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Sample records for activator complex polymorphisms

  1. The effect of the physical activity on polymorphic premature ventricular complexes in chronic kidney disease

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    Márcio G. Kiuchi

    2017-06-01

    Full Text Available Background: Polymorphic premature ventricular complexes (PVCs are very common, appearing most frequently in patients with hypertension, obesity, sleep apnea, and structural heart disease. Sympathetic hyperactivity plays a critical role in the development, maintenance, and aggravation of ventricular arrhythmias. Endurance exercise training clearly lowers sympathetic activity in sympatho-excitatory disease states and may be tolerated by patients with chronic kidney disease (CKD. Methods: We assessed 40 CKD patients with hypertension with polymorphic PVCs. Patients underwent a complete medical history and physical examination. We evaluated the effectiveness of β blocker only or β blocker + exercise during 12 months of follow-up regarding the changes of the numbers of PVCs and mean heart rate (HR by 24-hour-Holter. Results: We observed in the β blocker group a significant decrease in the number of polymorphic PVCs from baseline 36,515 ± 3,518 to 3, 6, 9 and 12 months of follow-up, 28,314 ± 2,938, 23,709 ± 1,846, 22,564 ± 1,673, and 22,725 ± 1,415, respectively (P < 0.001. In the β blocker + exercise group a significant decrease in the number of polymorphic PVCs also occurred from baseline 36,091 ± 3,327 to 3, 6, 9 and 12 months of follow-up, 29,252 ± 3,211, 20,948 ± 2,386, 14,238 ± 3,338, and 6,225 ± 2,319, respectively (P < 0.001. Comparisons between the two groups at the same time point showed differences from the sixth month onwards: the 6th (Δ = −2,761, P = 0.045, 9th (Δ = −8,325, P < 0.001 and 12th (Δ = −16,500, P < 0.001 months. There was an improvement during the 12 months of follow-up vs. baseline, after the β blocker or β blocker + exercise in mean 24-hour HR Holter monitoring, creatinine values, eGFR, and ACR. Conclusion: Polymorphic PVCs may be modifiable by physical activity in CKD patients with hypertension without structural heart disease.

  2. AMPLIFIED FRAGMENT LENGTH POLYMORPHISM ANALYSIS OF MYCOBACTERIUM AVIUM COMPLEX ISOLATES RECOVERED FROM SOUTHERN CALIFORNIA

    Science.gov (United States)

    Fine-scale genotyping methods are necessary in order to identify possible sources of human exposure to opportunistic pathogens belonging to the Mycobacterium avium complex (MAC). In this study, amplified fragment length polymorphism (AFLP) analysis was evaluated for fingerprintin...

  3. Polymorphism complexity and handedness inversion in serum albumin amyloid fibrils.

    Science.gov (United States)

    Usov, Ivan; Adamcik, Jozef; Mezzenga, Raffaele

    2013-12-23

    Protein-based amyloid fibrils can show a great variety of polymorphic structures within the same protein precursor, although the origins of these structural homologues remain poorly understood. In this work we investigate the fibrillation of bovine serum albumin--a model globular protein--and we follow the polymorphic evolution by a statistical analysis of high-resolution atomic force microscopy images, complemented, at larger length scales, by concepts based on polymer physics formalism. We identify six distinct classes of coexisting amyloid fibrils, including flexible left-handed twisted ribbons, rigid right-handed helical ribbons and nanotubes. We show that the rigid fibrils originate from flexible fibrils through two diverse polymorphic transitions, first, via a single-fibril transformation when the flexible left-handed twisted ribbons turn into the helical left-handed ribbons, to finally evolve into nanotube-like structures, and second, via a double-fibril transformation when two flexible left-handed twisted ribbons wind together resulting in a right-handed twisted ribbon, followed by a rigid right-handed helical ribbon polymorphic conformation. Hence, the change in handedness occurs with an increase in the level of the fibril's structural organization.

  4. Restriction fragment polymorphisms in the major histocompatibility complex of diabetic BB rats

    DEFF Research Database (Denmark)

    Kastern, W.; Dyrberg, T.; Scholler, J.

    1984-01-01

    DNA isolated from diabetic BB (BB/Hagedorn) rats was examined for restriction fragment length differences within the major histocompatibility complex (MHC) as compared with nondiabetic (W-subline) BB rats. Polymorphisms were detected using a mouse class I MHC gene as probe. Specifically, a 2-kb Bam......HI fragment was present in all the nondiabetic rats examined, but absent in the diabetic rats. Similar polymorphisms were observed with various other restriction enzymes, particularly XbaI, HindII, and SacI. There were no polymorphisms detected using either a human DR-alpha (class II antigen heavy chain...

  5. Polymorphisms in Isoniazid and Prothionamide Resistance Genes of the Mycobacterium tuberculosis Complex

    KAUST Repository

    Projahn, M.; Koser, C. U.; Homolka, S.; Summers, D. K.; Archer, John A.C.; Niemann, S.

    2011-01-01

    Sequence analyses of 74 strains that encompassed major phylogenetic lineages of the Mycobacterium tuberculosis complex revealed 10 polymorphisms in mshA (Rv0486) and four polymorphisms in inhA (Rv1484) that were not responsible for isoniazid or prothionamide resistance. Instead, some of these mutations were phylogenetically informative. This genetic diversity must be taken into consideration for drug development and for the design of molecular tests for drug resistance.

  6. Polymorphisms in Isoniazid and Prothionamide Resistance Genes of the Mycobacterium tuberculosis Complex

    KAUST Repository

    Projahn, M.

    2011-06-27

    Sequence analyses of 74 strains that encompassed major phylogenetic lineages of the Mycobacterium tuberculosis complex revealed 10 polymorphisms in mshA (Rv0486) and four polymorphisms in inhA (Rv1484) that were not responsible for isoniazid or prothionamide resistance. Instead, some of these mutations were phylogenetically informative. This genetic diversity must be taken into consideration for drug development and for the design of molecular tests for drug resistance.

  7. PARP1 Val762Ala polymorphism reduces enzymatic activity

    International Nuclear Information System (INIS)

    Wang Xiaogan; Wang Zhaoqi; Tong Weimin; Shen Yan

    2007-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K m of PARP1-Ala762 was increased to a 1.2-fold of the K m of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K m . This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding Cancer risk of carriers of the PARP1 Val762Ala polymorphism

  8. Assignment of Streptococcus agalactiae isolates to clonal complexes using a small set of single nucleotide polymorphisms.

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    Honsa, Erin; Fricke, Thomas; Stephens, Alex J; Ko, Danny; Kong, Fanrong; Gilbert, Gwendolyn L; Huygens, Flavia; Giffard, Philip M

    2008-08-19

    Streptococcus agalactiae (Group B Streptococcus (GBS)) is an important human pathogen, particularly of newborns. Emerging evidence for a relationship between genotype and virulence has accentuated the need for efficient and well-defined typing methods. The objective of this study was to develop a single nucleotide polymorphism (SNP) based method for assigning GBS isolates to multilocus sequence typing (MLST)-defined clonal complexes. It was found that a SNP set derived from the MLST database on the basis of maximization of Simpsons Index of Diversity provided poor resolution and did not define groups concordant with the population structure as defined by eBURST analysis of the MLST database. This was interpreted as being a consequence of low diversity and high frequency horizontal gene transfer. Accordingly, a different approach to SNP identification was developed. This entailed use of the "Not-N" bioinformatic algorithm that identifies SNPs diagnostic for groups of known sequence variants, together with an empirical process of SNP testing. This yielded a four member SNP set that divides GBS into 10 groups that are concordant with the population structure. A fifth SNP was identified that increased the sensitivity for the clinically significant clonal complex 17 to 100%. Kinetic PCR methods for the interrogation of these SNPs were developed, and used to genotype 116 well characterized isolates. A five SNP method for dividing GBS into biologically valid groups has been developed. These SNPs are ideal for high throughput surveillance activities, and combining with more rapidly evolving loci when additional resolution is required.

  9. Assignment of Streptococcus agalactiae isolates to clonal complexes using a small set of single nucleotide polymorphisms

    Directory of Open Access Journals (Sweden)

    Gilbert Gwendolyn L

    2008-08-01

    Full Text Available Abstract Background Streptococcus agalactiae (Group B Streptococcus (GBS is an important human pathogen, particularly of newborns. Emerging evidence for a relationship between genotype and virulence has accentuated the need for efficient and well-defined typing methods. The objective of this study was to develop a single nucleotide polymorphism (SNP based method for assigning GBS isolates to multilocus sequence typing (MLST-defined clonal complexes. Results It was found that a SNP set derived from the MLST database on the basis of maximisation of Simpsons Index of Diversity provided poor resolution and did not define groups concordant with the population structure as defined by eBURST analysis of the MLST database. This was interpreted as being a consequence of low diversity and high frequency horizontal gene transfer. Accordingly, a different approach to SNP identification was developed. This entailed use of the "Not-N" bioinformatic algorithm that identifies SNPs diagnostic for groups of known sequence variants, together with an empirical process of SNP testing. This yielded a four member SNP set that divides GBS into 10 groups that are concordant with the population structure. A fifth SNP was identified that increased the sensitivity for the clinically significant clonal complex 17 to 100%. Kinetic PCR methods for the interrogation of these SNPs were developed, and used to genotype 116 well characterized isolates. Conclusion A five SNP method for dividing GBS into biologically valid groups has been developed. These SNPs are ideal for high throughput surveillance activities, and combining with more rapidly evolving loci when additional resolution is required.

  10. Restriction fragment length polymorphism of the major histocompatibility complex of the dog.

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    Sarmiento, U M; Storb, R F

    1988-01-01

    Human major histocompatibility complex (HLA) cDNA probes were used to analyze the restriction fragment length polymorphism (RFLP) of the DLA-D region in dogs. Genomic DNA from peripheral blood leucocytes of 23 unrelated DLA-D-homozygous dogs representing nine DLA-D types (defined by mixed leucocyte reaction) was digested with restriction enzymes (Bam HI, Eco RI, Hind III, Pvu II, Taq I, Rsa I, Msp I, Pst I, and Bgl II), separated by agarose gel electrophoresis, and transferred onto Biotrace membrane. The Southern blots were successively hybridized with radiolabeled HLA cDNA probes corresponding to DR, DQ, DP, and DO beta genes. The autoradiograms for all nine enzyme digests displayed multiple bands with the DRb, DQb, and DPb probes while the DOb probe hybridized with one to two bands. The RFLP patterns were highly polymorphic but consistent within each DLA-D type. Standard RFLP patterns were established for nine DLA-D types which could be discriminated from each other by using two enzymes (Rsa I and Pst I) and the HLA-DPb probe. Cluster analysis of the polymorphic restriction fragments detected by the DRb probe revealed four closely related supertypic groups or DLA-DR families: Dw3 + Dw4 + D1, Dw8 + D10, D7 + D16 + D9, and Dw1. This study provides the basis for DLA-D genotyping at a population level by RFLP analysis. These results also suggest that the genetic organization of the DLA-D region may closely resemble that of the HLA complex.

  11. Functionalized active-nucleus complex sensor

    Science.gov (United States)

    Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

    2003-11-25

    A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

  12. Filling the Gap : Relationship Between the Serotonin-Transporter-Linked Polymorphic Region and Amygdala Activation

    NARCIS (Netherlands)

    Bastiaansen, Jojanneke A.; Servaas, Michelle N.; Marsman, Jan-Bernard; Ormel, Johan; Nolte, Ilja M.; Riese, Harriette; Aleman, Andre

    2014-01-01

    The alleged association between the serotonin-transporter-linked polymorphic region (5-HTTLPR) and amygdala activation forms a cornerstone of the common view that carrying the short allele of this polymorphism is a potential risk factor for affective disorders. The authors of a recent meta-analysis

  13. Filling the Gap : Relationship Between the Serotonin-Transporter-Linked Polymorphic Region and Amygdala Activation

    NARCIS (Netherlands)

    Bastiaansen, Jojanneke A.; Servaas, Michelle N.; Marsman, Jan-Bernard; Ormel, Johan; Nolte, Ilja M.; Riese, Harriette; Aleman, Andre

    The alleged association between the serotonin-transporter-linked polymorphic region (5-HTTLPR) and amygdala activation forms a cornerstone of the common view that carrying the short allele of this polymorphism is a potential risk factor for affective disorders. The authors of a recent meta-analysis

  14. A complex dominance hierarchy is controlled by polymorphism of small RNAs and their targets.

    Science.gov (United States)

    Yasuda, Shinsuke; Wada, Yuko; Kakizaki, Tomohiro; Tarutani, Yoshiaki; Miura-Uno, Eiko; Murase, Kohji; Fujii, Sota; Hioki, Tomoya; Shimoda, Taiki; Takada, Yoshinobu; Shiba, Hiroshi; Takasaki-Yasuda, Takeshi; Suzuki, Go; Watanabe, Masao; Takayama, Seiji

    2016-12-22

    In diploid organisms, phenotypic traits are often biased by effects known as Mendelian dominant-recessive interactions between inherited alleles. Phenotypic expression of SP11 alleles, which encodes the male determinants of self-incompatibility in Brassica rapa, is governed by a complex dominance hierarchy 1-3 . Here, we show that a single polymorphic 24 nucleotide small RNA, named SP11 methylation inducer 2 (Smi2), controls the linear dominance hierarchy of the four SP11 alleles (S 44 > S 60 > S 40 > S 29 ). In all dominant-recessive interactions, small RNA variants derived from the linked region of dominant SP11 alleles exhibited high sequence similarity to the promoter regions of recessive SP11 alleles and acted in trans to epigenetically silence their expression. Together with our previous study 4 , we propose a new model: sequence similarity between polymorphic small RNAs and their target regulates mono-allelic gene expression, which explains the entire five-phased linear dominance hierarchy of the SP11 phenotypic expression in Brassica.

  15. The role of androgen receptor activity mediated by the CAG repeat polymorphism in the pathogenesis of PCOS.

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    Baculescu, N

    2013-03-15

    Polycystic ovary syndrome (PCOS), one of the most common and complex endocrine disorders affecting up to 15 % of reproductive age women, is considered a predominantly hyperandrogenic syndrome according to the Androgen Excess Society. It is generally accepted that androgens determine the characteristic features of PCOS; in this context, a hyperactive androgen receptor (AR) at the levels of the GnRH pulse generator in the hypothalamus and at the granulosa cells in the ovary, skeletal muscle or adipocytes senses initially normal testosterone and dihydrotestosterone as biochemical hyperandrogenism and might be a crucial connection between the vicious circles of the PCOS pathogenesis. Polymorphism of the AR gene has been associated with different androgen pattern diseases. Several studies have demonstrated an association between AR with increased activity encoded by shorter CAG repeat polymorphism in the exon 1 of the AR gene and PCOS, although there are conflicting results in this field. The phenomenon is more complex because the AR activity is determined by the epigenetic effect of X chromosome inactivation (XCI). Moreover, we must evaluate the AR as a dynamic heterocomplex, with a large number of coactivators and corepressors that are essential to its function, thus mediating tissue-specific effects. In theory, any of these factors could modify the activity of AR, which likely explains the inconsistent results obtained when this activity was quantified by only the CAG polymorphism in PCOS.

  16. CdWO4 polymorphs: Selective preparation, electronic structures, and photocatalytic activities

    International Nuclear Information System (INIS)

    Yan, Tingjiang; Li, Liping; Tong, Wenming; Zheng, Jing; Wang, Yunjian; Li, Guangshe

    2011-01-01

    This work explored the selective synthesis of polymorphs of CdWO 4 in either tetragonal or monoclinic phase by optimizing the experimental parameters. Systematic characterization indicated that both polymorphs possessed similar spherical morphologies but different structural building blocks. Electronic structures calculations for both polymorphs demonstrated the same constructions of conduction band or valence band, while the conduction band widths of both polymorphs were quite different. Both CdWO 4 polymorphs exhibited good photocatalytic activity for degradation of methyl orange under UV light irradiation. When comparing to some other well-known tungstate oxide materials, the photocatalytic activity was found to follow such a consequence, monoclinic CdWO 4 ∼monoclinic ZnWO 4 >tetragonal CdWO 4 >tetragonal CaWO 4 . The specific photocatalytic activity of monoclinic CdWO 4 was even higher than that of commercial TiO 2 photocatalyst (Degussa P25). The increased activity from the tetragonal CdWO 4 to the monoclinic was consistent with the trend of the decreased symmetry, and this could be explained in terms of the geometric structures and electronic structures for both polymorphs. -- Graphical abstract: Monoclinic CdWO 4 exhibited a much higher photocatalytic activity than the tetragonal form owing to the lower symmetry, more distorted geometric structure, and the dispersive band configuration. Display Omitted Research highlights: → Polymorphs of CdWO 4 in either tetragonal or monoclinic phase were selectively synthesized. → Both polymorphs possessed similar spherical morphologies, while the relevant structural building blocks were different. → Photocatalytic activities of CdWO 4 polymorphs depended strongly on the symmetry, geometric structure, as well as band configuration.

  17. Promoter polymorphisms in genes involved in porcine myogenesis influence their transcriptional activity.

    Science.gov (United States)

    Bongiorni, Silvia; Tilesi, Francesca; Bicorgna, Silvia; Iacoponi, Francesca; Willems, Daniela; Gargani, Maria; D'Andrea, MariaSilvia; Pilla, Fabio; Valentini, Alessio

    2014-11-07

    Success of meat production and selection for improvement of meat quality is among the primary aims in animal production. Meat quality traits are economically important in swine; however, the underlying genetic nature is very complex. Therefore, an improved pork production strongly depends on identifying and studying how genetic variations contribute to modulate gene expression. Promoters are key regions in gene modulation as they harbour several binding motifs to transcription regulatory factors. Therefore, polymorphisms in these regions are likely to deeply affect RNA levels and consequently protein synthesis. In this study, we report the identification of single nucleotide polymorphisms (SNPs) in promoter regions of candidate genes involved in development, cellular differentiation and muscle growth in Sus scrofa. We identified SNPs in the promoter regions of genes belonging to the Myogenic Regulatory Factors (MRF) gene family (the Myogenic Differentiation gene, MYOD1) and to Growth and Differentiation Factors (GDF) gene family (Myostatin gene, MSTN, GDF8), in Casertana and Large White breeds. The purpose of this study was to investigate if polymorphisms in the promoters could affect the transcriptional activity of these genes. With this aim, we evaluated in vitro the functional activity of the luciferase reporter gene luc2 activity, driven by two constructs carrying different promoter haplotypes. We tested the effects of the G302A (U12574) transition on the promoter efficiency in MYOD1 gene. We ascertained a difference in transcription efficiency for the two variants. A stronger activity of the A-carrying construct is more evident in C2C12. The luciferase expression driven by the MYOD1-A allelic variant displayed a 3.8-fold increased transcriptional activity. We investigated the activity of two haplotype variants (AY527152) in the promoter of GDF8 gene. The haploptype-1 (A435-A447-A879) up-regulated the expression of the reporter gene by a two-fold increase, and

  18. Synthesis and polymorphic control for visible light active titania nanoparticles

    Science.gov (United States)

    Kaewgun, Sujaree

    Titania (TiO2) is useful for many applications in photocatalysis, antimicrobials, pigment, deodorization, and decomposition of harmful organics and undesirable compounds in the air and waste water under UV irradiation. Among the three phases of TiO2, Rutile, Anatase, and Brookite, studies have been more focused on the anatase and rutile phases. Pure brookite is the most difficult phase to prepare, even under hydrothermal conditions. Predominantly brookite phase TiO2 nanoparticles were prepared by the Water-based Ambient Condition Sol (WACS) process in our laboratory. The objectives of this research were to enhance visible light active (VLA) photocatalytic properties of polymorphic brookite TiO2 by minimizing the lattice defects and narrowing band gap of titania by nitrogen and/or carbon chromophone, and to investigate the deactivation, reusability, and regeneration of the VLA titania in order to design better titania catalysts for organic compound degradation applications. In order to study the influence of hydroxyl content on photocatalytic activities (PCAs) of polymorphic titania nanoparticles, the WACS samples were post-treated by a Solvent-based Ambient Condition Sol (SACS) process in sec-butanol (sec-BuOH). All samples were characterized for phase composition, surface area, hydroxyl contamination, and particle morphology by x-ray diffraction, N2 physisorption, FT-IR, solid state 1H NMR and scanning electron microscopy, and then compared to a commercial titania, Degussa P25. Evaluation of methyl orange (MO) degradation under UV irradiation results showed that the lower lattice hydroxyl content in SACS titania enhanced the PCA. As-prepared titania and SACS samples, which have similar surface areas and crystallinity, were compared in order to prove that the superior PCA came from the reduction in the lattice hydroxyl content. To enhance PCA and VLA properties of WACS, an alternative high boiling point polar solvent, N-methylpyrrolidone (NMP), was utilized in the

  19. Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

    Science.gov (United States)

    van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

    1992-01-01

    Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

  20. A molecular perspective on a complex polymorphic inversion system with cytological evidence of multiply reused breakpoints.

    Science.gov (United States)

    Orengo, D J; Puerma, E; Papaceit, M; Segarra, C; Aguadé, M

    2015-06-01

    Genome sequence comparison across the Drosophila genus revealed that some fixed inversion breakpoints had been multiply reused at this long timescale. Cytological studies of Drosophila inversion polymorphism had previously shown that, also at this shorter timescale, some breakpoints had been multiply reused. The paucity of molecularly characterized polymorphic inversion breakpoints has so far precluded contrasting whether cytologically shared breakpoints of these relatively young inversions are actually reused at the molecular level. The E chromosome of Drosophila subobscura stands out because it presents several inversion complexes. This is the case of the E1+2+9+3 arrangement that originated from the ancestral Est arrangement through the sequential accumulation of four inversions (E1, E2, E9 and E3) sharing some breakpoints. We recently identified the breakpoints of inversions E1 and E2, which allowed establishing reuse at the molecular level of the cytologically shared breakpoint of these inversions. Here, we identified and sequenced the breakpoints of inversions E9 and E3, because they share breakpoints at sections 58D and 64C with those of inversions E1 and E2. This has allowed establishing that E9 and E3 originated through the staggered-break mechanism. Most importantly, sequence comparison has revealed the multiple reuse at the molecular level of the proximal breakpoint (section 58D), which would have been used at least by inversions E2, E9 and E3. In contrast, the distal breakpoint (section 64C) might have been only reused once by inversions E1 and E2, because the distal E3 breakpoint is displaced >70 kb from the other breakpoint limits.

  1. Interleukin-21 gene polymorphism rs2221903 is associated with disease activity in patients with rheumatoid arthritis.

    Science.gov (United States)

    Malinowski, Damian; Paradowska-Gorycka, Agnieszka; Safranow, Krzysztof; Pawlik, Andrzej

    2017-08-01

    Interleukin-21 (IL-21) is a cytokine which plays a significant role in the pathogenesis and disease activity of rheumatoid arthritis (RA). Genetic polymorphisms in the IL-21 gene may alter the synthesis of IL-21. The aim of this study was to examine IL-21 and IL-21R polymorphisms in patients with RA. We examined 422 patients with RA and 338 healthy controls. Single nucleotide polymorphisms (SNPs) within the IL-21 (rs6822844 G>T, rs6840978 C>T, rs2221903 T>C) and IL-21R (rs2285452 G>A) genes were genotyped using TaqMan genotyping assays. There were no statistically significant differences in the distribution of studied genotypes and alleles between RA patients and the control group. To examine whether IL-21 polymorphisms affect disease activity in RA patients, we compared the distribution of IL-21 genotypes between patients with DAS28 ≤ 2.5 (patients with remission of disease symptoms) and patients with DAS28 > 2.5 (patients with active RA). Among patients with DAS28 > 2.5, increased prevalence of rs2221903 CT and CC genotypes was observed (OR = 1.54; 95% CI: 1.04-2.28; p = 0.035). The results of this study suggest that IL-21 and IL-21R gene polymorphisms are not risk loci for RA susceptibility, whereas the IL-21 rs2221903 polymorphism is associated with disease activity.

  2. Mineralogical characteristics of the silica polymorphs in relation to their biological activities

    Energy Technology Data Exchange (ETDEWEB)

    Guthrie, G.D. Jr. [Los Alamos National Lab., NM (United States); Heaney, P.J. [Princeton Univ., NJ (United States). Dept. of Geological and Geophysical Sciences

    1993-10-01

    Numerous aspects of minerals (including the silica polymorphs) can effect their biological activities. These include periodic structures, compositional variations, dissolution characteristics, surface properties, and particle size/shape. In order to understand mineral-induced pathogenesis in a mechanistic way, the links between these properties and biochemical processes must be elucidated. This paper presents some of the basic properties of the silica polymorphs that may relate to pathogenicity and mineralogical strategies for designing biological assays to evaluate these properties.

  3. Plasminogen activator inhibitor-2 polymorphism associates with recurrent coronary event risk in patients with high HDL and C-reactive protein levels.

    Directory of Open Access Journals (Sweden)

    James P Corsetti

    Full Text Available The objective of this work was to investigate whether fibrinolysis plays a role in establishing recurrent coronary event risk in a previously identified group of postinfarction patients. This group of patients was defined as having concurrently high levels of high-density lipoprotein cholesterol (HDL-C and C-reactive protein (CRP and was previously demonstrated to be at high-risk for recurrent coronary events. Potential risk associations of a genetic polymorphism of plasminogen activator inhibitor-2 (PAI-2 were probed as well as potential modulatory effects on such risk of a polymorphism of low-density lipoprotein receptor related protein (LRP-1, a scavenger receptor known to be involved in fibrinolysis in the context of cellular internalization of plasminogen activator/plansminogen activator inhibitor complexes. To this end, Cox multivariable modeling was performed as a function of genetic polymorphisms of PAI-2 (SERPINB, rs6095 and LRP-1 (LRP1, rs1800156 as well as a set of clinical parameters, blood biomarkers, and genetic polymorphisms previously demonstrated to be significantly and independently associated with risk in the study population including cholesteryl ester transfer protein (CETP, rs708272, p22phox (CYBA, rs4673, and thrombospondin-4 (THBS4, rs1866389. Risk association was demonstrated for the reference allele of the PAI-2 polymorphism (hazard ratio 0.41 per allele, 95% CI 0.20-0.84, p=0.014 along with continued significant risk associations for the p22phox and thrombospondin-4 polymorphisms. Additionally, further analysis revealed interaction of the LRP-1 and PAI-2 polymorphisms in generating differential risk that was illustrated using Kaplan-Meier survival analysis. We conclude from the study that fibrinolysis likely plays a role in establishing recurrent coronary risk in postinfarction patients with concurrently high levels of HDL-C and CRP as manifested by differential effects on risk by polymorphisms of several genes linked

  4. Genetic polymorphisms and activity of PON1 in a Mexican population

    International Nuclear Information System (INIS)

    Rojas-Garcia, A.E.; Solis-Heredia, M.J.; Pina-Guzman, B.; Vega, L.; Lopez-Carrillo, L.; Quintanilla-Vega, B.

    2005-01-01

    Human paraoxonase (PON1) plays a role in detoxification of organophosphorus (OP) compounds by hydrolyzing the bioactive oxons, and in reducing oxidative low-density lipoproteins, which may protect against atherosclerosis. Some PON1 polymorphisms have been found to be responsible for variations in catalytic activity and expression and have been associated with susceptibility to OP poisoning and vascular diseases. Both situations are of public health relevance in Mexico. Therefore, the aim of this study was to evaluate PON1 phenotype and the frequencies of polymorphisms PON1 -162, -108, 55, and 192 in a Mexican population. The studied population consisted of unrelated individuals (n = 214) of either gender, 18-52 years old. Serum PON1 activity was assayed using phenylacetate and paraoxon as substrates. PON1 variants, -162, 55, and 192, were determined by real-time PCR using the TaqMan System, and PON1 -108 genotype by PCR-RFLP. We found a wide interindividual variability of PON1 activity with a unimodal distribution; the range of enzymatic activity toward phenylacetate was 84.72 to 422.0 U/mL, and 88.37 to 1645.6 U/L toward paraoxon. All four PON1 polymorphisms showed strong linkage disequilibrium (D% >90). PON1 polymorphisms -108, 55, and 192 were independently associated with arylesterase activity; whereas the activity toward paraoxon was related only with PON1 192 polymorphism, suggesting that this polymorphism is determinant to infer PON1 activity. A better understanding of the phenotype and genotypes of PON1 in Mexican populations will facilitate further epidemiological studies involving PON1 variability in OP poisoning and in the development of atherosclerosis

  5. Tumour necrosis factor-α polymorphism as one of the complex inherited factors in pemphigus

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    Jolanta Dorota Torzecka

    2003-01-01

    Full Text Available The aim of our study was to analyse a significance of tumour necrosis factor (TNF-α promoter gene polymorphisms in relation to the HLA-DR locus in genetic predisposition to pemphigus. TNF-α gene polymorphisms in position -238 and -308 were identified using a modified polymerase chain reaction-restriction fragment length polymorphism method in 53 patients with pemphigus (38 with pemphigus vulgaris, 15 with pemphigus foliaceus and 87 healthy controls. The HLA-DRB1 locus was typed using the polymerase chain reaction SSO method in all the patients and 152 population controls.

  6. Data describing the effect of DRD4 promoter polymorphisms on promoter activity

    Directory of Open Access Journals (Sweden)

    Shoin Tei

    2016-06-01

    Full Text Available This data article tested whether polymorphisms within the dopamine D4 receptor (DRD4 gene promoter can lead to differences in the promoter activity. The variants, a 120-bp variable number tandem repeat (VNTR, −906 T/C, −809 G/A, −616G/C, and −521C/T, were introduced into the DRD4 promoter and the promoter activity was measured in a neural cell line using the luciferase assay. However, no differences were detected among the haplotypes investigated, and the in vitro data obtained from our protocol could not support the involvement of DRD4 promoter polymorphisms in heritable human traits.

  7. Bovine proteins containing poly-glutamine repeats are often polymorphic and enriched for components of transcriptional regulatory complexes

    LENUS (Irish Health Repository)

    Whan, Vicki

    2010-11-23

    Abstract Background About forty human diseases are caused by repeat instability mutations. A distinct subset of these diseases is the result of extreme expansions of polymorphic trinucleotide repeats; typically CAG repeats encoding poly-glutamine (poly-Q) tracts in proteins. Polymorphic repeat length variation is also apparent in human poly-Q encoding genes from normal individuals. As these coding sequence repeats are subject to selection in mammals, it has been suggested that normal variations in some of these typically highly conserved genes are implicated in morphological differences between species and phenotypic variations within species. At present, poly-Q encoding genes in non-human mammalian species are poorly documented, as are their functions and propensities for polymorphic variation. Results The current investigation identified 178 bovine poly-Q encoding genes (Q ≥ 5) and within this group, 26 genes with orthologs in both human and mouse that did not contain poly-Q repeats. The bovine poly-Q encoding genes typically had ubiquitous expression patterns although there was bias towards expression in epithelia, brain and testes. They were also characterised by unusually large sizes. Analysis of gene ontology terms revealed that the encoded proteins were strongly enriched for functions associated with transcriptional regulation and many contributed to physical interaction networks in the nucleus where they presumably act cooperatively in transcriptional regulatory complexes. In addition, the coding sequence CAG repeats in some bovine genes impacted mRNA splicing thereby generating unusual transcriptional diversity, which in at least one instance was tissue-specific. The poly-Q encoding genes were prioritised using multiple criteria for their likelihood of being polymorphic and then the highest ranking group was experimentally tested for polymorphic variation within a cattle diversity panel. Extensive and meiotically stable variation was identified

  8. Association between the polymorphisms of urokinase plasminogen activation system and cancer risk: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Xu Z

    2015-09-01

    Full Text Available Zhen Xu,1,* Li-Li Meng,2,* Jizong Lin,3 Yunbiao Ling,3 Shu-xian Chen,3 Nan Lin31Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 2Department of Gynecology and Obstetrics, Sun Yat-sen Memorial Hospital, 3Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this studyPurpose: The present study aimed to investigate the potential association between the urokinase plasminogen activation (uPA system polymorphisms (rs4065, rs2227564, and rs344781 and cancer risk.Methods: An extensive search was performed to identify published case–control studies on the association between the uPA system polymorphisms and cancer risk. Odds ratios (ORs with 95% confidence intervals (CIs were used to evaluate the relationship between the uPA system polymorphisms and cancer risk.Results: A total of 20 studies comprising 7,037 cancer cases and 10,094 controls were identified and included in the present meta-analysis. Overall, significantly increased cancer risk was associated with the uPA polymorphism rs4065 (T vs C: OR 1.50, 95% CI: 1.19–1.89; TT vs CC: OR 4.63, 95% CI: 3.10–6.91; dominant model: OR 1.93, 95% CI: 1.60–2.33; recessive model: OR 3.02, 95% CI: 1.26–7.25 and the uPA receptor polymorphism rs344781 (T vs C: OR 1.13, 95% CI: 1.04–1.23; TC vs CC: OR 1.26, 95% CI: 1.06–1.49; TT vs CC: OR 1.35, 95% CI: 1.13–1.63; dominant model: OR 1.29, 95% CI: 1.10–1.52. No significant association was found between the uPA polymorphism rs2227564 and cancer risk. Subgroup analysis suggests that the T allele of the rs4065 (T allele vs C allele: OR 1.50, 95% CI: 1.19–1.89 and rs344781 polymorphisms (T allele vs C allele: OR 1.13, 95% CI: 1.04–1.23 was associated with increased cancer risk in Asians.Conclusion: Our results suggest that the uPA polymorphism rs4065 and the uPA receptor polymorphism rs344781

  9. Transmembrane Domain Single-Nucleotide Polymorphisms Impair Expression and Transport Activity of ABC Transporter ABCG2

    NARCIS (Netherlands)

    Sjostedt, N.; Heuvel, J.J.M.W. van den; Koenderink, J.B.; Kidron, H.

    2017-01-01

    PURPOSE: To study the function and expression of nine naturally occurring single-nucleotide polymorphisms (G406R, F431L, S441N, P480L, F489L, M515R, L525R, A528T and T542A) that are predicted to reside in the transmembrane regions of the ABC transporter ABCG2. METHODS: The transport activity of the

  10. Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma

    Directory of Open Access Journals (Sweden)

    Lazarus Ross

    2005-06-01

    Full Text Available Abstract Background Identifying genetic determinants for lung function is important in providing insight into the pathophysiology of asthma. Signal transducer and activator of transcription 3 is a transcription factor latent in the cytoplasm; the gene (STAT3 is activated by a wide range of cytokines, and may play a role in lung development and asthma pathogenesis. Methods We genotyped six single nucleotide polymorphisms (SNPs in the STAT3 gene in a cohort of 401 Caucasian adult asthmatics. The associations between each SNP and forced expiratory volume in 1 second (FEV1, as a percent of predicted, at the baseline exam were tested using multiple linear regression models. Longitudinal analyses involving repeated measures of FEV1 were conducted with mixed linear models. Haplotype analyses were conducted using imputed haplotypes. We completed a second association study by genotyping the same six polymorphisms in a cohort of 652 Caucasian children with asthma. Results We found that three polymorphisms were significantly associated with baseline FEV1: homozygotes for the minor alleles of each polymorphism had lower FEV1 than homozygotes for the major alleles. Moreover, these associations persisted when we performed an analysis on repeated measures of FEV1 over 8 weeks. A haplotypic analysis based on the six polymorphisms indicated that two haplotypes were associated with baseline FEV1. Among the childhood asthmatics, one polymorphism was associated with both baseline FEV1 and the repeated measures of FEV1 over 4 years. Conclusion Our results indicate that genetic variants in STAT3, independent of asthma treatment, are determinants of FEV1 in both adults and children with asthma, and suggest that STAT3 may participate in inflammatory pathways that have an impact on level of lung function.

  11. Serum paraoxonase-1 gene polymorphism and enzyme activity in patients with urolithiasis.

    Science.gov (United States)

    Atar, Arda; Gedikbasi, Asuman; Sonmezay, Erkan; Kiraz, Zeynep Kusku; Abbasoglu, Semra; Tasci, Ali Ihsan; Tugcu, Volkan

    2016-01-01

    Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine and arginine at position 192 and the other leucine and methionine at position 55. Recent reports suggest that nephrolithiasis and atherosclerosis share a number of risk factors. Our study aimed to compare the effects of PON1 192, PON1 55 polymorphisms, and PON1 activity in patients with urolithiasis and controls. PON1's arylesterase/paraoxonase activities and phenotype were determined in 158 stone forming cases (Group 1) and 138 non-stone forming controls (Group 2). The PON1 192 and PON1 55 polymorphisms were studied by polymerase chain reaction/restriction fragment length polymorphism. Paraoxonase activity was significantly lower in Group 1 than Group 2 (112 ± 31.8 vs. 208 ± 53.1 IU/L) (p < 0.001). The PON1 L55M polymorphism was significantly higher in Group 1. The "M" allele coding for PON1 was higher in Group 1 (p < 0.001). PON1 192 RR homozygotes had significantly higher PON1 activity than QR and QQ genotypes among all the patients (p < 0.001). The results of our study demonstrate that the PON1 55 gene "M" allele is associated with renal stone disease. Individuals possessing the "M" allele have a higher incidence of urolithiasis. The results of this study provide genetic evidence that the PON1 gene may play a role in stone formation. PON1 genotype determination may provide a tool to identify individuals who are at risk of urolithiasis.

  12. Genetic polymorphism within the Leishmania donovani complex: correlation with geographic origin

    Czech Academy of Sciences Publication Activity Database

    Zemanová, Eva; Jirků, Milan; Mauricio, I. L.; Miles, M. A.; Lukeš, Julius

    2004-01-01

    Roč. 70, č. 6 (2004), s. 613-617 ISSN 0002-9637 Grant - others:European Community(XE) QLK2-CT-2001-01810 Institutional research plan: CEZ:AV0Z6022909 Keywords : genetic polymorphism * Leishmania donovani * RAPD Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.013, year: 2004

  13. Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease

    DEFF Research Database (Denmark)

    Meurs, Kathryn M.; Olsen, Lisbeth H.; Reimann, Maria J.

    2018-01-01

    a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated......Objectives Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified...... with alterations in ACE activity at different stages of cardiac disease. Methods Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Results Forty-three dogs were homozygous for the ACE polymorphism...

  14. Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis

    OpenAIRE

    Takemoto, Y.; Sakatani, M.; Takami, S.; Tachibana, T.; Higaki, J.; Ogihara, T.; Miki, T.; Katsuya, T.; Tsuchiyama, T.; Yoshida, A.; Yu, H.; Tanio, Y.; Ueda, E.

    1998-01-01

    BACKGROUND—Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SA...

  15. Haplotyping the human T-cell receptor β-chain gene complex by use of restriction fragment length polymorphisms

    International Nuclear Information System (INIS)

    Charmley, P.; Chao, A.; Gatti, R.A.; Concannon, P.; Hood, L.

    1990-01-01

    The authors have studied the genetic segregation of human T-cell receptor β-chain (TCRβ) genes on chromosome 7q in 40 CEPH (Centre d'Etude du Polymorphisme Humain) families by using restriction fragment length polymorphisms (RFLPs). They constructed haplotypes from eight RFLPs by using variable- and constant-region cDNA probes, which detect polymorphisms that span more than 600 kilobases of the TCRβ gene complex. Analysis of allele distributions between TCRβ genes revealed significant linkage disequilibrium between only 6 of the 28 different pairs of RFLPs. This linkage disequilibrium strongly influences the most efficient order to proceed for typing of these RFLPs in order to achieve maximum genetic informativeness, which in this study revealed a 97.3% level of heterozygosity within the TCRβ gene complex. The results should provide new insight into recent reports of disease associations with the TCRβ gene complex and should assist in designing future experiments to detect or confirm the existence of disease-susceptibility loci in this region of the human genome

  16. Designing complex systems - a structured activity

    NARCIS (Netherlands)

    van der Veer, Gerrit C.; van Vliet, Johannes C.; Lenting, Bert; Olson, Gary M.; Schuon, Sue

    1995-01-01

    This paper concerns the development of complex systems from the point of view of design as a structure of activities, related both to the clients and the users. Several modeling approaches will be adopted for different aspects of design, and several views on design will be integrated. The proposed

  17. Plasminogen activator inhibitor I 4G/5G polymorphism in neonatal respiratory distress syndrome.

    Science.gov (United States)

    Armangil, Didem; Yurdakök, Murat; Okur, Hamza; Gürgey, Aytemiz

    2011-08-01

    Fibrin monomers inhibit surfactant function. 4G/5G insertion/deletion polymorphism plays an important role in the regulation of plasminogen activator inhibitor 1 (PAI-1) gene expression. To examine the genotype distribution of PAI-1 polymorphism in 60 infants with respiratory distress syndrome (RDS) and 53 controls, an allele-specific polymerase chain reaction (PCR) was used. The proportion of 4G/4G, 4G/5G, and 5G/5G genotypes did not differ statistically between the RDS and control groups (P > .05). Having PAI-1 4G/4G genotype polymorphism appears to increase the risk of RDS (odds ratio [OR] =1.5; 95% confidence interval [CI], 0.5-4.3), although it was not statistically significant. No relation was found between the PAI-1 4G/5G polymorphisms and RDS, but there was an increased risk associated with the 4G variant of the PAI-1 gene. We believe that our findings of increased 4G allele of the PAI-1 gene in infants with RDS would also help to clarify the pathogenesis of RDS.

  18. Restriction fragment length polymorphism within the class I gene loci of the equine major histocompatibility complex

    International Nuclear Information System (INIS)

    Alexander, A.J.; Bailey, E.; Woodward, J.G.

