrs in dogs insensitive to AA. However, O3 increased airway responsiveness to AA in AA-sensitive dogs and significantly decreased log AA provocation concentration from 2.34 +/- 0.22 to 0.50 +/- 0.17 (SE) log protein nitrogen units/ml (P less than 0.01; n = 7). O3-induced hyperresponsiveness to ACh returned to the base-line level within 2 wk, but hyperresponsiveness to AA continued for greater than 2 wk. The plasma histamine concentration after AA challenge was significantly higher after than before O3 (P less than 0.01). Intravenous infusion of OKY-046 (100 micrograms.kg-1.min-1), an inhibitor of thromboxane synthesis, inhibited the O3-induced increase in responsiveness to ACh, but it had no effects on the O3-induced increase in responsiveness to AA and the increase in the plasma histamine concentration. These results suggest that O3 increases susceptibility to the antigen in sensitized dogs via a different mechanism from that of O3-induced muscarinic hyperresponsiveness.

  3. Comparison of three standardized disc susceptibility testing methods for colistin.

    Science.gov (United States)

    Tan, Thean Yen; Ng, Lily Siew Yong

    2006-10-01

    With increasing antibiotic resistance in Gram-negative bacteria, the use of the polymyxins has increased in recent years. Antibiotic disc susceptibility testing remains the most widely used method in clinical laboratories, but there is very little data on the accuracy of disc testing methods for colistin. In this study, the accuracy of three standardized methods of disc susceptibility testing for colistin was compared with agar dilution. A total of 228 clinical isolates of Acinetobacter spp., Pseudomonas aeruginosa and Enterobacteriaceae were included in the study. Isolates were tested by agar dilution for susceptibility to colistin, and results were compared with those obtained by three disc susceptibility testing methods (product insert based on CLSI methodology, British BSAC and French SFM). Colistin displayed good activity against Acinetobacter spp., Klebsiella spp. and Escherichia coli (MIC(90) 2 mg/L) but was less active against P. aeruginosa (MIC(90) 4 mg/L) and Enterobacter spp. (MIC(90) >or= 128 mg/L). Totally, 81%, 79% and 89% of colistin-resistant isolates were falsely reported as susceptible when tested by the product insert, BSAC and SFM testing methods, respectively. There were no false-resistant results. Disc susceptibility testing methods are unreliable at detecting colistin resistance. Dilution methods should be the method of choice for susceptibility testing of colistin.

  4. Accuracy of MRI-based Magnetic Susceptibility Measurements

    Science.gov (United States)

    Russek, Stephen; Erdevig, Hannah; Keenan, Kathryn; Stupic, Karl

    Magnetic Resonance Imaging (MRI) is increasingly used to map tissue susceptibility to identify microbleeds associated with brain injury and pathologic iron deposits associated with neurologic diseases such as Parkinson's and Alzheimer's disease. Field distortions with a resolution of a few parts per billion can be measured using MRI phase maps. The field distortion map can be inverted to obtain a quantitative susceptibility map. To determine the accuracy of MRI-based susceptibility measurements, a set of phantoms with paramagnetic salts and nano-iron gels were fabricated. The shapes and orientations of features were varied. Measured susceptibility of 1.0 mM GdCl3 solution in water as a function of temperature agreed well with the theoretical predictions, assuming Gd+3 is spin 7/2. The MRI susceptibility measurements were compared with SQUID magnetometry. The paramagnetic susceptibility sits on top of the much larger diamagnetic susceptibility of water (-9.04 x 10-6), which leads to errors in the SQUID measurements. To extract out the paramagnetic contribution using standard magnetometry, measurements must be made down to low temperature (2K). MRI-based susceptometry is shown to be as or more accurate than standard magnetometry and susceptometry techniques.

  5. Prediction of autism susceptibility genes based on association rules.

    Science.gov (United States)

    Gong, Lejun; Yan, Yunyang; Xie, Jianming; Liu, Hongde; Sun, Xiao

    2012-06-01

    Autism is a complex neuropsychiatric disorder with high heritability and an unclear etiology. The identification of key genes related to autism may elucidate its etiology. The current study provides an approach to predicting autism susceptibility genes. Genes are first extracted from the biomedical literature, and some autism susceptibility genes are then recognized as seeds by the prior knowledge. As candidates, the remaining genes are predicted by creating association rules between the seeds and candidates. In an evaluated data set, 27 autism susceptibility genes (type "Y") are extracted and 43 possible autism susceptibility genes (type "P") are predicted. The sum of "Y" and "P" genes accounts for 93.3% of the data set that are not contained in the typical database of autism susceptibility genes. Our approach can effectively extract and predict autism susceptibility genes from the biomedical literature. These predicted results complement the typical database of autism susceptibility genes. The web portal for the predicted results, which is freely available at http://biolab.hyit.edu.cn/ar, can be a valuable resource in studies of diseases related to genes. Copyright © 2012 Wiley Periodicals, Inc.