    1986-01-01

    Fourteen standard bred horses were serotyped as homozygous for 1 of 6 Equine Leukocyte Antigen (ELA) specificities. DNA was purified from peripheral leukocytes and digested with Hind III or Pvu II. Southern blot hybridization analysis was carried out using a 32 P-labeled mouse cDNA probe (PH2IIa) specific for class I MHC genes. Both enzymes generated blots that contained a large number of bands (23 to 30) per horse. Significant polymorphism existed among most fragment sizes, while a dozen highly conserved band sizes suggested the presence of Qa/tla - like genes. Only 2 animals (both W6's) showed identical band patterns. Polymorphism was greatest between horses of different serotypes and was significantly decreased within serotypes. Unique bands were present on both blots for both W1's and W6's and may account for the serologic specificity seen in ELA W1 and W6 horses. This study is consistent with the findings in other higher vertebrates and implies that the MHC of the horse includes a highly polymorphic class I multigene family

  19. Interaction between BDNF Polymorphism and Physical Activity on Inhibitory Performance in the Elderly without Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Anne Canivet

    2017-11-01

    Full Text Available Background: In the elderly, physical activity (PA enhances cognitive performances, increases brain plasticity and improves brain health. The neurotrophic hypothesis is that the release of brain-derived neurotrophic factor (BDNF, which is implicated in brain plasticity and cognition, is triggered by PA because motoneurons secrete BDNF into the bloodstream during exercise. Individual differences in cognitive performance may be explained by individual differences in genetic predisposition. A single nucleotide polymorphism on the BDNF gene, BDNFVal66Met, affects activity-dependent BDNF secretion. This study investigated the influence of the BDNFVal66Met polymorphism on the relationship between PA and controlled inhibition performance in older adults.Methods: A total of 114 healthy elderly volunteers (mean age = 71.53 years old were evaluated. Participants were genotyped for the BDNFVal66Met polymorphism. We evaluated inhibitory performance using choice reaction times (RT and error rates from a Simon-like task and estimated their PA using two self-reported questionnaires. We established four groups according to PA level (active vs. inactive and BDNFVal66Met genotype (Met carriers vs. Val-homozygous. The results were analyzed using ANOVA and ANCOVA, including age, gender and body mass index as covariates.Results: The BDNFVal66Met polymorphism interacted with PA on controlled inhibition performance. More specifically, inactive Val-homozygous participants exhibited a lower inhibition performance than active Val homozygotes and inactive Met carriers; the former had a higher error rate without differences in RT.Conclusion: Differences between individuals on inhibitory performance may be partially understood by the interaction between genetic influence in BDNF secretion and PA level. The results of this study clearly support the neurotrophic hypothesis that BDNF synthesis is an important mechanism underlying the influence of physical activity on brain

  20. Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity

    DEFF Research Database (Denmark)

    Tchatchou, Sandrine; Riedel, Angela; Lyer, Stefan

    2010-01-01

    ,466 unrelated German controls. Promoter studies in breast cancer cells demonstrate that the risk-increasing DMBT1 -93T allele displays significantly decreased promoter activity compared to the DMBT1 -93C allele, resulting in a loss of promoter activity. The data suggest that DMBT1 polymorphisms in the 5'-region......According to present estimations, the unfavorable combination of alleles with low penetrance but high prevalence in the population might account for the major part of hereditary breast cancer risk. Deleted in Malignant Brain Tumors 1 (DMBT1) has been proposed as a tumor suppressor for breast cancer...... and other cancer types. Genomewide mapping in mice further identified Dmbt1 as a potential modulator of breast cancer risk. Here, we report the association of two frequent and linked single-nucleotide polymorphisms (SNPs) with increased breast cancer risk in women above the age of 60 years: DMBT1 c.-93C...

  1. Gender differences in association between serotonin transporter gene polymorphism and resting-state EEG activity.

    Science.gov (United States)

    Volf, N V; Belousova, L V; Knyazev, G G; Kulikov, A V

    2015-01-22

    Human brain oscillations represent important features of information processing and are highly heritable. Gender has been observed to affect association between the 5-HTTLPR (serotonin-transporter-linked polymorphic region) polymorphism and various endophenotypes. This study aimed to investigate the effects of 5-HTTLPR on the spontaneous electroencephalography (EEG) activity in healthy male and female subjects. DNA samples extracted from buccal swabs and resting EEG recorded at 60 standard leads were collected from 210 (101 men and 109 women) volunteers. Spectral EEG power estimates and cortical sources of EEG activity were investigated. It was shown that effects of 5-HTTLPR polymorphism on electrical activity of the brain vary as a function of gender. Women with the S/L genotype had greater global EEG power compared to men with the same genotype. In men, current source density was markedly different among genotype groups in only alpha 2 and alpha 3 frequency ranges: S/S allele carriers had higher current source density estimates in the left inferior parietal lobule in comparison with the L/L group. In women, genotype difference in global power asymmetry was found in the central-temporal region. Contrasting L/L and S/L genotype carriers also yielded significant effects in the right hemisphere inferior parietal lobule and the right postcentral gyrus with L/L genotype carriers showing lower current source density estimates than S/L genotype carriers in all but gamma bands. So, in women, the effects of 5-HTTLPR polymorphism were associated with modulation of the EEG activity in a wide range of EEG frequencies. The significance of the results lies in the demonstration of gene by sex interaction with resting EEG that has implications for understanding sex-related differences in affective states, emotion and cognition. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease.

    Science.gov (United States)

    Meurs, Kathryn M; Olsen, Lisbeth H; Reimann, Maria J; Keene, Bruce W; Atkins, Clarke E; Adin, Darcy; Aona, Brent; Condit, Julia; DeFrancesco, Teresa; Reina-Doreste, Yamir; Stern, Joshua A; Tou, Sandra; Ward, Jessica; Woodruff, Kathleen

    2018-02-01

    Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

  3. An Association Between Functional Polymorphisms of the Interleukin 1 Gene Complex and Schizophrenia Using Transmission Disequilibrium Test.

    Science.gov (United States)

    Kapelski, Pawel; Skibinska, Maria; Maciukiewicz, Malgorzata; Pawlak, Joanna; Dmitrzak-Weglarz, Monika; Szczepankiewicz, Aleksandra; Zaremba, Dorota; Twarowska-Hauser, Joanna

    2016-12-01

    IL1 gene complex has been implicated in the etiology of schizophrenia. To assess whether IL1 gene complex is associated with susceptibility to schizophrenia in Polish population we conducted family-based study. Functional polymorphisms from IL1A (rs1800587, rs17561, rs11677416), IL1B (rs1143634, rs1143643, rs16944, rs4848306, rs1143623, rs1143633, rs1143627) and IL1RN (rs419598, rs315952, rs9005, rs4251961) genes were genotyped in 143 trio with schizophrenia. Statistical analysis was performed using transmission disequilibrium test. We have found a trend toward an association of rs1143627, rs16944, rs1143623 in IL1B gene with the risk of schizophrenia. Our results show a protective effect of allele T of rs4251961 in IL1RN against schizophrenia. We also performed haplotype analysis of IL1 gene complex and found a trend toward an association with schizophrenia of GAGG haplotype (rs1143627, rs16944, rs1143623, rs4848306) in IL1B gene, haplotypes: TG (rs315952, rs9005) and TT (rs4251961, rs419598) in IL1RN. Haplotype CT (rs4251961, rs419598) in IL1RN was found to be associated with schizophrenia. After correction for multiple testing associations did not reach significance level. Our results might support theory that polymorphisms of interleukin 1 complex genes (rs1143627, rs16944, rs1143623, rs4848306 in IL1B gene and rs4251961, rs419598, rs315952, rs9005 in IL1RN gene) are involved in the pathogenesis of schizophrenia, however, none of the results reach significance level after correction for multiple testing.

  4. Association of the macrophage activating factor (MAF) precursor activity with polymorphism in vitamin D-binding protein.

    Science.gov (United States)

    Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Kubo, Shinichi; Hori, Hitoshi

    2004-01-01

    Serum vitamin D-binding protein (Gc protein or DBP) is a highly expressed polymorphic protein, which is a precursor of the inflammation-primed macrophage activating factor, GcMAF, by a cascade of carbohydrate processing reactions. In order to elucidate the relationship between Gc polymorphism and GcMAF precursor activity, we estimated the phagocytic ability of three homotypes of Gc protein, Gc1F-1F, Gc1S-1S and Gc2-2, through processing of their carbohydrate moiety. We performed Gc typing of human serum samples by isoelectric focusing (IEF). Gc protein from human serum was purified by affinity chromatography with 25-hydroxyvitamin D3-sepharose. A phagocytosis assay of Gc proteins, modified using beta-glycosidase and sialidase, was carried out. The Gc1F-1F phenotype was revealed to possess Galbeta1-4GalNAc linkage by the analysis of GcMAF precursor activity using beta1-4 linkage-specific galactosidase from jack bean. The GcMAF precursor activity of the Gc1F-1F phenotype was highest among three Gc homotypes. The Gc polymorphism and carbohydrate diversity of Gc protein are significant for its pleiotropic effects.

  5. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

    Directory of Open Access Journals (Sweden)

    Kaja K Jasińska

    Full Text Available Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265 is associated with children's (age 6-10 neural activation patterns during a reading task (n = 81 using functional magnetic resonance imaging (fMRI, genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

  6. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

    Science.gov (United States)

    Jasińska, Kaja K; Molfese, Peter J; Kornilov, Sergey A; Mencl, W Einar; Frost, Stephen J; Lee, Maria; Pugh, Kenneth R; Grigorenko, Elena L; Landi, Nicole

    2016-01-01

    Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes.

  7. MDR-1 and MRP2 gene polymorphisms in Mexican epileptic pediatric patients with complex partial seizures.

    Directory of Open Access Journals (Sweden)

    David eEscalante-Santiago

    2014-10-01

    Full Text Available Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1 / ABCB1 and MRP2 / ABCC2 in patients with antiepileptic-drugs resistant epilepsy is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with antiepileptic-drugs resistant epilepsy (ADR and patients with good response to anti-epileptic drugs (CTR in a rigorously selected population. We analyzed 22 samples from drug-resistant patients with epilepsy and 7 samples from patients with good response to anti-epileptic drugs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA and rs2032582 (AT and AG were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT and 66744T>A (TG were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with AED-resistant epilepsy.

  8. Glass Durability Modeling, Activated Complex Theory (ACT)

    International Nuclear Information System (INIS)

    CAROL, JANTZEN

    2005-01-01

    The most important requirement for high-level waste glass acceptance for disposal in a geological repository is the chemical durability, expressed as a glass dissolution rate. During the early stages of glass dissolution in near static conditions that represent a repository disposal environment, a gel layer resembling a membrane forms on the glass surface through which ions exchange between the glass and the leachant. The hydrated gel layer exhibits acid/base properties which are manifested as the pH dependence of the thickness and nature of the gel layer. The gel layer has been found to age into either clay mineral assemblages or zeolite mineral assemblages. The formation of one phase preferentially over the other has been experimentally related to changes in the pH of the leachant and related to the relative amounts of Al +3 and Fe +3 in a glass. The formation of clay mineral assemblages on the leached glass surface layers ,lower pH and Fe +3 rich glasses, causes the dissolution rate to slow to a long-term steady state rate. The formation of zeolite mineral assemblages ,higher pH and Al +3 rich glasses, on leached glass surface layers causes the dissolution rate to increase and return to the initial high forward rate. The return to the forward dissolution rate is undesirable for long-term performance of glass in a disposal environment. An investigation into the role of glass stoichiometry, in terms of the quasi-crystalline mineral species in a glass, has shown that the chemistry and structure in the parent glass appear to control the activated surface complexes that form in the leached layers, and these mineral complexes ,some Fe +3 rich and some Al +3 rich, play a role in whether or not clays or zeolites are the dominant species formed on the leached glass surface. The chemistry and structure, in terms of Q distributions of the parent glass, are well represented by the atomic ratios of the glass forming components. Thus, glass dissolution modeling using simple

  9. Effects of BDNF polymorphism and physical activity on episodic memory in the elderly: a cross sectional study.

    Science.gov (United States)

    Canivet, Anne; Albinet, Cédric T; André, Nathalie; Pylouster, Jean; Rodríguez-Ballesteros, Montserrat; Kitzis, Alain; Audiffren, Michel

    2015-01-01

    The brain-derived neurotrophic factor (BDNF) concentration is highest in the hippocampus compared with that in other brain structures and affects episodic memory, a cognitive function that is impaired in older adults. According to the neurotrophic hypothesis, BDNF released during physical activity enhances brain plasticity and consequently brain health. However, even if the physical activity level is involved in the secretion of neurotrophin, this protein is also under the control of a specific gene. The aim of the present study was to examine the effect of the interaction between physical activity and BDNF Val66Met (rs6265), a genetic polymorphism, on episodic memory. Two hundred and five volunteers aged 55 and older with a Mini Mental State Examination score ≥ 24 participated in this study. Four groups of participants were established according to their physical activity level and polymorphism BDNF profile (Active Val homozygous, Inactive Val homozygous, Active Met carriers, Inactive Met carriers). Episodic memory was evaluated based on the delayed recall of the Logical Memory test of the MEM III battery. As expected, the physical activity level interacted with BDNF polymorphism to affect episodic memory performance (p physical activity and BDNF Val66Met polymorphism that affects episodic memory in the elderly and confirms that physical activity contributes to the neurotrophic mechanism implicated in cognitive health. The interaction shows that only participants with Val/Val polymorphism benefited from physical activity.

  10. Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with type 2 diabetes risk

    Science.gov (United States)

    Zhao, Luqian; Huang, Ping

    2013-01-01

    A number of studies were performed to assess the association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and susceptibility to type 2 diabetes (T2DM). However, the results were inconsistent and inconclusive. In the present study, the possible association was investigated by a meta-analysis. Eligible articles were identified for the period up to June 2013. Pooled odds ratios (OR) with 95% confidence intervals (CI) were appropriately derived from random-effects models or fixed-effects models. Fourteen case-control studies with a total of 2487 cases and 3538 controls were eligible. In recessive model, PAI-1 4G/5G polymorphism was associated with T2DM risk (OR = 1.23; 95% CI 1.07-1.41; P = 0.004). In the subgroup analysis by ethnicity, a significant association was found among Asians (OR = 1.27; 95% CI 1.08-1.51; P = 0.005). This meta-analysis suggested that PAI-1 4G/5G polymorphism may be associated with T2DM development. PMID:24040470

  11. Biologic activity of porphyromonas endodontalis complex lipids.

    Science.gov (United States)

    Mirucki, Christopher S; Abedi, Mehran; Jiang, Jin; Zhu, Qiang; Wang, Yu-Hsiung; Safavi, Kamran E; Clark, Robert B; Nichols, Frank C

    2014-09-01

    Periapical infections secondary to pulpal necrosis are associated with bacterial contamination of the pulp. Porphyromonas endodontalis, a gram-negative organism, is considered to be a pulpal pathogen. P. gingivalis is phylogenetically related to P. endodontalis and synthesizes several classes of novel complex lipids that possess biological activity, including the capacity to promote osteoclastogenesis and osteoclast activation. The purpose of this study was to extract and characterize constituent lipids of P. endodontalis and evaluate their capacity to promote proinflammatory secretory responses in the macrophage cell line, RAW 264.7, as well as their capacity to promote osteoclastogenesis and inhibit osteoblast activity. Constituent lipids of both organisms were fractionated by high-performance liquid chromatography and were structurally characterized using electrospray mass spectrometry or electrospray-mass spectrometry/mass spectrometry. The virulence potential of P. endodontalis lipids was then compared with known biologically active lipids isolated from P. gingivalis. P. endodontalis total lipids were shown to promote tumor necrosis factor alpha secretion from RAW 264.7 cells, and the serine lipid fraction appeared to account for the majority of this effect. P. endodontalis lipid preparations also increased osteoclast formation from RAW 264.7 cells, but osteoblast differentiation in culture was inhibited and appeared to be dependent on Toll-like receptor 2 expression. These effects underscore the importance of P. endodontalis lipids in promoting inflammatory and bone cell activation processes that could lead to periapical pathology. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  12. Association of serotonin transporter promoter regulatory region polymorphism and cerebral activity to visual presentation of food.

    Science.gov (United States)

    Kaurijoki, Salla; Kuikka, Jyrki T; Niskanen, Eini; Carlson, Synnöve; Pietiläinen, Kirsi H; Pesonen, Ullamari; Kaprio, Jaakko M; Rissanen, Aila; Tiihonen, Jari; Karhunen, Leila

    2008-07-01

    Recent functional magnetic resonance imaging (fMRI) studies have revealed links between genetic polymorphisms and cognitive and behavioural processes. Serotonin is a classical neurotransmitter of central nervous system, and it is connected to the control of appetite and satiety. In this study, the relationship between the functional variation in the serotonin transporter gene and the activity in the left posterior cingulate cortex (PCC), a brain area activated by visual food stimuli was explored. Thirty subjects underwent serial fMRI studies and provided DNA for genetic analyses. Subjects homozygous for the long allele exhibited greater left PCC activity in the comparison food > non-food compared with individuals heterozygous or homozygous for the short allele. The association between genotype and activation was linear, the subjects with two copies of the long allele variant having the strongest activation. These results demonstrate the possible genetically driven variation in the response of the left PCC to visual presentation of food in humans.

  13. Relationship between human paraoxonase-1 activity and PON1 polymorphisms in Mexican workers exposed to organophosphate pesticides.

    Science.gov (United States)

    López-Flores, I; Lacasaña, M; Blanco-Muñoz, J; Aguilar-Garduño, C; Sanchez-Villegas, P; Pérez-Méndez, O A; Gamboa-Avila, R

    2009-07-24

    Paraoxonase-1 (PON1) is a serum enzyme which catalyzes the hydrolysis of organophosphate pesticides. In this study we conducted a cross-sectional study and reported on the distribution of three common genetic polymorphisms of the PON1 gene in a population of floriculture workers from Mexico as well as the association between those polymorphisms and other predictors with serum PON1 activity on paraoxon, diazoxon and phenylacetate. The genotype frequencies at position PON1(55) were 89% (LL), 10% (LM) and 0.6% (MM), at position PON1(192) they were 16% (QQ), 47% (QR) and 37% (RR), and 26% (TT), 42% (TC) and 32% (CC) at position PON1(-108). Thus, the frequencies of alleles L, Q and T were 0.94, 0.40 and 0.47, respectively. The PON1(55) polymorphism had no significant effect on serum PON1 activity on any substrate. We found a significant association between the PON1(192) polymorphism and PON1 activity towards paraoxon and diazoxon, which increased in genotypes as follows: 192RR>192QR>192QQ for paraoxonase activity and, inversely, 192QQ>192QR>192RR for diazoxonase activity. The PON1(-108) polymorphism also had a significant effect on PON1 activity level towards paraoxon in the following order among the genotype groups: -108CC>-108TC>-108TT. Serum PON1 activity towards diazoxon was not associated with the PON1(-108) polymorphism but it was influenced by the intensity exposure to pesticides at the floriculture industry and the years of the occupational exposure to pesticides. No polymorphism significantly influenced serum PON1 activity on phenylacetate.

  14. Novel genetic polymorphisms that further delineate the phylogeny of the Mycobacterium tuberculosis complex.

    NARCIS (Netherlands)

    Huard, Richard C; Fabre, Michel; Haas, Petra de; Lazzarini, Luiz Claudio Oliveira; Soolingen, Dick van; Cousins, Debby; Ho, John L

    2006-01-01

    In a previous report, we described a PCR protocol for the differentiation of the various species of the Mycobacterium tuberculosis complex (MTC) on the basis of genomic deletions (R. C. Huard, L. C. de Oliveira Lazzarini, W. R. Butler, D. van Soolingen, and J. L. Ho, J. Clin. Microbiol.

  15. Size polymorphism of chicken major histocompatibility complex-encoded B-G molecules is due to length variation in the cytoplasmic heptad repeat region

    DEFF Research Database (Denmark)

    Kaufman, J; Salomonsen, J; Skjødt, K

    1990-01-01

    B-G antigens are cell-surface molecules encoded by a highly polymorphic multigene family located in the chicken major histocompatibility complex (MHC). Rabbit antisera to B-G molecules immunoprecipitate 3-6 bands from iodinated erythrocytes by sodium dodecyl sulfate (SDS) gels under reducing......, which bear intrachain disulfide bonds. All 3-6 bands have different mobilities in SDS gels between different haplotypes, ranging from 30 to 55 kDa. This size polymorphism is not affected by glycosidase treatment or addition of protease inhibitors. Partial proteolysis of cell surface-iodinated B...

  16. Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis.

    Science.gov (United States)

    Takemoto, Y; Sakatani, M; Takami, S; Tachibana, T; Higaki, J; Ogihara, T; Miki, T; Katsuya, T; Tsuchiyama, T; Yoshida, A; Yu, H; Tanio, Y; Ueda, E

    1998-06-01

    Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found. A study of the association of angiotensin II receptor gene polymorphisms with sarcoidosis was therefore undertaken. ACE (I/D), angiotensin II type 1 receptor (AGTR1), and angiotensin II type 2 receptor (AGTR2) gene polymorphisms were investigated by polymerase chain reaction (PCR) and SACE levels were measured in three groups of patients: those with sarcoidosis or tuberculosis and normal controls. There was no difference in allele frequency of AGTR1 and AGTR2 polymorphism among the three groups. Neither AGTR1 nor AGTR2 polymorphisms were associated with sarcoidosis. SACE activity was higher in patients with sarcoidosis with the AGTR1 A/C genotype than in others. However, this tendency was not detected in patients with tuberculosis. The AGTR1 allele C is associated with high activity of SACE in patients with sarcoidosis. It is another predisposing factor for high levels of SACE in patients with sarcoidosis and is considered to be an independent factor from the ACE D allele for high levels of SACE in sarcoidosis. This fact could be one of the explanations for the increased SACE activity in sarcoidosis.

  17. Differentiation in a geographical mosaic of plants coevolving with ants: phylogeny of the Leonardoxa africana complex (Fabaceae: Caesalpinioideae) using amplified fragment length polymorphism markers.

    Science.gov (United States)

    Brouat, C; McKey, D; Douzery, E J P

    2004-05-01

    Comprising four allopatric subspecies that exhibit various grades of ant-plant interactions, from diffuse to obligate and symbiotic associations, the Leonardoxa africana complex (Fabaceae, Caesalpinioideae) provides a good opportunity to investigate the evolutionary history of ant-plant mutualisms. A previous study of the L. africana complex based on chloroplast DNA noncoding sequences revealed a lack of congruence between clades suggested by morphological and plastid characters. In this study, we analysed phylogenetic relationships within the L. africana complex using a Bayesian probability approach on amplified fragment length polymorphism markers. The results reported permit partial validation of the four subspecies of L. africana previously defined by morphological and ecological markers. Incongruences between phylogenies based on chloroplast DNA and amplified fragment length polymorphism markers are discussed in the light of morphological and ecological data, and confronted with hypotheses of convergence, lineage sorting and introgression.

  18. A functional polymorphism in the prodynorphin gene affects cognitive flexibility and brain activation during reversal learning.

    Directory of Open Access Journals (Sweden)

    Mikhail eVotinov

    2015-07-01

    Full Text Available Whether the opioid system plays a role in the ability to flexibly adapt behavior is still unclear. We used fMRI to investigate the effect of a nucleotide tandem repeat (68-bp VNTR functional polymorphism of the prodynorphin gene on cerebral activation during a reversal learning task in which participants had to flexibly adapt stimulus-response associations. Past studies suggested that alleles with 3 or 4 repeats (HH genotype of this polymorphism are associated with higher levels of dynorphin peptides than alleles with 1 or 2 repeats (LL genotype. On the behavioral level, the HH group made more perseverative errors than the LL group. On the neural level, the HH group demonstrated less engagement of left orbitofrontal cortex (lOFC and cortico-striatal circuitry, and lower effective connectivity of lOFC with anterior midcingulate cortex and anterior insula/ventrolateral prefrontal cortex during reversal learning and processing negative feedback. This points to a lower ability of the HH genotype to monitor or adapt to changes in reward contingencies. These findings provide first evidence that dynorphins may contribute to individual differences in reversal learning, and that considering the opioid system may shed new light on the neurochemical correlates of decision-making and behavioral regulation.

  19. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    Science.gov (United States)

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  20. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudio Pulito

    Full Text Available Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR. It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954 human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative. These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.

  1. Computational Modeling of Complex Protein Activity Networks

    NARCIS (Netherlands)

    Schivo, Stefano; Leijten, Jeroen; Karperien, Marcel; Post, Janine N.; Prignet, Claude

    2017-01-01

    Because of the numerous entities interacting, the complexity of the networks that regulate cell fate makes it impossible to analyze and understand them using the human brain alone. Computational modeling is a powerful method to unravel complex systems. We recently described the development of a

  2. Sex determines the influence of smoking and gene polymorphism on glutathione peroxidase activity in erythrocytes

    DEFF Research Database (Denmark)

    Malling, Tine Halsen; Sigsgaard, Torben; Andersen, Helle Raun

    2009-01-01

    OBJECTIVE: Glutathione peroxidase 1 (GPX1) is one of the major oxidative enzymes. Our aim was to characterize factors influencing its activity and to determine whether or not the activity is associated with asthma. MATERIAL AND METHODS: Serum selenium concentration was measured, GPX1 polymorphisms...... %) had doctor-diagnosed asthma. RESULTS: The average serum selenium concentration was too low for optimal enzyme activity (mean (SE), 83.4 (0.76) ng/mL). GPX1 activity in men was lower than in women, 52.6 (0.66) and 56.4 (0.59) U/g protein, respectively (p... associated with serum selenium concentration (p = 0.005) and negatively associated with both active smoking (p = 0.009) and exposure to environmental tobacco smoke (p = 0.02). In women, activity was associated with genotypes with 59.2 (1.4), 56.0 (1.4) and 54.2 (1.4) U/g protein in the homozygote wild...

  3. Genome-wide macrosynteny among Fusarium species in the Gibberella fujikuroi complex revealed by amplified fragment length polymorphisms.

    Directory of Open Access Journals (Sweden)

    Lieschen De Vos

    Full Text Available The Gibberella fujikuroi complex includes many Fusarium species that cause significant losses in yield and quality of agricultural and forestry crops. Due to their economic importance, whole-genome sequence information has rapidly become available for species including Fusarium circinatum, Fusarium fujikuroi and Fusarium verticillioides, each of which represent one of the three main clades known in this complex. However, no previous studies have explored the genomic commonalities and differences among these fungi. In this study, a previously completed genetic linkage map for an interspecific cross between Fusarium temperatum and F. circinatum, together with genomic sequence data, was utilized to consider the level of synteny between the three Fusarium genomes. Regions that are homologous amongst the Fusarium genomes examined were identified using in silico and pyrosequenced amplified fragment length polymorphism (AFLP fragment analyses. Homology was determined using BLAST analysis of the sequences, with 777 homologous regions aligned to F. fujikuroi and F. verticillioides. This also made it possible to assign the linkage groups from the interspecific cross to their corresponding chromosomes in F. verticillioides and F. fujikuroi, as well as to assign two previously unmapped supercontigs of F. verticillioides to probable chromosomal locations. We further found evidence of a reciprocal translocation between the distal ends of chromosome 8 and 11, which apparently originated before the divergence of F. circinatum and F. temperatum. Overall, a remarkable level of macrosynteny was observed among the three Fusarium genomes, when comparing AFLP fragments. This study not only demonstrates how in silico AFLPs can aid in the integration of a genetic linkage map to the physical genome, but it also highlights the benefits of using this tool to study genomic synteny and architecture.

  4. Diversity of equine major histocompatiblity complex class II DRA locus in Posavina and Croatian Coldblood horse: a new polymorphism detected

    Directory of Open Access Journals (Sweden)

    Ino Curik

    2010-01-01

    Full Text Available Domestic equidae display polymorphism within ELA-DRA locus which is not characteristic for other species. We characterised sequence polymorphism present at ELADRA locus exon 2 and estimated allele frequencies in two autochthonous breeds, Posavina and Croatian Coldblood. In 88 horses, four different alleles were found, one of them not reported before in horses. The new allele shows non-synonymous mutation at position 65 (T→A causing amino acid change (Phe→Tyr in antigen binding site and synonymous mutation at position 105 (C→T. Our findings emphasize the importance of DRA polymorphism among equids and some specific DRA frequency pattern potentially specific in draught horses.

  5. Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

    Directory of Open Access Journals (Sweden)

    Abhijeet Kapoor

    Full Text Available Human dopamine β-hydroxylase (DBH is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering.Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function.The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and

  6. Structural insight of dopamine β-hydroxylase, a drug target for complex traits, and functional significance of exonic single nucleotide polymorphisms.

    Science.gov (United States)

    Kapoor, Abhijeet; Shandilya, Manish; Kundu, Suman

    2011-01-01

    Human dopamine β-hydroxylase (DBH) is an important therapeutic target for complex traits. Several single nucleotide polymorphisms (SNPs) have also been identified in DBH with potential adverse physiological effect. However, difficulty in obtaining diffractable crystals and lack of a suitable template for modeling the protein has ensured that neither crystallographic three-dimensional structure nor computational model for the enzyme is available to aid rational drug design, prediction of functional significance of SNPs or analytical protein engineering. Adequate biochemical information regarding human DBH, structural coordinates for peptidylglycine alpha-hydroxylating monooxygenase and computational data from a partial model of rat DBH were used along with logical manual intervention in a novel way to build an in silico model of human DBH. The model provides structural insight into the active site, metal coordination, subunit interface, substrate recognition and inhibitor binding. It reveals that DOMON domain potentially promotes tetramerization, while substrate dopamine and a potential therapeutic inhibitor nepicastat are stabilized in the active site through multiple hydrogen bonding. Functional significance of several exonic SNPs could be described from a structural analysis of the model. The model confirms that SNP resulting in Ala318Ser or Leu317Pro mutation may not influence enzyme activity, while Gly482Arg might actually do so being in the proximity of the active site. Arg549Cys may cause abnormal oligomerization through non-native disulfide bond formation. Other SNPs like Glu181, Glu250, Lys239 and Asp290 could potentially inhibit tetramerization thus affecting function. The first three-dimensional model of full-length human DBH protein was obtained in a novel manner with a set of experimental data as guideline for consistency of in silico prediction. Preliminary physicochemical tests validated the model. The model confirms, rationalizes and provides

  7. Plasminogen activator inhibitor-1 -675 4G/5G polymorphism and polycystic ovary syndrome risk: a meta analysis.

    Science.gov (United States)

    Liu, Ying; Sun, Mei-Guo; Jiang, Rong; Ding, Rui; Che, Zhen; Chen, Yan-Yan; Yao, Ci-Jiang; Zhu, Xiao-Xia; Cao, Ji-Yu

    2014-03-01

    Several studies have reported that excessive amounts of plasminogen activator inhibitor-1(PAI-1) might increase the incidence of polycystic ovary syndrome(PCOS), but so far the published results were inconsistent. The aim of this study was to further investigate the association between PAI-1 gene polymorphism and the susceptibility to PCOS by performing a meta-analysis. A comprehensive literature search for relevant studies was conducted on google scholar, PubMed, the Chinese National Knowledge Infrastructure (CNKI) and the Chinese Biomedical Literature Database (CBM). This meta-analysis was performed using the STATA 11.0 software and the pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Ten case-control studies were included in this meta-analysis with a total of 2,079 cases and 1,556 controls. The results showed that PAI-1 -675 4G/5G polymorphism may increase the risk of PCOS, especially among Asian populations. However, there was no statistically significant association between the polymorphism and PCOS risk in Caucasians. Our meta-analysis suggests that PAI-1 -675 4G/5G polymorphism may contribute to increasing susceptibility to PCOS in Asians. Detection of the PAI-1 gene polymorphism might be a promising biomarker for the susceptibility of PCOS.

  8. Meta-analysis of the association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss.

    Science.gov (United States)

    Li, Xuejiao; Liu, Yukun; Zhang, Rui; Tan, Jianping; Chen, Libin; Liu, Yinglin

    2015-04-11

    The association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and recurrent pregnancy loss (RPL) risk is still contradictory. We thus performed a meta-analysis. Relevant studies were searched for in PubMed, Web of Science, Embase, and Cochrane Library. An odds ratio (OR) with a 95% confidence interval (CI) was used to assess the association between PAI-1 4G/5G polymorphism and RPL risk. A total of 22 studies with 4306 cases and 3076 controls were included in this meta-analysis. We found that PAI-1 4G/5G polymorphism was significantly associated with an increased RPL risk (OR=1.89; 95% CI 1.34-2.67; P=0.0003). In the subgroup analysis by race, PAI-1 4G/5G polymorphism was significantly associated with an increased RPL risk in Caucasians (OR=2.23; 95% CI 1.44-3.46; P=0.0003). However, no significant association was observed in Asians (OR=1.47; 95% CI 0.84-2.59; P=0.18). In conclusion, this meta-analysis suggests that PAI-1 4G/5G polymorphism might be associated with RPL development in Caucasians.

  9. Transcriptionally active LTR retrotransposons in Eucalyptus genus are differentially expressed and insertionally polymorphic.

    Science.gov (United States)

    Marcon, Helena Sanches; Domingues, Douglas Silva; Silva, Juliana Costa; Borges, Rafael Junqueira; Matioli, Fábio Filippi; Fontes, Marcos Roberto de Mattos; Marino, Celso Luis

    2015-08-14

    In Eucalyptus genus, studies on genome composition and transposable elements (TEs) are particularly scarce. Nearly half of the recently released Eucalyptus grandis genome is composed by retrotransposons and this data provides an important opportunity to understand TE dynamics in Eucalyptus genome and transcriptome. We characterized nine families of transcriptionally active LTR retrotransposons from Copia and Gypsy superfamilies in Eucalyptus grandis genome and we depicted genomic distribution and copy number in two Eucalyptus species. We also evaluated genomic polymorphism and transcriptional profile in three organs of five Eucalyptus species. We observed contrasting genomic and transcriptional behavior in the same family among different species. RLC_egMax_1 was the most prevalent family and RLC_egAngela_1 was the family with the lowest copy number. Most families of both superfamilies have their insertions occurring Eucalyptus species. Using EST analysis and qRT-PCRs, we observed transcriptional activity in several tissues and in all evaluated species. In some families, osmotic stress increases transcript values. Our strategy was successful in isolating transcriptionally active retrotransposons in Eucalyptus, and each family has a particular genomic and transcriptional pattern. Overall, our results show that retrotransposon activity have differentially affected genome and transcriptome among Eucalyptus species.

  10. Polymorph characterization of active pharmaceutical ingredients (APIs) using low-frequency Raman spectroscopy.

    Science.gov (United States)

    Larkin, Peter J; Dabros, Marta; Sarsfield, Beth; Chan, Eric; Carriere, James T; Smith, Brian C

    2014-01-01

    Polymorph detection, identification, and quantitation in crystalline materials are of great importance to the pharmaceutical industry. Vibrational spectroscopic techniques used for this purpose include Fourier transform mid-infrared (FT-MIR) spectroscopy, Fourier transform near-infrared (FT-NIR) spectroscopy, Raman spectroscopy, and terahertz (THz) and far-infrared (FIR) spectroscopy. Typically, the fundamental molecular vibrations accessed using high-frequency Raman and MIR spectroscopy or the overtone and combination of bands in the NIR spectra are used to monitor the solid-state forms of active pharmaceutical ingredients (APIs). The local environmental sensitivity of the fundamental molecular vibrations provides an indirect probe of the long-range order in molecular crystals. However, low-frequency vibrational spectroscopy provides access to the lattice vibrations of molecular crystals and, hence, has the potential to more directly probe intermolecular interactions in the solid state. Recent advances in filter technology enable high-quality, low-frequency Raman spectra to be acquired using a single-stage spectrograph. This innovation enables the cost-effective collection of high-quality Raman spectra in the 200-10 cm(-1) region. In this study, we demonstrate the potential of low-frequency Raman spectroscopy for the polymorphic characterization of APIs. This approach provides several benefits over existing techniques, including ease of sampling and more intense, information-rich band structures that can potentially discriminate among crystalline forms. An improved understanding of the relationship between the crystalline structure and the low-frequency vibrational spectrum is needed for the more widespread use of the technique.

  11. Correlations among obesity-associated gene polymorphisms, body composition, and physical activity in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Sanae Saitoh

    2015-01-01

    Full Text Available Context: Various studies have focused on the correlation between β2-adrenergic receptor (β2AR, the β3-adrenergic receptor (β3AR, and the uncoupling protein 1 (UCP1 polymorphisms and obesity in patients with type 2 diabetes mellitus (T2DM. Aims: We examined the correlation between these polymorphisms and body composition variables and between body composition and lifestyle variables in Japanese T2DM patients. Materials and Methods: Of the 48, T2DM outpatients in Kanagawa prefecture recruited for participation, 32 (6 men and 26 women met the study criteria and were enrolled. Obesity-related gene polymorphisms were identified in 3 genes β3AR, UCP1, and β2AR using the SMart amplification process. Body composition variables were measured using a body composition analyzer. Data regarding food and nutrient consumption, family history, and lifestyle factors were collected via administration of questionnaires. Results: Because significant differences in body composition variables were found between men and women, statistical analysis was performed with data from the 25 female subjects only. On the basis of results of genetic testing, the subjects were divided into genotype groups for two-group and three-group comparison. The β3AR, UCP1, and β2AR polymorphisms and body composition significantly correlated with the percentage of subcutaneous fat in both arms as compared with the wild type or hetero groups with β3AR polymorphisms. However, physical activity correlated with several body composition variables. Conclusions: These results suggest that obesity in T2DM patients is not the result of presence of an obesity-related gene polymorphism but rather the absence of daily physical activity.

  12. Gene Network Polymorphism Illuminates Loss and Retention of Novel RNAi Silencing Components in the Cryptococcus Pathogenic Species Complex.

    Directory of Open Access Journals (Sweden)

    Marianna Feretzaki

    2016-03-01

    Full Text Available RNAi is a ubiquitous pathway that serves central functions throughout eukaryotes, including maintenance of genome stability and repression of transposon expression and movement. However, a number of organisms have lost their RNAi pathways, including the model yeast Saccharomyces cerevisiae, the maize pathogen Ustilago maydis, the human pathogen Cryptococcus deuterogattii, and some human parasite pathogens, suggesting there may be adaptive benefits associated with both retention and loss of RNAi. By comparing the RNAi-deficient genome of the Pacific Northwest Outbreak C. deuterogattii strain R265 with the RNAi-proficient genomes of the Cryptococcus pathogenic species complex, we identified a set of conserved genes that were lost in R265 and all other C. deuterogattii isolates examined. Genetic and molecular analyses reveal several of these lost genes play roles in RNAi pathways. Four novel components were examined further. Znf3 (a zinc finger protein and Qip1 (a homolog of N. crassa Qip were found to be essential for RNAi, while Cpr2 (a constitutive pheromone receptor and Fzc28 (a transcription factor are involved in sex-induced but not mitosis-induced silencing. Our results demonstrate that the mitotic and sex-induced RNAi pathways rely on the same core components, but sex-induced silencing may be a more specific, highly induced variant that involves additional specialized or regulatory components. Our studies further illustrate how gene network polymorphisms involving known components of key cellular pathways can inform identification of novel elements and suggest that RNAi loss may have been a core event in the speciation of C. deuterogattii and possibly contributed to its pathogenic trajectory.

  13. Selection, trans-species polymorphism, and locus identification of major histocompatibility complex class IIβ alleles of New World ranid frogs

    Science.gov (United States)

    Kiemnec-Tyburczy, Karen M.; Richmond, Jonathan Q.; Savage, Anna E.; Zamudio, Kelly R.

    2010-01-01

    Genes encoded by the major histocompatibility complex (MHC) play key roles in the vertebrate immune system. However, our understanding of the evolutionary processes and underlying genetic mechanisms shaping these genes is limited in many taxa, including amphibians, a group currently impacted by emerging infectious diseases. To further elucidate the evolution of the MHC in frogs (anurans) and develop tools for population genetics, we surveyed allelic diversity of the MHC class II ??1 domain in both genomic and complementary DNA of seven New World species in the genus Rana (Lithobates). To assign locus affiliation to our alleles, we used a "gene walking" technique to obtain intron 2 sequences that flanked MHC class II?? exon 2. Two distinct intron sequences were recovered, suggesting the presence of at least two class II?? loci in Rana. We designed a primer pair that successfully amplified an orthologous locus from all seven Rana species. In total, we recovered 13 alleles and documented trans-species polymorphism for four of the alleles. We also found quantitative evidence of selection acting on amino acid residues that are putatively involved in peptide binding and structural stability of the ??1 domain of anurans. Our results indicated that primer mismatch can result in polymerase chain reaction (PCR) bias, which influences the number of alleles that are recovered. Using a single locus may minimize PCR bias caused by primer mismatch, and the gene walking technique was an effective approach for generating single-copy orthologous markers necessary for future studies of MHC allelic variation in natural amphibian populations. ?? 2010 Springer-Verlag.

  14. Mathematical analysis of complex cellular activity

    CERN Document Server

    Bertram, Richard; Teka, Wondimu; Vo, Theodore; Wechselberger, Martin; Kirk, Vivien; Sneyd, James

    2015-01-01

    This book contains two review articles on mathematical physiology that deal with closely related topics but were written and can be read independently. The first article reviews the basic theory of calcium oscillations (common to almost all cell types), including spatio-temporal behaviors such as waves. The second article uses, and expands on, much of this basic theory to show how the interaction of cytosolic calcium oscillators with membrane ion channels can result in highly complex patterns of electrical spiking. Through these examples one can see clearly how multiple oscillatory processes interact within a cell, and how mathematical methods can be used to understand such interactions better. The two reviews provide excellent examples of how mathematics and physiology can learn from each other, and work jointly towards a better understanding of complex cellular processes. Review 1: Richard Bertram, Joel Tabak, Wondimu Teka, Theodore Vo, Martin Wechselberger: Geometric Singular Perturbation Analysis of Burst...

  15. Association of plasminogen activator inhibitor-1 and angiotensin converting enzyme polymorphisms with recurrent pregnancy loss in Iranian women

    Directory of Open Access Journals (Sweden)

    Fatemeh Shakarami

    2015-10-01

    Full Text Available Background: Recurrent pregnancy loss (RPL defined by two or more failed pregnancies before 20 weeks of gestation. Several factors play a role in RPL including thrombophilic conditions which can be influenced by gene polymorphisms. Plasminogen activator inhibitor-1 (PAI-1 and angiotensin converting enzyme (ACE genes are closely related to fibrinolytic process, embryonic development and pregnancy success. Objective: The aim of this study was to investigate the relationship between RPL and common polymorphisms in ACE and PAI-1 genes. Materials and Methods: In this case control study, 100 women with recurrent abortions (at least two were selected as cases and 100 healthy women with two or more normal term deliveries without a history of abortion as controls. Total genomic DNA was isolated from blood leukocytes. The status of the PAI-1 4G/5G and ACE (D/I polymorphism was determined by PCR-RFLP. Results: Homozygosity for PAI-1 4G polymorphism was seen in 17 cases (17%, and 5 controls (5% (p=0.006 so patients with homozygote 4G mutation were significantly more prone to RPL in contrast to control group (OR: 4.63, % 95 CI: 1.55-13.84. In addition, 7 patients (7 %, and no one from the control group, were homozygote (I/I for ACE polymorphism (p=0.034, suggesting no significant associations between ACE D allele or DD genotype and RPL. Conclusion: Considering these results, because 4G/4G polymorphism for PAI-1 gene could be a thrombophilic variant leading to abortion, analysis of this mutation and other susceptibility factors are recommended in patients with RPL.

  16. Clinicopathological significance of plasminogen activator inhibitor-1 promoter 4G/5G polymorphism in breast cancer: a meta-analysis.

    Science.gov (United States)

    Lee, Ju-Han; Kim, Younghye; Choi, Jung-Woo; Kim, Young-Sik

    2013-01-01

    Plasminogen activator inhibitor type 1 (PAI-1) is associated with poor prognosis in breast cancer. Transcriptional expression of the PAI-1 can be controlled by PAI-1 promoter 4G/5G polymorphism. However, the significance of PAI-1 promoter 4G/5G polymorphism in breast cancer patients is contentious. To address this controversy, we conducted a meta-analysis for the relationships between PAI-1 promoter polymorphism and clinicopathological characteristics of breast cancer. Relevant published studies were identified using a search of PubMed, Embase, and the ISI Web of Science. The effect sizes of PAI-1 promoter 4G/5G polymorphism on breast cancer risk, lymph node metastasis, histologic grade, and overall survival were calculated by odds ratio (OR) or hazard ratio. The effect sizes were combined using a random-effects model. Individuals with 4G/4G genotype had a higher risk of breast cancer than those with the combined 4G/5G and 5G/5G genotypes (OR = 1.388; p = 0.031). Breast cancer patients with the 5G/5G genotype displayed lymph node metastasis more than patients with either the combined other genotypes (OR = 1.495; p = 0.027) or with the 4G/4G genotype (OR = 1.623; p = 0.018). However, the PAI-1 promoter 4G/5G polymorphism was not associated with histological grade or overall survival. PAI-1 promoter 4G/5G polymorphism is associated with a relatively increased risk of breast cancer development and lymph node metastasis. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  17. Global fibrinolytic activity, PAI-1 level, and 4G/5G polymorphism in Thai children with arterial ischemic stroke.

    Science.gov (United States)

    Natesirinilkul, Rungrote; Sasanakul, Werasak; Chuansumrit, Ampaiwan; Kadegasem, Praguywan; Visudtibhan, Anannit; Wongwerawattanakoon, Pakawan; Sirachainan, Nongnuch

    2014-01-01

    Prolonged euglobulin clot lysis time (ECLT) and increased level of plasminogen activator inhibitor-1 (PAI-1) were reported to be risk factors of arterial ischemic stroke (AIS) by some studies; however, these findings were not supported by other studies. The objective of this study was to determine the association of ECLT, PAI-1 level, and polymorphisms of 4G and 5G of PAI-1 gene to the development of AIS in Thai children. This study included patients aged 1-18 years old. Diagnosis of AIS was confirmed by imaging study. The control group was age- and sex-matched healthy subjects. Demographic data were recorded, and blood was tested for ECLT, PAI-1 level, lipid profiles, fasting blood sugar (FBS), and 4G and 5G polymorphisms of PAI-1 gene. There were 70 subjects participating in this study, consisting of 30 patients and 40 controls. Demographic data, lipid profiles, and FBS were similar between the 2 groups. Furthermore, ECLT and PAI-1 level did not differ between patient and control groups; however, both showed significant correlation (r = .352, P = .006). The 4G/5G polymorphism was the most common genotype in both patient and control groups (69.0% vs. 80.0%). However, 4G and 5G polymorphisms of PAI-1 gene did not correlate with PAI-1 level in this study (P = .797). The PAI-1 level and 4G/5G polymorphism may not be a risk factor of AIS in this population. It was also found that the 4G/5G polymorphism was the most common PAI-1 genotype in this study. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  18. Signal transducer and activator of transcription 4 gene polymorphisms associated with rheumatoid arthritis in Northwestern Chinese Han population.

    Science.gov (United States)

    Liang, Ya-Ling; Wu, Hua; Li, Pei-Qiang; Xie, Xiao-Dong; Shen, Xi; Yang, Xiao-Qing; Cheng, Xuan; Liang, Li

    2011-08-01

    Signal transducer and activator of transcription 4 (STAT4) gene encode a transcriptional factor that transmits signals induced by several key cytokines which play important roles in the development of autoimmune diseases. Recently, several single nucleotide polymorphisms (SNPs) in STAT4 gene have been reported to be significantly associated with Rheumatoid arthritis (RA) in different ethnic populations. We undertook this study to investigate whether the association of STAT4 genetic polymorphisms with RA is present in Northwestern Chinese Han population. A case-control association study in individuals with RA (n=208) and healthy controls (n=312) was conducted. Four SNPs (rs7574865, rs8179673, rs10181656, rs11889341) in STAT4 gene were genotyped by using polymerase chain reaction followed by denaturing high-performance liquid chromatography (PCR-DHPLC) and DNA sequencing. The genotype and allele distributions of four polymorphisms were significantly different in individuals with RA compared to controls, with SNP rs7574865 T allele and T/T genotype showing the most significant association with susceptibility to RA (uncorrected P=1×10(-4), OR=1.645, 95% CI=1.272-2.129; uncorrected P=4.8×10(-5), OR=3.111, 95% CI=1.777-5.447, respectively). Stratification studies showed that STAT4 gene polymorphisms were significantly associated with anti-cyclic citrullinated peptide (anti-CCP) positive subgroup in Northwestern Chinese Han population. These findings strongly suggest that STAT4 genetic polymorphisms are associated with RA in Northwestern Chinese Han population, and support the hypothesis of STAT4 gene polymorphisms increasing the risk for RA across major populations. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Monoamine oxidase A gene polymorphisms and enzyme activity associated with risk of gout in Taiwan aborigines.

    Science.gov (United States)

    Tu, Hung-Pin; Ko, Albert Min-Shan; Wang, Shu-Jung; Lee, Chien-Hung; Lea, Rod A; Chiang, Shang-Lun; Chiang, Hung-Che; Wang, Tsu-Nai; Huang, Meng-Chuan; Ou, Tsan-Teng; Lin, Gau-Tyan; Ko, Ying-Chin

    2010-02-01

    Taiwanese aborigines have a high prevalence of hyperuricemia and gout. Uric acid levels and urate excretion have correlated with dopamine-induced glomerular filtration response. MAOs represent one of the major renal dopamine metabolic pathways. We aimed to identify the monoamine oxidase A (MAOA, Xp11.3) gene variants and MAO-A enzyme activity associated with gout risk. This study was to investigate the association between gout and the MAOA single-nucleotide polymorphisms (SNPs) rs5953210, rs2283725, and rs1137070 as well as between gout and the COMT SNPs rs4680 Val158Met for 374 gout cases and 604 controls. MAO-A activity was also measured. All three MAOA SNPs were significantly associated with gout. A synonymous MAOA SNP, rs1137070 Asp470Asp, located in exon 14, was associated with the risk of having gout (P = 4.0 x 10(-5), adjusted odds ratio 1.46, 95% confidence intervals [CI]: 1.11-1.91). We also showed that, when compared to individuals with the MAOA GAT haplotype, carriers of the AGC haplotype had a 1.67-fold (95% CI: 1.28-2.17) higher risk of gout. Moreover, we found that MAOA enzyme activity correlated positively with hyperuricemia and gout (P for trend = 2.00 x 10(-3) vs. normal control). We also found that MAOA enzyme activity by rs1137070 allele was associated with hyperuricemia and gout (P for trend = 1.53 x 10(-6) vs. wild-type allele). Thus, our results show that some MAOA alleles, which have a higher enzyme activity, predispose to the development of gout.

  20. The evolution of colour polymorphism in British winter-active Lepidoptera in response to search image use by avian predators.

    Science.gov (United States)

    Weir, Jamie Conor

    2018-05-10

    Phenotypic polymorphism in cryptic species is widespread. This may evolve in response to search image use by predators exerting negative frequency-dependent selection on intraspecific colour morphs, "apostatic selection". Evidence exists to indicate search image formation by predators and apostatic selection operating on wild prey populations, though not to demonstrate search image use directly resulting in apostatic selection. The present study attempted to address this deficiency, using British Lepidoptera active in winter as a model system. It has been proposed that the typically polymorphic wing colouration of these species represents an anti-search image adaptation against birds. To test (a) for search image driven apostatic selection, dimorphic populations of artificial moth-like models were established in woodland at varying relative morph frequencies and exposed to predation by natural populations of birds. In addition, to test (b) whether abundance and degree of polymorphism are correlated across British winter-active moths, as predicted where search image use drives apostatic selection, a series of phylogenetic comparative analyses were conducted. There was a positive relationship between artificial morph frequency and probability of predation, consistent with birds utilising search images and exerting apostatic selection. Abundance and degree of polymorphism were found to be positively correlated across British Lepidoptera active in winter, though not across all taxonomic groups analysed. This evidence is consistent with polymorphism in this group having evolved in response to search image driven apostatic selection and supports the viability of this mechanism as a means by which phenotypic and genetic variation may be maintained in natural populations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

    DEFF Research Database (Denmark)

    Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen

    2012-01-01

    A gene-drug interaction has been indicated between beta-1 selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). We studied the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR) and the genotype...

  2. First functional polymorphism in CFTR promoter that results in decreased transcriptional activity and Sp1/USF binding

    International Nuclear Information System (INIS)

    Taulan, M.; Lopez, E.; Guittard, C.; Rene, C.; Baux, D.; Altieri, J.P.; DesGeorges, M.; Claustres, M.; Romey, M.C.

    2007-01-01

    Growing evidences show that functionally relevant polymorphisms in various promoters alter both transcriptional activity and affinities of existing protein-DNA interactions, and thus influence disease progression in humans. We previously reported the -94G>T CFTR promoter variant in a female CF patient in whom any known disease-causing mutation has been detected. To investigate whether the -94G>T could be a regulatory variant, we have proceeded to in silico analyses and functional studies including EMSA and reporter gene assays. Our data indicate that the promoter variant decreases basal CFTR transcriptional activity in different epithelial cells and alters binding affinities of both Sp1 and USF nuclear proteins to the CFTR promoter. The present report provides evidence for the first functional polymorphism that negatively affects the CFTR transcriptional activity and demonstrates a cooperative role of Sp1 and USF transcription factors in transactivation of the CFTR gene promoter

  3. Influence of the 5-HT3A Receptor Gene Polymorphism and Childhood Sexual Trauma on Central Serotonin Activity.

    Directory of Open Access Journals (Sweden)

    Kuk-In Jang

    Full Text Available Gene-environment interactions are important for understanding alterations in human brain function. The loudness dependence of auditory evoked potential (LDAEP is known to reflect central serotonergic activity. Single nucleotide polymorphisms (SNPs in the 5-HT3A serotonin receptor gene are associated with psychiatric disorders. This study aimed to investigate the effect between 5-HT3A receptor gene polymorphisms and childhood sexual trauma on the LDAEP as an electrophysiological marker in healthy subjects.A total of 206 healthy subjects were recruited and evaluated using the childhood trauma questionnaire (CTQ and hospital anxiety and depression scale (HADS. Peak-to-peak N1/P2 was measured at five stimulus intensities, and the LDAEP was calculated as the linear-regression slope. In addition, the rs1062613 SNPs of 5-HT3A (CC, CT, and TT were analyzed in healthy subjects.There was a significant interaction between scores on the CTQ-sexual abuse subscale and 5-HT3A genotype on the LDAEP. Subjects with the CC polymorphism had a significantly higher LDEAP than T carriers in the sexually abused group. In addition, CC genotype subjects in the sexually abused group showed a significantly higher LDAEP compared with CC genotype subjects in the non-sexually abused group.Our findings suggest that people with the CC polymorphism of the 5-HT3A gene have a greater risk of developing mental health problems if they have experienced childhood sexual abuse, possibly due to low central serotonin activity. Conversely, the T polymorphism may be protective against any central serotonergic changes following childhood sexual trauma.

  4. Association of IRF5 polymorphisms with susceptibility to macrophage activation syndrome in patients with juvenile idiopathic arthritis.

    Science.gov (United States)

    Yanagimachi, Masakatsu; Naruto, Takuya; Miyamae, Takako; Hara, Takuma; Kikuchi, Masako; Hara, Ryoki; Imagawa, Tomoyuki; Mori, Masaaki; Sato, Hidenori; Goto, Hiroaki; Yokota, Shumpei

    2011-04-01

    Systemic-onset juvenile idiopathic arthritis (systemic JIA) and macrophage activation syndrome (MAS), the most devastating complication of systemic JIA, are characterized by abnormal levels of proinflammatory cytokines. Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, and acts as a master transcription factor in the activation of genes encoding proinflammatory cytokines. Polymorphisms in the IRF5 gene have been associated with susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Our aim was to assess associations of IRF5 gene polymorphisms with susceptibility to systemic JIA and MAS. Three IRF5 single-nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were genotyped using TaqMan assays in 81 patients with systemic JIA (33 with MAS, 48 without) and 190 controls. There were no associations of the IRF5 gene polymorphisms or haplotypes under study with susceptibility to systemic JIA. There was a significant association of the rs2004640 T allele with MAS susceptibility (OR 4.11; 95% CI 1.84, 9.16; p = 0.001). The IRF5 haplotype (rs729302 A, rs2004640 T, and rs2280714 T), which was reported as conferring an increased risk of SLE, was significantly associated with MAS susceptibility in patients with systemic JIA (OR 4.61; 95% CI 1.73, 12.3; p < 0.001). IRF5 gene polymorphism is a genetic factor influencing susceptibility to MAS in patients with systemic JIA, and IRF5 contributes to the pathogenesis of MAS in these patients.

  5. [Association of polymorphisms in signal transducer and activator of transcription 4 gene and the susceptibility to unexplained recurrent spontaneous abortions].

    Science.gov (United States)

    Li, Yin-Guang; You, Ze-Shan; Wu, Zai-Gui; Li, Zhu-Yu; Li, Jie; Zhang, Xiu-Ming; Fang, Li-Yuan; Jiang, Li

    2013-09-01

    To investigate the association between the polymorphisms of signal transducer and activator of transcription 4 (STAT4) gene and the susceptibility to unexplained recurrent spontaneous abortion(URSA). PCR-restriction fragment length polymorphism (PCR-RFLP) was used to detect genotype 3 loca (rs7574865 G/T, rs10181656 C/G and rs16833431 C/T) polymorphism of STAT4 in 246 URSA cases (URSA group) and 183 normal controls (control group) . (1)The frequencies of rs7574865 were genotype G/G of 36.2% (89/246) in URSA group and 46.4% (85/183) in control group, genotype G/T of 47.2% (116/246) in URSA group and 45.4% (83/183) in control group, and genotype T/T of 16.7% (41/246) in URSA group and 8.2% (15/183) in control group, which reached statistical difference (P rs7574865 T allele and rs10181656 G allele increased the risk of URSA (OR = 1.51, 1.44, all P rs7574865 G/T and rs10181656 C/G showed haplotype G-T conferring the susceptibility to URSA (OR = 1.49, P < 0.01), but haplotype C-G could provide protection on URSA (OR = 0.68, P < 0.01). Polymorphisms of STAT4 gene might confer the susceptibility to URSA by altering STAT4 function and (or) its expression.

  6. The Plasminogen Activator Inhibitor 1 4G/5G Polymorphism and the Risk of Alzheimer's Disease.

    Science.gov (United States)

    Fekih-Mrissa, Najiba; Mansour, Malek; Sayeh, Aicha; Bedoui, Ines; Mrad, Meriem; Riahi, Anis; Mrissa, Ridha; Nsiri, Brahim

    2017-09-01

    The aim of this study was to determine whether plasminogen activator inhibitor 1 (PAI-1) is associated with the risk of Alzheimer's disease (AD) in Tunisian patients. We analyzed the genotype and allele frequency distribution of the PAI-1 polymorphism in 60 Tunisian patients with AD and 120 healthy controls. The results show a significantly increased risk of AD in carriers of the 4G/4G and 4G/5G genotypes versus the wild-type 5G/5G genotype (4G/4G: 28.33% in patients vs 10.0% in controls; P 5G: 55.0% in patients vs 38.33% in controls; OR = 4.45; P < 10 -3 ). The 4G allele was also more frequently found in patients compared with controls; P < 10 -3 ; OR = 3.07. For all participants and by gender, homozygotic carriers (4G/4G) were at an increased risk of AD over heterozygotes and women were at an increased risk over their male genotype counterparts. The odds ratio for AD among 4G/4G carriers for any group was approximately twice that of heterozygotes in the same group. Women homozygotes ranked highest for AD risk (OR = 20.8) and, in fact, women heterozygotes (OR = 9.03) ranked higher for risk than male homozygotes (OR = 6.12). These preliminary exploratory results should be confirmed in a larger study.

  7. Association of catalase gene polymorphisms with catalase activity and susceptibility to systemic lupus erythematosus in the Suez Canal area, Egypt.

    Science.gov (United States)

    Ghaly, M S; Ghattas, M H; Labib, S M

    2012-10-01

    The present study evaluated the relationship of genetic variants in both promoter (-262 C/T) and in exonic (389 C/T) regions of the catalase (CAT) gene to CAT activity and risk of systemic lupus erythematosus (SLE) in Suez Canal-area patients. CAT gene polymorphisms were assessed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CAT activity was measured by using a spectrophotometer. We compared the frequencies of CAT 389 C/T and -262 C/T polymorphic variants between SLE patients (n = 103) and healthy controls (n = 103). CAT 389 C/T is associated with SLE susceptibility, with the T allele being significantly more frequent among SLE patients than healthy controls. There was no association, however, between CAT activity and genotypes of 389 C/T. We did not observe significant differences in the prevalence of CAT -262 C/T polymorphic variants in SLE patients and controls, however, we found that patients with the CAT -262 CT and TT genotypes had low CAT activity, and these genotypes showed a significant association with thrombocytopaenia, leukopaenia and the presence of anti-snRNP in SLE patients. In conclusion, the present study supports the notion of in vivo oxidative stress in SLE as indicated by the decrease in CAT activity. The allelic variations in the CAT gene -262 are more likely to affect the expression or the function of the enzyme. Since CAT may be pathogenetically linked to SLE, and owing to its free-radical origin, it appears reasonable to target lipid peroxidation by dietary and/or pharmacological antioxidants.

  8. Influence of PAI-1 gene promoter-675 (4G/5G) polymorphism on fibrinolytic activity after cardiac surgery employing cardiopulmonary bypass.

    Science.gov (United States)

    Ozolina, Agnese; Strike, Eva; Jaunalksne, Inta; Serova, Jelena; Romanova, Tatjana; Zake, Liene Nikitina; Sabelnikovs, Olegs; Vanags, Indulis

    2012-01-01

    The plasminogen activator inhibitor type-1 (PAI-1) gene promoter contains 675 (4G/5G) polymorphism. The aim of this study was evaluate the effect of the PAI-1 promoter-675 (4G/5G) polymorphism on the concentrations of PAI-1 and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex and bleeding volume after on-pump cardiac surgery. A total of 90 patients were included in the study at Pauls Stradins Clinical University Hospital. Seven patients were excluded due to surgical bleeding. Eighty-three patients were classified according to the PAI-1 genotype: 21 patients had the 4G/4G genotype; 42, the 4G/5G genotype; and 20, the 5G/5G genotype. The following fibrinolysis parameters were recorded: the PAI-1 level preoperatively, D-dimer level at 0, 6, and 24 hours after surgery, and t-PA/PAI-1 complex level 24 hours postoperatively. A postoperative bleeding volume was registered in mL 24 hours after surgery. The patients with the 5G/5G genotype had significantly lower preoperative PAI-1 levels (17 [SD, 10.8] vs. 24 ng/mL [SD, 9.6], P=0.04), higher D-dimer levels at 6 hours (371 [SD, 226] vs. 232 ng/mL [SD, 185], P=0.03) and 24 hours (326 [SD, 207] vs. 209 ng/mL [SD, 160], P=0.04), and greater postoperative blood loss (568 [SD, 192] vs. 432 mL [168], P=0.02) compared with the 4G/4G carriers. There were no significant differences in the levels of the t-PA/PAI-1 complex comparing different genotype groups. The carriers of the 5G/5G genotype showed the lower preoperative PAI-1 levels, greater chest tube blood loss, and higher D-dimer levels indicating that the 5G/5G carriers may have enhanced fibrinolysis.

  9. Polymorphism of major histocompatibility complex class II B genes in different carp lines of the common carp (Cyprinus carpio L.)

    NARCIS (Netherlands)

    Rakus, K.L.; Wiegertjes, G.F.; Stet, R.J.M.; Savelkoul, H.F.J.; Pilarczyk, A.; Irnazarow, I.

    2003-01-01

    Regular observation of survival of the carp breeding lines constituting a living gene bank at the Institute of Ichthyobiology and Aquaculture in Golysz (Poland) over a period of at least 15 years showed different survival rates for various lines. In this study, we have examined the polymorphism of

  10. The Fc Receptor Polymorphisms and Expression of Neutrophil Activation Markers in Patients with Sickle Cell Disease from Western India

    Directory of Open Access Journals (Sweden)

    Harshada K. Kangne

    2013-01-01

    Full Text Available Objective. Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India. Methods. In this paper 127 sickle cell anemia patients and 58 patients with sickle-β-thalassemia (median age 12±8.58 years with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry. Results. The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074, P-0.0471, resp.. We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231, whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312. Conclusion. The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.

  11. Meta-analysis reveals an association between signal transducer and activator of transcription-4 polymorphism and hepatocellular carcinoma risk.

    Science.gov (United States)

    Zhang, Li; Xu, Kuihua; Liu, Chuanmiao; Chen, Jiasheng

    2017-03-01

    Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Signal transducer and activator of transcription (STAT) proteins play a multitude of important functions in liver pathophysiology. Recent studies have indicated associations of rs7574865 single nucleotide polymorphism (SNP) in the STAT4 gene with various autoimmune diseases. The association between STAT4 polymorphism and the risk of HCC has been analyzed in several studies, but results remain inconsistent. This study used a meta-analysis approach to comprehensively investigate the correlation between STAT4 polymorphism and HCC risk based on previously published reports. Studies were searched from the databases of PubMed, EMBase, Web of Science, and the Chinese National Knowledge Infrastructure up to 31 December 2015. The meta-analysis was carried out based on the statement of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Eight published studies, consisting of 7503 HCC patients (cases) and 13 831 individuals without HCC (controls), were included in the present study. Meta-analysis of the included studies revealed that STAT4 rs7574865 polymorphism contributed to the risk of HCC under all four genetic models, consisting of the allelic model (G vs. T: odds ratio [OR], 1.25; 95% confidence interval [CI], 1.19-1.30), the dominant effect model (GG + GT vs. TT: OR, 1.52; 95% CI, 1.26-1.84), the recessive effect model (GG vs. GT + TT: OR, 1.35; 95% CI, 1.21-1.50), and the co-dominant effect model (GG vs.. TT: OR, 1.72; 95% CI, 1.42-2.10) comparisons. No publication bias was indicated from either visualization of the funnel plot or Egger's test. A significantly increased risk of HCC associated with the rs7574865 G was found. The rs7574865 polymorphism might be used as one risk factor for HCC. © 2016 The Japan Society of Hepatology.

  12. Using activity theory to study cultural complexity in medical education

    NARCIS (Netherlands)

    Frambach, J.M.; Driessen, E.W.; Vleuten, C.P.M. van der

    2014-01-01

    There is a growing need for research on culture, cultural differences and cultural effects of globalization in medical education, but these are complex phenomena to investigate. Socio-cultural activity theory seems a useful framework to study cultural complexity, because it matches current views on

  13. Using activity theory to study cultural complexity in medical education

    NARCIS (Netherlands)

    Frambach, Janneke M; Driessen, Erik W; van der Vleuten, Cees P M

    There is a growing need for research on culture, cultural differences and cultural effects of globalization in medical education, but these are complex phenomena to investigate. Socio-cultural activity theory seems a useful framework to study cultural complexity, because it matches current views on

  14. bond activation and catalysis by Ru -pac complexes

    Indian Academy of Sciences (India)

    and their reactivity towards oxidation of a few organic compounds. Keywords. Kinetics; catalysis; -O–O- bond activation; Ru-pac complex; oxidation. 1. Introduction. Ru-pac complexes exhibit catalytic properties,1 in homogeneous conditions in the presence of oxygen atom donors, that mimic the biological enzymatic oxi-.

  15. Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms and Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    Jean Dallongeville

    2009-01-01

    Full Text Available Single nucleotide polymorphisms (SNPs in the peroxisome proliferator-activated receptor γ (PPARG gene have been associated with cardiovascular risk factors, particularly obesity and diabetes. We assessed the relationship between 4 PPARG SNPs (C-681G, C-689T, Pro12Ala, and C1431T and coronary heart disease (CHD in the PRIME (249 cases/494 controls, only men and ADVANCE (1,076 cases/805 controls, men or women studies. In PRIME, homozygote individuals for the minor allele of the PPARG C-689T, Pro12Ala, and C1431T SNPs tended to have a higher risk of CHD than homozygote individuals for the frequent allele (adjusted OR [95% CI] = 3.43 [0.96–12.27], P=.058, 3.41 [0.95–12.22], P=.060 and 5.10 [0.99–26.37], P=.050, resp.. No such association could be detected in ADVANCE. Haplotype distributions were similar in cases and control in both studies. A meta-analysis on the Pro12Ala SNP, based on our data and 11 other published association studies (6,898 CHD cases/11,287 controls, revealed that there was no evidence for a significant association under the dominant model (OR=0.99 [0.92–1.07], P=.82. However, there was a borderline association under the recessive model (OR=1.29 [0.99–1.67], P=.06 that became significant when considering men only (OR=1.73 [1.20–2.48], P=.003. In conclusion, the PPARG Ala12Ala genotype might be associated with a higher CHD risk in men but further confirmation studies are needed.

  16. Impact of the 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene on primary nephrotic syndrome.

    Science.gov (United States)

    Luo, Yuezhong; Wang, Chao; Tu, Haitao

    2014-03-01

    The aim of the present study was to investigate whether the four guanosines (4G)/five guanosines (5G) polymorphism in the gene coding for plasminogen activator inhibitor-1 (PAI-1) affects the clinical features of primary nephrotic syndrome (PNS). A cohort of 200 biopsy-diagnosed PNS patients was studied, with 40 healthy subjects as controls. The PAI-1 gene polymorphism was detected by polymerase chain reaction and DNA sequencing. Associations between the PAI-1 4G/5G polymorphism and clinical features and pathological types of PNS were analyzed. The results indicated that the PAI-1 genotype distribution is significantly different between patients with PNS and healthy controls, with significantly higher numbers of the 4G/4G genotype and lower numbers of the 5G5G genotype detected in PNS patients compared to controls (both P5G genotypes, as well as of the 4G allele. The increased 4G frequency was also detected in patients with minimal change disease (MCD). Significantly increased international normalized ratio (INR) and prolonged activated partial thromboplastin time (APTT) were observed in 4G/4G compared to 5G/5G PNS subjects. The response to steroids was not significantly different among the three genotypes. In conclusion, the 4G allele of the PAI-1 gene appears to be associated with PNS, especially in MN and IgAN patients. These findings suggest that specific targeting may be required for the treatment of PNS patients with the 4G/4G genotype.

  17. The role of polymorphisms in the spliced leader addition domain in determining promoter activity in Brugia malayi.

    Science.gov (United States)

    Bailey, Michelle; Chauhan, Chitra; Liu, Canhui; Unnasch, Thomas R

    2011-03-01

    Previous studies of Brugia malayi promoters have suggested that they are unusual in that they lack the CAAT or TATAA boxes that are often emblematic of eucaryotic core promoter domains. Instead, the region surrounding the spliced leader (SL) addition site appears to function as the core promoter domain in B. malayi. To test the hypothesis that polymorphisms in this SL addition domain are important determinants of promoter activity, a series of domain swap mutants were prepared replacing the SL addition domain of the B. malayi 13kDa large subunit ribosomal protein (BmRPL13) with those of other ribosomal protein (RP) promoters exhibiting a wide range of activities. These constructs were then tested for promoter activity in a homologous transient transfection system. On average, polymorphisms in the SL addition domain were found to be responsible for 80% of the variation in promoter activity exhibited by the RP promoters tested. Essentially all of this effect could be attributable to polymorphisms in the 10nt located directly upstream of the SL addition site. A comparison of the sequence of this domain to the promoter activity exhibited by the domain swap mutants suggested that promoter activity was related to the number of T residues present in the coding strand of the upstream domain. Confirming this, mutation of the upstream domain of the promoter of the BmRPS4 gene to a homogeneous stretch of 10 T residues resulted in a significant increase in promoter activity. Copyright © 2010 Elsevier B.V. All rights reserved.

  18. PON1 polymorphisms are associated with polycystic ovary syndrome susceptibility, related traits, and PON1 activity in Indian women with the syndrome.

    Science.gov (United States)

    Dadachanji, Roshan; Shaikh, Nuzhat; Khavale, Sushma; Patil, Anushree; Shah, Nalini; Mukherjee, Srabani

    2015-07-01

    To investigate the association of paraoxonase 1 (PON1) polymorphisms (L55M and Q192R) with polycystic ovary syndrome (PCOS) susceptibility and its related traits in Indian women. Case-control study. Academic research institute, infertility, and endocrinology clinics. Controls (n = 326), women with PCOS (n = 482). None. Genotypic and allelic frequency distribution, genotype-phenotype association, different PON1 activities (lactonase, arylesterase, and paraoxonase). The genotypic and allelic frequency distributions of the L55M polymorphism were significantly different between lean controls and lean women with PCOS, and this polymorphism reduced the risk of PCOS development in lean but not in obese Indian women. Furthermore, this polymorphism was significantly associated with decreased 2-hour glucose, apolipoprotein B, free and bioavailable T, and free androgen index concurrent with increased sex hormone-binding globulin (SHBG) and FSH levels only in lean women with PCOS. However, Q192R polymorphism showed comparable genotypic frequency distribution between controls and women with PCOS. PON1 lactonase and arylesterase activities were significantly decreased in women with PCOS compared with controls. PON1 polymorphisms were shown to influence its activities. Our study showed that L55M, but not Q192R, polymorphism is significantly associated with reduced PCOS susceptibility only in lean women and also impacts glucose metabolism, lipid parameters, and hyperandrogenemia in them. Our study therefore suggests the possibility of differential genetic pathophysiology of PCOS between lean and obese women. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk

    DEFF Research Database (Denmark)

    Méplan, Catherine; Dragsted, Lars Ove; Ravn-Haren, Gitte

    2013-01-01

    Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases...... and 975 controls matched for age and hormone replacement therapy (HRT) use was genotyped for five functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast cancer risk was assessed using conditional...... logistic regression. Additionally pre-diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the population. A 60% reduction in risk of developing overall BC and ductal BC was observed in women who were homozygous Thr carriers for SEPP1 rs3877899. Additionally, Leu carriers for GPX1 Pro...

  20. Complexity of the HVR-1 quasispecies and disease activity in patients with hepatitis C.

    Science.gov (United States)

    Kumagai, N; Kaneko, F; Tsunematsu, S; Tsuchimoto, K; Tada, S; Saito, H; Hibi, T

    2007-07-01

    Hepatitis C virus (HCV) easily undergoes genomic changes, especially in the hypervariable region (HVR) in the N-terminus of the E2/NS1 region. The quasispecies nature of HCV may have important biological implications in relation to viral persistence; however, the relationship between disease activity of chronic HCV infection and development of the genomic complexity have yielded conflicting results. We explored the changes in the complexity of the HVR-1 in the natural course of chronic HCV infection with and without elevation of serum alanine transaminase (ALT) levels. Ten patients with chronic hepatitis C proven by liver biopsy, who showed persistent elevation of the serum ALT levels, and 15 patients with chronic HCV infection and persistently normal serum ALT levels (PNAL) were enrolled in this study. The number of the HCV quasispecies was determined twice for each patient at an interval of mean 2.5 years by fluorescence single-strand conformation polymorphism and sequence analysis. There was no significant difference in the changes in the number of quasispecies during the follow-up period between chronic hepatitis C and PNAL. There was also no significant difference in the change in the number of variable nucleotides sites between the two groups. In these patients, the number of quasispecies and the diversity of HVR-1 were correlated with platelet counts and serum hyaluronic acid levels previously shown to be associated with disease progression. Our results suggested that the disease activity is not always related to the generation of the HVR-1 quasispecies complexity.

  1. Superoxide scavenging activity of pirfenidone-iron complex

    International Nuclear Information System (INIS)

    Mitani, Yoshihiro; Sato, Keizo; Muramoto, Yosuke; Karakawa, Tomohiro; Kitamado, Masataka; Iwanaga, Tatsuya; Nabeshima, Tetsuji; Maruyama, Kumiko; Nakagawa, Kazuko; Ishida, Kazuhiko; Sasamoto, Kazumi

    2008-01-01

    Pirfenidone (PFD) is focused on a new anti-fibrotic drug, which can minimize lung fibrosis etc. We evaluated the superoxide (O 2 ·- ) scavenging activities of PFD and the PFD-iron complex by electron spin resonance (ESR) spectroscopy, luminol-dependent chemiluminescence assay, and cytochrome c reduction assay. Firstly, we confirmed that the PFD-iron complex was formed by mixing iron chloride with threefold molar PFD, and the complex was stable in distillated water and ethanol. Secondary, the PFD-iron complex reduced the amount of O 2 ·- produced by xanthine oxidase/hypoxanthine without inhibiting the enzyme activity. Thirdly, it also reduced the amount of O 2 ·- released from phorbor ester-stimulated human neutrophils. PFD alone showed few such effects. These results suggest the possibility that the O 2 ·- scavenging effect of the PFD-iron complex contributes to the anti-fibrotic action of PFD used for treating idiopathic pulmonary fibrosis

  2. Using activity theory to study cultural complexity in medical education.

    Science.gov (United States)

    Frambach, Janneke M; Driessen, Erik W; van der Vleuten, Cees P M

    2014-06-01

    There is a growing need for research on culture, cultural differences and cultural effects of globalization in medical education, but these are complex phenomena to investigate. Socio-cultural activity theory seems a useful framework to study cultural complexity, because it matches current views on culture as a dynamic process situated in a social context, and has been valued in diverse fields for yielding rich understandings of complex issues and key factors involved. This paper explains how activity theory can be used in (cross-)cultural medical education research. We discuss activity theory's theoretical background and principles, and we show how these can be applied to the cultural research practice by discussing the steps involved in a cross-cultural study that we conducted, from formulating research questions to drawing conclusions. We describe how the activity system, the unit of analysis in activity theory, can serve as an organizing principle to grasp cultural complexity. We end with reflections on the theoretical and practical use of activity theory for cultural research and note that it is not a shortcut to capture cultural complexity: it is a challenge for researchers to determine the boundaries of their study and to analyze and interpret the dynamics of the activity system.

  3. Association of FXII 5’UTR 46C>T polymorphism with FXII activity and risk of thrombotic disease

    Directory of Open Access Journals (Sweden)

    Parisa Rasighaemi

    2010-03-01

    Full Text Available Objective: Thrombotic diseases are caused by genetic and environmental factors. There are a number of well-characterized genetic defects that lead to increased risk of thrombosis. Results from previous studies have indicated that FXII is involved in the pathogenesis of thrombophilic diseases. However, the results in this regard are highly controversial. One of the most important determinants of Plasma FXII level is 46CgT polymorphism in the FXII gene. In the present study, the risk of thrombophilic diseases related to this polymorphism was investigated in a case-control study. Material and Methods: One hundred and sixty subjects were studied: 120 patients diagnosed with thrombophilia (96 venous thromboembolism, 24 arterial thrombosis, and 40 age-gender-matched controls. For each subject, FXII activity level was measured by a one-step clotting assay with FXII-deficient plasma, and 46CγT polymorphism was genotyped using a restriction fragment length polymorphism (RFLP method. Results: In this study, the previous observation that individuals with different genotypes for the 46 CγT polymorphism show significant differences in FXII activity levels was confirmed. Most importantly, FXII activity ≤68% was associated with an increased risk of venous thrombosis with an adjusted odds ratio (OR of 4.7 (95% confidence interval [CI]: 1.03-21.1, p=0.04. However, it was not a risk factor for arterial thrombosis with adjusted OR of 5 (95% CI: 0.91-27.1, p=0.09. In CT and TT genotype, the adjusted ORs were 2 (95% CI: 0.9-4.4, p=0.11 and 2.3 (95% CI: 0.45-11, p=0.48, respectively, for patients with venous thrombosis compared with the controls. Similarly, the adjusted ORs in arterial thrombosis were 1.2 (95% CI: 0.4-3.6, p=0.76 for CT and 1.8 (95% CI: 0.2-14.9, p=0.59 for TT genotype. Thus, we did not find any association of the mutated T allele in the heterozygous or homozygous state with an increased risk of venous or arterial thrombosis. Conclusion: Lower

  4. Influence of the OGG1 Ser326Cys polymorphism on oxidatively damaged DNA and repair activity

    DEFF Research Database (Denmark)

    Jensen, Annie Aarup; Løhr, Mille; Eriksen, Louise

    2012-01-01

    of the comet assay. We collected blood samples from 1,019 healthy subjects and genotyped for the OGG1 Ser326Cys polymorphism. We found 49 subjects homozygous for the variant genotype (Cys/Cys) and selected same numbers of age-matched subjects with the heterozygous (Ser/Cys) and homozygous wild-type genotype...

  5. Cellular polymorphism and nitrogenase activity of Azotobacter nigricans During Kerosene removal

    International Nuclear Information System (INIS)

    Garcia-Esquivel, G.; Rodriguez-Casasola, T.; Ferrera-Cerrato, R.; Rodriguez-Vazquez, R.; Calva-Calva, G.; Esparza-Garcia, F.

    2009-01-01

    It has been reported that certain plants grow in soils contaminated with hydrocarbons developing nitrogen-fixing bacteria. for example in the rhizosphere of beams plants grown in soil contaminated with kerosene it was found the presence of Azotobacter which removed kerosene and produced polymorphic cells when they grew in nitrogen free cultures. (Author)

  6. Plasminogen activator inhibitor-1 4G/5G polymorphism, factor V Leiden, prothrombin mutations and the risk of VTE recurrence.

    Science.gov (United States)

    Sundquist, Kristina; Wang, Xiao; Svensson, Peter J; Sundquist, Jan; Hedelius, Anna; Larsson Lönn, Sara; Zöller, Bengt; Memon, Ashfaque A

    2015-11-25

    Plasminogen-activator inhibitor (PAI)-1 is an important inhibitor of the plasminogen/plasmin system. PAI-1 levels are influenced by the 4G/5G polymorphism in the PAI-1 promoter. We investigated the relationship between the PAI-1 polymorphism and VTE recurrence, and its possible modification by factor V Leiden (FVL) and prothrombin (PTM) mutations. Patients (n=1,069) from the Malmö Thrombophilia Study were followed from discontinuation of anticoagulant treatment until diagnosis of VTE recurrence or the end of the study (maximum follow-up 9.8 years). One hundred twenty-seven patients (11.9 %) had VTE recurrence. PAI-1 was genotyped by TaqMan PCR. Cox regression analysis adjusted for age, sex and acquired risk factors of VTE showed no evidence of an association between PAI-1 genotype and risk of VTE recurrence in the study population as a whole. However, by including an interaction term in the analysis we showed that FVL but not PTM modified the effect of PAI-1 genotype: patients with the 4G allele plus FVL had a higher risk of VTE recurrence [hazard ratio (HR) =2.3, 95 % confidence interval (CI) =1.5-3.3] compared to patients with the 4G allele but no FVL (reference group) or FVL irrespective of PAI-1 genotype (HR=1.8, 95 % CI=1.3-2.5). Compared to reference group, 5G allele irrespective of FVL was associated with lower risk of VTE recurrence only when compared with 4G allele together with FVL. In conclusion, FVL has a modifying effect on PAI-1 polymorphism in relation to risk of VTE recurrence. The role of PAI-1 polymorphism as a risk factor of recurrent VTE may be FVL dependent.