  6. Quantitative susceptibility mapping of small objects using volume constraints.

    Science.gov (United States)

    Liu, Saifeng; Neelavalli, Jaladhar; Cheng, Yu-Chung N; Tang, Jin; Mark Haacke, E

    2013-03-01

    Microbleeds have been implicated to play a role in many neurovascular and neurodegenerative diseases. The diameter of each microbleed has been used previously as a possible quantitative measure for grading microbleeds. We propose that magnetic susceptibility provides a new quantitative measure of extravasated blood. Recently, a Fourier-based method has been used that allows susceptibility quantification from phase images for any arbitrarily shaped structures. However, when very small objects, such as microbleeds, are considered, the accuracy of this susceptibility mapping method still remains to be evaluated. In this article, air bubbles and glass beads are taken as microbleed surrogates to evaluate the quantitative accuracy of the susceptibility mapping method. We show that when an object occupies only a few voxels, an estimate of the true volume of the object is necessary for accurate susceptibility quantification. Remnant errors in the quantified susceptibilities and their sources are evaluated. We show that quantifying magnetic moment, rather than the susceptibility of these small structures, may be a better and more robust alternative. Copyright © 2012 Wiley Periodicals, Inc.

  7. Susceptibility of lady beetles (Coleoptera: Coccinellidae) to entomopathogenic nematodes.

    Science.gov (United States)

    Shapiro-Ilan, David I; Cottrell, Ted E

    2005-06-01

    We investigated differential susceptibility of lady beetles to entomopathogenic nematodes, for two reasons: (1) to estimate potential nontarget effects on natural lady beetle populations, (2) to compare the susceptibility of exotic versus native lady beetle species. We hypothesize that successful establishment of some exotically introduced arthropods may be due, in part, to a lower susceptibility relative to competing native species. In laboratory studies, we compared the pathogenicity, virulence, and reproductive capacity of Heterorhabditis bacteriophora and Steinernema carpocapsae among two native (Coleomegilla maculata and Olla v-nigrum) and two successfully established exotic (Harmonia axyridis and Coccinella septempunctata) lady beetles, and a known susceptible lepidopteran host, Agrotis ipsilon. After 1 and 2 days of exposure to either nematode species, mortality of A. ipsilon was higher than in all lady beetles. Thus, we predict that nematode field applications would have significantly less impact on lady beetle populations than on a susceptible target pest. Additionally, the impact of soil-applied nematodes may be lower on lady beetles than on soil-dwelling hosts because the former spends relatively less time on the soil. Exotic lady beetles were less susceptible to nematode infection than native species. Reproductive capacity data also indicated lower host suitability in H. axyridis, but not in C. septempunctata. Overall, the hypothesis that low susceptibility to pathogens in certain exotic lady beetles may have contributed to competitive establishment was supported (especially for H. axyridis). Additional studies incorporating different hosts and pathogens from various geographic locations will be required to further address the hypothesis.

  8. Toxoplasmosis and Polygenic Disease Susceptibility Genes: Extensive Toxoplasma gondii Host/Pathogen Interactome Enrichment in Nine Psychiatric or Neurological Disorders

    OpenAIRE

    C. J. Carter

    2013-01-01

    Toxoplasma gondii is not only implicated in schizophrenia and related disorders, but also in Alzheimer's or Parkinson's disease, cancer, cardiac myopathies, and autoimmune disorders. During its life cycle, the pathogen interacts with ~3000 host genes or proteins. Susceptibility genes for multiple sclerosis, Alzheimer's disease, schizophrenia, bipolar disorder, depression, childhood obesity, Parkinson's disease, attention deficit hyperactivity disorder (P??from??8.01E ? 05??(ADHD)??to??1.22E ?...

  9. Is Streptococcus pyogenes Resistant or Susceptible to Trimethoprim-Sulfamethoxazole?

    Science.gov (United States)

    Lilliebridge, Rachael A.; Tong, Steven Y. C.; Baird, Robert W.; Ward, Peter; McDonald, Malcolm I.; Currie, Bart J.; Carapetis, Jonathan R.

    2012-01-01

    Streptococcus pyogenes is commonly believed to be resistant to trimethoprim-sulfamethoxazole (SXT), resulting in reservations about using SXT for skin and soft tissue infections (SSTI) where S. pyogenes is involved. S. pyogenes' in vitro susceptibility to SXT depends on the medium's thymidine content. Thymidine allows S. pyogenes to bypass the sulfur-mediated inhibition of folate metabolism and, historically, has resulted in apparently reduced susceptibility of S. pyogenes to sulfur antibacterials. The low thymidine concentration in Mueller-Hinton agar (MHA) is now regulated. We explored S. pyogenes susceptibility to SXT on various media. Using two sets of 100 clinical S. pyogenes isolates, we tested for susceptibility using SXT Etests on MHA containing defibrinated horse blood and 20 mg/liter β-NAD (MHF), MHA with sheep blood (MHS), MHA alone, MHA with horse blood (MHBA), and MHA with lysed horse blood (MHLHBA). European Committee on Antibacterial Susceptibility Testing (EUCAST) breakpoints defined susceptibility (MIC, ≤1 mg/liter) and resistance (MIC, >2 mg/liter). In study 1, 99% of S. pyogenes isolates were susceptible to SXT on MHA, MHBA, and MHLHBA, with geometric mean MICs of 0.04, 0.04, and 0.05 mg/liter, respectively. In study 2, all 100 S. pyogenes isolates were susceptible to SXT on MHF, MHS, MHA, and MHLHBA with geometric mean MICs of 0.07, 0.16, 0.07, and 0.09 mg/liter, respectively. This study confirms the in vitro susceptibility of S. pyogenes to SXT, providing support for the use of SXT for SSTIs. A clinical trial using SXT for impetigo is ongoing. PMID:23052313

  10. Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes

    Directory of Open Access Journals (Sweden)

    Moreno Víctor

    2008-12-01

    Full Text Available Abstract Background Recent advances in whole-genome association studies (WGASs for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined. Methods We applied an integrative approach for identifying candidate low-penetrance breast cancer susceptibility genes, their characteristics and molecular networks through the analysis of diverse sources of biological evidence. Results First, examination of the distribution of Gene Ontology terms in ordered WGAS results identified asymmetrical distribution of Cell Communication and Cell Death processes linked to risk. Second, analysis of 11 different types of molecular or functional relationships in genomic and proteomic data sets defined the "omic" properties of candidate genes: i/ differential expression in tumors relative to normal tissue; ii/ somatic genomic copy number changes correlating with gene expression levels; iii/ differentially expressed across age at diagnosis; and iv/ expression changes after BRCA1 perturbation. Finally, network modeling of the effects of variants on germline gene expression showed higher connectivity than expected by chance between novel candidates and with known susceptibility genes, which supports functional relationships and provides mechanistic hypotheses of risk. Conclusion This study proposes that cell communication and cell death are major biological processes perturbed in risk of breast cancer conferred by low-penetrance variants, and defines the common

  11. Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes.

    Science.gov (United States)

    Bonifaci, Núria; Berenguer, Antoni; Díez, Javier; Reina, Oscar; Medina, Ignacio; Dopazo, Joaquín; Moreno, Víctor; Pujana, Miguel Angel

    2008-12-18

    Recent advances in whole-genome association studies (WGASs) for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined. We applied an integrative approach for identifying candidate low-penetrance breast cancer susceptibility genes, their characteristics and molecular networks through the analysis of diverse sources of biological evidence. First, examination of the distribution of Gene Ontology terms in ordered WGAS results identified asymmetrical distribution of Cell Communication and Cell Death processes linked to risk. Second, analysis of 11 different types of molecular or functional relationships in genomic and proteomic data sets defined the "omic" properties of candidate genes: i/ differential expression in tumors relative to normal tissue; ii/ somatic genomic copy number changes correlating with gene expression levels; iii/ differentially expressed across age at diagnosis; and iv/ expression changes after BRCA1 perturbation. Finally, network modeling of the effects of variants on germline gene expression showed higher connectivity than expected by chance between novel candidates and with known susceptibility genes, which supports functional relationships and provides mechanistic hypotheses of risk. This study proposes that cell communication and cell death are major biological processes perturbed in risk of breast cancer conferred by low-penetrance variants, and defines the common omic properties, molecular interactions and possible functional

  12. Constitutive expression of SMAR1 confers susceptibility to Mycobacterium tuberculosis infection in a transgenic mouse model.

    Science.gov (United States)

    Yadav, Bhawna; Malonia, Sunil K; Majumdar, Subeer S; Gupta, Pushpa; Wadhwa, Neerja; Badhwar, Archana; Gupta, Umesh D; Katoch, Vishwa M; Chattopadhyay, Samit

    2015-12-01

    Studies involving animal models of experimental tuberculosis have elucidated the predominant role of cytokines secreted by T cells and macrophages to be an essential component of the immune response against Mycobacterium tuberculosis infection. The immune activities of CD4+ T cells are mediated in part by Th1 cytokine interferon gamma (IFN-γ) which is produced primarily by T cells and natural killer (NK) cells and critical for initiating the immune response against intracellular pathogen such as M. tuberculosis. Nuclear matrix protein SMAR1 plays an important role in V(D)J recombination, T helper cell differentiation and inflammatory diseases. In this study a transgenic mouse model was used to study the role of SMAR1 in M. tuberculosis infection. Wild type BALB/c, C57BL/6, BALB/c-EGFP-SMAR1 and C57BL/6-SMAR1 transgenic mice were infected with M. tuberculosis (H37Rv). A dose of 100 bacilli was used for infection via respiratory route. Bacterial load in lung and spleen of infected mice was determined at 2, 4, 6 and 8 wk post-infection. Gene expression analysis for Th1 cytokines and inducible nitric oxide synthase (iNOS) was performed in infected lung tissues by quantitative reverse transcription (RT)-PCR. SMAR1 transgenic mice from both BALB/c and C57BL/6 genetic background displayed higher bacillary load and susceptibility to M. tuberculosis infection compared to wild type mice. This susceptibility was attributed due to compromised of Th1 response exhibited by transgenic mice. SMAR1 transgenic mice exhibited susceptibility to M. tuberculosis infection in vivo irrespective of genetic background. This susceptibility was attributed to downregulation of Th1 response and its hallmark cytokine IFN-γ. Hence, SMAR1 plays an important role in modulating host immune response after M. tuberculosis infection.