  7. Peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk.

    Science.gov (United States)

    Wang, Wei; Shao, Yan; Tang, Shenhua; Cheng, Xianyong; Lian, Haifeng; Qin, Chengyong

    2015-01-01

    The association between the peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala polymorphism and colorectal cancer (CRC) risk was inconclusive. We conducted a meta-analysis to evaluate the association between PPARγ Pro12Ala polymorphism and CRC risk. We searched Pubmed, EMBASE, and China National Knowledge Infrastructure databases. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 17 case-control studies with 12635 and 15803 controls were included in this meta-analysis. Overall, PPARγ Pro12Ala polymorphism was associated with CRC risk (OR = 0.84, 95% CI 0.75-0.94, P = 0.003, I(2) = 35%). In the subgroup analysis by ethnicity, a significant association was found among Caucasians (OR = 0.85, 95% CI 0.75-0.96, P = 0.007, I(2) = 38%) but not among Asians (OR = 0.76, 95% CI 0.51-1.12, P = 0.17, I(2) = 28%). In the subgroup analysis by CRC site, a significant association was found among colon cancer (OR = 0.81, 95% CI 0.66-0.98, P = 0.03, I(2) = 16%) but not among rectal cancer (OR = 0.83, 95% CI 0.57-1.21, P = 0.34, I(2) = 63%). The sensitivity analysis did not influence the result by omitting low-quality studies (OR = 0.76, 95% CI 0.63-0.93, P = 0.006, I(2) = 51%). In conclusion, this meta-analysis suggested that PPARγ Pro12Ala polymorphism was significant associated with CRC risk.

  8. The Associations between RNA Splicing Complex Gene SF3A1 Polymorphisms and Colorectal Cancer Risk in a Chinese Population.

    Directory of Open Access Journals (Sweden)

    Xiaohua Chen

    Full Text Available Aberrant alternative splicing included alterations in components of the mRNA splicing machinery often occurred in colon cancer. However, the role of SF3A1, one key component of the mRNA splicing machinery, on colorectal cancer (CRC risk was still not elucidated.We performed a hospital-based case-control study containing 801 CRC patients and 817 cancer-free controls to examine the association between SF3A1 polymorphisms and CRC risk in a Chinese population. Four candidate SNPs (rs10376, rs5753073, rs2839998 and rs2074733 were selected based on bioinformatics analysis and previous findings. The results showed no significant associations between these SNPs and CRC risk (P > 0.05. Besides, the stratified analysis based on the smoking and alcohol use status obtained no statistically significant results.Our study was the first one to investigate the association between SF3A1 polymorphisms and CRC risk. The results suggested these four SNPs in SF3A1 were not associated with CRC risk in a Chinese population, however, further more studies are needed to confirm our findings.

  9. Association of genetic polymorphisms of PON1 and CETP with the presence of metabolic syndrome; the effects of genotypes on their serum activity and concentrations

    Directory of Open Access Journals (Sweden)

    Behdokht Fathi Dizaji

    2018-01-01

    Conclusions: There were no associations between the PON1 polymorphisms, or haplotypes with MetS. There was an association between CETPrs5882 and metabolic syndrome. AA genotype of CETPrs5882 appeared to be protective against MetS in our studied population. There were no association between the PON1 and CETP polymorphisms with PON1enzymatic activities and CETP protein levels at base line and after curcumin supplementation.

  10. Plasminogen activator inhibitor-1 4G/5G polymorphism in infertile women with and without endometriosis.

    Science.gov (United States)

    Gonçalves-Filho, Rubens P; Brandes, Ariel; Christofolini, Denise M; Lerner, Tatiana G; Bianco, Bianca; Barbosa, Caio P

    2011-05-01

    To evaluate PAI-1 genotypes in a group of infertile women with or without endometriosis and control subjects. Case-control study. Human Reproduction Center of Medicina do ABC Faculty. One hundred and forty infertile women with endometriosis, 64 women with idiopathic infertility and 148 fertile women as control subjects. The PAI-1 4G/5G polymorphism was identified by restriction fragment length polymorphism-polymerase chain reaction. Genotype distribution and allele frequency of the 4G/5G polymorphism of the PAI-1 gene. The frequencies of genotypes 4G/4G, 4G/5G and 5G/5G of the PAI-1 gene in the infertile women with endometriosis were 38.6, 37.1 and 24.3%, respectively, and in the control group 24.3, 33.8 and 41.9%, respectively (p=0.003). When the infertile women with endometriosis were divided according to their endometriosis stage, genotypes 4G/4G, 4G/5G and 5G/5G were identified, respectively, in 36.7, 32.9 and 30.4% of the patients with minimal/mild endometriosis (p=0.102) and in 41.0, 42.6 and 16.4% of the patients with moderate/severe endometriosis (p=0.001); in the women with idiopathic infertility, these genotypes were found at a frequency of 29.7, 34.3 and 36%, respectively (p=0.637). The data suggest that, in Brazilian women, the PAI-1 4G/5G polymorphism may be associated with a risk of endometriosis-associated infertility. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

  11. The role of genetic (PON1 polymorphism and environmental factors, especially physical activity, in antioxidant function of paraoxonase*

    Directory of Open Access Journals (Sweden)

    Aneta Otocka-Kmiecik

    2009-12-01

    Full Text Available Paraoxonase 1 ([i]PON1[/i] is a member of a three-gene family ([i]PON1, PON2[/i], and [i]PON3[/i]. PON1 activity dominates in human plasma. It is secreted from hepatic cells and is found in the circulation bound to high-density lipoproteins (HDLs. For many years it has been known only for its ability to hydrolyze organophosphate derivatives. More recently, PON1’s antioxidant activity draws attention as the enzyme was described to prevent oxidation of lipoproteins by reactive oxygen species formed during oxidative stress. PON1 was also shown to hydrolyze atherogenic products of oxidative lipid modification such as phospholipid peroxides and cholesterol ester hydroperoxides. Some studies indicate that the enzyme presents a lipolactonase activity and hydrolyzes homocysteine thiolactone (HCTL. There is growing evidence as to PON1’s protective role in atherosclerosis. Genetic (PON1 polymorphism and environmental factors and lifestyle may influence PON1 blood concentration and biological activity. Among the many recognized factors accounting for lifestyle, physical activity plays an important role. Various, often opposite, effects on PON1 status are observed in regular training and single physical activities. The results of different studies are often contradictory. It may depend on the time, intensity, and frequency of physical activity. Additionally, it seems that the effects of physical activity on [i]PON1[/i] blood concentration and activity are modified by environmental and lifestyle factors as well as [i]PON1[/i] polymorphism.

  12. CURRENT AND KINETIC HELICITY OF LONG-LIVED ACTIVITY COMPLEXES

    International Nuclear Information System (INIS)

    Komm, Rudolf; Gosain, Sanjay

    2015-01-01

    We study long-lived activity complexes and their current helicity at the solar surface and their kinetic helicity below the surface. The current helicity has been determined from synoptic vector magnetograms from the NSO/SOLIS facility, and the kinetic helicity of subsurface flows has been determined with ring-diagram analysis applied to full-disk Dopplergrams from NSO/GONG and SDO/HMI. Current and kinetic helicity of activity complexes follow the hemispheric helicity rule with mainly positive values (78%; 78%, respectively, with a 95% confidence level of 31%) in the southern hemisphere and negative ones (80%; 93%, respectively, with a 95% confidence level of 22% and 14%, respectively) in the northern hemisphere. The locations with the dominant sign of kinetic helicity derived from Global Oscillation Network Group (GONG) and SDO/HMI data are more organized than those of the secondary sign even if they are not part of an activity complex, while locations with the secondary sign are more fragmented. This is the case for both hemispheres even for the northern one where it is not as obvious visually due to the large amount of magnetic activity present as compared to the southern hemisphere. The current helicity shows a similar behavior. The dominant sign of current helicity is the same as that of kinetic helicity for the majority of the activity complexes (83% with a 95% confidence level of 15%). During the 24 Carrington rotations analyzed here, there is at least one longitude in each hemisphere where activity complexes occur repeatedly throughout the epoch. These ''active'' longitudes are identifiable as locations of strong current and kinetic helicity of the same sign

  13. Association of a specific major histocompatibility complex class IIβ single nucleotide polymorphism with resistance to lactococcosis in rainbow trout, Oncorhynchus mykiss (Walbaum).

    Science.gov (United States)

    Colussi, S; Prearo, M; Bertuzzi, S A; Scanzio, T; Peletto, S; Favaro, L; Modesto, P; Maniaci, M G; Ru, G; Desiato, R; Acutis, P L

    2015-01-01

    Major histocompatibility complex (MHC) loci encode glycoproteins that bind to foreign peptides and initiate immune responses through their interaction with T cells. MHC class II molecules are heterodimers consisting of α and β chains encoded by extremely variable genes; variation in exon 2 is responsible for the majority of observed polymorphisms, mostly concentrated in the codons specifying the peptide-binding region. Lactococcus garvieae is the causative agent of lactococcosis, a warm-water bacterial infection pathogenic for cultured freshwater and marine fish. It causes considerable economic losses, limiting the profitability and development of fish industries in general and the intensive production of rainbow trout, Oncorhynchus mykiss (Walbaum), in particular. The disease is currently controlled with vaccines and antibiotics; however, vaccines have short-term efficacy, and increasing concerns regarding antibiotic residues have called for alternative strategies. To explore the involvement of the MHC class II β-1 domain as a candidate gene for resistance to lactococcosis, we exposed 400 rainbow trout to naturally contaminated water. One single nucleotide polymorphism (SNP) and one haplotype were associated with resistance (P trout resistant to lactococcosis. © 2014 John Wiley & Sons Ltd.

  14. The "adjuvant effect" of the polymorphic B-G antigens of the chicken major histocompatibility complex analyzed using purified molecules incorporated in liposomes

    DEFF Research Database (Denmark)

    Salomonsen, J; Eriksson, H; Skjødt, K

    1991-01-01

    The polymorphic B-G region of the chicken major histocompatibility complex has previously been shown to mediate an "adjuvant effect" on the humoral response to other erythrocyte alloantigens. We demonstrate here that B-G molecules purified with monoclonal antibodies exert this adjuvant effect...... on the production of alloantibodies to chicken class I (B-F) molecules, when the two are in the same liposome. The adjuvant effect may in part be mediated by antibodies, since the antibody response to B-G molecules occurs much faster than the response to B-F molecules, and conditions in which antibodies to B......-G are present increase the speed of the response to B-F molecules. We also found that the presence of B-G molecules in separate liposomes results in a lack of response to B-F molecules. In the light of this and other data, we consider the possible roles for the polymorphic B-G molecules, particularly...

  15. Small organic compounds enhance antigen loading of class II major histocompatibility complex proteins by targeting the polymorphic P1 pocket

    DEFF Research Database (Denmark)

    Höpner, Sabine; Dickhaut, Katharina; Hofstätter, Maria

    2006-01-01

    the peptide loading rate. The effect was evident only for an allelic subset and strictly correlated with the presence of glycine at the dimorphic position beta86 of the HLA-DR molecule. The residue forms the floor of the conserved pocket P1, located in the peptide binding site of MHC molecule. Apparently......, transient occupation of this pocket by the organic compound stabilizes the peptide-receptive conformation permitting rapid antigen loading. This interaction appeared restricted to the larger Gly(beta86) pocket and allowed striking enhancements of T cell responses for antigens presented by these "adamantyl......-susceptible" MHC molecules. As catalysts of antigen loading, compounds targeting P1 may be useful molecular tools to amplify the immune response. The observation, however, that the ligand repertoire can be affected through polymorphic sites form the outside may also imply that environmental factors could induce...

  16. Environmental layout complexity affects neural activity during navigation in humans.

    Science.gov (United States)

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  17. Assembly and activation of neurotrophic factor receptor complexes.

    Science.gov (United States)

    Simi, Anastasia; Ibáñez, Carlos F

    2010-04-01

    Neurotrophic factors play important roles in the development and function of both neuronal and glial elements of the central and peripheral nervous systems. Their functional diversity is in part based on their ability to interact with alternative complexes of receptor molecules. This review focuses on our current understanding of the mechanisms that govern the assembly and activation of neurotrophic factor receptor complexes. The realization that many, if not the majority, of these complexes exist in a preassembled form at the plasma membrane has forced the revision of classical ligand-mediated oligomerization models, and led to the discovery of novel mechanisms of receptor activation and generation of signaling diversity which are likely to be shared by many different classes of receptors.

  18. Peroxisome proliferator activated receptor gamma polymorphism Pro12Ala in polycystic ovary syndrome (PCOS of South Indian Population

    Directory of Open Access Journals (Sweden)

    Raichel Jacob

    2016-05-01

    Conclusion: PPARγ2 gene Pro12Ala polymorphism was supposed to be susceptible genes in PCOS. The present study demonstrated that there is a statistical difference between the distributions of PPAR gamma Pro12Ala polymorphism in South Indian Population.

  19. Ibandronate metal complexes: solution behavior and antiparasitic activity.

    Science.gov (United States)

    Demoro, Bruno; Rostán, Santiago; Moncada, Mauricio; Li, Zhu-Hong; Docampo, Roberto; Olea Azar, Claudio; Maya, Juan Diego; Torres, Julia; Gambino, Dinorah; Otero, Lucía

    2018-03-01

    To face the high costs of developing new drugs, researchers in both industry and academy are looking for ways to repurpose old drugs for new uses. In this sense, bisphosphonates that are clinically used for bone diseases have been studied as agents against Trypanosoma cruzi, causative parasite of Chagas disease. In this work, the development of first row transition metal complexes (M = Co 2+ , Mn 2+ , Ni 2+ ) with the bisphosphonate ibandronate (iba, H 4 iba representing the neutral form) is presented. The in-solution behavior of the systems containing iba and the selected 3d metal ions was studied by potentiometry. Mononuclear complexes [M(H x iba)] (2-x)- (x = 0-3) and [M(Hiba) 2 ] 4- together with the formation of the neutral polynuclear species [M 2 iba] and [M 3 (Hiba) 2 ] were detected for all studied systems. In the solid state, complexes of the formula [M 3 (Hiba) 2 (H 2 O) 4 ]·6H 2 O were obtained and characterized. All obtained complexes, forming [M(Hiba)] - species under the conditions of the biological studies, were more active against the amastigote form of T. cruzi than the free iba, showing no toxicity in mammalian Vero cells. In addition, the same complexes were selective inhibitors of the parasitic farnesyl diphosphate synthase (FPPS) enzyme showing poor inhibition of the human one. However, the increase of the anti-T. cruzi activity upon coordination could not be explained neither through the inhibition of TcFPPS nor through the inhibition of TcSPPS (T. cruzi solanesyl-diphosphate synthase). The ability of the obtained metal complexes of catalyzing the generation of free radical species in the parasite could explain the observed anti-T. cruzi activity.

  20. Antibacterial activity of nicotine and its copper complex

    International Nuclear Information System (INIS)

    Zaidi, M.I.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Cu(II)-nicotine was isolated from leaves of Nicotiana tabacum using metal ions following the method of Munir et al., 1994. Their antibacterial activity against ten different species of gram positive and gram negative bacteria were studied. For comparative study, pure sample of nicotine and metal salts used for complexation; Copper(II) chloride were also subjected to antibacterial tests with the same species of bacteria under similar conditions. Results indicated that nicotine had no effect on all the bacteria tested except Escherichia coli, Pseudomonas aeroginosa and Enterococcus faecalis, which showed 14 mm zone of inhibition at 200 mu g l00 mul/sup -1/ Copper(II) chloride was found to be effective against seven species and ineffective against three species of selected bacteria. On the other hand, Cu(II)-nicotine complex was ineffective against five species of bacteria at lower level while at higher level, only one species of bacteria showed resistance against this complex. The complex was compared with three standard antibiotics. Thus, this complex can be used against a variety of microorganisms at higher level. (author)

  1. CFH Y402H polymorphism and the complement activation product C5a: effects on NF-κB activation and inflammasome gene regulation.

    Science.gov (United States)

    Cao, Sijia; Wang, Jay Ching Chieh; Gao, Jiangyuan; Wong, Matthew; To, Elliott; White, Valerie A; Cui, Jing Z; Matsubara, Joanne A

    2016-05-01

    The Y402H polymorphism in the complement factor H (CFH) gene is an important risk factor for age-related macular degeneration (AMD). Complement activation products and proinflammatory cytokines are associated with this polymorphism at the systemic level, but less is known of the associations in the outer retina of the genotyped eye. Here we investigate complement activation products and their role in nuclear factor (NF)-κB activation and gene expression of the NLRP3 inflammasome pathway. Postmortem donor eyes were genotyped for the CFH Y402H polymorphism and assessed for complement C3a, C5a, interleukin (IL)-18 and tumour necrosis factor (TNF)-α. ARPE19 cells were stimulated basolaterally with C5a or TNF-α in polarised cultures. NF-κB activation was assessed with a reporter cell line. Gene expression of inflammasome-related (NLRP3, caspase-1, IL-1β and IL-18) and classic inflammatory (IL-6 and IL-8) genes was studied. The distribution of inflammasome products, IL-1β and IL-18, was studied in postmortem donor eyes with AMD pathologies. Eyes with the homozygous at-risk variant demonstrated higher levels of C5a, IL-18 and TNF-α in Bruch's membrane and choroid. C5a promoted NF-κB activation and upregulation of IL-18 in polarised ARPE19. TNF-α promoted NF-κB activation and gene expression of caspase-1, IL-1β, IL-18, IL-6 and IL-8, but downregulated NLRP3. In eyes with geographic atrophy, strong immunoreactivity was observed for inflammasome products IL-1β and IL-18 compared with age-matched controls. The at-risk polymorphism of the CFH Y402H may contribute to AMD disease process through increased complement and NF-κB activation, and the upregulation of IL-18, a product of inflammasome activation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Plasminogen activator inhibitor-1 4G/5G polymorphism and ischemic stroke risk: a meta-analysis in Chinese population.

    Science.gov (United States)

    Cao, Yuezhou; Chen, Weixian; Qian, Yun; Zeng, Yanying; Liu, Wenhua

    2014-12-01

    The guanosine insertion/deletion polymorphism (4G/5G) of plasminogen activator inhibitor-1 (PAI-1) gene has been suggested as a risk factor for ischemic stroke (IS), but direct evidence from genetic association studies remains inconclusive even in Chinese population. Therefore, we performed a meta-analysis to evaluate this association. All of the relevant studies were identified from PubMed, Embase, Chinese National Knowledge Infrastructure database and Chinese Wanfang database up to September 2013. Statistical analyses were conducted with Revman 5.2 and STATA 12.0 software. Odds ratio (OR) with 95% confidence interval (CI) values were applied to evaluate the strength of the association. Heterogeneity was evaluated by Q-test and the I² statistic. The Begg's test and Egger's test were used to assess the publication bias. A significant association and a borderline association between the PAI-1 4G/5G polymorphism and IS were found under the recessive model (OR = 1.639, 95% CI = 1.136-2.364) and allelic model (OR = 1.256, 95% CI = 1.000-1.578), respectively. However, no significant association was observed under homogeneous comparison model (OR = 1.428, 95% CI = 0.914-2.233), heterogeneous comparison model (OR = 0.856, 95% CI = 0.689-1.063) and dominant model (OR = 1.036, 95% CI = 0.846-1.270). This meta-analysis suggested that 4G4G genotype of PAI-1 4G/5G polymorphism might be a risk factor for IS in the Chinese population.

  3. Association of the SOD2 polymorphism (Val6Ala and SOD activity with vaso-occlusive crisis and acute splenic sequestration in children with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Isabela Cristina Cordeiro Farias

    2018-02-01

    Full Text Available The SOD2 polymorphism Val16Ala TàC influences the antioxidative response. This study investigated the association of the SOD2 polymorphism and superoxide dismutase (SOD activity with vaso-occlusive crisis (VOC and acute splenic sequestration (ASS in children with sickle cell anemia (SCA. One hundred ninety-five children aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (p=0.0321; p=0.0253, respectively. Furthermore, TC/CC were more frequent in patients with VOC or ASS (p=0.0285; p=0.0090, respectively. These results suggest that the SOD2 polymorphism associated with low SOD activity could be involved in SCA physiopathology.

  4. Antifungal activity of nicotine and its cadmium complex

    International Nuclear Information System (INIS)

    Zaidi, I.M.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Cd(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activities against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cadmium(II) iodide was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine is quite effective against the rare pathogenic and Non pathogenic fungi but comparatively less effective against Pathogenic fungi. Nicotine was found to be completely ineffective against the selected species of Occasional pathogenic fungi. Cadmium(II) iodide effectively inhibited Pathogenic and Non pathogenic fungi whereas relatively ineffective against the Occasional pathogenic and Rare pathogenic fungi. On the other hand, Cadmium(II) nicotine complex inhibited all the selected species of fungi except Fusarium solani. (author)

  5. Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhang Tengyue

    2013-01-01

    Full Text Available Abstract Background Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1 is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. Methods Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs with 95% confidence intervals (CIs were used to assess the strength of associations. Results Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52. In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77. When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00. We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57. Conclusions The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of

  6. Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis.

    Science.gov (United States)

    Zhang, Tengyue; Pang, Chong; Li, Ningdong; Zhou, Elaine; Zhao, Kanxing

    2013-01-02

    Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52). In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77). When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00). We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57). The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of diabetes (more than 10 years) indicated a gene

  7. GPX1 Pro(198)Leu polymorphism, erythrocyte GPX activity, interaction with alcohol consumption and smoking, and risk of colorectal cancer

    DEFF Research Database (Denmark)

    Hansen, Rikke Dalgaard; Krath, Britta N.; Frederiksen, Kirsten

    2009-01-01

    polymorphism and several lifestyle factors predict GPX activity in erythrocytes. The present study was nested within the prospective “Diet, Cancer and Health” study of 57,053 Danes including 375 colorectal cancer cases and a comparison group of 779 individuals matched on gender. Biomaterial was sampled...... and information on lifestyle factors was obtained from questionnaires filled in at enrolment in 1993–1997. GPX1 Pro198Leu, hOGG1 Ser326Cys and erythrocyte GPX enzyme activity were not associated with risk of colorectal cancer. We observed a higher risk associated with alcohol consumption and smoking among......198Leu genotype, gender, smoking intensity, and intake of fruits and vegetables. Our results indicate that lifestyle-related oxidative stress may be a risk factor for colorectal cancer among subjects with a lowered defence....

  8. Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis.

    Science.gov (United States)

    Vuckovic, Biljana A; Djeric, Mirjana J; Tomic, Branko V; Djordjevic, Valentina J; Bajkin, Branislav V; Mitic, Gorana P

    2018-01-01

    : Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis.Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs).Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20).Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.

  9. Allelic inhibition of displacement activity: a simplified one tube allele-specific PCR for evaluation of ITPA polymorphisms.

    Science.gov (United States)

    Galmozzi, E; Facchetti, F; Degasperi, E; Aghemo, A; Lampertico, P

    2013-02-01

    Recently, genome-wide association studies (GWAS) in patients with chronic hepatitis C virus (HCV) infection have identified two functional single nucleotide polymorphisms (SNPs) in the inosine triphosphatase (ITPA) gene, that are associated strongly and independently with hemolytic anemia in patients exposed to pegylated-interferon (Peg-IFN) plus ribavirin (RBV) combined therapy. Here has been developed a simplified allele discrimination polymerase chain reaction (PCR) assay named allelic inhibition of displacement activity (AIDA) for evaluation of ITPA polymorphisms. AIDA system relies on three unlabeled primers only, two outer common primers and one inner primer with allele-specific 3' terminus mismatch. DNA samples from 192 patients with chronic HCV infection were used to validate the AIDA system and results were compared with the gold standard TaqMan(®) SNP genotyping assay. Concordant data were obtained for all samples, granting for high specificity of the method. In conclusion, AIDA is a practical one-tube method to reproducibly and to assess accurately rs7270101 and rs1127354 ITPA SNPs. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. The COMT Val/Met polymorphism is associated with reading related skills and consistent patterns of functional neural activation

    Science.gov (United States)

    Landi, Nicole; Frost, Stephen J.; Mencl, W. Einar; Preston, Jonathan L.; Jacobsen, Leslie K.; Lee, Maria; Yrigollen, Carolyn; Pugh, Kenneth R.; Grigorenko, Elena L.

    2013-01-01

    In both children and adults there is large variability in reading skill, with approximately 5–10% of individuals characterized as having reading disability; these individuals struggle to learn to read despite adequate intelligence and opportunity. Although it is well established that a substantial portion of this variability is attributed to the genetic differences between individuals, specifics of the connections between reading and the genome are not understood. This article presents data that suggest that variation in the COMT gene, which has previously been associated with variation in higher-order cognition, is associated with reading and reading-related skills, both at the level of brain and behavior. In particular, we found that the COMT Val/Met polymorphism at rs4680, which results in the substitution of the ancestral Valine (Val) by Methionine (Met), was associated with better performance on a number of critical reading measures and with patterns of functional neural activation that have been linked to better readers. We argue that this polymorphism, known for its broad effects on cognition, may modulate (likely through frontal lobe function) reading skill. PMID:23278923

  11. The COMT Val/Met polymorphism is associated with reading-related skills and consistent patterns of functional neural activation.

    Science.gov (United States)

    Landi, Nicole; Frost, Stephen J; Mencl, W Einar; Preston, Jonathan L; Jacobsen, Leslie K; Lee, Maria; Yrigollen, Carolyn; Pugh, Kenneth R; Grigorenko, Elena L

    2013-01-01

    In both children and adults there is large variability in reading skill, with approximately 5-10% of individuals characterized as having reading disability; these individuals struggle to learn to read despite adequate intelligence and opportunity. Although it is well established that a substantial portion of this variability is attributed to the genetic differences between individuals, specifics of the connections between reading and the genome are not understood. This article presents data that suggest that variation in the COMT gene, which has previously been associated with variation in higher-order cognition, is associated with reading and reading-related skills, at the level of both brain and behavior. In particular, we found that the COMT Val/Met polymorphism at rs4680, which results in the substitution of the ancestral Valine (Val) by Methionine (Met), was associated with better performance on a number of critical reading measures and with patterns of functional neural activation that have been linked to better readers. We argue that this polymorphism, known for its broad effects on cognition, may modulate (likely through frontal lobe function) reading skill. © 2012 Blackwell Publishing Ltd.

  12. [Signal transducer and activator of transcription 4 gene polymorphisms associated with dilated cardiomyopathy in Chinese Han population].

    Science.gov (United States)

    Fu, Kai; Peng, Ying; Li, Ya-Jiao; Xie, Qiu; Yang, Hao; Zhou, Bin; Rao, Li

    2013-07-01

    To investigate the association between signal transducer and activator of transcription 4 (STAT4) gene polymorphism and dilated cardiomyopathy (DCM). Two single nucleotide polymorphisms (SNP) (rs7574865 and rs11889341) in STAT4 gene were determined using PCR-RFLP method. The genotype and allele frequencies of these two SNPs were compared between 294 DCM patients and 334 normal controls to test whether SNPs in STAT4 was associated with DCM. Compared to healthy controls, the frequency of GG genotype (55.8% in patients vs. 47.9% in controls, P = 0.039) and the G allele in rs11889341 (76.4% in patients vs. 70.7% in controls, P = 0.023) were significantly increased in D C M patients. We found that increased DCM risk is associated with CC+AC genotypes of rs574865 (94.2% in patients vs. 89.2% in controls, P = 0.025). No significant difference was observed in the distribution of allele frequency in rs7874865 between DCM patients and the controls. SNPs in STAT4 gene is associated with DCM. G allele and GG genotype in rs11889341, and CC+AC genotypes in rs7574865, may be associated with significantly increased risk of DCM.

  13. Task complexity modulates pilot electroencephalographic activity during real flights.

    Science.gov (United States)

    Di Stasi, Leandro L; Diaz-Piedra, Carolina; Suárez, Juan; McCamy, Michael B; Martinez-Conde, Susana; Roca-Dorda, Joaquín; Catena, Andrés

    2015-07-01

    Most research connecting task performance and neural activity to date has been conducted in laboratory conditions. Thus, field studies remain scarce, especially in extreme conditions such as during real flights. Here, we investigated the effects of flight procedures of varied complexity on the in-flight EEG activity of military helicopter pilots. Flight procedural complexity modulated the EEG power spectrum: highly demanding procedures (i.e., takeoff and landing) were associated with higher EEG power in the higher frequency bands, whereas less demanding procedures (i.e., flight exercises) were associated with lower EEG power over the same frequency bands. These results suggest that EEG recordings may help to evaluate an operator's cognitive performance in challenging real-life scenarios, and thus could aid in the prevention of catastrophic events. © 2015 Society for Psychophysiological Research.

  14. Antifungal activity of nicotine and its cobalt complex

    International Nuclear Information System (INIS)

    Zaidi, M.I.; Gul, A.

    2005-01-01

    Nicotine and its metal complex; Co(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activity against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cobalt(II) chloride was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine had antifungal activity against all species of fungi studied except Candida albicans, Microsporum canis, Epidermophyton floccosum, Candida tropicalis, and Alternaria infectoria. Cobalt(II) nicotine was found to be effective against all selected species of fungi but ineffective against Candida solani, Penicillium notalum, Microsporum canis, Fusarium solani and Fusarium moniliforme. (author)

  15. Genotyping of major histocompatibility complex Class II DRB gene in Rohilkhandi goats by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing

    Directory of Open Access Journals (Sweden)

    Kush Shrivastava

    2015-10-01

    Full Text Available Aim: To study the major histocompatibility complex (MHC Class II DRB1 gene polymorphism in Rohilkhandi goat using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and nucleotide sequencing techniques. Materials and Methods: DNA was isolated from 127 Rohilkhandi goats maintained at sheep and goat farm, Indian Veterinary Research Institute, Izatnagar, Bareilly. A 284 bp fragment of exon 2 of DRB1 gene was amplified and digested using BsaI and TaqI restriction enzymes. Population genetic parameters were calculated using Popgene v 1.32 and SAS 9.0. The genotypes were then sequenced using Sanger dideoxy chain termination method and were compared with related breeds/species using MEGA 6.0 and Megalign (DNASTAR software. Results: TaqI locus showed three and BsaI locus showed two genotypes. Both the loci were found to be in Hardy–Weinberg equilibrium (HWE, however, population genetic parameters suggest that heterozygosity is still maintained in the population at both loci. Percent diversity and divergence matrix, as well as phylogenetic analysis revealed that the MHC Class II DRB1 gene of Rohilkhandi goats was found to be in close cluster with Garole and Scottish blackface sheep breeds as compared to other goat breeds included in the sequence comparison. Conclusion: The PCR-RFLP patterns showed population to be in HWE and absence of one genotype at one locus (BsaI, both the loci showed excess of one or the other homozygote genotype, however, effective number of alleles showed that allelic diversity is present in the population. Sequence comparison of DRB1 gene of Rohilkhandi goat with other sheep and goat breed assigned Rohilkhandi goat in divergence with Jamanupari and Angora goats.

  16. Structural complexities in the active layers of organic electronics.

    Science.gov (United States)

    Lee, Stephanie S; Loo, Yueh-Lin

    2010-01-01

    The field of organic electronics has progressed rapidly in recent years. However, understanding the direct structure-function relationships between the morphology in electrically active layers and the performance of devices composed of these materials has proven difficult. The morphology of active layers in organic electronics is inherently complex, with heterogeneities existing across multiple length scales, from subnanometer to micron and millimeter range. A major challenge still facing the organic electronics community is understanding how the morphology across all of the length scales in active layers collectively determines the device performance of organic electronics. In this review we highlight experiments that have contributed to the elucidation of structure-function relationships in organic electronics and also point to areas in which knowledge of such relationships is still lacking. Such knowledge will lead to the ability to select active materials on the basis of their inherent properties for the fabrication of devices with prespecified characteristics.

  17. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

  18. Population structure of a lodgepole pine (Pinus contorta) and jack pine (P. banksiana) complex as revealed by random amplified polymorphic DNA.

    Science.gov (United States)

    Ye, Terrance Z; Yang, Rong-Cai; Yeh, Francis C

    2002-06-01

    We studied the population structure of a lodgepole (Pinus contorta Dougl.) and jack pine (Pinus banksiana Lamb.) complex in west central Alberta and neighboring areas by assessing random amplified polymorphic DNA (RAPD) variability in 23 lodgepole pine, 9 jack pine, and 8 putative hybrid populations. Of 200 random primers screened, 10 that amplified 39 sharp and reproducible RAPDs were chosen for the study. None of the 39 RAPDs were unique to the parental species. RAPD diversity ranged from 0.085 to 0.190 among populations and averaged 0.143 for lodgepole pine, 0.156 for jack pine, 0.152 for hybrids, and 0.148 for all 40 populations. The estimated population differentiation based on G(ST) was 0.168 for hybrids, 0.162 for lodgepole pine, 0.155 for jack pine, and 0.247 across all 40 populations. Cluster analysis of genetic distances generally separated jack pine from lodgepole pine and hybrids, but no division could be identified that further separated lodgepole pine from hybrids. The observed weak to mild trend of "introgression by distance" in the complex and neighbouring areas was consistent with the view that introgressive hybridization between lodgepole and jack pines within and outside the hybrid zone may have been through secondary contact and primary intergradation, respectively.

  19. Lovesongs and period gene polymorphisms indicate Lutzomyia cruzi (Mangabeira, 1938) as a sibling species of the Lutzomyia longipalpis (Lutz and Neiva, 1912) complex.

    Science.gov (United States)

    Vigoder, Felipe M; Araki, Alejandra S; Bauzer, Luiz G S R; Souza, Nataly A; Brazil, Reginaldo P; Peixoto, Alexandre A

    2010-08-01

    The sand fly Lutzomyia cruzi (Mangabeira, 1938) is implicated as a vector of American visceral leishmaniasis (AVL) in some areas of Brazil. Lutzomyia cruzi is closely related to Lutzomyia longipalpis s.l. (Lutz and Neiva, 1912) the main Latin American vector of AVL and a species complex. Although females of the two species are identical, the males can be distinguished by differences in the genitalia. Nevertheless, pheromone analysis shows that Lu. cruzi males produce 9-methyl-germacrene-B, which has also been found in a number of Latin American populations of Lu. longipalpis s.l. In addition, analysis of microsatellite loci shows that the level of divergence between Lu. cruzi and Lu. longipalpis s.l. is similar to that observed among the Lu. longipalpis s.l. sibling species. Here we present the lovesongs of Lu. cruzi males which are similar to the Burst-type songs produced by one of the Lu. longipalpis s.l. sibling species. We also present data on the molecular polymorphisms of the period gene of Lu. cruzi that indicate this species as another sibling within the Lu. longipalpis complex. The results highlight the importance of an integrative approach to understand the patterns of genetic and phenotypic divergence among very closely related vector species. Copyright 2010. Published by Elsevier B.V.

  20. Characterization and biological activity of Solidago canadensis complex.

    Science.gov (United States)

    Šutovská, M; Capek, P; Kocmálová, M; Fraňová, S; Pawlaczyk, I; Gancarz, R

    2013-01-01

    Polyphenolic-polysaccharide-protein complex has been isolated from flowers of Solidago canadensis L. by hot alkaline extraction procedure. Compositional analyses of S canadensis complex revealed the presence of carbohydrates (43 wt%), protein (27 wt%), phenolics (12 wt%), uronic acids (10 wt%) and inorganic material (8 wt%). The carbohydrate part was rich in neutral sugars (81 wt%) while uronids were determined in lower amount (19 wt%). Monosaccharide analysis of carbohydrate part revealed the presence of five main sugar components, i.e. rhamnose (~23 wt%), arabinose (~20 wt%), uronic acids (~19 wt%), galactose (~17 wt%) and glucose (~14 wt%), and indicated thus the presence of rhamnogalacturonan and arabinogalactan in S. canadensis complex. HPLC analysis of complex showed one single peak of molecule mass at 11.2 kDa. Antitussive activity tests, performed in three doses of Solidago complex, showed the reduction of the number of cough efforts in the dose-dependent manner. Higher doses (50 and 75 mg/kg b.w.) were shown to be by 15 and 20% more effective than that of lower one (25mg/kg b.w.). However, the antitussive effect of the highest dose (75 mg/kg b.w.) was by 10% lower in comparison with that of codeine, the strongest antitussive agent. Besides, the highest dose of the complex (75 mg/kg b.w.) significantly decreased values of specific airways resistance and their effect remained longer as that of salbutamol, a representative of classic antiasthmatic drugs. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity

    Directory of Open Access Journals (Sweden)

    Monika Dabrzalska

    2017-02-01

    Full Text Available The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer—methylene blue (MB. As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines.

  2. Mixed-waste minimization activities in the nuclear weapons complex

    International Nuclear Information System (INIS)

    Marchetti, J.A.; Suffern, J.S.

    1991-01-01

    Over the past 40 years, the US Department of Energy (DOE) and the nuclear weapons complex have successfully executed their mission of providing the country with a strong nuclear deterrent. Now, however, they must attain another mission at the same time: to eliminate or greatly reduce the environmental, safety, and health problems in the complex. Mixed-waste minimization activities have taken place in 11 of the complex production plants and laboratories: the Pinellas plant, the Mount plant, the Kansas City plant, the Y-12 plant, the Rocky Flats plant, the Savannah River Site (SRS), the Savannah River Site (SRS), the Pantex plant, the Nevada Test Site, Sandia National Laboratories, Los Alamos National Laboratory, and the Lawrence Livermore National Laboratory. The mixed-waste minimization opportunities that have been implemented to date by the production facilities are different from those that have been implemented by the laboratories. Areas of opportunity at the plants involve the following activities: (1) process design or improvement; (2) substitution of materials; (3) waste segregation; (4) recycling; and (5) administrative controls

  3. A novel mutation in the P2Y12 receptor and a function-reducing polymorphism in protease-activated receptor 1 in a patient with chronic bleeding.

    Science.gov (United States)

    Patel, Y M; Lordkipanidzé, M; Lowe, G C; Nisar, S P; Garner, K; Stockley, J; Daly, M E; Mitchell, M; Watson, S P; Austin, S K; Mundell, S J

    2014-05-01

    The study of patients with bleeding problems is a powerful approach in determining the function and regulation of important proteins in human platelets. We have identified a patient with a chronic bleeding disorder expressing a homozygous P2RY(12) mutation, predicting an arginine to cysteine (R122C) substitution in the G-protein-coupled P2Y(12) receptor. This mutation is found within the DRY motif, which is a highly conserved region in G-protein-coupled receptors (GPCRs) that is speculated to play a critical role in regulating receptor conformational states. To determine the functional consequences of the R122C substitution for P2Y(12) function. We performed a detailed phenotypic analysis of an index case and affected family members. An analysis of the variant R122C P2Y(12) stably expressed in cells was also performed. ADP-stimulated platelet aggregation was reduced as a result of a significant impairment of P2Y(12) activity in the patient and family members. Cell surface R122C P2Y(12) expression was reduced both in cell lines and in platelets; in cell lines, this was as a consequence of agonist-independent internalization followed by subsequent receptor trafficking to lysosomes. Strikingly, members of this family also showed reduced thrombin-induced platelet activation, owing to an intronic polymorphism in the F2R gene, which encodes protease-activated receptor 1 (PAR-1), that has been shown to be associated with reduced PAR-1 receptor activity. Our study is the first to demonstrate a patient with deficits in two stimulatory GPCR pathways that regulate platelet activity, further indicating that bleeding disorders constitute a complex trait. © 2014 International Society on Thrombosis and Haemostasis.

  4. Impact of the -675 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene on childhood IgA nephropathy.

    Science.gov (United States)

    Han, Su-Ryun; Kim, Cheon-Jong; Lee, Byung-Cheol

    2012-04-01

    Plasminogen activator inhibitor-1 (PAI-1) is an important regulator of the fibrinolytic pathway and extracellular matrix (ECM) turnover. The -675 4G/5G polymorphism in the PAI-1 promoter is associated with altered PAI-1 transcription, suggesting that this polymorphism may be a candidate risk factor for diseases characterized by ECM accumulation, such as immunoglobulin A nephropathy (IgAN) and mesangial proliferative glomerulonephritis (MesPGN). We genotyped childhood patients with biopsy-confirmed IgAN (n=111) and MesPGN (n=47), and healthy control subjects (n=230) for the -675 4G/5G PAI-1 polymorphism by polymerase chain reaction-restriction fragment length polymorphism methods. The distribution of the 4G/4G (27.9%), 4G/5G (45.1%) and 5G/5G (27.0%) genotypes in IgAN patients was significantly different from the healthy controls (32.2, 54.3 and 13.5%, respectively) (p=0.0092). There was no significant difference in the genotype distributions of the 4G/5G polymorphism between MesPGN patients and the healthy controls. Regarding the impact of the polymorphism on IgAN, the 4G/4G genotype was markedly increased in patients with proteinuria (≥1,000 mg/day) and/or hypertension when compared to patients without proteinuria and hypertension (OR=5.23, 95% CI 1.34-20.38, P=0.0183). These findings indicate that the PAI-1 gene polymorphism may affect the susceptibility of childhood IgAN.