  13. AS3MT, GSTO, and PNP polymorphisms: impact on arsenic methylation and implications for disease susceptibility.

    Science.gov (United States)

    Antonelli, Ray; Shao, Kan; Thomas, David J; Sams, Reeder; Cowden, John

    2014-07-01

    Oral exposure to inorganic arsenic (iAs) is associated with adverse health effects. Epidemiological studies suggest differences in susceptibility to these health effects, possibly due to genotypic variation. Genetic polymorphisms in iAs metabolism could lead to increased susceptibility by altering urinary iAs metabolite concentrations. To examine the impact of genotypic polymorphisms on iAs metabolism. We screened 360 publications from PubMed and Web of Science for data on urinary mono- and dimethylated arsenic (MMA and DMA) percentages and polymorphic genes encoding proteins that are hypothesized to play roles in arsenic metabolism. The genes we examined were arsenic (+3) methyltransferase (AS3MT), glutathione-s-transferase omega (GSTO), and purine nucleoside phosphorylase (PNP). Relevant data were pooled to determine which polymorphisms are associated across studies with changes in urinary metabolite concentration. In our review, AS3MT polymorphisms rs3740390, rs11191439, and rs11191453 were associated with statistically significant changes in percent urinary MMA. Studies of GSTO polymorphisms did not indicate statistically significant associations with methylation, and there are insufficient data on PNP polymorphisms to evaluate their impact on metabolism. Collectively, these data support the hypothesis that AS3MT polymorphisms alter in vivo metabolite concentrations. Preliminary evidence suggests that AS3MT genetic polymorphisms may impact disease susceptibility. GSTO polymorphisms were not associated with iAs-associated health outcomes. Additional data are needed to evaluate the association between PNP polymorphisms and iAs-associated health outcomes. Delineation of these relationships may inform iAs mode(s) of action and the approach for evaluating low-dose health effects for iAs. Genotype impacts urinary iAs metabolite concentrations and may be a potential mechanism for iAs-related disease susceptibility. Published by Elsevier Inc.

  14. Cell-Type-Specific Epigenetic Editing at the Fosb Gene Controls Susceptibility to Social Defeat Stress.

    Science.gov (United States)

    Hamilton, Peter J; Burek, Dominika J; Lombroso, Sonia I; Neve, Rachael L; Robison, Alfred J; Nestler, Eric J; Heller, Elizabeth A

    2018-01-01

    Chronic social defeat stress regulates the expression of Fosb in the nucleus accumbens (NAc) to promote the cell-type-specific accumulation of ΔFosB in the two medium spiny neuron (MSN) subtypes in this region. ΔFosB is selectively induced in D1-MSNs in the NAc of resilient mice, and in D2-MSNs of susceptible mice. However, little is known about the consequences of such selective induction, particularly in D2-MSNs. This study examined how cell-type-specific control of the endogenous Fosb gene in NAc regulates susceptibility to social defeat stress. Histone post-translational modifications (HPTMs) were targeted specifically to Fosb using engineered zinc-finger proteins (ZFPs). Fosb-ZFPs were fused to either the transcriptional repressor, G9a, which promotes histone methylation or the transcriptional activator, p65, which promotes histone acetylation. These ZFPs were expressed in D1- vs D2-MSNs using Cre-dependent viral expression in the NAc of mice transgenic for Cre recombinase in these MSN subtypes. We found that stress susceptibility is oppositely regulated by the specific cell type and HPTM targeted. We report that Fosb-targeted histone acetylation in D2-MSNs or histone methylation in D1-MSNs promotes a stress-susceptible, depressive-like phenotype, while histone methylation in D2-MSNs or histone acetylation in D1-MSNs increases resilience to social stress as quantified by social interaction behavior and sucrose preference. This work presents the first demonstration of cell- and gene-specific targeting of histone modifications, which model naturally occurring transcriptional phenomena that control social defeat stress behavior. This epigenetic-editing approach, which recapitulates physiological changes in gene expression, reveals clear differences in the social defeat phenotype induced by Fosb gene manipulation in MSN subtypes.

  15. Trends in antimicrobial susceptibility of the Streptococcus milleri group.

    Science.gov (United States)

    Yamamoto, Natsuo; Kubota, Toru; Tohyama, Masato; Kanamori, Shuzo; Shinzato, Takashi; Higa, Futoshi; Tateyama, Masao; Saito, Atsushi

    2002-06-01

    A collection of 114 clinical Streptococcus milleri group (SMG) strains at the Ryukyu University Hospital obtained in 1999 and 2000, was identified and tested for susceptibility to 12 antibiotics. The percentage of strains with intermediate susceptibility to penicillin G was relatively high (14%). Cefaclor and cefotiam, with a MIC 90 of 2 microg/ml, were less active than cefotaxime. Strains nonsusceptible to erythromycin, clindamycin, and azithromycin were found with a frequency of 8%, 5%, and 4%, respectively. Almost all of the SMG strains were susceptible to fluoroquinolones (except for 1% of the strains nonsusceptible to levofloxacin), and sitafloxacin (DU-6859a) was the most active agent among the 12 tested antibiotics.

  16. Ciprofloxacin susceptibility of Pseudomonas aeruginosa isolates from keratitis

    DEFF Research Database (Denmark)

    Lomholt, JA; Kilian, Mogens

    2003-01-01

    AIM: To examine the ciprofloxacin susceptibility of 106 Pseudomonas aeruginosa eye isolates from the United Kingdom, Denmark, India, the United States, and Australia, and to determine the molecular mechanisms of resistance. METHODS: Ciprofloxacin susceptibility was tested by an agar dilution method...... isolates of P aeruginosa from European countries are fully susceptible to ciprofloxacin and the concentration of ciprofloxacin eye drops used for local treatment (3000 mg/l) exceeds MIC values for strains recorded as resistant. Mutations in more than one target gene were associated with higher MIC values....

  17. Pediatric hemiplegic migraine: susceptibility weighted and MR perfusion imaging abnormality

    Energy Technology Data Exchange (ETDEWEB)

    Altinok, Deniz; Agarwal, Ajay [Children' s Hospital of Michigan, Department of Radiology, Detroit, MI (United States); Ascadi, Gyula; Luat, Aimee; Tapos, Daniela [Children' s Hospital of Michigan, Department of Neurology, Detroit, MI (United States)

    2010-12-15

    We report on an 11-year-old girl suffering from a typical attack of hemiplegic migraine with characteristic abnormalities in perfusion MR and susceptibility-weighted MR imaging findings. The imaging abnormalities were resolved 48 h after the attack. Susceptibility-weighted MR imaging findings correlated well with the MR perfusion, thus it can be used along with conventional MRI for evaluation of children with complex migraine attacks. Susceptibility-weighted MR imaging might have a diagnostic role in assessing the vascular events in hemiplegic migraine. (orig.)

  18. A non-synonymous single nucleotide polymorphism in IFNAR1 affects susceptibility to chronic hepatitis B virus infection.

    Science.gov (United States)

    Zhou, J; Smith, D K; Lu, L; Poon, V K M; Ng, F; Chen, D-Q; Huang, J-D; Yuen, K-Y; Cao, K-Y; Zheng, B-J

    2009-01-01

    The type I interferon (IFN-alpha/beta) receptor 1 (IFNAR1) mediates the potent antiviral and immuno-regulatory effects of IFN-alpha/beta that are believed to be pivotal to eradicate hepatitis B virus (HBV) infection. IFNAR1 promoter polymorphisms (at -568/-77) have been shown to be associated with susceptibility to chronic HBV infection; however, whether these markers are genetic determinants of HBV infection remains unknown. The functional significance of promoter -568/-77 polymorphisms was assessed by mutagenesis and luciferase assays. Sequencing and restriction fragment length polymorphisms in 328 chronic HBV patients, 130 spontaneous resolvers and 148 healthy blood donors identified other polymorphism at IFNAR1 open reading frame. IFNAR1 expression levels in peripheral blood cells were detected by flow cytometry. We found that the -568/-77 promoter variants were unlikely to affect transcription levels. A C/G single nucleotide polymorphism, in strong linkage disequilibrium with the promoter polymorphisms, was found in the coding sequence of IFNAR1 (nt19158). This resulted in a nonsynonymous substitution in the extracellular region of IFNAR1 protein and correlated with susceptibility to chronic HBV infection. Bioinformatic analysis suggested decreased stability of the IFNAR1 protein. Chronic HBV patients with the 19158C/C genotype (Leu141) exhibited higher IFNAR1 protein expression levels in peripheral blood monocytes than those with the 19158G/G genotype (Val141). In conclusion, IFNAR1 19158C/G polymorphism is primarily associated with susceptibility to chronic HBV infection.

  19. The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria

    NARCIS (Netherlands)

    Ellington, M.J.; Ekelund, O.; Aarestrup, F.M.; Canton, R.; Doumith, M.; Giske, C.; Grundman, H.; Hasman, H.; Holden, M.T.G.; Hopkins, K.L.; Iredell, J.; Kahlmeter, G.; Köser, C.U.; MacGowan, A.; Mevius, D.; Mulvey, M.; Naas, T.; Peto, T.; Rolain, J.M.; Samuelsen,; Woodford, N.

    2017-01-01

    Whole genome sequencing (WGS) offers the potential to predict antimicrobial susceptibility from a single assay. The European Committee on Antimicrobial Susceptibility Testing established a subcommittee to review the current development status of WGS for bacterial antimicrobial susceptibility testing

  20. Cardiovascular biomarkers predict susceptibility to lung injury in World Trade Center dust-exposed firefighters.

    Science.gov (United States)

    Weiden, Michael D; Naveed, Bushra; Kwon, Sophia; Cho, Soo Jung; Comfort, Ashley L; Prezant, David J; Rom, William N; Nolan, Anna