  5. Spontaneous brain network activity: Analysis of its temporal complexity

    Directory of Open Access Journals (Sweden)

    Mangor Pedersen

    2017-06-01

    Full Text Available The brain operates in a complex way. The temporal complexity underlying macroscopic and spontaneous brain network activity is still to be understood. In this study, we explored the brain’s complexity by combining functional connectivity, graph theory, and entropy analyses in 25 healthy people using task-free functional magnetic resonance imaging. We calculated the pairwise instantaneous phase synchrony between 8,192 brain nodes for a total of 200 time points. This resulted in graphs for which time series of clustering coefficients (the “cliquiness” of a node and participation coefficients (the between-module connectivity of a node were estimated. For these two network metrics, sample entropy was calculated. The procedure produced a number of results: (1 Entropy is higher for the participation coefficient than for the clustering coefficient. (2 The average clustering coefficient is negatively related to its associated entropy, whereas the average participation coefficient is positively related to its associated entropy. (3 The level of entropy is network-specific to the participation coefficient, but not to the clustering coefficient. High entropy for the participation coefficient was observed in the default-mode, visual, and motor networks. These results were further validated using an independent replication dataset. Our work confirms that brain networks are temporally complex. Entropy is a good candidate metric to explore temporal network alterations in diseases with paroxysmal brain disruptions, including schizophrenia and epilepsy. In recent years, connectomics has provided significant insights into the topological complexity of brain networks. However, the temporal complexity of brain networks still remains somewhat poorly understood. In this study we used entropy analysis to demonstrate that the properties of network segregation (the clustering coefficient and integration (the participation coefficient are temporally complex

  6. Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study

    DEFF Research Database (Denmark)

    Ravn-Haren, Gitte; Olsen, A.; Tjonneland, A.

    2006-01-01

    Breast cancer may be related to oxidative stress. Breast cancer patients have been reported to have lower antioxidant enzyme activity than healthy controls and the polymorphism GPX1 Pro198Leu has been associated with risk of lung and breast cancer. The purpose of the present nested case...

  7. Immersion freezing of ice nucleation active protein complexes

    Directory of Open Access Journals (Sweden)

    S. Hartmann

    2013-06-01

    Full Text Available Utilising the Leipzig Aerosol Cloud Interaction Simulator (LACIS, the immersion freezing behaviour of droplet ensembles containing monodisperse particles, generated from a Snomax™ solution/suspension, was investigated. Thereto ice fractions were measured in the temperature range between −5 °C to −38 °C. Snomax™ is an industrial product applied for artificial snow production and contains Pseudomonas syringae} bacteria which have long been used as model organism for atmospheric relevant ice nucleation active (INA bacteria. The ice nucleation activity of such bacteria is controlled by INA protein complexes in their outer membrane. In our experiments, ice fractions increased steeply in the temperature range from about −6 °C to about −10 °C and then levelled off at ice fractions smaller than one. The plateau implies that not all examined droplets contained an INA protein complex. Assuming the INA protein complexes to be Poisson distributed over the investigated droplet populations, we developed the CHESS model (stoCHastic modEl of similar and poiSSon distributed ice nuclei which allows for the calculation of ice fractions as function of temperature and time for a given nucleation rate. Matching calculated and measured ice fractions, we determined and parameterised the nucleation rate of INA protein complexes exhibiting class III ice nucleation behaviour. Utilising the CHESS model, together with the determined nucleation rate, we compared predictions from the model to experimental data from the literature and found good agreement. We found that (a the heterogeneous ice nucleation rate expression quantifying the ice nucleation behaviour of the INA protein complex is capable of describing the ice nucleation behaviour observed in various experiments for both, Snomax™ and P. syringae bacteria, (b the ice nucleation rate, and its temperature dependence, seem to be very similar regardless of whether the INA protein complexes inducing ice

  8. Polymorphism in the tyrosine hydroxylase (TH gene is associated with activity-impulsivity in German Shepherd Dogs.

    Directory of Open Access Journals (Sweden)

    Eniko Kubinyi

    Full Text Available We investigated the association between repeat polymorphism in intron 4 of the tyrosine hydroxylase (TH gene and two personality traits, activity-impulsivity and inattention, in German Shepherd Dogs. The behaviour of 104 dogs was characterized by two instruments: (1 the previously validated Dog-Attention Deficit Hyperactivity Disorder Rating Scale (Dog-ADHD RS filled in by the dog owners and (2 the newly developed Activity-impulsivity Behavioural Scale (AIBS containing four subtests, scored by the experimenters. Internal consistency, inter-observer reliability, test-retest reliability and convergent validity were demonstrated for AIBS. Dogs possessing at least one short allele were proved to be more active-impulsive by both instruments, compared to dogs carrying two copies of the long allele (activity-impulsivity scale of Dog-ADHD RS: p = 0.007; AIBS: p = 0.023. The results have some potential to support human studies; however, further research should reveal the molecular function of the TH gene variants, and look for the effect in more breeds.

  9. Genetic variability in chronic irradiated plant populations - Polymorphism and activity of antioxidant enzymes in chronic irradiated plant populations

    Energy Technology Data Exchange (ETDEWEB)

    Volkova, Polina Y.; Geras' kin, Stanislav A. [Russian Institute of Agricultural Radiology and Agroecology, 249030, Obninsk, Kievskoe shosse 109 km (Russian Federation)

    2014-07-01

    Introduction: The gene pool of natural population is constantly changing in order to provide the greatest fitness at this time. Ability of population to adapt to changing environmental conditions depends on genetic polymorphism of traits which are operates by selection. Chronic stress exposure can change amount or structure intra-population variability. Therefore, it is necessary to analyze the relationships between genetic polymorphism and stress factors, such as radiation exposure. This studies my assist in the development of new bio-indication methods. Materials and methods: Studying sites: Bryansk region is the most contaminated region of Russia as a result of Chernobyl accident. The initial activity by {sup 137}Cs on this territory reached 1 MBq/m{sup 2} above surface. Our study conducted in several districts of Bryansk region, which are characterized the most dose rate. Experimental sites similar to climate characteristics, stand of trees is homogeneous, pine trees take up a significant part of phytocenosis. Heavy metals content in soils and cones be within background. Dose rates vary from 0.14 to 130 mGy/year. Object: Pinus sylvestris L.,the dominant tree species in North European and Asian boreal forests. Scots pine has a long maturation period (18-20 month), which means that significant DNA damage may accumulate in the undifferentiated stem cells, even at low doses (or dose rates) during exposure to low concentrations of contaminants Isozyme analysis: We evaluated isozyme polymorphism of three antioxidant enzymes: superoxide dismutase, glutatione reductase and glutatione peroxidase. Analysis of enzymes activities: We chose key enzymes of antioxidant system for this experiment: superoxide dismutase, catalase and peroxidase. Results and conclusions: We estimated frequency of each allele in reference and experimental populations. based It was showed that frequency of rare alleles increase in chronic irradiated populations, i.e. increase the sampling variance

  10. Evaluation of HLA-G 14 bp Ins/Del and +3142G>C Polymorphism with Susceptibility and Early Disease Activity in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Mohammad Hashemi

    2016-01-01

    Full Text Available Purpose/Background. Mounting evidence designates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. There are controversial reports concerning the impact of HLA-G gene polymorphism on rheumatoid arthritis (RA. This study was aimed at examining the impact of 14 bp ins/del and +3142G>C polymorphism with susceptibility and early disease activity in RA patients in a sample of the Iranian population. Methods. This case-control study was done on 194 patients with RA and 158 healthy subjects. The HLA-G rs1063320 (+3142G>C and rs66554220 (14 bp ins/del variants were genotype by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP and PCR method, respectively. Results. The HLA-G +3142G>C polymorphism significantly decreased the risk of RA in codominant (OR = 0.61, 95% CI = 0.38–0.97, p=0.038, GC versus GG; OR = 0.36, 95% CI = 0.14–0.92, p=0.034, CC versus GG, dominant (OR = 0.56, 95% CI = 0.36–0.87, p=0.011, GC + CC versus GG, and allele (OR = 0.58, 95% CI = 0.41–0.84, p=0.004, C versus G inheritance models tested. Our finding did not support an association between HLA-G 14 bp ins/del variant and risk/protection of RA. In addition, no significant association was found between the polymorphism and early disease activity. Conclusion. In summary, our results showed that HLA-G +3142G>C gene polymorphism significantly decreased the risk of RA in a sample of the Iranian population.

  11. Proton Flares in Solar Activity Complexes: Possible Origins and Consequences

    Science.gov (United States)

    Isaeva, E. S.; Tomozov, V. M.; Yazev, S. A.

    2018-03-01

    Solar flares observed during the 24th solar-activity cycle and accompanied by fluxes of particles detected at the Earth's orbit with intensities exceeding 10 particles cm-2 s-1 and energies of more than 10 MeV per particle mainly occurred in activity complexes (82% of cases), with 80% of these occurring no more than 20 heliographic degrees from the nearest coronal holes. The correlation between the X-ray classes of flares and the proton fluxes detected at the Earth's orbit is weak. The work presented here supports the hypothesis that the leakage of particles into the heliosphere is due to the existence of long-lived magnetic channels, which facilitate the transport of flare-accelerated particles into the boundary regions of open magnetic structures of coronal holes. The possible contribution of exchange reconnection in the formation of such channels and the role of exchange reconnection in the generation of flares are discussed.

  12. Multifractality as a Measure of Complexity in Solar Flare Activity

    Science.gov (United States)

    Sen, Asok K.

    2007-03-01

    In this paper we use the notion of multifractality to describe the complexity in H α flare activity during the solar cycles 21, 22, and 23. Both northern and southern hemisphere flare indices are analyzed. Multifractal behavior of the flare activity is characterized by calculating the singularity spectrum of the daily flare index time series in terms of the Hölder exponent. The broadness of the singularity spectrum gives a measure of the degree of multifractality or complexity in the flare index data. The broader the spectrum, the richer and more complex is the structure with a higher degree of multifractality. Using this broadness measure, complexity in the flare index data is compared between the northern and southern hemispheres in each of the three cycles, and among the three cycles in each of the two hemispheres. Other parameters of the singularity spectrum can also provide information about the fractal properties of the flare index data. For instance, an asymmetry to the left or right in the singularity spectrum indicates a dominance of high or low fractal exponents, respectively, reflecting a relative abundance of large or small fluctuations in the total energy emitted by the flares. Our results reveal that in the even (22nd) cycle the singularity spectra are very similar for the northern and southern hemispheres, whereas in the odd cycles (21st and 23rd) they differ significantly. In particular, we find that in cycle 21, the northern hemisphere flare index data have higher complexity than its southern counterpart, with an opposite pattern prevailing in cycle 23. Furthermore, small-scale fluctuations in the flare index time series are predominant in the northern hemisphere in the 21st cycle and are predominant in the southern hemisphere in the 23rd cycle. Based on these findings one might suggest that, from cycle to cycle, there exists a smooth switching between the northern and southern hemispheres in the multifractality of the flaring process. This new

  13. Thymidylate synthase genetic polymorphism and plasma total homocysteine level in a group of Turkish patients with rheumatoid arthritis: relationship with disease activity and methotrexate toxicity.

    Science.gov (United States)

    Borman, Pınar; Taşbaş, Özgur; Karabulut, Halil; Tukun, Ajlan; Yorgancıoğlu, Rezan

    2015-01-01

    The polymorphism of thymidylate synthase (TS) gene and homocysteine are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine homocysteine levels and the frequency of TS gene triple repeat (TS3R) and double repeat (TS2R) polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity and disease activity. Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 ± 12.5 and 46.2 ± 13.4 years, were enrolled to the study. Demographic characteristics were obtained and number of patients with MTX-related adverse affects, were recorded in the patient group. The homocysteine levels and TS2R/TS3R polymorphisms of the TS gene were analyzed and the distribution of genotypes according to MTX toxicity and disease activity, were determined. The demographic properties were similar between the patient and control subjects. Folic acid supplementation with a mean dose of 5mg folic acid/week, was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment. The frequency of TS2R and TS3R polymorphisms were found to be similar in the patient and control groups. TS2R and TS3R gene polymorphisms were found to be similar in patients with and without MTX-related adverse events. The mean homocysteine level was also similar in patients with and without TS gene polymorphism, but was found to be higher (12.45μmol/L vs 10.7μmol/L) in patients with MTX-related side effects than in patients without side effects. The mean level of homocysteine was correlated with levels of ESR in the patient group. In conclusion, homocysteine levels might effect the disease activity and toxicity of MTX but 2R and 3R polymorphisms in the TS gene, were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible from the MTX

  14. Associations of activated coagulation factor VII and factor VIIa-antithrombin levels with genome-wide polymorphisms and cardiovascular disease risk.

    Science.gov (United States)

    Olson, N C; Raffield, L M; Lange, L A; Lange, E M; Longstreth, W T; Chauhan, G; Debette, S; Seshadri, S; Reiner, A P; Tracy, R P

    2018-01-01

    Essentials A fraction of coagulation factor VII circulates in blood as an activated protease (FVIIa). We evaluated FVIIa and FVIIa-antithrombin (FVIIa-AT) levels in the Cardiovascular Health Study. Polymorphisms in the F7 and PROCR loci were associated with FVIIa and FVIIa-AT levels. FVIIa may be an ischemic stroke risk factor in older adults and FVIIa-AT may assess mortality risk. Background A fraction of coagulation factor (F) VII circulates as an active protease (FVIIa). FVIIa also circulates as an inactivated complex with antithrombin (FVIIa-AT). Objective Evaluate associations of FVIIa and FVIIa-AT with genome-wide single nucleotide polymorphisms (SNPs) and incident coronary heart disease, ischemic stroke and mortality. Patients/Methods We measured FVIIa and FVIIa-AT in 3486 Cardiovascular Health Study (CHS) participants. We performed a genome-wide association scan for FVIIa and FVIIa-AT in European-Americans (n = 2410) and examined associations of FVII phenotypes with incident cardiovascular disease. Results In European-Americans, the most significant SNP for FVIIa and FVIIa-AT was rs1755685 in the F7 promoter region on chromosome 13 (FVIIa, β = -25.9 mU mL -1 per minor allele; FVIIa-AT, β = -26.6 pm per minor allele). Phenotypes were also associated with rs867186 located in PROCR on chromosome 20 (FVIIa, β = 7.8 mU mL -1 per minor allele; FVIIa-AT, β = 9.9 per minor allele). Adjusted for risk factors, a one standard deviation higher FVIIa was associated with increased risk of ischemic stroke (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.01, 1.23). Higher FVIIa-AT was associated with mortality from all causes (HR, 1.08; 95% CI, 1.03, 1.12). Among European-American CHS participants the rs1755685 minor allele was associated with lower ischemic stroke (HR, 0.69; 95% CI, 0.54, 0.88), but this association was not replicated in a larger multi-cohort analysis. Conclusions The results support the importance of the F7 and PROCR loci in

  15. Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population.

    Science.gov (United States)

    Firouzabadi, Negar; Shafiei, Massoumeh; Bahramali, Ehsan; Ebrahimi, Soltan Ahmed; Bakhshandeh, Hooman; Tajik, Nader

    2012-12-30

    Genetic factors contribute substantially to the likelihood of developing major depressive disorder (MDD). The importance of renin-angiotensin system (RAS) elements in cognition and behaviour and their involvement in aetiology and treatment of depression imply that RAS gene polymorphism(s) associated with RAS overactivity might also be associated with depression. In the present study, genotype and allele frequencies of six common polymorphisms of genes encoding for RAS components were determined in DNAs extracted from venous blood of 191 depressed and 104 healthy individuals using polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum angiotensin-converting enzyme (ACE) activity was assayed using a high-performance liquid chromatography (HPLC) method. The results showed, for the first time, that GG genotype of ACE A2350G was significantly associated with MDD among Iranian participants (P=0.001; odds ratio (OR)=6.2; 95% confidence interval (CI)=2.1-18.3). Significant higher serum ACE activity (P=0.0001) as well as higher diastolic blood pressure (P=0.036) were observed in depressed patients compared to the healthy control group. Depressed patients carrying GG genotype of the A2350G polymorphism had a significantly higher serum ACE activity (P=0.02) than individuals with either AA or AG genotype. In conclusion, this study supports the hypothesis of RAS overactivity in depression in that the genotype associated with higher serum ACE activity in an Iranian population was also associated with MDD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. DRD2 C313T and DRD4 48-bp VNTR polymorphisms and physical activity of healthy men in Lower Silesia, Poland (HALS study).

    Science.gov (United States)

    Jozkow, Pawel; Slowinska-Lisowska, Malgorzata; Laczmanski, Lukasz; Medras, Marek

    2013-03-01

    Both animal and human studies have proved that the dopaminergic system of the brain controls many aspects of behavior, e.g. motivation, addiction, motor movement, locomotion. It has been hypothesized that dopamine signalling may regulate spontaneous physical activity as well. Literature data suggests that an intact function of dopamine receptors (DRD2-DRD4) inhibits physical activity. This study searched for associations between a propensity to be active (or sedentary) and genetic variants of DRD2 and DRD4. Invitations to participate in the study were sent to 900 randomly selected, adult men living in Lower Silesia, Poland. Genotyping of DRD2 C313T and DRD4 48-bp VNTR polymorphisms of enrolled subjects (371 (DRD2 C313T) and 397 (DRD4 48-bp VNTR)) was performed. Level of physical activity was evaluated using the International Physical Activity Questionnaire (IPAQ). No associations were found between level of physical activity (low, moderate, high) and the two polymorphisms: DRD2 C313T (p = 0.49) and DRD4 48-bp VNTR (p = 0.31). Studied subjects did not differ as to the number of hours spent sitting either. The results exclude the presence of significant relationships between polymorphic variants of the dopamine receptors genes and the level of physical activity in men.

  17. Influence of plasminogen activator inhibitor-1 (SERPINE1) 4G/5G polymorphism on circulating SERPINE-1 antigen expression in HCC associated with viral infection.

    Science.gov (United States)

    Divella, Rosa; Mazzocca, Antonio; Gadaleta, Cosimo; Simone, Giovanni; Paradiso, Angelo; Quaranta, Michele; Daniele, Antonella

    2012-01-01

    Hepatocarcinogenesis is heavily influenced by chronic hepatitis B (HBV) and C (HCV) infection. Elevated levels of plasminogen activator inhibitor-1 (SERPINE1/PAI-1) have been reported in patients with hepatocellular carcinoma (HCC) associated with viral infection. The gene encoding SERPINE1 is highly polymorphic and the frequently associated 4/5 guanosine (4G/5G) polymorphism in the gene promoter may influence its expression. Here, we investigated the distribution of genotypes and the frequency of alleles of the 4G/5G polymorphism in patients with HCC, the influence of the 4G/5G polymorphism on plasma SERPINE1 levels and its association with viral infection. A total of 75 patients with HCC were enrolled: 32 (42.6%) were HBV(+)/HCV(+), 11 (14.6%) were only HCV(+), and 32 (42.6%) were negative for both viruses. A control group of healthy donors was also enrolled (n=50). SERPINE1 plasma concentrations were determined by ELISA and the detection of the promoter 4G/5G polymorphism was performed by an allele-specific PCR analysis. We found that the frequency of both the 4G/4G genotype (p=0.02) and the 4G allele (p=0.006) were significantly higher in patients with HCC compared to the control group, and particularly higher in patients with HCC co-infected with HBV(+)/HCV(+) than in those with no viral infection. We also found that patients with the 4G/4G genotype had significantly higher plasma SERPINE1 protein levels when compared with patients with the 4G/5G or 5G/5G genotype (p5G SERPINE1 polymorphism with a higher level of SERPINE1 protein in patients with HCC with HBV(+)/HCV(+) than those without infection, suggest the presence of two distinct pathogenic mechanisms in hepatocarcinogenesis, depending on the etiology.

  18. Effects of DISC1 Polymorphisms on Resting-State Spontaneous Neuronal Activity in the Early-Stage of Schizophrenia

    Directory of Open Access Journals (Sweden)

    Ningzhi Gou

    2018-05-01

    Full Text Available Background: Localized abnormalities in the synchrony of spontaneous neuronal activity, measured with regional homogeneity (ReHo, has been consistently reported in patients with schizophrenia (SCZ and their unaffected siblings. To date, little is known about the genetic influences affecting the spontaneous neuronal activity in SCZ. DISC1, a strong susceptible gene for SCZ, has been implicated in neuronal excitability and synaptic function possibly associated with regional spontaneous neuronal activity. This study aimed to examine the effects of DISC1 variations on the regional spontaneous neuronal activity in SCZ.Methods: Resting-state fMRI data were obtained from 28 SCZ patients and 21 healthy controls (HC for ReHo analysis. Six single nucleotide polymorphisms (SNPs of DISC1 gene were genotyped using the PCR and direct sequencing.Results: Significant diagnosis × genotype interactions were noted for three SNPs (rs821616, rs821617, and rs2738880. For rs821617, the interactions were localized to the precuneus, basal ganglia and pre-/post-central regions. Significant interactive effects were identified at the temporal and post-central gyri for rs821616 (Ser704Cys and the inferior temporal gyrus for rs2738880. Furthermore, post-hoc analysis revealed that the DISC1 variations on these SNPs exerted different influences on ReHo between SCZ patients and HC.Conclusion: To our knowledge this is the first study to unpick the influence of DISC1 variations on spontaneous neuronal activity in SCZ; Given the emerging evidence that ReHo is a stable inheritable phenotype for schizophrenia, our findings suggest the DISC1 variations are possibly an inheritable source for the altered ReHo in this disorder.

  19. Synthesis of molecular complexes for small molecule activation

    International Nuclear Information System (INIS)

    Andrez, Julie

    2016-01-01

    The redox chemistry of f-elements is drawing the attention of inorganic chemists due to their unusual reaction pathways. Notably low-valent f-element complexes have been shown to be able to activate small molecules such as CO_2 and N_2 in mild conditions. Compared to d-block metals, f-elements present a coordination chemistry dominated by electrostatic interactions and steric constraints. Molecular complexes of f-elements could thus provide new catalytic routes to transform small molecules into valuable chemicals. However the redox chemistry of low valent f-elements is dominated by single-electron transfers while the reductions of CO_2 and N_2 require multi-electronic processes. Accordingly the first approach of this PhD work was the use of redox active ligands as electron reservoir to support f-element centres increasing the electron number available for reduction events. The coordination of uranium with tridentate Schiff base ligand was investigated and led to isolation of a dinuclear electron-rich species able to undertake up to eight-electron reduction combining the redox activity of the ligands and the uranium centres. In order to obtain electron-rich compounds potentially able to polarize the C=O bond of CO_2, the synthesis of hetero-bimetallic species supported by salophen Schiff base ligand was also studied. In a second approach we have used bulky ligands with strong donor-character to tune the reducing abilities of low valent f-elements. In this case a bimolecular electron-transfer process is often observed. The reactivity of the U(III) siloxid complex [U(OSi(OtBu)_3)_4K] was further investigated. Notably, reaction with Ph_3PS led to the formation of a terminal U(IV) sulfide complex with multiple U-S bond which was analysed by DFT studies to better understand the bonding nature. Preliminary studies on the role of the counter-cation (M) in the system [U(OSi(OtBu)_3)_4M] on the outcome of the reactivity with CS_2 and CO_2 have also been performed. The

  20. Anticancer Activity of Metal Complexes: Involvement of Redox Processes

    Science.gov (United States)

    Jungwirth, Ute; Kowol, Christian R.; Keppler, Bernhard K.; Hartinger, Christian G.; Berger, Walter; Heffeter, Petra

    2012-01-01

    Cells require tight regulation of the intracellular redox balance and consequently of reactive oxygen species for proper redox signaling and maintenance of metal (e.g., of iron and copper) homeostasis. In several diseases, including cancer, this balance is disturbed. Therefore, anticancer drugs targeting the redox systems, for example, glutathione and thioredoxin, have entered focus of interest. Anticancer metal complexes (platinum, gold, arsenic, ruthenium, rhodium, copper, vanadium, cobalt, manganese, gadolinium, and molybdenum) have been shown to strongly interact with or even disturb cellular redox homeostasis. In this context, especially the hypothesis of “activation by reduction” as well as the “hard and soft acids and bases” theory with respect to coordination of metal ions to cellular ligands represent important concepts to understand the molecular modes of action of anticancer metal drugs. The aim of this review is to highlight specific interactions of metal-based anticancer drugs with the cellular redox homeostasis and to explain this behavior by considering chemical properties of the respective anticancer metal complexes currently either in (pre)clinical development or in daily clinical routine in oncology. PMID:21275772

  1. Polymorphisms in genes related to activation or detoxification of carcinogens might interact with smoking to increase renal cancer risk: Results from The Netherlands Cohort Study on diet and cancer

    NARCIS (Netherlands)

    Smits, K.M.; Schouten, L.J.; Dijk, B.A.C. van; Houwelingen, K. van; Hulsbergen-Kaa, C.A. van de; Kiemeney, L.A.L.M.; Houwelingen, K. van; Goldbohm, R.A.; Oosterwijk, E.; Brandt, P.A. van den

    2008-01-01

    Metabolic gene polymorphisms have previously been suggested as risk factors for renal cell carcinoma (RCC). These polymorphisms are involved in activation or detoxification of carcinogens in cigarette smoke which is another RCC risk factor. We evaluated gene-environment interactions between CYP1A1,

  2. Natural lecithin promotes neural network complexity and activity

    Science.gov (United States)

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-01-01

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called “essential” fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications. PMID:27228907

  3. Natural lecithin promotes neural network complexity and activity.

    Science.gov (United States)

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-05-27

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called "essential" fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications.

  4. Association of Single Nucleotide Polymorphisms in the ST3GAL4 Gene with VWF Antigen and Factor VIII Activity.

    Directory of Open Access Journals (Sweden)

    Jaewoo Song

    Full Text Available VWF is extensively glycosylated with biantennary core fucosylated glycans. Most N-linked and O-linked glycans on VWF are sialylated. FVIII is also glycosylated, with a glycan structure similar to that of VWF. ST3GAL sialyltransferases catalyze the transfer of sialic acids in the α2,3 linkage to termini of N- and O-glycans. This sialic acid modification is critical for VWF synthesis and activity. We analyzed genetic and phenotypic data from the Atherosclerosis Risk in Communities (ARIC study for the association of single nucleotide polymorphisms (SNPs in the ST3GAL4 gene with plasma VWF levels and FVIII activity in 12,117 subjects. We also analyzed ST3GAL4 SNPs found in 2,535 subjects of 26 ethnicities from the 1000 Genomes (1000G project for ethnic diversity, SNP imputation, and ST3GAL4 haplotypes. We identified 14 and 1,714 ST3GAL4 variants in the ARIC GWAS and 1000G databases respectively, with 46% being ethnically diverse in their allele frequencies. Among the 14 ST3GAL4 SNPs found in ARIC GWAS, the intronic rs2186717, rs7928391, and rs11220465 were associated with VWF levels and with FVIII activity after adjustment for age, BMI, hypertension, diabetes, ever-smoking status, and ABO. This study illustrates the power of next-generation sequencing in the discovery of new genetic variants and a significant ethnic diversity in the ST3GAL4 gene. We discuss potential mechanisms through which these intronic SNPs regulate ST3GAL4 biosynthesis and the activity that affects VWF and FVIII.

  5. Association of Single Nucleotide Polymorphisms in the ST3GAL4 Gene with VWF Antigen and Factor VIII Activity.

    Science.gov (United States)

    Song, Jaewoo; Xue, Cheng; Preisser, John S; Cramer, Drake W; Houck, Katie L; Liu, Guo; Folsom, Aaron R; Couper, David; Yu, Fuli; Dong, Jing-Fei

    2016-01-01

    VWF is extensively glycosylated with biantennary core fucosylated glycans. Most N-linked and O-linked glycans on VWF are sialylated. FVIII is also glycosylated, with a glycan structure similar to that of VWF. ST3GAL sialyltransferases catalyze the transfer of sialic acids in the α2,3 linkage to termini of N- and O-glycans. This sialic acid modification is critical for VWF synthesis and activity. We analyzed genetic and phenotypic data from the Atherosclerosis Risk in Communities (ARIC) study for the association of single nucleotide polymorphisms (SNPs) in the ST3GAL4 gene with plasma VWF levels and FVIII activity in 12,117 subjects. We also analyzed ST3GAL4 SNPs found in 2,535 subjects of 26 ethnicities from the 1000 Genomes (1000G) project for ethnic diversity, SNP imputation, and ST3GAL4 haplotypes. We identified 14 and 1,714 ST3GAL4 variants in the ARIC GWAS and 1000G databases respectively, with 46% being ethnically diverse in their allele frequencies. Among the 14 ST3GAL4 SNPs found in ARIC GWAS, the intronic rs2186717, rs7928391, and rs11220465 were associated with VWF levels and with FVIII activity after adjustment for age, BMI, hypertension, diabetes, ever-smoking status, and ABO. This study illustrates the power of next-generation sequencing in the discovery of new genetic variants and a significant ethnic diversity in the ST3GAL4 gene. We discuss potential mechanisms through which these intronic SNPs regulate ST3GAL4 biosynthesis and the activity that affects VWF and FVIII.

  6. Mannose-binding lectin gene polymorphisms are associated with disease activity and physical disability in untreated, anti-cyclic citrullinated peptide-positive patients with early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Garred, Peter; Madsen, Hans Ole

    2009-01-01

    OBJECTIVE: To study the association between polymorphisms in the mannose-binding lectin gene (MBL2) and disease activity, physical disability, and joint erosions in patients with newly diagnosed rheumatoid arthritis (RA). METHODS: Patients with early RA (n=158) not previously treated with disease...... modifying antirheumatic drugs, participating in a treatment trial (CIMESTRA study) were examined at inclusion for MBL2 pooled structural genotypes (O/O, A/O, A/A), regulatory MBL2 promoter polymorphism in position -221 (XX, XY, YY), anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), disease...... activity by Disease Activity Score-28 (DAS28 score), physical disability by Health Assessment Questionnaire (HAQ) score, and erosive changes in hands and feet (Sharp-van der Heijde score). RESULTS: Eight patients were homozygous MBL2 defective (O/O), 101 belonged to an intermediate group, and 49 were MBL2...

  7. Antibacterial, antimalarial and leishmanicidal activities of Cu (II) and nickel (II) complexes of diclofenac sodium

    International Nuclear Information System (INIS)

    Rehman, F.U.; Khan, M.F.; Khan, G.M.; Khan, H.; Khan, I.U.

    2010-01-01

    Metal complexes are famous for a wide array of chemotherapeutic effects. The current study was designed to synthesize and evaluate unexplored chemotherapeutic effects of Cu (II) and Nickel (II) complexes of the non-steroidal anti-inflammatory drug diclofenac. Nickel complex exhibited significant leishmanicidal activity against Lieshmania major, while the copper complex was found to possess low activity against the same pathogen. Both of the complexes revealed low antibacterial activities and were interestingly failed to produce any considerable antimalarial activity against Plasmodium falciparum 3D7. Selective leishmanicidal activities of Nickel (II) complex of diclofenac needs further improvement to be developed as potential new metal-based leishmanicidal agent.(author)

  8. Antibacterial, antimalarial and leishmanicidal activities of Cu (II) and nickel (II) complexes of diclofenac sodium

    Energy Technology Data Exchange (ETDEWEB)

    Rehman, F U; Khan, M F; Khan, G M; Khan, H [Gomal University, D.I. Khan (Pakistan). Dept. of Faculty of Pharmacy; Khan, I U [University of Peshawar (Pakistan). Dept. of Faculty of Pharmacy

    2010-08-15

    Metal complexes are famous for a wide array of chemotherapeutic effects. The current study was designed to synthesize and evaluate unexplored chemotherapeutic effects of Cu (II) and Nickel (II) complexes of the non-steroidal anti-inflammatory drug diclofenac. Nickel complex exhibited significant leishmanicidal activity against Lieshmania major, while the copper complex was found to possess low activity against the same pathogen. Both of the complexes revealed low antibacterial activities and were interestingly failed to produce any considerable antimalarial activity against Plasmodium falciparum 3D7. Selective leishmanicidal activities of Nickel (II) complex of diclofenac needs further improvement to be developed as potential new metal-based leishmanicidal agent.(author)

  9. Preparation and evaluation of famotidine polymorphs.

    Science.gov (United States)

    Nagaraju, Ravouru; Prathusha, Ande Penchala; Subhash Chandra Bose, Penjury; Kaza, Rajesh; Bharathi, Koganti

    2010-06-01

    The main objective of this study was to compare the behaviour of drug release among the famotidine polymorphs prepared by using various additives and solvents, by solvent evaporation method. The famotidine polyvinyl pyrrolidone polymorphs with different concentrations (0.5, 1 and 1.5%) were prepared by using solvent evaporation method. In these polymorphs of different concentrations 1% w/v polymorphs showed better release. Similarly, famotidine polymorphs of Tween 80 with different concentrations, polyethylene glycol 1% w/v and methanol was prepared. Famotidine polymorphs prepared the PVP (1% w/v) showed better drug release and solubility. DSC, FTIR, SEM and XRD studies were carried out. DSC studies revealed that PVP polymorphs were found to stable compared to other polymorphs. FTIR studies of the polymorphs prepared indicated that there was an interaction found in all polymorphs except PVP polymorphs indicating the absence of drug-additive interaction. SEM studies of PVP and methanol polymorphs revealed that they are tabular and prismatic and columnar respectively. These changes in morphology were due to variations in face dimensions and also properties of additives and solvent used in the preparation. XRD studies revealed that there is an increase in crystallinity in methanol polymorphs when compared to PVP polymorphs and pure drug. The mechanism of drug release was determined using zero order, first order and Hixon-Crowel equations. From the drug release kinetics these polymorphs followed first order and Hixon-Crowel release kinetics, exhibited fair linearity in their dissolution data. Further, in vivo studies were carried out for the evaluation of antiulcer activity. Based upon the drug release pattern and its kinetics only two of the prepared polymorphs of famotidine i.e. famotidine PVP polymorphs and famotidine methanol polymorphs were selected for animal studies. Antiulcer studies were carried out using pylorus ligation model and estimation of antioxidant

  10. Active Learning for Directed Exploration of Complex Systems

    Science.gov (United States)

    Burl, Michael C.; Wang, Esther

    2009-01-01

    Physics-based simulation codes are widely used in science and engineering to model complex systems that would be infeasible to study otherwise. Such codes provide the highest-fidelity representation of system behavior, but are often so slow to run that insight into the system is limited. For example, conducting an exhaustive sweep over a d-dimensional input parameter space with k-steps along each dimension requires k(sup d) simulation trials (translating into k(sup d) CPU-days for one of our current simulations). An alternative is directed exploration in which the next simulation trials are cleverly chosen at each step. Given the results of previous trials, supervised learning techniques (SVM, KDE, GP) are applied to build up simplified predictive models of system behavior. These models are then used within an active learning framework to identify the most valuable trials to run next. Several active learning strategies are examined including a recently-proposed information-theoretic approach. Performance is evaluated on a set of thirteen synthetic oracles, which serve as surrogates for the more expensive simulations and enable the experiments to be replicated by other researchers.

  11. Interaction Effect between Handedness and CNTNAP2 Polymorphism (rs7794745 genotype on Voice-specific Frontotemporal Activity in Healthy Individuals: An fMRI Study

    Directory of Open Access Journals (Sweden)

    Michihiko eKoeda

    2015-04-01

    Full Text Available Recent neuroimaging studies have demonstrated that Contactin-associated protein-like2 (CNTNAP2 polymorphisms affect left-hemispheric function of language processing in healthy individuals, but no study has investigated the influence of these polymorphisms on right-hemispheric function involved in human voice perception. Further, although recent reports suggest that determination of handedness is influenced by genetic effect, the interaction effect between handedness and CNTNAP2 polymorphisms for brain activity in human voice perception and language processing has not been revealed. We aimed to investigate the interaction effect of handedness and CNTNAP2 polymorphisms in respect to brain function for human voice perception and language processing in healthy individuals. Brain function of 108 healthy volunteers (74 right-handed and 34 non-right-handed was examined while they were passively listening to reverse sentences (rSEN, identifiable non-vocal sounds (SND, and sentences (SEN. Full factorial design analysis was calculated by using three factors: 1 rs7794745 (A/A or A/T, 2 rs2710102 (G/G or A carrier (A/G and A/A, and 3 voice-specific response (rSEN or SND. The main effect of rs7794745 (A/A or A/T was significantly revealed at the right middle frontal gyrus (MFG and bilateral superior temporal gyrus (STG. This result suggests that rs7794745 genotype affects voice-specific brain function. Furthermore, interaction effect was significantly observed among MFG-STG activations by human voice perception, rs7794745 (A/A or A/T, and handedness. These results suggest that CNTNAP2 polymorphisms could be one of the important factors in the neural development related to vocal communication and language processing in both right-handed and non-right-handed healthy individuals.

  12. Complex relationships between occupation, environment, DNA adducts, genetic polymorphisms and bladder cancer in a case-control study using a structural equation modeling.

    Directory of Open Access Journals (Sweden)

    Stefano Porru

    Full Text Available DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs and polycyclic aromatic hydrocarbons (PAHs. No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028, whereas XRCC1 Arg 399 (p<0.006 was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001, coffee (p<0.001, cumulative AAs exposure (p = 0.041 and MnSOD (p = 0.009 and a decreased risk by MPO (p<0.008 were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different

  13. Lack of association between PCK1 polymorphisms and obesity, physical activity, and fitness in European Youth Heart Study (EYHS)

    DEFF Research Database (Denmark)

    Vimaleswaran, Karani S; Franks, Paul W; Brage, Soren

    2010-01-01

    genetic variation in the PCK1 gene influences obesity-related traits, PA, and fitness, and to examine whether PA and fitness attenuate the influence of the PCK1 polymorphisms on obesity in children. Analyses were undertaken on data from Danish and Estonian children (958 boys and 1,104 girls) from...... the European Youth Heart Study (EYHS), a school-based, cross-sectional study of children (mean ± s.d. age: 9.6 ± 0.4 years) and adolescents (15.5 ± 0.5 years). We genotyped eight polymorphisms that captured the common genetic variations in the PCK1 gene. The association between the PCK1 polymorphisms and BMI......, waist circumference (WC), sum of four skinfolds, PA, and fitness was tested using an additive model adjusted for age, age-group, gender, maturity, and country. Interactions were tested by including interaction terms in the model. None of the polymorphisms were significantly associated with BMI, WC, sum...

  14. Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with coronary artery disease risk: a meta-analysis.

    Science.gov (United States)

    Zhang, Huifeng; Dong, Pingshuan; Yang, Xuming; Liu, Zhenghao

    2014-01-01

    The aim of the current study was to evaluate the association of PAI-1 4G/5G polymorphism with coronary artery disease (CAD) risk using a meta-analysis. All eligible studies were identified through a search of PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Database of Chinese Scientific and Technical Periodicals, and China Biology Medical literature database (CBM) before June 2014. The association between the PAI-1 4G/5G polymorphism and CAD risk was estimated by odds ratio (OR) and 95% confidence interval (CI). A total of 72 studies including 23557 cases and 21526 controls were eventually collected. The PAI-1 4G/5G polymorphism was significant associated with CAD risk in overall population (OR=1.19, 95% CI 1.10-1.28, P 5G polymorphism was a risk factor for CAD.

  15. Plasminogen activator inhibitor-1 4G/5G gene polymorphism and coronary artery disease in the Chinese Han population: a meta-analysis.

    Science.gov (United States)

    Li, Yan-yan

    2012-01-01

    The polymorphism of plasminogen activator inhibitor-1 (PAI-1) 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD) susceptibility, but study results are still debatable. The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR) for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI) was assessed by the random effect model. The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004). The heterogeneity test was also significant (P5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD.

  16. Effect of polymorphism in the peroxisome proliferator-activated receptor gamma gene on litter size of pigs.

    Science.gov (United States)

    Wang, Guiying; Kong, Lujun; Hu, Peng; Fu, Jinlian; Wang, Aiguo

    2011-03-01

    The association of polymorphisms in peroxisome proliferator-activated receptor γ (PPARγ) gene with litter size was studied in Large White and Landrace pig. Three SNP loci (P1, P2 and P7) on PPARγ(2) gene were determined by PCR-SSCP and the results showed that there were A → G mutations at 220 and 324 bp in 5'-regulator region and at 147 bp in exon 6, respectively. Allele frequencies were analysed in two breeds. Information on 2341 litter records from 564 sows was used to analyse the trait total number born (TNB) and number born alive (NBA). In Large White, TNB and NBA of genotype BB for P2 locus were the lowest, and the TNB and NBA of third and following parities and all parities were 0.74 and 0.51 piglets per litter less (P NBA of the first parity of genotype BB for P1 locus were 2.0 piglets per litter higher than AA (P NBA of genotype BB were 0.66 and 0.97 piglets per litter (P NBA of the second parity of genotype AA were obviously higher than those of AB (P NBA of each parity of genotype AA were both about 2 piglets per litter more than those of BB (P < 0.05). The results indicated that PPARγ gene was significantly associated with litter size in pigs.

  17. Nicotinergic Modulation of Attention-Related Neural Activity Differentiates Polymorphisms of DRD2 and CHRNA4 Receptor Genes.