    2013-05-01

    Pulmonary vascular loss is an early feature of chronic obstructive pulmonary disease. Biomarkers of inflammation and of metabolic syndrome predict loss of lung function in World Trade Center (WTC) lung injury (LI). We investigated if other cardiovascular disease (CVD) biomarkers also predicted WTC-LI. This nested case-cohort study used 801 never-smoker, WTC-exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March 2008. A representative subcohort of 124 out of 801 subjects with serum drawn within 6 months of 9/11 defined CVD biomarker distribution. Post-9/11 forced expiratory volume in 1 s (FEV1) at defined cases were as follows: susceptible WTC-LI cases with FEV1 ≤77% predicted (66 out of 801) and resistant WTC-LI cases with FEV1 ≥107% predicted (68 out of 801). All models were adjusted for WTC exposure intensity, body mass index at SPE, age on 9/11 and pre-9/11 FEV1. Susceptible WTC-LI cases had higher levels of apolipoprotein-AII, C-reactive protein and macrophage inflammatory protein-4 with significant relative risks (RRs) of 3.85, 3.93 and 0.26, respectively, with an area under the curve (AUC) of 0.858. Resistant WTC-LI cases had significantly higher soluble vascular cell adhesion molecule and lower myeloperoxidase, with RRs of 2.24 and 2.89, respectively (AUC 0.830). Biomarkers of CVD in serum 6 months post-9/11 predicted either susceptibility or resistance to WTC-LI. These biomarkers may define pathways either producing or protecting subjects from pulmonary vascular disease and associated loss of lung function after an irritant exposure.

  1. Polymorphic variation in TIRAP is not associated with susceptibility to childhood TB but may determine susceptibility to TBM in some ethnic groups.

    Directory of Open Access Journals (Sweden)

    Shobana Rebecca Dissanayeke

    2009-08-01

    Full Text Available Host recognition of mycobacterial surface molecules occurs through toll like receptors (TLR 2 and 6. The adaptor protein TIRAP mediates down stream signalling of TLR2 and 4, and polymorphisms in the TIRAP gene (TIRAP have been associated with susceptibility and resistance to tuberculosis (TB in adults. In order to investigate the role of polymorphic variation in TIRAP in childhood TB in South Africa, which has one of the highest TB incidence rates in the world, we screened the entire open reading frame of TIRAP for sequence variation in two cohorts of childhood TB from different ethnic groups (Xhosa and mixed ancestry. We identified 13 SNPs, including seven previously unreported, in the two cohorts, and found significant differences in frequency of the variants between the two ethnic groups. No differences in frequency between individual SNPs or combinations were found between TB cases and controls in either cohort. However the 558C-->T SNP previously associated with TB meningitis (TBM in a Vietnamese population was found to be associated with TBM in the mixed ancestry group. Polymorphisms in TIRAP do not appear to be involved in childhood TB susceptibility in South Africa, but may play a role in determining occurrence of TBM.

  2. BoLA-DRB3 gene polymorphism and FMD resistance or susceptibility in Wanbei cattle.

    Science.gov (United States)

    Lei, Wei; Liang, Qinglong; Jing, Luo; Wang, Chengmin; Wu, Xiaobing; He, Hongxuan

    2012-09-01

    For the further characterization of foot-and-mouth disease virus (FMDV)-induced foot-and-mouth disease, we investigated the association between polymorphism of BoLA-DRB3 gene and FMD resistance/susceptibility of Wanbei cattle challenged with FMDV. One hundred cattle were challenged with FMDV and exon 2 of BoLA-DRB3 genes was amplified by hemi-nested polymerase chain reaction from asymptomatic animals and from animals with FMD. PCR products were characterized by the RFLP technique using restriction enzymes Hae III. The results revealed extensive polymorphisms, 6 RFLP patterns were identified. By analyzing alleles and genotypic frequencies between healthy and infection with FMD cattle, we found that allele Hae III A was associated with susceptibility to FMD in Wanbei cattle (P FMD (P FMD. Hae IIICC and Hae III BC genotype were associated with resistance to FMD (P FMD (P < 0.01). Sequence analysis show that 89 amino acids were translated in exon 2 of BoLA-DRB3 and 13.70 % of nucleotide mutated, which resulted in 14.61 % of amino acid change. One PKC, one Tyr and one CAMP phosphorylation were increased; the hydrophobicity and secondary structure of proteins produced change after amino acid substitution. These results revealed that Wanbei cattle had the ability of resistance to disease by mutation which result changes of the protein structure to perform the regulation of the cell using different signaling pathways in the long process of choice evolution.

  3. Identification of genes differentially expressed during interaction of resistant and susceptible apple cultivars (Malus x domestica) with Erwinia amylovora.

    Science.gov (United States)

    Baldo, Angela; Norelli, Jay L; Farrell, Robert E; Bassett, Carole L; Aldwinckle, Herb S; Malnoy, Malnoy

    2010-01-04

    The necrogenic enterobacterium, Erwinia amylovora is the causal agent of the fire blight (FB) disease in many Rosaceae species, including apple and pear. During the infection process, the bacteria induce an oxidative stress response with kinetics similar to those induced in an incompatible bacteria-plant interaction. No resistance mechanism to E. amylovora in host plants has yet been characterized, recent work has identified some molecular events which occur in resistant and/or susceptible host interaction with E. amylovora: In order to understand the mechanisms that characterize responses to FB, differentially expressed genes were identified by cDNA-AFLP analysis in resistant and susceptible apple genotypes after inoculation with E. amylovora. cDNA were isolated from M.26 (susceptible) and G.41 (resistant) apple tissues collected 2 h and 48 h after challenge with a virulent E. amylovora strain or mock (buffer) inoculated. To identify differentially expressed transcripts, electrophoretic banding patterns were obtained from cDNAs. In the AFLP experiments, M.26 and G.41 showed different patterns of expression, including genes specifically induced, not induced, or repressed by E. amylovora. In total, 190 ESTs differentially expressed between M.26 and G.41 were identified using 42 pairs of AFLP primers. cDNA-AFLP analysis of global EST expression in a resistant and a susceptible apple genotype identified different major classes of genes. EST sequencing data showed that genes linked to resistance, encoding proteins involved in recognition, signaling, defense and apoptosis, were modulated by E. amylovora in its host plant. The expression time course of some of these ESTs selected via a bioinformatic analysis has been characterized. These data are being used to develop hypotheses of resistance or susceptibility mechanisms in Malus to E. amylovora and provide an initial categorization of genes possibly involved in recognition events, early signaling responses the

  4. Staphylococcus aureus SrrAB Affects Susceptibility to Hydrogen Peroxide and Co-Existence with Streptococcus sanguinis.