    Directory of Open Access Journals (Sweden)

    Thomas P K Breckel

    Full Text Available Cognitive and neuronal effects of nicotine show high interindividual variability. Recent findings indicate that genetic variations that affect the cholinergic and dopaminergic neurotransmitter system impact performance in cognitive tasks and effects of nicotine. The current pharmacogenetic functional magnetic resonance imaging (fMRI study aimed to investigate epistasis effects of CHRNA4/DRD2 variations on behavioural and neural correlates of visuospatial attention after nicotine challenge using a data driven partial least squares discriminant analysis (PLS-DA approach. Fifty young healthy non-smokers were genotyped for CHRNA4 (rs1044396 and DRD2 (rs6277. They received either 7 mg transdermal nicotine or a matched placebo in a double blind within subject design prior to performing a cued target detection task with valid and invalid trials. On behavioural level, the strongest benefits of nicotine in invalid trials were observed in participants carrying both, the DRD2 T- and CHRNA4 C+ variant. Neurally, we were able to demonstrate that different DRD2/CHRNA4 groups can be decoded from the pattern of brain activity in invalid trials under nicotine. Neural substrates of interindividual variability were found in a network of attention-related brain regions comprising the pulvinar, the striatum, the middle and superior frontal gyri, the insula, the left precuneus, and the right middle temporal gyrus. Our findings suggest that polymorphisms in the CHRNA4 and DRD2 genes are a relevant source of individual variability in pharmacological studies with nicotine.

  18. Functional analysis and molecular dynamics simulation of LOX-1 K167N polymorphism reveal alteration of receptor activity.

    Directory of Open Access Journals (Sweden)

    Silvia Biocca

    Full Text Available The human lectin-like oxidized low density lipoprotein receptor 1 LOX-1, encoded by the ORL1 gene, is the major scavenger receptor for oxidized low density lipoprotein in endothelial cells. Here we report on the functional effects of a coding SNP, c.501G>C, which produces a single amino acid change (K>N at codon 167. Our study was aimed at elucidating whether the c.501G>C polymorphism changes the binding affinity of LOX-1 receptor altering its function. The presence of p.K167N mutation reduces ox-LDL binding and uptake. Ox-LDL activated extracellular signal-regulated kinases 1 and 2 (ERK 1/2 is inhibited. Furthermore, ox-LDL induced biosynthesis of LOX-1 receptors is dependent on the p.K167N variation. In human macrophages, derived from c.501G>C heterozygous individuals, the ox-LDL induced LOX-1 46 kDa band is markedly lower than in induced macrophages derived from c.501G>C controls. Investigation of p.K167N mutation through molecular dynamics simulation and electrostatic analysis suggests that the ox-LDL binding may be attributed to the coupling between the electrostatic potential distribution and the asymmetric flexibility of the basic spine residues. The N/N-LOX-1 mutant has either interrupted electrostatic potential and asymmetric fluctuations of the basic spine arginines.

  19. Peroxisome Proliferator-Activated Receptor Genetic Polymorphisms and Nonalcoholic Fatty Liver Disease: Any Role in Disease Susceptibility?

    Directory of Open Access Journals (Sweden)

    Paola Dongiovanni

    2013-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD defines a wide spectrum of liver diseases that extend from simple steatosis, that is, increased hepatic lipid content, to nonalcoholic steatohepatitis (NASH, a condition that may progress to cirrhosis with its associated complications. Nuclear hormone receptors act as intracellular lipid sensors that coordinate genetic networks regulating lipid metabolism and energy utilization. This family of transcription factors, in particular peroxisome proliferator-activated receptors (PPARs, represents attractive drug targets for the management of NAFLD and NASH, as well as related conditions such as type 2 diabetes and the metabolic syndrome. The impact on the regulation of lipid metabolism observed for PPARs has led to the hypothesis that genetic variants within the human PPARs genes may be associated with human disease such as NAFLD, the metabolic syndrome, and/or coronary heart disease. Here we review the available evidence on the association between PPARs genetic polymorphism and the susceptibility to NAFLD and NASH, and we provide a meta-analysis of the available evidence. The impact of PPAR variants on the susceptibility to NASH in specific subgroup of patients, and in particular on the response to therapies, especially those targeting PPARs, represents promising new areas of investigation.

  20. Polymorphic drug metabolising enzymes : Assessment of activities by phenotyping and genotyping in clinical pharmacology

    NARCIS (Netherlands)

    Tamminga, Willem Jan

    2001-01-01

    Drug effects (pharmacodynamics) are determined by drug concentration at target site and the affinity of the drug for a target. Pharmacogenetics describes inherited differences in drug metabolising enzyme activities and differences in drug transporters and receptors.Answers were sought on the

  1. Biological activities of some Fluoroquinolones-metal complexes

    African Journals Online (AJOL)

    McRoy

    DNA cleavage studies of some synthesized metal complexes of fluoroquinolone ... Although the FQs are generally characterized by a broad antimicrobial spectrum ..... six Coordinate 3rd metal complexes with N- (5 –Phenyl-3,4- thiadiazol-2-yl).

  2. ON MAGNETIC ACTIVITY BAND OVERLAP, INTERACTION, AND THE FORMATION OF COMPLEX SOLAR ACTIVE REGIONS

    Energy Technology Data Exchange (ETDEWEB)

    McIntosh, Scott W. [High Altitude Observatory, National Center for Atmospheric Research, P.O. Box 3000, Boulder, CO 80307 (United States); Leamon, Robert J., E-mail: mscott@hao.ucar.edu [Department of Physics, Montana State University, Bozeman, MT 59717 (United States)

    2014-11-20

    Recent work has revealed a phenomenological picture of the how the ∼11 yr sunspot cycle of the Sun arises. The production and destruction of sunspots is a consequence of the latitudinal-temporal overlap and interaction of the toroidal magnetic flux systems that belong to the 22 yr magnetic activity cycle and are rooted deep in the Sun's convective interior. We present a conceptually simple extension of this work, presenting a hypothesis on how complex active regions can form as a direct consequence of the intra- and extra-hemispheric interaction taking place in the solar interior. Furthermore, during specific portions of the sunspot cycle, we anticipate that those complex active regions may be particularly susceptible to profoundly catastrophic breakdown, producing flares and coronal mass ejections of the most severe magnitude.

  3. Associations of ACE Gene Insertion/Deletion Polymorphism, ACE Activity, and ACE mRNA Expression with Hypertension in a Chinese Population

    OpenAIRE

    He, Qingfang; Fan, Chunhong; Yu, Min; Wallar, Gina; Zhang, Zuo-Feng; Wang, Lixin; Zhang, Xinwei; Hu, Ruying

    2013-01-01

    Background The present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored. Methods The research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written i...

  4. Enhanced proteolysis of thiopurine S-methyltransferase (TPMT) encoded by mutant alleles in humans (TPMT∗3A, TPMT∗2): Mechanisms for the genetic polymorphism of TPMT activity

    OpenAIRE

    Tai, Hung-Liang; Krynetski, Eugene Y.; Schuetz, Erin G.; Yanishevski, Yuri; Evans, William E.

    1997-01-01

    TPMT is a cytosolic enzyme that catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds, including medications such as mercaptopurine and thioguanine. TPMT activity exhibits autosomal codominant genetic polymorphism, and patients inheriting TPMT deficiency are at high risk of potentially fatal hematopoietic toxicity. The most prevalent mutant alleles associated with TPMT deficiency in humans have been cloned and characterized (TPMT∗2 and TPMT∗3A), but the mechanisms for ...

  5. Identification of BDNF sensitive electrophysiological markers of synaptic activity and their structural correlates in healthy subjects using a genetic approach utilizing the functional BDNF Val66Met polymorphism.

    Directory of Open Access Journals (Sweden)

    Fruzsina Soltész

    Full Text Available Increasing evidence suggests that synaptic dysfunction is a core pathophysiological hallmark of neurodegenerative disorders. Brain-derived neurotropic factor (BDNF is key synaptogenic molecule and targeting synaptic repair through modulation of BDNF signalling has been suggested as a potential drug discovery strategy. The development of such "synaptogenic" therapies depend on the availability of BDNF sensitive markers of synaptic function that could be utilized as biomarkers for examining target engagement or drug efficacy in humans. Here we have utilized the BDNF Val66Met genetic polymorphism to examine the effect of the polymorphism and genetic load (i.e. Met allele load on electrophysiological (EEG markers of synaptic activity and their structural (MRI correlates. Sixty healthy adults were prospectively recruited into the three genetic groups (Val/Val, Val/Met, Met/Met. Subjects also underwent fMRI, tDCS/TMS, and cognitive assessments as part of a larger study. Overall, some of the EEG markers of synaptic activity and brain structure measured with MRI were the most sensitive markers of the polymorphism. Met carriers showed decreased oscillatory activity and synchrony in the neural network subserving error-processing, as measured during a flanker task (ERN; and showed increased slow-wave activity during resting. There was no evidence for a Met load effect on the EEG measures and the polymorphism had no effects on MMN and P300. Met carriers also showed reduced grey matter volume in the anterior cingulate and in the (left prefrontal cortex. Furthermore, anterior cingulate grey matter volume, and oscillatory EEG power during the flanker task predicted subsequent behavioural adaptation, indicating a BDNF dependent link between brain structure, function and behaviour associated with error processing and monitoring. These findings suggest that EEG markers such as ERN and resting EEG could be used as BDNF sensitive functional markers in early

  6. The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis

    OpenAIRE

    Lamana, Amalia; Balsa, Alejandro; Rueda, Blanca; Ortiz, Ana M.; Nuño, Laura; Miranda-Carus, Maria Eugenia; Gonzalez-Escribano, Maria F.; Lopez-Nevot, Miguel A.; Pascual-Salcedo, Dora; Martin, Javier; González-Álvaro, Isidoro

    2012-01-01

    Background: The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. Methodology and Results: We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-...

  7. Plasminogen activator inhibitor-1 4G/5G and the MTHFR 677C/T polymorphisms and susceptibility to polycystic ovary syndrome: a meta-analysis.

    Science.gov (United States)

    Lee, Young Ho; Song, Gwan Gyu

    2014-04-01

    The aim of this study was to explore whether the plasminogen activator inhibitor-1 (PAI-1) 4G/5G and the methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphisms are associated with susceptibility to polycystic ovary syndrome (PCOS). Meta-analyses were conducted to determine the association between the PAI-1 4G/5G and MTHFR 677C/T polymorphisms and PCOS using: (1) allele contrast (2) homozygote contrast, (3) recessive, and (4) dominant models. For meta-analysis, nine studies of the PAI-1 4G/5G polymorphism with 2384 subjects (PCOS, 1615; controls, 769) and eight studies of the MTHFR 677C/T polymorphism with 1270 study subjects were included. Meta-analysis of all study subjects showed no association between PCOS and the PAI-1 4G allele (OR=0.949, 95% CI=0.671-1.343, p=0.767). Stratification by ethnicity, however, indicated a significant association between the PAI-1 4G allele and PCOS in Turkish and Asian populations (OR=0.776, 95% CI=0.602-0.999, p=0.049; OR=1.749, 95% CI=1.297-2.359, p=2.5×10(-5) respectively). In addition, meta-analysis indicated an association between PCOS and the PAI-1 4G4G+4G5G genotype in Europeans (OR=1.406, 95% CI=1.025-1.928, p=0.035). However, meta-analysis of all study subjects showed no association between PCOS and the MTHFR 677T allele (OR=0.998, 95% CI=0.762-1.307, p=0.989), including Europeans (OR=0.806, 95% CI=0.610-1.063, p=0.126). Meta-analysis showed no association between PCOS and the MTHFR 677C/T polymorphism using homozygote contrast, and recessive and dominant models. In conclusion, meta-analysis suggests the PAI-1 4G/5G polymorphism is associated with susceptibility to PCOS in European, Turkish, and Asian populations, but the MTHFR 677C/T polymorphism is not associated with susceptibility to PCOS in Europeans. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. ISOENZYMATIC POLYMORPHISM AND ACTIVITY OF PEROXIDASES OF COMMON BEAN (Phaseolus vulgaris L. UNDER SALINE STRESS

    Directory of Open Access Journals (Sweden)

    F. BROETTO

    1997-09-01

    Full Text Available One of the uses of the technique of tissue culture for plant breeding is the identification of cell lines tolerant to salt stress.In order to study the biochemical mechanisms involved in the genetic expression to salt tolerance, callus from embryo axis of four bean cultivars (cv. IAC-carioca; cv. IAPAR-14; cv. JALO-EEP558; CV. BAT-93 were grown in Murashige & Skoog (1962 medium, supplemented with NaCl in the concentrations of 0, 20, 40, 60 and 80 mM. After 14 days callus were harvested and analyzed according to their isoenzymatic patterns and peroxidase activities. BAT and IAPAR cultivars showed two common activity zones in the anodic region, with only one specific enzymatic band to each one (the two fastest migration band; it is possible that the two middle anodic zones detected are products of the same enzymatic locus but from different alleles with different eletrophoretic mobilities. Cv. JALO showed two anodic activities in common with cvs IAC and IAPAR with an exclusive anodic zone of slower migration which showed the most intense activity of all cultivars analyzed. This cv. still showed a dimeric heterozygotic catodic zone in all treated samples. Probably this is the same zone which occurs in homozygosis with fixation of the slower allele for all cvs BAT and IAPAR submitted to all treatments. Cv. IAC showed two anodic bands in common with Cv. IAPAR and cv. JALO. It still showed a faster anodic band in common with cv. IAPAR and an exclusive anodic band of slower migration. It is interesting to say that for this cv. IAC resulting from cultivation in NaCl 20 mM did not show activity in the three slower anodic zones. Cv. IAC showed only one dimeric heterozygotic catodic zone in all treatments. This zone is probably composed by two different alleles from the same locus detected in cv. JALO. Samples from cv. IAC treated with 40 and 60 mM showed a more intense enzymatic activity in the catodic zone. Analyses of the peroxidase activity in the

  9. Activation of cutaneous immune responses in complex regional pain syndrome

    Science.gov (United States)

    Birklein, Frank; Drummond, Peter D.; Li, Wenwu; Schlereth, Tanja; Albrecht, Nahid; Finch, Philip M.; Dawson, Linda F.; Clark, J. David; Kingery, Wade S.

    2014-01-01

    The pathogenesis of complex regional pain syndrome (CRPS) is unresolved, but TNF-α and IL-6 are elevated in experimental skin blister fluid from CRPS affected limbs, as is tryptase, a marker for mast cells. In the rat fracture model of CRPS exaggerated sensory and sympathetic neural signaling stimulate keratinocyte and mast cell proliferation, causing the local production of high levels of inflammatory cytokines leading to pain behavior. The current investigation used CRPS patient skin biopsies to determine whether keratinocyte and mast cell proliferation occur in CRPS skin and to identify the cellular source of the up-regulated TNF-α, IL-6, and tryptase observed in CRPS experimental skin blister fluid. Skin biopsies were collected from the affected skin and the contralateral mirror site in 55 CRPS patients and the biopsy sections were immunostained for keratinocyte, cell proliferation, mast cell markers, TNF-α, and IL-6. In early CRPS keratinocytes were activated in the affected skin, resulting in proliferation, epidermal thickening, and up-regulated TNF-α and IL-6 expression. In chronic CRPS there was reduced keratinocyte proliferation with epidermal thinning in the affected skin. Acute CRPS patients also had increased mast cell accumulation in the affected skin, but there was no increase in mast cell numbers in chronic CRPS. PMID:24462502

  10. HAMLET - A protein-lipid complex with broad tumoricidal activity.

    Science.gov (United States)

    Ho, James C S; Nadeem, Aftab; Svanborg, Catharina

    2017-01-15

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process. In subsequent studies, we have identified a sequence of interactions that starts with the membrane integration of HAMLET and the activation of ion fluxes followed by HAMLET internalization, progressive inhibition of MAPK kinases and GTPases and sorting of HAMLET to different cellular compartments, including the nuclei. Therapeutic efficacy of HAMLET has been demonstrated in animal models of glioblastoma, bladder cancer and intestinal cancer. In clinical studies, HAMLET has been shown to target skin papillomas and bladder cancers. The findings identify HAMLET as a new drug candidate with promising selectivity for cancer cells and a strong therapeutic potential. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation

    DEFF Research Database (Denmark)

    Andreasen, Camilla H; Stender-Petersen, Kirstine L; Mogensen, Mette S

    2008-01-01

    (-16)). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive...... homozygous risk A-allele carriers had a 1.95 +/- 0.3 kg/m(2) increase in BMI compared with homozygous T-allele carriers. CONCLUSIONS: We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical......OBJECTIVE: Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes...

  12. Gender difference of serum angiotensin-converting enzyme (ACE) activity in DD genotype of ACE insertion/deletion polymorphism in elderly Chinese.

    Science.gov (United States)

    Zhang, Ya-Feng; Cheng, Qiong; Tang, Nelson L S; Chu, Tanya T W; Tomlinson, Brian; Liu, Fan; Kwok, Timothy C Y

    2014-12-01

    In this study we investigated the gender difference of serum angiotensin-converting enzyme (ACE) activity in a population of Hong Kong-dwelling elderly Chinese. A total of 1767 (843 male, 924 female) Hong Kong-dwelling elderly Chinese were recruited. ACE I/D genotypes were identified by polymerase chain reaction amplification and serum ACE activity was determined using a commercially available kinetic kit. ACE I/D genotype distribution was compared by chi-square test, the correlation between ACE I/D polymorphism and serum ACE activity was analysed by ANOVA test and gender difference of serum ACE activity of different genotypes was compared by independent sample t-test. No statistically significant difference of genotype distribution between male and female subjects was found. Serum ACE activity was significantly correlated with ACE genotype. Overall, there was no gender difference of serum ACE activity; however, when sub-grouping the subjects by ACE I/D genotype, male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. No significant gender difference of genotype distribution was found in elderly Chinese. Serum ACE activity was significantly correlated with ACE I/D polymorphism in elderly Chinese. Male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. © The Author(s) 2013.

  13. Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity.

    Science.gov (United States)

    Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; Mota, Glória de Fátima Alves da; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

    2018-01-01

    Previous studies have linked angiotensin-converting enzyme ( ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O 2 consumption (VO 2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two -way repeated-measures ANOVA were used. In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO 2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N-domain activity is dependent on the DD

  14. Molecular chaperone complexes with antagonizing activities regulate stability and activity of the tumor suppressor LKB1.

    Science.gov (United States)

    Gaude, H; Aznar, N; Delay, A; Bres, A; Buchet-Poyau, K; Caillat, C; Vigouroux, A; Rogon, C; Woods, A; Vanacker, J-M; Höhfeld, J; Perret, C; Meyer, P; Billaud, M; Forcet, C

    2012-03-22

    LKB1 is a tumor suppressor that is constitutionally mutated in a cancer-prone condition, called Peutz-Jeghers syndrome, as well as somatically inactivated in a sizeable fraction of lung and cervical neoplasms. The LKB1 gene encodes a serine/threonine kinase that associates with the pseudokinase STRAD (STE-20-related pseudokinase) and the scaffolding protein MO25, the formation of this heterotrimeric complex promotes allosteric activation of LKB1. We have previously reported that the molecular chaperone heat shock protein 90 (Hsp90) binds to and stabilizes LKB1. Combining pharmacological studies and RNA interference approaches, we now provide evidence that the co-chaperone Cdc37 participates to the regulation of LKB1 stability. It is known that the Hsp90-Cdc37 complex recognizes a surface within the N-terminal catalytic lobe of client protein kinases. In agreement with this finding, we found that the chaperones Hsp90 and Cdc37 interact with an LKB1 isoform that differs in the C-terminal region, but not with a novel LKB1 variant that lacks a portion of the kinase N-terminal lobe domain. Reconstitution of the two complexes LKB1-STRAD and LKB1-Hsp90-Cdc37 with recombinant proteins revealed that the former is catalytically active whereas the latter is inactive. Furthermore, consistent with a documented repressor function of Hsp90, LKB1 kinase activity was transiently stimulated upon dissociation of Hsp90. Finally, disruption of the LKB1-Hsp90 complex favors the recruitment of both Hsp/Hsc70 and the U-box dependent E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein) that triggers LKB1 degradation. Taken together, our results establish that the Hsp90-Cdc37 complex controls both the stability and activity of the LKB1 kinase. This study further shows that two chaperone complexes with antagonizing activities, Hsp90-Cdc37 and Hsp/Hsc70-CHIP, finely control the cellular level of LKB1 protein.

  15. Binuclear Copper(I Borohydride Complex Containing Bridging Bis(diphenylphosphino Methane Ligands: Polymorphic Structures of [(µ2-dppm2Cu2(η2-BH42] Dichloromethane Solvate

    Directory of Open Access Journals (Sweden)

    Natalia V. Belkova

    2017-10-01

    Full Text Available Bis(diphenylphosphinomethane copper(I tetrahydroborate was synthesized by ligands exchange in bis(triphenylphosphine copper(I tetrahydroborate, and characterized by XRD, FTIR, NMR spectroscopy. According to XRD the title compound has dimeric structure, [(μ2-dppm2Cu2(η2-BH42], and crystallizes as CH2Cl2 solvate in two polymorphic forms (orthorhombic, 1, and monoclinic, 2 The details of molecular geometry and the crystal-packing pattern in polymorphs were studied. The rare Twisted Boat-Boat conformation of the core Cu2P4C2 cycle in 1 is found being more stable than Boat-Boat conformation in 2.

  16. Heterolytic activation of dihydrogen by platinum and palladium complexes

    NARCIS (Netherlands)

    Almeida Leñero, K.Q.; Guari, Y.; Kramer, P.C.J.; van Leeuwen, P.W.N.M.; Donnadieu, B.; Sabo-Etienne, S.; Chaudret, B.; Lutz, M.; Spek, A.L.

    2013-01-01

    Wide bite angle diphosphine ligands were used to prepare [(diphosphine)M(2-(diphenylphosphino)pyridine)]2+ complexes (M = Pd, Pt). Except for the ligand with the largest bite angle, 2-(diphenylphosphino)pyridine coordinates in a bidentate mode leading to bis-chelate complexes. In the case of

  17. [Physico-chemical features of dinitrosyl iron complexes with natural thiol-containing ligands underlying biological activities of these complexes].

    Science.gov (United States)

    Vanin, A F; Borodulin, R R; Kubrina, L N; Mikoian, V D; Burbaev, D Sh

    2013-01-01

    Current notions and new experimental data of the authors on physico-chemical features of dinitrosyl iron complexes with natural thiol-containing ligands (glutathione or cysteine), underlying the ability of the complexes to act as NO molecule and nitrosonium ion donors, are considered. This ability determines various biological activities of dinitrosyl iron complexes--inducing long-lasting vasodilation and thereby long-lasting hypotension in human and animals, inhibiting pellet aggregation, increasing red blood cell elasticity, thereby stimulating microcirculation, and reducing necrotic zone in animals with myocardial infarction. Moreover, dinitrosyl iron complexes are capable of accelerating skin wound healing, improving the function of penile cavernous tissue, blocking apoptosis development in cell cultures. When decomposed dinitrosyl iron complexes can exert cytotoxic effect that can be used for curing infectious and carcinogenic pathologies.

  18. Synthesis and Anticancer Activity of Gold(I)-Chloroquine Complexes

    OpenAIRE

    Navarro, Maribel; Castro, William; González, Sorenlis; Abad, María Jesús; Taylor, Peter

    2013-01-01

    Two new gold(I) -chloroquine complexes, Au(CQ)(Cl) (1) and Au(CQ)(tgta) (2), were prepared and their most probable structure were established through a combination of different spectroscopic and analytical techniques. Their interaction with two important targets of action, DNA and thioredoxin reductase (TrxR), were investigated. These studies showed that complexes 1 and 2 displayed two types of interaction with DNA, covalent binding through the metal center, and additionally a non-covalent in...

  19. Nuclease-like activity of some Cu(II) complexes

    International Nuclear Information System (INIS)

    Durackova, Z.; Fenikova, L.; Svorenova, L.; Labudova, O.; Kollarova, M.; Labuda, J.

    1995-01-01

    The nuclease reaction of a copper complex with the macrocyclic Schiff base ligand tetrabenzo[b,f,j,n][a,3,9,13]tetraaza cyclohexadecine (TAAB) at the cleavage of DNA in aerobic conditions and the presence of ascorbic acid has been investigated and compared with that of the copper phenanthroline complex. The AT specifity of the Cu(TAAB) 2+ for both single-stranded and double-stranded DNA templates was observed. (authors), 4 figs., 6 refs

  20. Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

    Directory of Open Access Journals (Sweden)

    García-Arias Carlota

    2009-06-01

    Full Text Available Abstract Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases and 31 patients with severe hypertriglyceridaemia (controls were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS. Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood.

  1. Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

    Science.gov (United States)

    2009-01-01

    Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood. PMID:19534808

  2. Non-Synonymous Single-Nucleotide Polymorphisms and Physical Activity Interactions on Adiposity Parameters in Malaysian Adolescents

    Directory of Open Access Journals (Sweden)

    Nur Lisa Zaharan

    2018-04-01

    Full Text Available BackgroundSeveral non-synonymous single-nucleotide polymorphisms (nsSNPs have been shown to be associated with obesity. Little is known about their associations and interactions with physical activity (PA in relation to adiposity parameters among adolescents in Malaysia.MethodsWe examined whether (a PA and (b selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151. Body mass indices, waist–hip ratio, and percentage body fat (% BF were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C. Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3 rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS. Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model.ResultsPAQ-C scores were associated with % BF (β = −0.44 [95% confidence interval −0.72, −0.16], p = 0.002. The CC genotype of ADRB3 rs4994 (β = −0.16 [−0.28, −0.05], corrected p = 0.01 and AA genotype of MC3R rs3827103 (β = −0.06 [−0.12, −0.00], p = 0.02 were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = −0.05 [−0.10, −0.01], p = 0.02 and combined GRS (β = −0.03 [−0.04, −0.01], p = 0.01 for % BF.ConclusionHigher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention

  3. Non-Synonymous Single-Nucleotide Polymorphisms and Physical Activity Interactions on Adiposity Parameters in Malaysian Adolescents.

    Science.gov (United States)

    Zaharan, Nur Lisa; Muhamad, Nor Hanisah; Jalaludin, Muhammad Yazid; Su, Tin Tin; Mohamed, Zahurin; Mohamed, M N A; A Majid, Hazreen

    2018-01-01

    Several non-synonymous single-nucleotide polymorphisms (nsSNPs) have been shown to be associated with obesity. Little is known about their associations and interactions with physical activity (PA) in relation to adiposity parameters among adolescents in Malaysia. We examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study ( n  = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model. PAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p  = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p  = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p  = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p  = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p  = 0.01) for % BF. Higher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.

  4. Polymorphic Contracts

    Science.gov (United States)

    Belo, João Filipe; Greenberg, Michael; Igarashi, Atsushi; Pierce, Benjamin C.

    Manifest contracts track precise properties by refining types with predicates - e.g., {x : Int |x > 0 } denotes the positive integers. Contracts and polymorphism make a natural combination: programmers can give strong contracts to abstract types, precisely stating pre- and post-conditions while hiding implementation details - for example, an abstract type of stacks might specify that the pop operation has input type {x :α Stack |not ( empty x )} . We formalize this combination by defining FH, a polymorphic calculus with manifest contracts, and establishing fundamental properties including type soundness and relational parametricity. Our development relies on a significant technical improvement over earlier presentations of contracts: instead of introducing a denotational model to break a problematic circularity between typing, subtyping, and evaluation, we develop the metatheory of contracts in a completely syntactic fashion, omitting subtyping from the core system and recovering it post facto as a derived property.

  5. Association analysis between mitogen-activated protein/extracellular signal-regulated kinase (MEK) gene polymorphisms and depressive disorder in the Han Chinese population.

    Science.gov (United States)

    Hu, Yingyan; Hong, Wu; Smith, Alicia; Yu, Shunying; Li, Zezhi; Wang, Dongxiang; Yuan, Chengmei; Cao, Lan; Wu, Zhiguo; Huang, Jia; Fralick, Drew; Phillips, Michael Robert; Fang, Yiru

    2017-11-01

    Recent research findings suggest that BDNF and BDNF signaling pathways participate in the development of major depressive disorder. Mitogen-activated extracellular signal-regulated kinase (MEK) is the most important kinase in the extracellular signal-regulated kinase pathway, and the extracellular signal-regulated kinase pathway is the key signaling pathway of BDNF, so it may play a role in development of depressive disorder. The aim of this study is to investigate the association between polymorphisms of the MAP2K1 (also known as MEK) gene and depressive disorder. Three single nucleotide polymorphisms (SNPs), were significantly associated with depressive disorder: rs1549854 (p = 0.006), rs1432441 (p = 0.025), and rs7182853 (p = 0.039). When subdividing the sample by gender, two of the SNPs remained statistically associated with depressive disorder in females: rs1549854 (p = 0.013) and rs1432441 (p = 0.04). The rs1549854 and rs1432441 polymorphisms of the MAP2K1 gene may be associated with major depressive disorder, especially in females. This study is the first to report that the MAP2K1 gene may be a genetic marker for depressive disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 4G/5G Polymorphism of Plasminogen Activator Inhibitor -1 Gene Is Associated with Mortality in Intensive Care Unit Patients with Severe Pneumonia

    Science.gov (United States)

    Sapru, Anil; Hansen, Helen; Ajayi, Temitayo; Brown, Ron; Garcia, Oscar; Zhuo, HanJing; Wiemels, Joseph; Matthay, Michael A.; Wiener-Kronish, Jeanine

    2011-01-01

    Background Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia. Methods The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination. Results A total of 111 patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype. Conclusions The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia. PMID:19387177

  7. The −675 4G/5G Polymorphism in Plasminogen Activator Inhibitor-1 Gene Is Associated with Risk of Asthma: A Meta-Analysis

    Science.gov (United States)

    Xiu, Qing-yu

    2012-01-01

    Background A number of studies assessed the association of −675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. Methods Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. Results Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12–2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06–1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17–2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07–1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08–1.68, P = 0.008). Conclusions This meta-analysis suggested that the −675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma. PMID:22479620

  8. 4G/5G polymorphism of plasminogen activator inhibitor-1 gene is associated with mortality in intensive care unit patients with severe pneumonia.

    Science.gov (United States)

    Sapru, Anil; Hansen, Helen; Ajayi, Temitayo; Brown, Ron; Garcia, Oscar; Zhuo, HanJing; Wiemels, Joseph; Matthay, Michael A; Wiener-Kronish, Jeanine

    2009-05-01

    Higher plasma and pulmonary edema fluid levels of plasminogen activator inhibitor-1 (PAI-1) are associated with increased mortality in patients with pneumonia and acute lung injury. The 4G allele of the 4G/5G polymorphism of the PAI-1 gene is associated with higher PAI-1 levels and an increased incidence of hospitalizations for pneumonia. The authors hypothesized that the 4G allele would be associated with worse clinical outcomes (mortality and ventilator-free days) in patients with severe pneumonia. The authors enrolled patients admitted with severe pneumonia in a prospective cohort. Patients were followed until hospital discharge. DNA was isolated from blood samples, and genotyping detection for the PAI-1 4G/5G polymorphism was carried out using Taqman-based allelic discrimination. A total of 111 patients were available for analysis. Distribution of genotypes was 4G/4G 26 of 111 (23%), 4G/5G 59 of 111 (53%), and 5G/5G 26 of 111 (23%). Of 111 patients, 32 (29%) died before hospital discharge and 105 patients (94%) received mechanical ventilation. Patients with the 4G/4G and the 4G/5G genotypes had higher mortality (35% vs. 8%, P = 0.007) and fewer ventilator-free days (median 4 vs. 13, P = 0.04) compared to patients with the 5G/5G genotype. The 4G allele of the 4G/5G polymorphism in the PAI-1 gene is associated with fewer ventilator-free days and increased mortality in hospitalized patients with severe pneumonia. These findings suggest that PAI-1 may have a role in pathogenesis and that the 4G/5G polymorphism may be an important biomarker of risk in patients with severe pneumonia.

  9. The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis.

    Science.gov (United States)

    Nie, Wei; Li, Bing; Xiu, Qing-Yu

    2012-01-01

    A number of studies assessed the association of -675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12-2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06-1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17-2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07-1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08-1.68, P = 0.008). This meta-analysis suggested that the -675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.

  10. The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Wei Nie

    Full Text Available BACKGROUND: A number of studies assessed the association of -675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility. METHODS: Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI and Weipu Database were searched to find relevant studies. Odds ratios (ORs with 95% confidence intervals (CIs were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model. RESULTS: Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12-2.18, P = 0.008, 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06-1.80, P = 0.02, 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17-2.76, P = 0.007, 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07-1.84, P = 0.02, and 4G vs. 5G (OR = 1.35, 95% CI 1.08-1.68, P = 0.008. CONCLUSIONS: This meta-analysis suggested that the -675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.

  11. Collectin-11/MASP complex formation triggers activation of the lectin complement pathway--the fifth lectin pathway initiation complex

    DEFF Research Database (Denmark)

    Ma, Ying Jie; Skjoedt, Mikkel-Ole; Garred, Peter

    2013-01-01

    Collectins and ficolins are important in the clearance of endogenous and exogenous danger materials. A new human collectin-11 was recently identified in low concentration in serum in complex with mannose-binding lectin (MBL)/ficolin-associated serine proteases. Collectin-11 binds to carbohydrate...... complement complex on C. albicans. Moreover, spiking collectin-11-depleted serum, which did not mediate complement activation, with recombinant collectin-11 restored the complement activation capability. These results define collectin-11 as the fifth recognition molecule in the lectin complement pathway...

  12. Do dopaminergic gene polymorphisms affect mesolimbic reward activation of music listening response? Therapeutic impact on Reward Deficiency Syndrome (RDS).

    Science.gov (United States)

    Blum, Kenneth; Chen, Thomas J H; Chen, Amanda L H; Madigan, Margaret; Downs, B William; Waite, Roger L; Braverman, Eric R; Kerner, Mallory; Bowirrat, Abdalla; Giordano, John; Henshaw, Harry; Gold, Mark S

    2010-03-01

    Using fMRI, Menon and Levitin [9] clearly found for the first time that listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the nucleus accumbens (NAc) and the ventral tegmental area (VTA), as well as the hypothalamus, and insula, which are thought to be involved in regulating autonomic and physiological responses to rewarding and emotional stimuli. Importantly, responses in the NAc and VTA were strongly correlated pointing to an association between dopamine release and NAc response to music. Listing to pleasant music induced a strong response and significant activation of the VTA-mediated interaction of the NAc with the hypothalamus, insula, and orbitofrontal cortex. Blum et al. [10] provided the first evidence that the dopamine D2 receptor gene (DRD2) Taq 1 A1 allele significantly associated with severe alcoholism whereby the author's suggested that they found the first "reward gene" located in the mesolimbic system. The enhanced functional and effective connectivity between brain regions mediating reward, autonomic, and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. However, little is known about why some people have a more or less powerful mesolimbic experience when they are listening to music. It is well-known that music may induce an endorphinergic response that is blocked by naloxone, a known opioid antagonist (Goldstein [19]). Opioid transmission in the NAc is associated with dopamine release in the VTA. Moreover, dopamine release in the VTA is linked to polymorphisms of the DRD2 gene and even attention-deficit hyperactivity disorder (ADHD), whereby carriers of the DRD2 A1 allele show a reduced NAc release of dopamine (DA). Thus it is conjectured that similar mechanisms in terms of adequate dopamine release and subsequent activation of reward circuitry by listening to music might also be

  13. The association between the 4G/5G polymorphism in the promoter of the plasminogen activator inhibitor-1 gene and extension of postsurgical calf vein thrombosis.

    Science.gov (United States)

    Ferrara, Filippo; Meli, Francesco; Raimondi, Francesco; Montalto, Salvatore; Cospite, Valentina; Novo, Giuseppina; Novo, Salvatore

    2013-04-01

    The objective of this study was to evaluate whether the presence of a plasminogen activator inhibitor type 1 (PAI-1) promoter polymorphism 4G/5G could significantly influence the proximal extension of vein thrombosis in spite of anticoagulant treatment in patients with calf vein thrombosis (CVT) following orthopaedic, urological and abdominal surgery. We studied 168 patients with CVT, who had undergone orthopaedic, urological and abdominal surgery, subdivided as follows: first, 50 patients with thrombosis progression; second, 118 patients without thrombosis progression. The 4G/5G polymorphism of the plasminogen activator inhibitor 1 was evaluated in all patients and in 70 healthy matched controls. We also studied PAI-1 activity in plasma. The presence of 4G/5G genotype was significantly increased in the group of patients with the extension of thrombotic lesions and was associated with an increase in CVT extension risk (odds ratio adjusted for sex 2.692; 95% confidence interval 1.302-4.702). Moreover, we observed a significant increase of PAI-1 plasma activity in patients with extension of thrombotic lesion vs. patients without extension (P=0.0001). Patients with 4G/5G genotype in the promoter of the plasminogen activator inhibitor - 1 gene present a higher risk of extension of thrombotic lesions.

  14. Complex-forming capacity of some biologically active imidazoles

    Energy Technology Data Exchange (ETDEWEB)

    Lenarcik, B; Wisniewski, M

    1983-01-01

    By using the potentiometric and spectrophotometric methods, formation of Co(2), Cu(2), Zn(2), Ni(2) and Cd(2) complexes of (3S-cis)-3-ethyl-dihydro-4-((1-methyl-1H-imidazol-5-yl)-methyl)-2(3H)-furanone (pilocarpine, PLC), 4,5-dihydro-2-(phenylmethyl)-1H-imidazole (tolazoline, TLZ), 2-methyl-5-nitro-1H-imidazole-1-ethanol (metronidazole, MET) and 1H-imidazole-4-ethanamine (histamine, HIST) was investigated. The stability constants, ..beta../sub n/, of these complexes were determined. It was shown that the electron-donor strength of the ligands was controlled by the heterocyclic nitrogen atom, and that the formation of the Zn(2)-PLC complex was accompanied by the change in the structure of the coordination sphere of the metal. With Cu(2), the PLC and TLZ ligands were shown to enhance the Jahn-Teller deformation.

  15. Recent Progress in Some Active Topics on Complex Networks

    International Nuclear Information System (INIS)

    Gu, J; Zhu, Y; Wang, Q A; Guo, L; Jiang, J; Chi, L; Li, W; Cai, X

    2015-01-01

    Complex networks have been extensively studied across many fields, especially in interdisciplinary areas. It has since long been recognized that topological structures and dynamics are important aspects for capturing the essence of complex networks. The recent years have also witnessed the emergence of several new elements which play important roles in network study. By combining the results of different research orientations in our group, we provide here a review of the recent advances in regards to spectral graph theory, opinion dynamics, interdependent networks, graph energy theory and temporal networks. We hope this will be helpful for the newcomers of those fields to discover new intriguing topics. (paper)

  16. Selection of index complex for the NPP operator activity efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Kolesnik, A I; Chertorizhskij, E A

    1984-01-01

    Preconditions for choice of NPP operator activity efficiency index are determined. Results of the choice are given and a method for determination of generalized and particular parameters by means of which NPP operator activity efficiency can be estimated is considered. An algorithm of diagnosis of reason for unsuccess of operator activity based on assessment of psychological factors of complicacy is suggested.

  17. Brain and gonadal aromatase activity and steroid hormone levels in female and polymorphic males of the peacock blenny Salaria pavo.

    Science.gov (United States)

    Gonçalves, David; Teles, Magda; Alpedrinha, João; Oliveira, Rui F

    2008-11-01

    In the peacock blenny Salaria pavo large males with well-developed secondary sexual characters establish nests and attract females while small "sneaker" males mimic female sexual displays in order to approach the nests of larger males and parasitically fertilize eggs. These alternative reproductive tactics are sequential, as sneakers irreversibly switch into nesting males. This transition involves major morphologic and behavioral changes and is likely to be mediated by hormones. This study focuses on the role of aromatase, an enzyme that catalyses the conversion of androgens into estrogens, in the regulation of male sexual polymorphism in S. pavo. For this, sex steroid plasma levels and aromatase activity (AA) in gonads, whole brain and brain macroareas were determined in sneakers, transitional males (i.e. sneakers undergoing the transition into nesting males), nesting males and females collected in the field. AA was much higher in ovarian tissue than in testicular tissue and accordingly circulating estradiol levels were highest in females. This supports the view that elevated AA and estradiol levels are associated with the development of a functional ovary. Transitional males are in a non-reproductive phase and had underdeveloped testes when compared with sneakers and nesting males. Testicular AA was approximately 10 times higher in transitional males when compared with sneakers and nesting males, suggesting high AA has a suppressive effect on testicular development. Nesting males had significantly higher plasma levels of both testosterone (T) and 11-ketotestosterone when compared with the other male morphs and previous studies demonstrated that these androgens suppress female-like displays in sneakers. In the brain, AA was highest in macroareas presumably containing hypothalamic nuclei traditionally associated with the regulation of reproductive behaviors. Overall, females presented the highest levels of brain AA. In male morphs AA increased from sneakers, to

  18. Antibacterial activity of cobalt(II complexes with some benzimidazole derivatives

    Directory of Open Access Journals (Sweden)

    S. O. PODUNAVAC-KUZMANOVIC

    2008-12-01

    Full Text Available The antibacterial activities of cobalt(II complexes with two series of benzimidazoles were evaluated in vitro against three Gram-positive bacterial strains (Bacillus cereus, Staphylococcus aureus, and Sarcina lutea and one Gram-negative isolate (Pseudomonas aeruginosa. The minimum inhibitory concentration was determined for all the complexes. The majority of the investtigated complexes displayed in vitro inhibitory activity against very persistent bacteria. They were found to be more active against Gram-positive than Gram-negative bacteria. It may be concluded that the antibacterial activity of the compounds is related to the cell wall structure of the tested bacteria. Comparing the inhibitory activities of the tested complexes, it was found that the 1-substituted-2-aminobenzimidazole derivatives were more active than complexes of 1-substituted-2-amino-5,6-dimethylbenzimidazoles. The effect of chemical structure on the antibacterial activity is discussed.

  19. False Memories for Shape Activate the Lateral Occipital Complex

    Science.gov (United States)

    Karanian, Jessica M.; Slotnick, Scott D.

    2017-01-01

    Previous functional magnetic resonance imaging evidence has shown that false memories arise from higher-level conscious processing regions rather than lower-level sensory processing regions. In the present study, we assessed whether the lateral occipital complex (LOC)--a lower-level conscious shape processing region--was associated with false…

  20. DNA interactions and biocidal activity of metal complexes of ...

    Indian Academy of Sciences (India)

    Narendrula Vamsikrishna

    The Schiff bases and metal complexes were characterized by analytical and spectral methods like elemental analysis, ... cleavages.8–10 Cisplatin and its second generation com- ..... in DMSO. The test microorganisms were grown on nutrient agar medium in ...... effects on polymer characteristics Appl. Organomet. Chem.

  1. Peptide and small molecules rescue the functional activity and agonist potency of dysfunctional human melanocortin-4 receptor polymorphisms.

    Science.gov (United States)

    Xiang, Zhimin; Pogozheva, Irina D; Sorenson, Nicholas B; Wilczynski, Andrzej M; Holder, Jerry Ryan; Litherland, Sally A; Millard, William J; Mosberg, Henry I; Haskell-Luevano, Carrie

    2007-07-17

    The melanocortin pathway, specifically the melanocortin-4 receptor and the cognate endogenous agonist and antagonist ligands, have been strongly implicated in the regulation of energy homeostasis and satiety. Genetic studies of morbidly obese human patients and normal weight control patients have resulted in the discovery of over 70 human melanocortin-4 receptor (MC4R) polymorphisms observed as both heterozygous and homozygous forms. A number of laboratories have been studying these hMC4R polymorphisms attempting to understand the molecular mechanism(s) that might explain the obese human phenotype. Herein, we have studied 13 polymorphic hMC4Rs that have been identified to possess statistically significant decreased endogenous agonist potency with synthetic peptides and small molecules attempting to identify ligands that can pharmacologically rescue the hMC4R polymorphic agonist response. The ligands examined in this study include NDP-MSH, MTII, Ac-His-DPhe-Arg-Trp-NH2 (JRH887-9), Ac-Anc-DPhe-Arg-Trp-NH2 (amino-2-naphtylcarboxylic acid, Anc, JRH420-12), Ac-His-(pI)DPhe-Arg-Trp-NH2 (JRH322-18), chimeric AGRP-melanocortin based ligands (Tyr-c[Cys-His-DPhe-Arg-Trp-Asn-Ala-Phe-Cys]-Tyr-NH2, AMW3-130 and Ac-mini-(His-DPhe-Arg-Trp)-hAGRP-NH2, AMW3-106), and the small molecules JB25 and THIQ. The hMC4R polymorphisms included in this study are S58C, N97D, I102S, L106P, S127L, T150I, R165Q, R165W, L250Q, G252S, C271Y, Y287Stop, and I301T. These studies resulted in the NDP-MSH, MTII, AMW3-130, THIQ, and AMW3-106 ligands possessing nanomolar to subnanomolar agonist potency at the hMC4R polymorphisms examined in this study. Thus, these ligands could generically rescue the potency and stimulatory response of the abnormally functioning hMC4Rs studied and may provide tools to further clarify the molecular mechanism(s) involving these receptor modifications.

  2. Postglacial seismic activity along the Isovaara-Riikonkumpu fault complex

    Science.gov (United States)

    Ojala, Antti E. K.; Mattila, Jussi; Ruskeeniemi, Timo; Palmu, Jukka-Pekka; Lindberg, Antero; Hänninen, Pekka; Sutinen, Raimo

    2017-10-01

    Analysis of airborne LiDAR-based digital elevation models (DEMs), trenching of Quaternary deposits, and diamond drilling through faulted bedrock was conducted to characterize the geological structure and full slip profiles of the Isovaara-Riikonkumpu postglacial fault (PGF) complex in northern Finland. The PGF systems are recognized from LiDAR DEMs as a complex of surface ruptures striking SW-NE, cutting through late-Weichselian till, and associated with several postglacial landslides within 10 km. Evidence from the terrain rupture characteristics, the deformed and folded structure of late-Weichselian till, and the 14C age of 11,300 cal BP from buried organic matter underneath the Sotka landslide indicates a postglacial origin of the Riikonkumpu fault (PGF). The fracture frequency and lithology of drill cores and fault geometry in the trench log indicate that the Riikonkumpu PGF dips to WNW with a dip angle of 40-45° at the Riikonkumpu site and close to 60° at the Riikonvaara site. A fault length of 19 km and the mean and maximum cumulative vertical displacement of 1.3 m and 4.1 m, respectively, of the Riikonkumpu PGF system indicate that the fault potentially hosted an earthquake with a moment magnitude MW ≈ 6.7-7.3 assuming that slip was accumulated in one seismic event. Our interpretation further suggests that the Riikonkumpu PGF system is linked to the Isovaara PGF system and that, together, they form a larger Isovaara-Riikonkumpu fault complex. Relationships between the 38-km-long rupture of the Isovaara-Riikonkumpu complex and the fault offset parameters, with cumulative displacement of 1.5 and 8.3 m, respectively, indicate that the earthquake(s) contributing to the PGF complex potentially had a moment magnitude of MW ≈ 6.9-7.5. In order to adequately sample the uncertainty space, the moment magnitude was also estimated for each major segment within the Isovaara-Riikonkumpu PGF complex. These estimates vary roughly between MW ≈ 5-8 for the individual

  3. PPAR2Pro12Ala Polymorphism and Human Health

    Directory of Open Access Journals (Sweden)

    Weimin He

    2009-01-01

    Full Text Available The nuclear hormone receptor peroxisome proliferator activated receptor gamma (PPAR is an important transcription factor regulating adipocyte differentiation, lipid and glucose homeostasis, and insulin sensitivity. Numerous genetic mutations of PPAR have been identified and these mutations positively or negatively regulate insulin sensitivity. Among these, a relatively common polymorphism of PPAR, Pro12Ala of PPAR2, the isoform expressed only in adipose tissue has been shown to be associated with lower body mass index, enhanced insulin sensitivity, and resistance to the risk of type 2 diabetes in human subjects carrying this mutation. Subsequent studies in different ethnic populations, however, have revealed conflicting results, suggesting a complex interaction between the PPAR2 Pro12Ala polymorphism and environmental factors such as the ratio of dietary unsaturated fatty acids to saturated fatty acids and/or between the PPAR2 Pro12Ala polymorphism and genetic factors such as polymorphic mutations in other genes. In addition, this polymorphic mutation in PPAR2 is associated with other aspects of human diseases, including cancers, polycystic ovary syndrome, Alzheimer disease and aging. This review will highlight findings from recent studies.

  4. Brain-derived neurotrophic factor Val66Met polymorphism and hippocampal activation during episodic encoding and retrieval tasks

    OpenAIRE

    Dennis, Nancy A.; Cabeza, Roberto; Need, Anna C.; Waters-Metenier, Sheena; Goldstein, David B.; LaBar, Kevin S.

    2010-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin which has been shown to regulate cell survival and proliferation, as well as synaptic growth and hippocampal long-term potentiation. A naturally occurring single nucleotide polymorphism in the human BDNF gene (val66met) has been associated with altered intercellular trafficking and regulated secretion of BDNF in met compared to val carriers. Additionally, previous studies have found a relationship between the BDNF val66met genotype an...

  5. Synthesis, Characterization and Antimicrobial Activity of Zirconium (IV) Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Shobhana; Jain, Asha; Saxena, Sanjiv [Univ. of Rajasthan, Jaipur (India)

    2012-08-15

    Heteroleptic complexes of zirconium (IV) derived from bulky Schiff base ligands containing a sulphur atom and oximes of heterocyclic β-diketones of the general formula ZrLL' (where L'H{sub 2}=RCNH(C{sub 6}H{sub 4})SC : C(OH)N(C{sub 6}H{sub 5})N : CCH{sub 3}, R=-C{sub 6}H{sub 5}, -C{sub 6}H{sub 4}Cl(p) and L'H{sub 2}=R'C : (NOH)C : C(OH)N(C{sub 6}H{sub 5})N : CCH{sub 3}, R' = -CH{sub 2}CH{sub 3}, -C{sub 6}H{sub 5}, -C{sub 6}H{sub 4}Cl (p) were prepared by the reactions of zirconium tetrachloride with disodium salts of Schiff bases (L Na{sub 2}) and oximes of heterocyclic β-diketones (L' Na{sub 2}) in 1:1:1 molar ratio in dry refluxing THF. The structures of these monomeric zirconium (IV) complexes were elucidated with the help of elemental analysis, molecular weight measurements, spectroscopic (IR, NMR and mass) studies. A distorted trigonal bipyramidal geometry may be suggested for these heteroleptic zirconium (IV) complexes. The ligands (bulky Schiff base ligands containing a sulphur atom and oximes of heterocyclic β-diketones) and their heteroleptic complexes of zirconium (IV) were screened against A. flavus, P. aeruginesa and E. coli.

  6. Association of peroxisome proliferator-activated receptor single-nucleotide polymorphisms and gene-gene interactions with the lipoprotein(a)

    Institute of Scientific and Technical Information of China (English)

    解惠坚

    2014-01-01

    Objective To examine the associations of 10 singlenucleotide polymorphisms(SNPs)in peroxisome proliferator-activated receptor(PPARs)gene with lipoprotein(a)level,and to investigate if there is gene-gene interaction among the SNPs on lipoprotein(a)level.Methods Totally 644 subjects(234 men and 410 women)were enrolled from Prevention of Multiple Metabolic Disorders and Metabolic Syndrome Study Cohort,which was an urban community survey study conducted in Jiangsu province.Ten SNPs in PPARα(rs135539,rs4253778,

  7. Association of Angiotensin-Converting Enzyme ACE Gene Polymorphism with ACE Activity and Susceptibility to Vitiligo in Egyptian Population.

    Science.gov (United States)

    Badran, Dahlia I; Nada, Hesham; Hassan, Ranya

    2015-05-01

    The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with vitiligo in the Indians and Koreans, but not in those of English or Turkish background. We investigated the ACE (I/D) polymorphism in vitiligo patients for the first time in Egypt and compared serum ACE levels between vitiligo patients and controls. The present study was carried out in 100 vitiligo patients (40 males and 60 females) and in 100 healthy controls of an Egyptian population using the polymerase chain reaction genotyping method. The ACE genotype and allele frequency was significantly different between vitiligo patients and controls. Our results revealed a significant increase in the frequency of the ACE I allele (p=0.002; odds ratio: 1.99; 95% confidence intervals: 1.207-3.284) with an overrepresentation of I/D genotype in the vitiligo patient group. Furthermore, there was a significant difference between the segmental, nonsegmental, and focal vitiligo in ACE gene genotype distribution. Serum ACE levels were significantly increased in vitiligo patients compared to controls (p=0.034). This study suggests that, for the first time, ACE gene polymorphism confers susceptibility to vitiligo in the Egyptian population.

  8. Enhancement of antibacterial activity of ciprofloxacin hydrochloride by complexation with sodium cholate

    Directory of Open Access Journals (Sweden)

    Uduma E. Osonwa

    2017-12-01

    Full Text Available Ciprofloxacin is a broad spectrum bactericidal anti-infective agent of the fluoroquinolones class used in treatment of many bacterial infections. In recent times, there has been increasing resistance to the antibiotic. In this work, we investigated the effect of making an ion- pair complex of Ciprofloxacin – hydrochloride with Sodium cholate on bacterial activity. The optimal ratio of the reactants and pH were determined using UV spectrometry. The complex was characterized by octanol-water partitioning, melting point, and IR spectrometry. The antibacterial activity of the complex was determined against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae by the agar-well diffusion method. The complex was whitish to off-white in color and crystalline, with a melting point of 238 °C. The stoichiometry of the complex shows a molar ratio of 1:1 of sodium cholate to ciprofloxacin. The best pH for complexation was pH 9. The complex partitioned 3.38 times into octanol than in water. The FTIR revealed interaction between the 4-nitrogen atom in the 7-piperazinyl group of ciprofloxacin and the carbonyl of the cholate. The drug in complex form gave double the antibacterial activity of the uncomplexed drug. This study showed that development of hydrophobic ion pair complex enhances antibacterial activity of ciprofloxacin hydrochloride. Keywords: Ciprofloxacin, Sodium cholate, Ion-pair complex, Antibacterial activity, Enhanced activity

  9. The role of activity complexes in the distribution of solar magnetic fields.

    Science.gov (United States)

    García de La Rosa, J. I.; Reyes, R. C.

    Using published data on the large-scale distribution of solar activity, the authors conclude that the longlived coronal holes are formed and maintained by the unbalanced magnetic flux which developes at both extremes of the complexes of activity.

  10. Coding the Complexity of Activity in Video Recordings

    DEFF Research Database (Denmark)

    Harter, Christopher Daniel; Otrel-Cass, Kathrin

    2017-01-01

    This paper presents a theoretical approach to coding and analyzing video data on human interaction and activity, using principles found in cultural historical activity theory. The systematic classification or coding of information contained in video data on activity can be arduous and time...... Bødker’s in 1996, three possible areas of expansion to Susanne Bødker’s method for analyzing video data were found. Firstly, a technological expansion due to contemporary developments in sophisticated analysis software, since the mid 1990’s. Secondly, a conceptual expansion, where the applicability...... of using Activity Theory outside of the context of human–computer interaction, is assessed. Lastly, a temporal expansion, by facilitating an organized method for tracking the development of activities over time, within the coding and analysis of video data. To expand on the above areas, a prototype coding...

  11. The rs1800629 polymorphism in the TNF gene interacts with physical activity on the changes in C-reactive protein levels in the Finnish Diabetes Prevention Study

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas; Laaksonen, D E; Lakka, T A

    2010-01-01

    /L) baseline CRP levels ( P = 0.034 for interaction). Carriers of the GG genotype showed a greater decrease in CRP with increasing physical activity than the individuals with the A allele. No interaction between the rs1800795 SNP in IL6 and changes in moderate-to-vigorous physical activity on the 1-year change......Physical activity exerts anti-inflammatory effects, but genetic variation may modify its influence. In particular, the rs1800629 single-nucleotide polymorphism (SNP) in the tumor necrosis factor ( TNF) gene and the rs1800795 SNP in the interleukin-6 ( IL6) gene have been found to modify the effect...... of exercise training on circulating levels of C-reactive protein (CRP) and IL-6, respectively. We assessed whether rs1800629 and rs1800795 modified the effect of moderate-to-vigorous physical activity on changes in serum levels of high-sensitivity CRP and IL-6 in the Finnish Diabetes Prevention Study (DPS...

  12. Antimalarial, antimicrobial, cytotoxic, DNA interaction and SOD like activities of tetrahedral copper(II) complexes

    Science.gov (United States)

    Mehta, Jugal V.; Gajera, Sanjay B.; Patel, Mohan N.

    2015-02-01

    The mononuclear copper(II) complexes with P, O-donor ligand and different fluoroquinolones have been synthesized and characterized by elemental analysis, electronic spectra, TGA, EPR, FT-IR and LC-MS spectroscopy. An antimicrobial efficiency of the complexes has been tested against five different microorganisms in terms of minimum inhibitory concentration (MIC) and displays very good antimicrobial activity. The binding strength and binding mode of the complexes with Herring Sperm DNA (HS DNA) have been investigated by absorption titration and viscosity measurement studies. The studies suggest the classical intercalative mode of DNA binding. Gel electrophoresis assay determines the ability of the complexes to cleave the supercoiled form of pUC19 DNA. Synthesized complexes have been tested for their SOD mimic activity using nonenzymatic NBT/NADH/PMS system and found to have good antioxidant activity. All the complexes show good cytotoxic and in vitro antimalarial activities.

  13. Tracking Activities in Complex Settings Using Smart Environment Technologies.

    Science.gov (United States)

    Singla, Geetika; Cook, Diane J; Schmitter-Edgecombe, Maureen

    2009-01-01

    The pervasive sensing technologies found in smart homes offer unprecedented opportunities for providing health monitoring and assistance to individuals experiencing difficulties living independently at home. A primary challenge that needs to be tackled to meet this need is the ability to recognize and track functional activities that people perform in their own homes and everyday settings. In this paper we look at approaches to perform real-time recognition of Activities of Daily Living. We enhance other related research efforts to develop approaches that are effective when activities are interrupted and interleaved. To evaluate the accuracy of our recognition algorithms we assess them using real data collected from participants performing activities in our on-campus smart apartment testbed.

  14. Activity of Pure Streptovaricins and Fractionated Streptovaricin Complex Against Friend Virus

    Science.gov (United States)

    Horoszewicz, Julius S.; Rinehart, Kenneth L.; Leong, Susan S.; Carter, William A.

    1975-01-01

    Chromatographic fractionation of streptovaricin complex yields two stable components enriched (4- to 16-fold) in activity directed against the polycythemic strain of Friend virus; both components apparently contain no streptovaricins. When compared with their unfractionated parent streptovaricin complex, eight individual intact streptovaricins (A through G and J) show at least a 30-fold reduction in antiviral activity. These results further support the conclusion that the diversified biological properties of streptovaricin complex probably reside in different molecular structures. PMID:237470

  15. Generalization of the Activated Complex Theory of Reaction Rates. I. Quantum Mechanical Treatment

    Science.gov (United States)

    Marcus, R. A.

    1964-01-01

    In its usual form activated complex theory assumes a quasi-equilibrium between reactants and activated complex, a separable reaction coordinate, a Cartesian reaction coordinate, and an absence of interaction of rotation with internal motion in the complex. In the present paper a rate expression is derived without introducing the Cartesian assumption. The expression bears a formal resemblance to the usual one and reduces to it when the added assumptions of the latter are introduced.

  16. Purification of Ovine Respiratory Complex I Results in a Highly Active and Stable Preparation*

    Science.gov (United States)

    Letts, James A.; Degliesposti, Gianluca; Fiedorczuk, Karol; Skehel, Mark; Sazanov, Leonid A.

    2016-01-01

    NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies. PMID:27672209

  17. Biological activities of some Fluoroquinolones-metal complexes

    African Journals Online (AJOL)

    McRoy

    Background: Metal ions play a vital role in the design of more biologically active drugs. Aim: The paper reviewed the .... 2H2O by direct reaction of copper(II) sulphate pentahydrate with ciprofloxacin in distilled water. ... membered ring and the chloride ion completes the seven coordination around the Ca2+ion.[37-39].

  18. Complex modulation of peptidolytic activity of cathepsin D by sphingolipids

    Czech Academy of Sciences Publication Activity Database

    Žebrakovská, Iva; Máša, Martin; Srp, Jaroslav; Horn, Martin; Vávrová, K.; Mareš, Michael

    2011-01-01

    Roč. 1811, č. 12 (2011), s. 1097-1104 ISSN 1388-1981 R&D Projects: GA AV ČR IAA400550705 Institutional research plan: CEZ:AV0Z40550506 Keywords : sphingolipid * phospholipid * inhibition * activation * cathepsin D * enzyme regulation Subject RIV: CE - Biochemistry Impact factor: 5.269, year: 2011

  19. Antiproliferative activity of some novel platinum complexes on C6 ...

    African Journals Online (AJOL)

    MCF-7) and glioma cells (C6). IC50 values of the three compounds were lower in the cisplatin-resistant cell type C6 cell lines than in MCF-7 cells. Key words: Cisplatin, antiproliferative activity, breast cancer cells (MCF-7), glioma cells (C6), IC50.

  20. Synthesis and characterization of transition metal complexes derived from some biologically active furoic acid hydrazones

    Directory of Open Access Journals (Sweden)

    P. Venkateswar Rao

    2007-04-01

    Full Text Available Two new physiologically active ligands, N’-2-[(E-1-hydroxy-4-methyl-2-oxo-2H-8-chromenyl ethylidene-2-furan carbohydrazide (HMCFCH and N’-2-[(Z-1-(4-hydroxy-6-methyl-2-oxo-2H-pyranyl ethylidene]-furan carbohydrazide (HMPFCH and their VO(II, Mn(II, Fe(II, Co(II, Ni(II and Cu(II complexes have been prepared. The ligands and the metal complexes have been characterized by elemental analyses, electrical conductance, magnetic susceptibility measurements, UV-Vis, IR, and ESR spectroscopic data. Basing on the above data, Fe(II and Co(II complexes of HMCFCH and HMPFCH have been assigned a dimeric octahedral geometry. VO(II complexes of HMCFCH and HMPFCH have been assigned sulfate bridged dimeric square pyramidal geometry. Mn(II complex of HMCFCH has been assigned a dimeric octahedral geometry, where as Mn(II complex of HMPFCH has been ascribed to monomeric octahedral geometry. Cu(II and Ni(II complexes of HMCFCH have been ascribed to a polymeric structure. Ni(II complex of HMPFCH has been assigned a dimeric square planar geometry. Cu(II complex of HMPFCH has been proposed an octahedral geometry. The ligands and their metal chelates were screened against S. aureus and P. aeruginosa. The ligands and the metal complexes have been found to be active against these microorganisms. The ligands show more activity than the metal complexes.

  1. Active Transforming Growth Factor-beta2 in the Aqueous Humor of Posterior Polymorphous Corneal Dystrophy Patients

    Czech Academy of Sciences Publication Activity Database

    Stádníková, A.; Ďuďáková, L.; Skalická, P.; Valenta, Zdeněk; Filipec, M.; Jirsová, K.

    2017-01-01

    Roč. 12, č. 4 (2017), č. článku e0175509. E-ISSN 1932-6203 Grant - others:GA ČR(CZ) GA17-12355S; GA MŠk(CZ) 7F14156 Institutional support: RVO:67985807 Keywords : transforming growth factor-beta2 * posterior polymorphous corneal dystrophy * corneal endothelial cells * general linear mixed-effect modelling * restricted maximum likelihood estimation Subject RIV: BB - Applied Statistics, Operational Research OBOR OECD: Statistics and probability Impact factor: 2.806, year: 2016

  2. Antiviral activity of platinum (II) and palladium (II) complexes of dimethyl sulfoxide (DMSO) in vitro

    International Nuclear Information System (INIS)

    Al-Allaf, T.; Rashan, L

    1996-01-01

    The antiviral activity of complexes cis-[Pt(DMSO) 2 CI 2 ] and trans-[Pd(DMSO) 2 CI 2 ] against the reverse transcriptase enzyme, herpes and influenza viruses have been studied in vitro. Both complexes demonstrated some activity against the reverse transcriptase enzyme in which the inhibition concentration (IC 5 0) of the cis-Pt and the trans-Pd complexes were shown to be 37.6 and 35.5 μ g/ml respectively. This activity was compared with that of the standard reference; the phosphonoformate (PFA). On the other hand, both complexes have no antiviral activity against herpes and influenza viruses No cytotoxic effects on the three cell lines, Raji, K562 and Mrc-5 were demonstrated by these complexes at the concentrations studied in vitro. (authors). 16 refs., 1 tab., 2 figs

  3. Effects of Mind-Body Training on Personality and Behavioral Activation and Inhibition System According to BDNF Val66Met Polymorphism.

    Science.gov (United States)

    Jung, Ye-Ha; Lee, Ul Soon; Jang, Joon Hwan; Kang, Do-Hyung

    2016-05-01

    It has been known that mind-body training (MBT) can affect personality and behavior system as well as emotional well-being, but different effects of MBT on them has not been reported according to BDNF genetic polymorphism. Healthy subjects consisted of 64 subjects and the MBT group who practiced meditation regularly consisted of 72 practitioners. Participants completed neuroticism-extraversion-openness (NEO) Five-Factor Inventory and Behavioral Activation System/Behavioral Inhibition System (BAS/BIS) scales. All subjects were genotyped for the BDNF Val66Met polymorphism. In the same genotypes of the BDNF Val/Val+Val/Met group, MBT group showed the increased Extraversion (p=0.033) and the increased Openness to Experience (p=0.004) compared to the control group. Also, in the same Met/Met carriers, MBT group exhibited the increase of Extraversion (p=0.008), the reduction of Neuroticism (p=0.002), and the increase of Openness to Experience (p=0.008) compared to the control group. In the same genotypes of the BDNF Val/Val+Val/Met group, MBT group showed the decreased BAS-Reward Responsiveness (p=0.016) and the decrease of BIS (p=0.004) compared to the control group. In the BDNF Met/Met group, MBT group increased BAS-Fun Seeking (p=0.045) and decreased BIS (p=0.013) compared to the control group. MBT would differently contribute to NEO personality and BAS/BIS according to BDNF genetic polymorphism, compensating for different vulnerable traits based on each genotype.

  4. Plasminogen activator inhibitor type 1 serum levels and 4G/5G gene polymorphism in morbidly obese Hispanic patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Espino, Alberto; Villagrán, Andrea; Vollrath, Valeska; Hanckes, Paulina; Salas, Roberto; Farah, Andrea; Solís, Nancy; Pizarro, Margarita; Escalona, Alex; Boza, Camilo; Pérez, Gustavo; Carrasco, Gonzalo; Padilla, Oslando; Miquel, Juan Francisco; Nervi, Flavio; Chavez-Tapia, Norberto C; Arab, Juan Pablo; Alvarez-Lobos, Manuel; Arrese, Marco; Riquelme, Arnoldo

    2011-01-01

    The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibrinolysis and extracellular matrix components. The single base pair guanine insertion/deletion polymorphism (4G/5G) within the promoter region of the PAI-1 gene influences PAI-1 synthesis and may modulate hepatic fibrogenesis. To evaluate the influence of PAI-1 serum levels and 4G/5G polymorphism on the risk of liver fibrosis associated to non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients. Case-control study of 50 obese patients undergoing bariatric surgery and 71 non-obese subjects matched by age and sex. Anthropometric and biochemical measurements were performed, including PAI-1 serum levels. Genomic DNA was obtained to assess the presence of 4G/5G polymorphism. BMI, insulinemia, triglycerides, HOMA-IR, hypertension and diabetes were significantly higher in obese patients compared to control subjects. PAI-1 serum levels observed in obese patients were significantly lower (10.63 ± 4.82) compared to controls (14.26 ± 11.4; p 5G promoter genotypes frequencies (p = 0.12). No differences were observed in PAI-1 plasma levels among obese patients with liver fibrosis (10.64 ± 4.35) compared to patients without liver fibrosis (10.61 ± 5.2; p = 0.985). PAI-1 4G/5G promoter genotypes frequencies were similar in patients with or without liver fibrosis associated to NASH (p = 0.6). Morbidly obese patients had significantly lower PAI-1 serum levels with similar PAI-1 4G/5G genotypes frequencies compared to non-obese subjects. The frequency of 4G/5G genotypes in Chilean Hispanic healthy subjects was similar to that described in other populations. No association was found between PAI-1 serum levels or 4G/5G genotype with liver fibrosis in obese patients.

  5. 4G/5G Polymorphism of the plasminogen activator inhibitor-1 gene is associated with multiple organ dysfunction in critically ill patients.

    Science.gov (United States)

    Huq, Muhammad Aminul; Takeyama, Naoshi; Harada, Makoto; Miki, Yasuo; Takeuchi, Akinori; Inoue, Sousuke; Nakagawa, Takashi; Kanou, Hideki; Hirakawa, Akihiko; Noguchi, Hiroshi

    2012-01-01

    Impaired fibrinolysis is associated with a higher incidence of both multiple organ dysfunction and mortality in the intensive care unit (ICU). Plasminogen activator inhibitor (PAI)-1 is the chief inhibitor of fibrinolysis. We investigated the influence of the 4G/5G polymorphism (rs1799768) of the PAI-1 gene on the plasma PAI-1 level and the outcome of critically ill patients. In 41 consecutive patients admitted to the ICU, PAI-1 gene polymorphism was assessed, plasma PAI-1 and arterial lactate concentrations were measured and clinical severity scores were recorded. Homozygotes for the 4G allele had higher plasma levels of PAI-1 antigen. The mean ± SD PAI-1 antigen level was 193.31 ± 167.93 ng/ml for the 4G/4G genotype, 100.67 ± 114.16 ng/ml for the 4G/5G genotype and 0.43 ± 0.53 ng/ml for the 5G/5G genotype. There was a significant correlation between plasma PAI-1 and arterial lactate concentrations, as well as between PAI-1 and severity scores. The mortality rate was 63, 33 and 0% for patients with the 4G/4G, 4G/5G and 5G/5G genotypes, respectively. These results demonstrate that the 4G/5G polymorphism of the PAI-1 gene affects the plasma PAI-1 concentration, which could impair fibrinolysis and cause organ failure, and thus the presence of the 4G allele increases the risk of death. Copyright © 2011 S. Karger AG, Basel.

  6. Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and risk of venous thromboembolism: a meta-analysis.

    Science.gov (United States)

    Wang, Jiarong; Wang, Chengdi; Chen, Nan; Shu, Chi; Guo, Xiaojiang; He, Yazhou; Zhou, Yanhong

    2014-12-01

    The plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism was considered to be associated with risk of venous thromboembolism (VTE), while evidence remains inadequate. To provide a more accurate estimation of this relationship, we performed an updated meta-analysis of all eligible studies. A systematical search was performed in PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure (CNKI) and Cqvip databases to identify relevant studies published before March 6(th) 2014. The odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using the fixed/random-effects model using Review Manager 5.1 and STATA 12.0. A total of 34 studies with 3561 cases and 5693 controls were analyzed. Overall, significant association between the PAI-1 4G/5G variant and VTE risk in total population (dominant model: OR=1.32, 95%CI: 1.13-1.54) was observed. And this variant was also related to the deep vein thrombosis risk (dominant model: OR=1.60, 95%CI: 1.24-2.06, P=0.0003). In the subgroup analyses on ethnicity, significant results were obtained in both Asians (dominant model: OR=2.08, 95%CI: 1.29-3.35, P=0.003) and Caucasians (dominant model: OR=1.31, 95%CI: 1.10-1.56, P=0.003). However, no significant association was found in patients with provoked VTE. In terms of subgroup analyses on co-existence of other thrombotic risk factors, the PAI-1 4G/5G polymorphism was significantly associated with VTE risk in patients with factor V Leiden mutation (dominant model: OR=1.72, 95%CI: 1.17-2.53), but not in patients with cancer or surgery. Our findings demonstrate the role of PAI-1 4G/5G polymorphism being a risk candidate locus for VTE susceptibility, especially in patients with other genetic thrombophilic disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Active listening for spatial orientation in a complex auditory scene.

    Science.gov (United States)

    Moss, Cynthia F; Bohn, Kari; Gilkenson, Hannah; Surlykke, Annemarie

    2006-04-01

    To successfully negotiate a complex environment, an animal must control the timing of motor behaviors in coordination with dynamic sensory information. Here, we report on adaptive temporal control of vocal-motor behavior in an echolocating bat, Eptesicus fuscus, as it captured tethered insects close to background vegetation. Recordings of the bat's sonar vocalizations were synchronized with high-speed video images that were used to reconstruct the bat's three-dimensional flight path and the positions of target and vegetation. When the bat encountered the difficult task of taking insects as close as 10-20 cm from the vegetation, its behavior changed significantly from that under open room conditions. Its success rate decreased by about 50%, its time to initiate interception increased by a factor of ten, and its high repetition rate "terminal buzz" decreased in duration by a factor of three. Under all conditions, the bat produced prominent sonar "strobe groups," clusters of echolocation pulses with stable intervals. In the final stages of insect capture, the bat produced strobe groups at a higher incidence when the insect was positioned near clutter. Strobe groups occurred at all phases of the wingbeat (and inferred respiration) cycle, challenging the hypothesis of strict synchronization between respiration and sound production in echolocating bats. The results of this study provide a clear demonstration of temporal vocal-motor control that directly impacts the signals used for perception.

  8. Active listening for spatial orientation in a complex auditory scene.

    Directory of Open Access Journals (Sweden)

    Cynthia F Moss

    2006-04-01

    Full Text Available To successfully negotiate a complex environment, an animal must control the timing of motor behaviors in coordination with dynamic sensory information. Here, we report on adaptive temporal control of vocal-motor behavior in an echolocating bat, Eptesicus fuscus, as it captured tethered insects close to background vegetation. Recordings of the bat's sonar vocalizations were synchronized with high-speed video images that were used to reconstruct the bat's three-dimensional flight path and the positions of target and vegetation. When the bat encountered the difficult task of taking insects as close as 10-20 cm from the vegetation, its behavior changed significantly from that under open room conditions. Its success rate decreased by about 50%, its time to initiate interception increased by a factor of ten, and its high repetition rate "terminal buzz" decreased in duration by a factor of three. Under all conditions, the bat produced prominent sonar "strobe groups," clusters of echolocation pulses with stable intervals. In the final stages of insect capture, the bat produced strobe groups at a higher incidence when the insect was positioned near clutter. Strobe groups occurred at all phases of the wingbeat (and inferred respiration cycle, challenging the hypothesis of strict synchronization between respiration and sound production in echolocating bats. The results of this study provide a clear demonstration of temporal vocal-motor control that directly impacts the signals used for perception.

  9. Assessment of complex microwaves occupational exposure in radar maintenance activity

    International Nuclear Information System (INIS)

    Danulescu, R.

    1996-01-01

    The modern of the society teas determined the increase of thousand times greater than the natural fond of the humankind exposure to a complex combination of electromagnetic man-made fields and radiations of extremely various strength and frequencies. A special contribution to this environmental change has had in the last decade the appearance and the explosive development of the microwaves generating appliances such as radars used in a great variety of military and civilian applications and which essentially contributes to the electromagnetic pollution. In the above mentioned content which firstly interests the occupational environment, it is necessary to improve the exposure limits, as well as, the emission standards, in order to better protect the human health and well-being. From this point of view, the estimation of the microwave occupational exposure risk constitutes, alongside the health status assessment, one of the priorities of the Occupational Health because the theoretical and practical problems related to the bioeffects of this kind of radiations are far to be clarified. Our study has been carried out in a factory where one performs research, production and especially maintenance of microwaves generating devices. (author)

  10. Synthesis, Physical Characterization and Biological Activity of Some Schiff Base Complexes

    Directory of Open Access Journals (Sweden)

    R. Rajavel

    2008-01-01

    Full Text Available Structural modification of organic molecule has considerable biological relevance. Further, coordination of a biomolecules to the metal ions significantly alters the effectiveness of the biomolecules. In view of the antimicrobial activity ligand [bis-(2-aminobenzaldehyde] malonoyl dihydrazone], metal complexes with Cu(II, Ni(II, Zn(II and oxovanadium(IV have been synthesized and found to be potential antimicrobial agents. An attempt is also made to correlate the biological activities with geometry of the complexes. The complexes have been characterized by elemental analysis, molar conductance, spectra and cyclicvoltammetric measurements. The structural assessment of the complexes has been carried out based on electronic, infrared and molar conductivity values.

  11. Common HEXB polymorphisms reduce serum HexA and HexB enzymatic activities, potentially masking Tay-Sachs disease carrier identification.

    Science.gov (United States)

    Vallance, Hilary; Morris, Tara J; Coulter-Mackie, Marion; Lim-Steele, Joyce; Kaback, Michael

    2006-02-01

    A DNA-proven Tay-Sachs disease (TSD) carrier and his brother were found to have serum percent Hexosaminidase A (%HexA) enzymatic activities in the non-carrier range, while the leukocyte %HexA profiles clearly identified them as TSD heterozygotes. Both their serum HexA and HexB enzymatic activities were below reference range, suggesting inheritance of mutations in both the HEXA (alpha-subunit) and HEXB (beta-subunit) genes. DNA sequencing revealed that both individuals, carried the common HEXA 1277_1278insTATC mutation, and two common HEXB polymorphisms: [619A>G (+) delTG]. To determine if these HEXB polymorphisms reduce HexA and HexB enzymatic activities, 69 DNA samples from subjects previously screened enzymatically in both serum and leukocytes for TSD carrier status were selected for either high, mid-range or low serum Total Hex (defined as the sum of HexA and HexB) activities and were tested for the HEXB mutations. Further, three additional TSD carriers ascertained by the atypical pattern of normal serum %HexA but carrier leukocyte %HexA, were found to have the [delTG (+) 619A>G] genotype. In addition, the frequency of the [delTG (+) 619A>G] genotype was significantly higher (P G] haplotype in the Ashkenazi Jewish population (approximately 10%), up to 10% of TSD carriers may have normal serum %HexA values with low total Hex. Accordingly, serum %HexA should not be the sole criterion used for carrier status determination. Where total Hex activity is reduced, further testing with leukocyte Hex profiles is indicated.

  12. Association of the plasminogen activator inhibitor-1 (PAI-1) Gene -675 4G/5G and -844 A/G promoter polymorphism with risk of keloid in a Chinese Han population.

    Science.gov (United States)

    Wang, Yongjie; Long, Jianhong; Wang, Xiaoyan; Sun, Yang

    2014-10-28

    A keloid is pathological scar caused by aberrant response to skin injuries, characterized by excessive accumulation of histological extracellular matrix, and occurs in genetically susceptible individuals. Plasminogen activator inhibitor-1 (PAI-1) has been implicated in the pathogenesis of keloid. We investigated the association between PAI-1 polymorphisms and plasma PAI-1 level with keloid risk. A total of 242 Chinese keloid patients and 207 controls were enrolled in this study. Polymerase chain reaction-restriction technique was used to determine PAI-1 promoter polymorphism (-675 4G/5G and -844 A/G) distribution. Plasma PAI-1 levels were detected using enzyme-linked immunosorbent assay (ELISA). There was a statistically significant difference in the distribution of PAI-1 -675 4G/5G polymorphism between keloid patients and healthy controls. 4G/4G carriers were more likely to develop keloid. In contrast, the -844 A/G polymorphism distribution did not vary significantly between keloid patients and controls. The keloid patients group had a significantly higher plasma PAI-1 level than the control group. In the -675 4G/4G carrier population, the plasma PAI-1 levels were significant higher in keloid patients compared with controls. Our study provides evidence that PAI-1 promoter polymorphism -675 4G/5G and plasma PAI-1 level are associated with keloid risk. PAI-1 -675 4G/5G polymorphism may be an important hereditary factor responsible for keloid development in the Chinese Han population.

  13. Homodinuclear lanthanide complexes of phenylthiopropionic acid: Synthesis, characterization, cytotoxicity, DNA cleavage, and antimicrobial activity

    Science.gov (United States)

    Shiju, C.; Arish, D.; Kumaresan, S.

    2013-03-01

    Lanthanide complexes of La(III), Pr(III), Nd(III), Sm(III), and Ho(III) with phenylthiopropionic acid were synthesized and characterized by elemental analysis, mass, IR, electronic spectra, molar conductance, TGA, and powder XRD. The results show that the lanthanide complexes are homodinuclear in nature. The two lanthanide ions are bridged by eight oxygen atoms from four carboxylate groups. Thermal decomposition profiles are consistent with the proposed formulations. Powder XRD studies show that all the complexes are amorphous in nature. Antimicrobial studies indicate that these complexes exhibit more activity than the ligand itself. The DNA cleavage activity of the ligand and its complexes were assayed on Escherichia coli DNA using gel electrophoresis in the presence of H2O2. The result shows that the Pr(III) and Nd(III) complexes have completely cleaved the DNA. The anticancer activities of the complexes have also been studied towards human cervical cancer cell line (HeLa) and colon cancer cells (HCT116) and it was found that the La(III) and Nd(III) complexes are more active than the corresponding Pr(III), Sm(III), Ho(III) complexes, and the free ligand on both the cancer cells.

  14. GINS complex protein Sld5 recruits SIK1 to activate MCM helicase during DNA replication.

    Science.gov (United States)

    Joshi, Kiranmai; Shah, Varun Jayeshkumar; Maddika, Subbareddy

    2016-12-01

    In eukaryotes, proper loading and activation of MCM helicase at chromosomal origins plays a central role in DNA replication. Activation of MCM helicase requires its association with CDC45-GINS complex, but the mechanism of how this complex activates MCM helicase is poorly understood. Here we identified SIK1 (salt-inducible kinase 1), an AMPK related protein kinase, as a molecular link that connects GINS complex with MCM helicase activity. We demonstrated that Sld5 a component of GINS complex interacts with SIK1 and recruits it to the sites of DNA replication at the onset of S phase. Depletion of SIK1 leads to defective DNA replication. Further, we showed that SIK1 phosphorylates MCM2 at five conserved residues at its N-terminus, which is essential for the activation of MCM helicase. Collectively, our results suggest SIK1 as a novel integral component of CMG replicative helicase during eukaryotic DNA replication. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Plasminogen activator inhibitor-1 4G/5G gene polymorphism and coronary artery disease in the Chinese Han population: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Yan-yan Li

    Full Text Available BACKGROUND: The polymorphism of plasminogen activator inhibitor-1 (PAI-1 4G/5G gene has been indicated to be correlated with coronary artery disease (CAD susceptibility, but study results are still debatable. OBJECTIVE AND METHODS: The present meta-analysis was performed to investigate the association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population. A total of 879 CAD patients and 628 controls from eight separate studies were involved. The pooled odds ratio (OR for the distribution of the 4G allele frequency of PAI-1 4G/5G gene and its corresponding 95% confidence interval (CI was assessed by the random effect model. RESULTS: The distribution of the 4 G allele frequency was 0.61 for the CAD group and 0.51 for the control group. The association between PAI-1 4G/5G gene polymorphism and CAD in the Chinese Han population was significant under an allelic genetic model (OR = 1.70, 95% CI = 1.18 to 2.44, P = 0.004. The heterogeneity test was also significant (P<0.0001. Meta-regression was performed to explore the heterogeneity source. Among the confounding factors, the heterogeneity could be explained by the publication year (P = 0.017, study region (P = 0.014, control group sample size (P = 0.011, total sample size (P = 0.011, and ratio of the case to the control group sample size (RR (P = 0.019. In a stratified analysis by the total sample size, significantly increased risk was only detected in subgroup 2 under an allelic genetic model (OR = 1.93, 95% CI = 1.09 to 3.35, P = 0.02. CONCLUSIONS: In the Chinese Han population, PAI-1 4G/5G gene polymorphism was implied to be associated with increased CAD risk. Carriers of the 4G allele of the PAI-1 4G/5G gene might predispose to CAD.