    Science.gov (United States)

    Oogai, Yuichi; Kawada-Matsuo, Miki; Komatsuzawa, Hitoshi

    2016-01-01

    Staphylococcus aureus is a pathogen and a commensal bacterial species that is found in humans. Bacterial two-component systems (TCSs) sense and respond to environmental stresses, which include antimicrobial agents produced by other bacteria. In this study, we analyzed the relation between the TCS SrrAB and susceptibility to the hydrogen peroxide (H2O2) that is produced by Streptococcus sanguinis, which is a commensal oral streptococcus. An srrA-inactivated S. aureus mutant demonstrated low susceptibility to the H2O2 produced by S. sanguinis. We investigated the expression of anti-oxidant factors in the mutant. The expression of katA in the mutant was significantly higher than in the wild-type (WT) in the presence or absence of 0.4 mM H2O2. The expression of dps in the mutant was significantly increased compared with the WT in the presence of H2O2 but not in the absence of H2O2. A katA or a dps-inactivated mutant had high susceptibility to H2O2 compared with WT. In addition, we found that the nitric oxide detoxification protein (flavohemoglobin: Hmp), which is regulated by SrrAB, was related to H2O2 susceptibility. The hmp-inactivated mutant had slightly lower susceptibility to the H2O2 produced by S. sanguinis than did WT. When a srrA-inactivated mutant or the WT were co-cultured with S. sanguinis, the population percentage of the mutant was significantly higher than the WT. In conclusion, SrrAB regulates katA, dps and hmp expression and affects H2O2 susceptibility. Our findings suggest that SrrAB is related in vivo to the co-existence of S. aureus with S. sanguinis.

  5. Efficacy of phosphatidylcholine in the modulation of motion sickness susceptibility

    Science.gov (United States)

    Kohl, R. L.; Ryan, P.; Homick, J. L.

    1985-01-01

    This study evaluated the efficacy of pharmacological doses of phosphatidylcholine (lecithin) in the modulation of motion sickness induced by exposure to coriolis stimulation in a rotating chair. Subjects received daily dietary supplements of 25 grams of lecithin (90 percent phosphatidylcholine) and were tested for their susceptibility to motion sickness after 4 h, 2 d, and 21 d. A small but statistically significant increase in susceptibility (+15 percent) was noted 4 h after supplemental phosphatidylcholine, with four of nine subjects demonstrating a marked increase in susceptibility. This finding was attributed to choline's stimulatory action on cholinergic systems, an action which opposes that of the classical antimotion sickness drug scopolamine. Chronic lecithin loading revealed a trend towards reduced susceptibility, possibly indicating the occurrence of adaptive mechanisms such as receptor down-regulation. Withdrawal from lecithin loading, perhaps coupled with anticholinergic treatment, might prove to be a potent prophylactic regimen and ought to be tested.

  6. Theoretical Calculations of The Magnetic Susceptibility in Some Organic Molecules

    OpenAIRE

    Sadykova, A. Yu.

    1990-01-01

    Magnetic susceptibility of a number of sizeable organic molecules is calculated by using the model of additivity of localized molecular fragments. The results are in a good agreement with available experimental data.

  7. Local magnetic susceptibility in rare-earth compounds

    CERN Document Server

    Shiozawa, H; Obu, K

    2003-01-01

    The element specific magnetic susceptibilities of some rare-earth compounds are estimated by measuring magnetic circular dichroism at rare-earth M sub 4 sub , sub 5 absorption edges. The temperature dependences of the rare-earth 4f local magnetic susceptibilities in dense Kondo materials, CeNi, CeSn sub 3 and CeRu sub 4 Sb sub 1 sub 2 , are remarkably different from those of the bulk magnetic susceptibilities measured by a conventional magnetometer, although the 4f electron is regarded to mainly hold the magnetic moment in these compounds. In contrast, the rare-earth 4f local magnetic susceptibility of ferromagnetic NdFe sub 4 P sub 1 sub 2 shows almost as similar behavior as the bulk one.

  8. Antiobiotics susceptibility of Salmonella isolates from Wdal Test ...

    African Journals Online (AJOL)

    Antiobiotics susceptibility of Salmonella isolates from Wdal Test Positive Patients at the Federal Medical Center, Gusau. SB Manga, IG Ameh, S Bashir, AG Muazu, B Danjuma, ML Ibrahim, K Abdullahi, J Mawak ...

  9. Breast Cancer Susceptibility Genes in High Risk Women

    National Research Council Canada - National Science Library

    Hamilton, Ann

    2003-01-01

    ...%. It has been hypothesized that susceptibility genes of lower penetrance may also affect breast cancer risk, and a likely group of such genes are those that regulate the production, intracellular...

  10. Breast Cancer Susceptibility Genes in High Risk Women

    National Research Council Canada - National Science Library

    Hamilton, Ann

    2004-01-01

    ...). It has been hypothesized that susceptibility genes of lower penetrance are more prevalent than among the latter, and a likely group of such genes are those that regulate the production, intracellular...

  11. Breast Cancer Susceptibility Genes in High Risk Women

    National Research Council Canada - National Science Library

    Hamilton, Ann

    2002-01-01

    ...%. It has been hypothesized that susceptibility genes of lower penetrance may also affect breast cancer risk, and a likely group of such genes are those that regulate the production, intracellular...

  12. Breast Cancer Susceptibility Genes in High Risk Women

    National Research Council Canada - National Science Library

    Hamilton, Ann

    2001-01-01

    ...%. It has been hypothesized that susceptibility genes of lower penetrance may also affect breast cancer risk, and a likely group of such genes are those that regulate the production, intracellular...

  13. SPECIATION AND ANTIFUNGAL SUSCEPTIBILITY TESTING OF CANDIDA ISOLATED FROM URINE

    OpenAIRE

    Dr. M.N. Sumana*, Satya Sai B, Netra Devraj Kademani, Madhuri M J

    2017-01-01

    Candiduria is uncommon and appears more often in females and catheterized males. C.albicans& C.tropicals were the species most frequently identified. Our results provide contemporary insight into the antifungal susceptibility profile of Candida species causing candiduria

  14. Antibiotic susceptibility profiles of anaerobic pathogens in The Netherlands

    NARCIS (Netherlands)

    Veloo, A. C. M.; van Winkelhoff, A. J.

    The antibiotic susceptibility profile of the Bacteroides fragilis group, Gram-positive anaerobic cocci (GPAC), Fusobacterium spp., Prevotella spp., Veillonella spp. and Bilophila wadsworthia for amoxicillin, amoxicillin-clavulanic acid, clindamycin and metronidazole was determined. Human clinical

  15. Antimicrobial susceptibility testing in biofilm‐growing bacteria

    National Research Council Canada - National Science Library

    Macià, M. D; Rojo‐Molinero, E; Oliver, A

    2014-01-01

    .... The lack of correlation between conventional susceptibility test results and therapeutic success in chronic infections is probably a consequence of the use of planktonically growing instead of biofilm‐growing bacteria...

  16. Biochemical characters and antibiotic susceptibility of Staphylococcus aureus isolates

    National Research Council Canada - National Science Library

    Subhankari Prasad Chakraborty Santanu Kar Mahapatra Somenath Roy

    2011-01-01

    ... and sucrose.Antibiotic susceptibility were carried out by minimum inhibilory concentration test,minium bactericidal concentration test,disc agar diffusion test and brain heart infusion oxacillin screening...

  17. In vitro susceptibility of multi-drug resistant Pseudomonas ...

    African Journals Online (AJOL)

    spectrum β- (ESBL) producing Klebsiella pneumoniae isolated from clinical specimens ... for their in vitro susceptibility to piperacillin-tazobactam 100/10μg using disc diffusion test as recommended by Clinical Laboratory Standard Institute (CLSI).

  18. Antibiotic susceptibility of organisms causing urinary tract infection in ...

    African Journals Online (AJOL)

    Antibiotic susceptibility of organisms causing urinary tract infection in patients presenting at Kenyatta National Hospital, Nairobi. ... encourage prudent use of antimicrobials. Objectives: To identify bacterial pathogens causing UTI and determine the association between the pathogens isolated from patients attending KNH.

  19. Magnetic Susceptibilities as they appeared to me - An Amperian approach

    Energy Technology Data Exchange (ETDEWEB)

    Van den Bosch, A.

    2008-08-15

    Starting from scratch, the book narrates a systematic story of the basic ideas you need for understanding quasi static magnetic susceptibilities. The story leans on the authors 25 year experience measuring susceptibilities following the Faraday technique (related with solid state physics, radiation effects, materials and magneto chemistry). The base of magnetism, the current-current interaction, is the linkage between the topics treated. The number of mathematical equations are reduced to a minimum and can be skipped without losing the thread of the story. The story is positive towards the sound bases of magnetism. However, room is left for the interpretation of measuring data. As the word susceptibility covers different meanings, the story answers for different situations the question: what is susceptible to what for creating what?

  20. Antimicrobial susceptibilities of Lactobacillus, Pediococcus and Lactococcus human isolates and cultures intended for probiotic or nutritional use

    National Research Council Canada - National Science Library

    Klare, Ingo; Konstabel, Carola; Werner, Guido; Huys, Geert; Vankerckhoven, Vanessa; Kahlmeter, Gunnar; Hildebrandt, Bianca; Müller-Bertling, Sibylle; Witte, Wolfgang; Goossens, Herman

    2007-01-01

    ... susceptibilities by broth microdilution using LAB susceptibility test medium (LSM). Tentative ECOFFs were defined according to the recommendations of the European Committee on Antimicrobial Susceptibility Testing...