  16. Psychocorrection activities in complex therapy of patients with psoriasis

    Directory of Open Access Journals (Sweden)

    Filonova A.V.

    2015-09-01

    Full Text Available Aim: to examine the psycho-emotional state of patients with psoriasis and to choose the optimal methods of correctional interventions with patients and their family-relatives. Materials and methods. The study included 230 patients with various different forms of psoriasis (150 men and 80 women, mean age 42±2,3 and 183 of their cohabitating relatives. The method of С D. Spielberg and J. L. Khanin was used for the assessment of anxiety degree, quality of life assessment (SF-36 health status survey, as well as a questionnaire, elaborated by our team, for patients with psoriasis. Results. After psychocorrection events in the patients there were noticed the following: decreased anxiety, increased vitality, improved relationships with loved ones, improved emotional state. Conclusion. When using psychotherapy in combination with medication, psoriasis treatment becomes more effective: reduced levels of anxiety, increased life activity, interaction with loved ones becomes more confident, improves emotional state.

  17. CV activities on the LHC complex during the long shutdown

    CERN Document Server

    Deleval, S; Body, Y; Obrecht, M; Moccia, S; Peon, G

    2011-01-01

    The presentation gives an overview of the major projects and work foreseen to be performed during next long shutdown on cooling and ventilation plants. Several projects are needed following the experience of the last years when LHC was running, in particular the modifications in the water cooling circuits presently in overflow. Some other projects are linked to the CV consolidation plan. Finally, most of the work shall be done to respond to additional requests: SR buildings air conditioning, the need to be able to clean and maintain the LHC cooling towers without a complete stop of cooling circuits, the upgrade of the air conditioning of the CCC rack room cooling etc. For all these activities, the author will detail constraints and the impact on the schedule and on the operation of the plants that will however need to run for most of the shutdown duration. The consequence of postponing the long shutdown from 2012 to 2013 will be also covered.

  18. Association between CISH polymorphisms and spontaneous clearance of hepatitis B virus in hepatitis B extracellular antigen-positive patients during immune active phase.

    Science.gov (United States)

    Song, Guangjun; Rao, Huiying; Feng, Bo; Wei, Lai

    2014-01-01

    Some hepatitis B extracellular antigen (HBeAg)-positive chronic hepatitis B (CHB) patients in their immune active phase can clear the virus spontaneously and enter into an inactive hepatitis B virus (HBV) carrier state, indicating a benign prognosis. In this study, the association between cytokine-inducible SRC homology 2 domain protein (CISH) gene polymorphisms at -292 (rs414171) and the spontaneous clearance of HBV in HBeAg-positive CHB patients in immune the active phase was investigated. Seventy HBeAg-positive CHB patients in the immune active phase were followed up for 76 weeks without antiviral therapy. The alanine transaminase, aspartate transaminase, HBV DNA, HBeAg and hepatitis B extracellular antibody levels were tested regularly. At week 76, 27 patients were classified into group A (HBV DNA level below 2 104 IU/ml and the value of HBeAg declined below 10% of the baseline at week 76), and 43 patients were classified into group B (HBV DNA level higher than 2×10(4) IU/ml or the value of HBeAg did not decline substantially at week 76). CISH (rs414171) polymorphisms were also tested using the iPLEX system. The HBV DNA levels at week 12 were significantly greater in group B compared with group A (group A: (6.87±1.40) log10IU/ml; group B: (7.61±1.38) log10IU/ml, P = 0.034) and the HBeAg values were greater in group B at week 28 compared with group A (P = 0.001). The differences in HBV DNA and HBeAg values increased between the groups over time. Sixteen patients in group A and 11 in group B were genotype AA. Those with genotype AT or TT included 11 in group A and 31 in group B (AA vs. AT and TT, odds ratio 4.10 (95% confidence interval: 1.462-11.491), P = 0.006). CISH gene polymorphisms at -292 (rs414171) are associated with HBV clearance in HBeAg-positive CHB patients in the immune active phase, and AA is a favorable genotype for this effect.

  19. The Association of Plasminogen Activator Inhibitor Type 1 (PAI-1) Level and PAI-1 4G/5G Gene Polymorphism with the Formation and the Grade of Endometrial Cancer.

    Science.gov (United States)

    Yıldırım, Malik Ejder; Karakuş, Savas; Kurtulgan, Hande Küçük; Kılıçgün, Hasan; Erşan, Serpil; Bakır, Sevtap

    2017-08-01

    Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor (Serpine 1), and it inhibits both tissue plasminogen activator and urokinase plasminogen activator which are important in fibrinolysis. We aimed to find whether there is a possible association between PAI-1 level, PAI-1 4G/5G polymorphism, and endometrial cancer. PAI-1 levels in peripheral blood were determined in 82 patients with endometrial carcinoma and 76 female healthy controls using an enzyme-linked immunoassay (ELISA). Then, the genomic DNA was extracted and screened by reverse hybridization procedure (Strip assay) to detect PAI 1 4G/5G polymorphism. The levels of PAI-1 in the patients were higher statistically in comparison to controls (P 5G polymorphism was quite different between patients and controls (P = 0.008), and 4G allelic frequency was significantly higher in the patients of endometrial cancer than in controls (P = 0.026). We found significant difference between Grade 1 and Grade 2+3 patients in terms of the PAI-1 levels (P = 0.047). There was no association between PAI-1 4G/5G polymorphism and the grades of endometrial cancer (P = 0.993). Our data suggest that the level of PAI-1 and PAI-1 4G/5G gene polymorphism are effective in the formation of endometrial cancer. PAI-1 levels are also associated with the grades of endometrial cancer.

  20. Associations of ACE Gene Insertion/Deletion Polymorphism, ACE Activity, and ACE mRNA Expression with Hypertension in a Chinese Population

    Science.gov (United States)

    He, Qingfang; Fan, Chunhong; Yu, Min; Wallar, Gina; Zhang, Zuo-Feng; Wang, Lixin; Zhang, Xinwei; Hu, Ruying

    2013-01-01

    Background The present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored. Methods The research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written informed consent was obtained prior to the investigation. 221 hypertensives (cases) and 221 normotensives (controls) were interviewed, subjected to a physical examination, and provided blood for biochemical and genetic tests. The ACE mRNA expression was analyzed by real time fluorescent quantitative Reverse Transcription PCR (FQ-RT-PCR). We performed logistic regression to assess associations of ACE I/D genotypes, ACE activity, and ACE mRNA expression levels with hypertension. Results The results of the multivariate logistic regression analysis showed that the additive model (ID, DD versus II) of the ACE genotype revealed an association with hypertension with adjusted OR of 1.43(95% CI: 1.04-1.97), and ACE ID genotype with adjusted OR of 1.72(95% CI: 1.01-2.92), DD genotype with adjusted OR of 1.94(95% CI: 1.01-3.73), respectively. In addition, our data also indicate that plasma ACE activity (adjusted OR was 1.13(95% CI: 1.08-1.18)) was significantly related to hypertension. However, the plasma ACE mRNA expressions were not different between the cases and controls. Conclusion ACE I/D polymorphism and ACE activity revealed significant influence on hypertension, while circulating ACE mRNA expression was not important factors associated with hypertension in this Chinese population. The detection of circulating ACE mRNA expression by FQ-RT-PCR might be a useful method for early screening and monitoring of EH. PMID:24098401

  1. STAT4 rs7574865 G/T polymorphism is associated with rheumatoid arthritis and disease activity, but not with anti-CCP antibody levels in a Mexican population.

    Science.gov (United States)

    Durán-Avelar, Ma de Jesús; Vibanco-Pérez, Norberto; Hernández-Pacheco, Raquel Rocío; Castro-Zambrano, América Del Carmen; Ortiz-Martínez, Liliana; Zambrano-Zaragoza, José Francisco

    2016-12-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease in whose etiology genetic factors are known to play an important role. Among the genes associated with RA, STAT4 could be an important factor in conducting helper T cells toward the pro-inflammatory Th1 and Th17 lineages. The aim of this study is to determine the association of the STAT4 polymorphism rs7574865 with RA, disease activity, and anti-cyclic citrullinated peptide (CCP) antibody levels in a Mexican population. Genotyping was carried out using the Taqman® system from Applied Biosystems in 140 patients with RA and 150 healthy subjects. Disease activity was evaluated by a rheumatologist using the DAS28 and Spanish-HAQ-DI instruments. Anti-CCP levels were determined by ELISA. Associations of the genotypes of rs7574865 with DAS28, HAQ, and anti-CCP antibody levels with RA were determined. Findings showed that the GT and TT genotypes and the T allele from rs7574865 were all associated as risk factors for RA, independently of their anti-CCP status. An association with moderate-to-high disease activity (DAS28 ≥ 3.2) was also found. Additionally, patients with the GT or TT genotypes showed lower HAQ values than those who carried the GG genotype. No differences in anti-CCP antibody levels or DAS28 and genotypes were found. This work supports the association of the STAT4 rs7574865 polymorphism with RA and disease activity, but not with anti-CCP antibody levels in a Mexican population.

  2. 4G/5G polymorphism of plasminogen activator inhibitor-1 gene is associated with polycystic ovary syndrome in Chinese patients: a meta-analysis.

    Science.gov (United States)

    Wang, Li-Hong; Wang, Li-Mei; Zhou, Na

    2015-09-01

    To date, case-control studies on the association between a single-nucleotide polymorphism (SNP) in the plasminogen activator inhibitor-1 (PAI-1) gene and polycystic ovary syndrome (PCOS) have provided controversial results. The electronic databases PubMed, Embase, Web of Science, and CNKI (China National Knowledge Infrastructure) were searched for studies to include in the present meta-analysis. The fixed effects and random effects models showed that the 4G allele was associated with a risk of PCOS compared with the 5G allele in Chinese patients (OR = 2.05; 95 % CI = 1.56-2.69), but not in Caucasian patients (OR = 1.05; 95 % CI = 0.81-1.37). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast. Our pooled data suggest evidence for a major role of PAI-1 gene 4G/5G polymorphism in the pathogenesis of PCOS among Chinese patients.

  3. Transition metal complexes of some biologically active ligands; synthesis characterization and bioactivities

    International Nuclear Information System (INIS)

    Rehman, S.; Ali, N.; Nisar, M.

    2009-01-01

    Transition/representative transition metals complexes of biologically active chelating agent 1,2-dipyrolodinoethane were synthesized and characterized through spectral and analytical data. The complexes are of the formula (M(L)X/sub 2/). Where (M = Co (II), Ni (II), Cu (II), Zn (II), Hg (II) and Cd (II) and X = CI, Br, NO/sub 3/). Tetrahedral geometry has been proposed to these-metal complexes with the help of magnetic measurements, elemental analysis, chemical stoichiometry and spectroscopic data Antibacterial activity of the ligand and its metal complexes were screened against Eschereschi coli, Klebsiello pneumonia, Proteus mirabilis, Proteus vulhari, Streptococcus pneumonia, Salmonella Iyphi, Bacilh,s anthrax, Streptococcus fecalis and Staphylococcus aureus. Complexes were found to be active against Eschereschi coli, Klebsiella pneumonia, Proteus mirabilis and Proteus vulharis. (author)

  4. Coordinating complex decision support activities across distributed applications

    Science.gov (United States)

    Adler, Richard M.

    1994-01-01

    Knowledge-based technologies have been applied successfully to automate planning and scheduling in many problem domains. Automation of decision support can be increased further by integrating task-specific applications with supporting database systems, and by coordinating interactions between such tools to facilitate collaborative activities. Unfortunately, the technical obstacles that must be overcome to achieve this vision of transparent, cooperative problem-solving are daunting. Intelligent decision support tools are typically developed for standalone use, rely on incompatible, task-specific representational models and application programming interfaces (API's), and run on heterogeneous computing platforms. Getting such applications to interact freely calls for platform independent capabilities for distributed communication, as well as tools for mapping information across disparate representations. Symbiotics is developing a layered set of software tools (called NetWorks! for integrating and coordinating heterogeneous distributed applications. he top layer of tools consists of an extensible set of generic, programmable coordination services. Developers access these services via high-level API's to implement the desired interactions between distributed applications.

  5. The Role of Dopamine in Anticipatory Pursuit Eye Movements: Insights from Genetic Polymorphisms in Healthy Adults.

    Science.gov (United States)

    Billino, Jutta; Hennig, Jürgen; Gegenfurtner, Karl R

    2016-01-01

    There is a long history of eye movement research in patients with psychiatric diseases for which dysfunctions of neurotransmission are considered to be the major pathologic mechanism. However, neuromodulation of oculomotor control is still hardly understood. We aimed to investigate in particular the impact of dopamine on smooth pursuit eye movements. Systematic variability in dopaminergic transmission due to genetic polymorphisms in healthy subjects offers a noninvasive opportunity to determine functional associations. We measured smooth pursuit in 110 healthy subjects genotyped for two well-documented polymorphisms, the COMT Val 158 Met polymorphism and the SLC6A3 3'-UTR-VNTR polymorphism. Pursuit paradigms were chosen to particularly assess the ability of the pursuit system to initiate tracking when target motion onset is blanked, reflecting the impact of extraretinal signals. In contrast, when following a fully visible target sensory, retinal signals are available. Our results highlight the crucial functional role of dopamine for anticipatory, but not for sensory-driven, pursuit processes. We found the COMT Val 158 Met polymorphism specifically associated with anticipatory pursuit parameters, emphasizing the dominant impact of prefrontal dopamine activity on complex oculomotor control. In contrast, modulation of striatal dopamine activity by the SLC6A3 3'-UTR-VNTR polymorphism had no significant functional effect. Though often neglected so far, individual differences in healthy subjects provide a promising approach to uncovering functional mechanisms and can be used as a bridge to understanding deficits in patients.

  6. Association between single nucleotide polymorphisms in the antioxidant genes CAT, GR and SOD1, erythrocyte enzyme activities, dietary and life style factors and breast cancer risk in a Danish, prospective cohort study

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov; Vogel, Ulla; Dragsted, Lars Ove

    2017-01-01

    investigated in 703 breast cancer case-control pairs in the Danish, prospective "Diet, Cancer and Health" cohort together with gene-environment interactions between the polymorphisms, enzyme activities and intake of fruits and vegetables, alcohol and smoking in relation to breast cancer risk. Our results...... showed that genetically determined variations in the antioxidant enzyme activities of SOD1, CAT and GSR were not associated with risk of breast cancer per se. However, intake of alcohol, fruit and vegetables, and smoking status interacted with some of the polymorphisms in relation to breast cancer risk...

  7. Effects of Polyelectrolyte Complex Micelles and Their Components on the Enzymatic Activity of Lipase

    NARCIS (Netherlands)

    Lindhoud, Saskia; Norde, Willem; Cohen Stuart, Martinus Abraham

    2010-01-01

    The enzymatic activity of Hl-lipase embedded in complexes of poly-2-methylvinylpyridinium-co-poly(ethylene oxide) (P2MVP41−PEO205) and poly(acrylic acid)(PAA139) is studied as a function of the PAA139 + P2MVP41−PEO205 complex composition. The measurements revealed that there are several factors that

  8. Effects of Polyelectrolyte Complex Micelles and Their Components on the Enzymatic Activity of Lipase

    NARCIS (Netherlands)

    Lindhoud, Saskia; Norde, Willem; Stuart, Martien Cohen

    2010-01-01

    The enzymatic activity of Hi-lipase embedded in complexes of poly-2-methylvinylpyridinium-co-poly(ethylene oxide) (P2MVP(41)-PEG(205)) and poly(acrylic acid)(PAA(139)) is studied as a function of the PAA(139) + P2MVP(41) - PEO(205) complex composition. The measurements revealed that there are

  9. Alpha S1-casein polymorphisms in camel (Camelus dromedarius) and descriptions of biological active peptides and allergenic epitopes.

    Science.gov (United States)

    Erhardt, Georg; Shuiep, El Tahir Salih; Lisson, Maria; Weimann, Christina; Wang, Zhaoxin; El Zubeir, Ibtisam El Yas Mohamed; Pauciullo, Alfredo

    2016-06-01

    Milk samples of 193 camels (Camelus dromedarius) from different regions of Sudan were screened for casein variability by isoelectric focusing. Kappa-casein and beta-casein were monomorphic, whereas three protein patterns named αs1-casein A, C, and D were identified. The major allele A revealed frequencies of 0.79 (Lahaoi), 0.75 (Shanbali), 0.90 (Arabi Khali), and 0.88 (Arabi Gharbawi) in the different ecotypes. CSN1S1*C shows a single G > T nucleotide substitution in the exon 5, leading to a non-synonymous amino acid exchange (p.Glu30 > Asp30) in comparison to CSN1S1*A and D. At cDNA level, no further single nucleotide polymorphisms could be identified in CSN1S1* A, C, and D, whereas the variants CSN1S1*A and CSN1S1*C are characterized by missing of exon 18 compared to the already described CSN1S1*B, as consequence of DNA insertion of 11 bp at intron 17 which alter the pre-mRNA spliceosome machinery. A polymerase chain-restriction fragment length polymorphism method (PCR-RFLP) was established to type for G > T nucleotide substitution at genomic DNA level. The occurrence and differences of IgE-binding epitopes and bioactive peptides between αs1-casein A, C, and D after digestion were analyzed in silico. The amino acid substitutions and deletion affected the arising peptide pattern and thus modifications between IgE-binding epitopes and bioactive peptides of the variants were found. The allergenic potential of these different peptides will be investigated by microarray immunoassay using sera from milk-sensitized individuals, as it was already demonstrated for bovine αs1-casein variants.

  10. Synthesis, physico-chemical characterization and biological activity of 2-aminobenzimidazole complexes with different metal ions

    Directory of Open Access Journals (Sweden)

    Podunavac-Kuzmanović Sanja O.

    2004-01-01

    Full Text Available Complexes of 2-aminobenzimidazole (L with nitrates of cobalt(II nickel(II, copper (II, zinc(II and silver(I were synthesized. The molar ratio metal:ligand in the reaction of the complex formation was 1:2. It should be noticed, that the reaction of all the metal salts yielded bis(ligand complexes of the general formula M(L2(NO32 × nH2O (M=Co, Ni Cu, Zn or Ag; n=0, 1, 2 or 6. The complexes were characterized by elemental analysis of the metal, molar conductivity, magnetic susceptibility measurements and IR spectra. Co(II, Ni(II and Cu(II complexes behave as non-electrolytes, whilst Zn(II and Ag(I are 1:1 electrolytes. Cu(II complex has a square-planar stereochemistry, Ag(I complex is linear, whilst the Co(II, Ni(II and Zn(II complexes have a tetrahedral configuration. In all the complexes ligand is coordinated by participation of the pyridine nitrogen of the benzimidazole ring. The antimicrobial activity of the ligand and its complexes against Pseudomonas aeruginosa, Bacillus sp. Staphylococcus aureus and Saccharomyces cerevisiae was investigated. The effect of metal on the ligand antimicrobial activity is discussed.

  11. Diversification of companies' activity of the Arctic fuel and energy complex

    Directory of Open Access Journals (Sweden)

    Fedoseev S. V.

    2015-09-01

    Full Text Available The analysis of diversification role in company's activity has been considered. Special attention has been paid to the levels of strategy for a diversified company of the fuel and energy complex

  12. Using visual information analysis to explore complex patterns in the activity of designers

    DEFF Research Database (Denmark)

    Cash, Philip; Stanković, Tino; Štorga, Mario

    2014-01-01

    The analysis of complex interlinked datasets poses a significant problem for design researchers. This is addressed by proposing an information visualisation method for analysing patterns of design activity, qualitatively and quantitatively, with respect to time. This method visualises the tempora...

  13. Hemostatic profile changes in patients with traumatic brain injury with regard to the genotypes of -675 4G/5G polymorphism of plasminogen activator inhibitor-1 gene

    Directory of Open Access Journals (Sweden)

    O. O. Potapov

    2016-10-01

    Full Text Available Traumatic brain injury (TBI is a significant problem in modern clinical medicine that has both medical and social importance. Analysis of hemostatic changes is a very important aspect of clinical course of TBI and should be paid special attention on it. This analysis is necessary to make prognosis for the treatment outcomes taking into account associations with genetic factors. The aim of research was to analyze hemostatic profile changes in patients with TBI with regard to the genotype of -675 4G/5G polymorphism of plasminogen activator inhibitor-1 gene (РАІ-1. Methods and materials. The research was based on the investigation results of 200 patients with isolated TBI, who were undergoing in-patient treatment at the neurosurgery department at Sumy Regional Clinical Hospital in 2011–2013, and 95 apparently healthy individuals of the control group. The following change cycling was confirmed during the study: a tendency to hypercoagulability on the 1st day transforming into a state of being incapable of coagulation on the 3rd day. On the 7 day hypercoagulability signs dominated and by the 14 day the laboratory findings had gradually become normal. Conclusions. According to the analysis of routine hemostatic profile parameters (activated partial thromboplastin time, prothrombin index, platelet count, plasma tolerance to heparin, activated recalcification time, euglobulin clot lysis assay, plasma fibrinogen level we concluded that there is no association between the studied parameters and the genotypes of the -675 4G/5G polymorphism in the PAI-1 gene in patients with TBI and controls. Our study confirms the necessity of further monitoring of fibrinolytic system, since routine laboratory tests of haemostasis are not always informative as for the fibrinolytic disorders in patients with TBI.

  14. Complex active regions as the main source of extreme and large solar proton events

    Science.gov (United States)

    Ishkov, V. N.

    2013-12-01

    A study of solar proton sources indicated that solar flare events responsible for ≥2000 pfu proton fluxes mostly occur in complex active regions (CARs), i.e., in transition structures between active regions and activity complexes. Different classes of similar structures and their relation to solar proton events (SPEs) and evolution, depending on the origination conditions, are considered. Arguments in favor of the fact that sunspot groups with extreme dimensions are CARs are presented. An analysis of the flare activity in a CAR resulted in the detection of "physical" boundaries, which separate magnetic structures of the same polarity and are responsible for the independent development of each structure.

  15. The activity state of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues.

    OpenAIRE

    Wagenmakers, A J; Schepens, J T; Veldhuizen, J A; Veerkamp, J H

    1984-01-01

    An assay is described to define the proportion of the branched-chain 2-oxo acid dehydrogenase complex that is present in the active state in rat tissues. Activities are measured in homogenates in two ways: actual activities, present in tissues, by blocking both the kinase and phosphatase of the enzyme complex during homogenization, preincubation, and incubation with 1-14C-labelled branched-chain 2-oxo acid, and total activities by blocking only the kinase during the 5 min preincubation (neces...

  16. Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria.

    Science.gov (United States)

    Singh, Namrata; Hroudová, Jana; Fišar, Zdeněk

    2015-08-01

    The aim of this study was to investigate changes in the activity of individual mitochondrial respiratory chain complexes (I, II/III, IV) and citrate synthase induced by pharmacologically different cannabinoids. In vitro effects of selected cannabinoids on mitochondrial enzymes were measured in crude mitochondrial fraction isolated from pig brain. Both cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol, anandamide, and R-(+)-WIN55,212-2, and antagonist/inverse agonists of cannabinoid receptors, AM251, and cannabidiol were examined in pig brain mitochondria. Different effects of these cannabinoids on mitochondrial respiratory chain complexes and citrate synthase were found. Citrate synthase activity was decreased only by Δ(9)-tetrahydrocannabinol and AM251. Significant increase in the complex I activity was induced by anandamide. At micromolar concentration, all the tested cannabinoids inhibited the activity of electron transport chain complexes II/III and IV. Stimulatory effect of anandamide on activity of complex I may participate on distinct physiological effects of endocannabinoids compared to phytocannabinoids or synthetic cannabinoids. Common inhibitory effect of cannabinoids on activity of complex II/III and IV confirmed a non-receptor-mediated mechanism of cannabinoid action on individual components of system of oxidative phosphorylation.

  17. Purification of Ovine Respiratory Complex I Results in a Highly Active and Stable Preparation.

    Science.gov (United States)

    Letts, James A; Degliesposti, Gianluca; Fiedorczuk, Karol; Skehel, Mark; Sazanov, Leonid A

    2016-11-18

    NADH-ubiquinone oxidoreductase (complex I) is the largest (∼1 MDa) and the least characterized complex of the mitochondrial electron transport chain. Because of the ease of sample availability, previous work has focused almost exclusively on bovine complex I. However, only medium resolution structural analyses of this complex have been reported. Working with other mammalian complex I homologues is a potential approach for overcoming these limitations. Due to the inherent difficulty of expressing large membrane protein complexes, screening of complex I homologues is limited to large mammals reared for human consumption. The high sequence identity among these available sources may preclude the benefits of screening. Here, we report the characterization of complex I purified from Ovis aries (ovine) heart mitochondria. All 44 unique subunits of the intact complex were identified by mass spectrometry. We identified differences in the subunit composition of subcomplexes of ovine complex I as compared with bovine, suggesting differential stability of inter-subunit interactions within the complex. Furthermore, the 42-kDa subunit, which is easily lost from the bovine enzyme, remains tightly bound to ovine complex I. Additionally, we developed a novel purification protocol for highly active and stable mitochondrial complex I using the branched-chain detergent lauryl maltose neopentyl glycol. Our data demonstrate that, although closely related, significant differences exist between the biochemical properties of complex I prepared from ovine and bovine mitochondria and that ovine complex I represents a suitable alternative target for further structural studies. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Characterization and antioxidant activity of the complex of pomegranate polyphenol extract and lecithin

    International Nuclear Information System (INIS)

    Li, G.; Zhao, R.

    2013-01-01

    The pomegranate polyphenol extract (PPE) was a nutraceutical with good prospect in food and medicinal industry. But its poor oil solubility limits its application in hydrophilic system. In this study, by forming the complex with lecithin, the hydrophilic solubility of PPE could be significantly improved. The physicochemical properties of the complex were analyzed by ultraviolet-visible spectrometry (UV), infrared spectrometry (IR) and X-ray diffractometry (XRD). The result showed that PPE in the complex had been completely dispersed in the lecithin matrix, not forming a new compound. It was found that the DPPH radical scavenging activity and reducing power of the complex were inferior to that of PPE while the antioxidant activity of the complex in oil was superior to that of PPE. (author)

  19. Antimicrobial Activity of Some Thiourea Derivatives and Their Nickel and Copper Complexes

    Directory of Open Access Journals (Sweden)

    Cevdet Akbay

    2009-01-01

    Full Text Available Five thiourea derivative ligands and their Ni2+ and Cu2+ complexes have been synthesized. The compounds were screened for their in vitro anti-bacterial activity using Gram-positive bacteria (two different standard strains of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes, Bacillus cereus and Gram-negative bacteria (Esherichia coli, Pseudomonas aeruginosa, Enterobacter cloacae, Proteus vulgaris, Enterobacter aerogenes and in vitro anti-yeast activity (Candida albicans, Candida krusei, Candida glabrata, Candida tropicalis, Candida parapsilosis. The minimum inhibitory concentration was determined for all ligands and their complexes. In vitro anti-yeast activity of both ligands and their metal complexes is greater than their in vitro anti-bacterial activity. The effect of the structure of the investigated compounds on the antimicrobial activity is discussed.

  20. Synthesis, characterization and biological activity of symmetric dinuclear complexes derived from a novel macrocyclic compartmental ligand

    Energy Technology Data Exchange (ETDEWEB)

    Mruthyunjayaswamy, B.H.M.; Ijare, Omkar B.; Jadegoud, Y. [Gulbarga University (India). Dept. of Chemistry]. E-mail: bhmmswamy53@rediffmail.com

    2005-07-15

    A phenol based novel macrocyclic binucleating compartmental ligand N,N-bis(2,6-diiminomethyl-4-methyl-1-hydroxyphenyl)malonoyldicarboxamide was prepared. The complexes were prepared by template method by reacting 2,6-diformyl-4-methylphenol, malonoyl dihydrazide and the metal chlorides of Cu(II), Ni(II), Co(II), Cd(II), Zn(II) and Hg(II) in methanol to get a series of dinuclear complexes. The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibility data, IR, UV-Vis, ESR, NMR and FAB mass spectral data. The dinuclear nature of the complexes was confirmed on the basis of elemental analyses, magnetic susceptibility, ESR and FAB mass spectral data. The ligand as well as Cu(II), Ni(II), Co(II) and Zn(II) complexes were tested for their antibacterial and antifungal properties against Escherichia coli, Staphyloccocus aureus, Aspergillus niger and Fusarium oxysporum. Magnetic susceptibility measurements of Cu(II), Ni(II) and Co(II) complexes reveal that these complexes exhibit antiferromagnetic coupling behavior due to the presence of two metal ions in close proximity. FAB mass spectrum of the Cu(II) complex gave a clear evidence for the dinuclear nature. The ligand and the complexes were found to be less active against the tested bacteria, but the ligand alone was found active against the fungus Fusarium oxysporum. (author)

  1. Synthesis, characterization and biological activity of symmetric dinuclear complexes derived from a novel macrocyclic compartmental ligand

    International Nuclear Information System (INIS)

    Mruthyunjayaswamy, B.H.M.; Ijare, Omkar B.; Jadegoud, Y.

    2005-01-01

    A phenol based novel macrocyclic binucleating compartmental ligand N,N-bis(2,6-diiminomethyl-4-methyl-1-hydroxyphenyl)malonoyldicarboxamide was prepared. The complexes were prepared by template method by reacting 2,6-diformyl-4-methylphenol, malonoyl dihydrazide and the metal chlorides of Cu(II), Ni(II), Co(II), Cd(II), Zn(II) and Hg(II) in methanol to get a series of dinuclear complexes. The complexes were characterized by elemental analyses, conductivity measurements, magnetic susceptibility data, IR, UV-Vis, ESR, NMR and FAB mass spectral data. The dinuclear nature of the complexes was confirmed on the basis of elemental analyses, magnetic susceptibility, ESR and FAB mass spectral data. The ligand as well as Cu(II), Ni(II), Co(II) and Zn(II) complexes were tested for their antibacterial and antifungal properties against Escherichia coli, Staphyloccocus aureus, Aspergillus niger and Fusarium oxysporum. Magnetic susceptibility measurements of Cu(II), Ni(II) and Co(II) complexes reveal that these complexes exhibit antiferromagnetic coupling behavior due to the presence of two metal ions in close proximity. FAB mass spectrum of the Cu(II) complex gave a clear evidence for the dinuclear nature. The ligand and the complexes were found to be less active against the tested bacteria, but the ligand alone was found active against the fungus Fusarium oxysporum. (author)

  2. The Role of G22 A Adenosine Deaminase 1 Gene Polymorphism and the Activities of ADA Isoenzymes in Fertile and Infertile Men.

    Science.gov (United States)

    Fattahi, Amir; Khodadadi, Iraj; Amiri, Iraj; Latifi, Zeinab; Ghorbani, Marzieh; Tavilani, Heidar

    2015-10-01

    To evaluate frequency distribution of adenosine deaminase 1 (ADA1) G22 A alleles and genotypes in fertile and infertile men. In this study we evaluate frequency distribution of ADA1 G22 A alleles and genotypes in 200 fertile and 200 infertile men. The polymerase chain reaction-restriction fragment length polymorphism technique was used for determining ADA1 G22 A variants. In addition, ADA isoenzymes activities (ADA1 and ADA2) were measured using colorimetric method. The frequency of GG genotype was significantly higher and GA genotype was lower in infertile males compared with fertile men (P = .048 and P = .045, respectively). However, there was not any noticeable difference in allele distribution between groups (P >.05). Based on logistic regression analysis, the GA genotype has a protective role and can decrease the risk of male infertility 1.7 times (P = .046). There were significantly higher activities of ADAT and its isoenzymes in infertile males compared with fertile men (P ADA1 activity with GG genotype was higher than GA carriers in all population (P = .001). Our results revealed that the activity of ADA isoenzymes and distribution of ADA1 G22 A genotypes were different among fertile and infertile men and more likely the GA genotype, which had lower ADA1 activity and was higher in fertile men is a protective factor against infertility. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Synthesis, structural characterization and cytotoxic activity of two new organoruthenium(II complexes

    Directory of Open Access Journals (Sweden)

    SANJA GRGURIC-SIPKA

    2008-06-01

    Full Text Available Two new p-cymene ruthenium(II complexes containing as additional ligands N-methylpiperazine ([(η6-p-cymeneRuCl2(CH3NH(CH24NH]PF6, complex 1 or vitamin K3-thiosemicarbazone ([(η6-p-cymeneRuCl2(K3tsc], complex 2 were synthesized starting from [(η6-p-cymene2RuCl2]2 and the corresponding ligand. The complexes were characterized by elemental analysis, IR, electronic absorption and NMR spectroscopy. The X-ray crystal structure determination of complex 1 revealed “piano-stool” geometry. The differences in the cytotoxic activity of the two complexes are discussed in terms of the ligand present.

  4. Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands.

    Science.gov (United States)

    Hubin, Timothy J; Amoyaw, Prince N-A; Roewe, Kimberly D; Simpson, Natalie C; Maples, Randall D; Carder Freeman, TaRynn N; Cain, Amy N; Le, Justin G; Archibald, Stephen J; Khan, Shabana I; Tekwani, Babu L; Khan, M O Faruk

    2014-07-01

    Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal complexes of the dibenzyl cross-bridged cyclam ligand exhibited potent antimalarial activity. The Mn(2+) complex of this ligand was the most potent with IC50s of 0.127 and 0.157μM against the chloroquine-sensitive (D6) and chloroquine-resistant (W2) P. falciparum strains, respectively. In general, the dibenzyl hydrophobic ligands showed better anti-malarial activity compared to the activity of monobenzyl ligands, potentially because of their higher lipophilicity and thus better cell penetration ability. The higher antimalarial activity displayed by the manganese complex for the cyclam ligand in comparison to that of the cyclen, correlates with the larger pocket of cyclam compared to that of cyclen which produces a more stable complex with the Mn(2+). Few of the Cu(2+) and Fe(2+) complexes also showed improvement in activity but Ni(2+), Co(2+) and Zn(2+) complexes did not show any improvement in activity upon the metal-free ligands for anti-malarial development. Published by Elsevier Ltd.

  5. Plasticity of TOM complex assembly in skeletal muscle mitochondria in response to chronic contractile activity.

    Science.gov (United States)

    Joseph, Anna-Maria; Hood, David A

    2012-03-01

    We investigated the assembly of the TOM complex within skeletal muscle under conditions of chronic contractile activity-induced mitochondrial biogenesis. Tom40 import into mitochondria was increased by chronic contractile activity, as was its time-dependent assembly into the TOM complex. These changes coincided with contractile activity-induced augmentations in the expression of key protein import machinery components Tim17, Tim23, and Tom22, as well as the cytosolic chaperone Hsp90. These data indicate the adaptability of the TOM protein import complex and suggest a regulatory role for the assembly of this complex in exercise-induced mitochondrial biogenesis. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved. All rights reserved.

  6. Synthesis, characterization, antiplasmodial and antitrypanosomal activity of some metal(III complexes of sulfadiazine

    Directory of Open Access Journals (Sweden)

    P.A. Ajibade

    2008-08-01

    Full Text Available The Fe(III, Ru(III, Rh(III, and Cr(III complexes of 4-amino-N-(2-pyrimidinylbenzene sulfonamide (sulfadiazine have been synthesized and characterized by elemental analysis, electronic and IR spectroscopy, conductance and room temperature magnetic susceptibility measurements. Sulfadiazine acts as a bidentate ligand through the sulfonamido and the pyrimidinic N-atoms. The compounds are non-electrolytes and the electronic spectra are consistent with the proposed octahedral geometry around the metal ions. The complexes were tested for in vitro activity against cultures of the resistant strains of Plasmodium falciparum, tripamastigotes T. b. rhodesiense and amastigotes L. donovani to determine their antiprotozoal activities. The Fe(III complex is more active than the other complexes against the parasitic protozoa.

  7. Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction.

    Science.gov (United States)

    Costa, Mônica S; Gonçalves, Yasmim G; Nunes, Débora C O; Napolitano, Danielle R; Maia, Pedro I S; Rodrigues, Renata S; Rodrigues, Veridiana M; Von Poelhsitz, Gustavo; Yoneyama, Kelly A G

    2017-10-01

    Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania. The many complications presented by the current treatment - including high toxicity, high cost and parasite resistance - make the development of new therapeutic agents indispensable. The present study aims to evaluate the anti-Leishmania potential of new ruthenium(II) complexes, cis‑[Ru II (η 2 -O 2 CR)(dppm) 2 ]PF 6 , with dppm=bis(diphenylphosphino)methane and R=4-butylbenzoate (bbato) 1, 4-(methylthio)benzoate (mtbato) 2 and 3-hydroxy-4-methoxybenzoate (hmxbato) 3, in promastigote cytotoxicity and their effect on parasite-host interaction. The cytotoxicity of complexes was analyzed by MTT assay against Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Leishmania) infantum promastigotes and the murine macrophage (RAW 264.7). The effect of complexes on parasite-host interaction was evaluated by in vitro infectivity assay performed in the presence of two different concentrations of each complex: the promastigote IC 50 value and the concentration nontoxic to 90% of RAW 264.7 macrophages. Complexes 1-3 exhibited potent cytotoxic activity against all Leishmania species assayed. The IC 50 values ranged from 7.52-12.59μM (complex 1); 0.70-3.28μM (complex 2) and 0.52-1.75μM (complex 3). All complexes significantly inhibited the infectivity index at both tested concentrations. The infectivity inhibitions ranged from 37 to 85%. Interestingly, the infectivity inhibitions due to complex action did not differ significantly at either of the tested concentrations, except for the complex 1 against Leishmania (Leishmania) infantum. The infectivity inhibitions resulted from reductions in both percentage of infected macrophages and number of parasites per macrophage. Taken together the results suggest remarkable leishmanicidal activity in vitro by these new ruthenium(II) complexes. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Simple, Low-Cost Detection of Candida parapsilosis Complex Isolates and Molecular Fingerprinting of Candida orthopsilosis Strains in Kuwait by ITS Region Sequencing and Amplified Fragment Length Polymorphism Analysis.

    Science.gov (United States)

    Asadzadeh, Mohammad; Ahmad, Suhail; Hagen, Ferry; Meis, Jacques F; Al-Sweih, Noura; Khan, Ziauddin

    2015-01-01

    Candida parapsilosis has now emerged as the second or third most important cause of healthcare-associated Candida infections. Molecular studies have shown that phenotypically identified C. parapsilosis isolates represent a complex of three species, namely, C. parapsilosis, C. orthopsilosis and C. metapsilosis. Lodderomyces elongisporus is another species phenotypically closely related to the C. parapsilosis-complex. The aim of this study was to develop a simple, low cost multiplex (m) PCR assay for species-specific identification of C. parapsilosis complex isolates and to study genetic relatedness of C. orthopsilosis isolates in Kuwait. Species-specific amplicons from C. parapsilosis (171 bp), C. orthopsilosis (109 bp), C. metapsilosis (217 bp) and L. elongisporus (258 bp) were obtained in mPCR. Clinical isolates identified as C. parapsilosis (n = 380) by Vitek2 in Kuwait and an international collection of 27 C. parapsilosis complex and L. elongisporus isolates previously characterized by rDNA sequencing were analyzed to evaluate mPCR. Species-specific PCR and DNA sequencing of internal transcribed spacer (ITS) region of rDNA were performed to validate the results of mPCR. Fingerprinting of 19 clinical C. orthopsilosis isolates (including 4 isolates from a previous study) was performed by amplified fragment length polymorphism (AFLP) analysis. Phenotypically identified C. parapsilosis isolates (n = 380) were identified as C. parapsilosis sensu stricto (n = 361), C. orthopsilosis (n = 15), C. metapsilosis (n = 1) and L. elongisporus (n = 3) by mPCR. The mPCR also accurately detected all epidemiologically unrelated C. parapsilosis complex and L. elongisporus isolates. The 19 C. orthopsilosis isolates obtained from 16 patients were divided into 3 haplotypes based on ITS region sequence data. Seven distinct genotypes were identified among the 19 C. orthopsilosis isolates by AFLP including a dominant genotype (AFLP1) comprising 11 isolates recovered from 10 patients. A

  9. A complex of equine lysozyme and oleic acid with bactericidal activity against Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Emily A Clementi

    Full Text Available HAMLET and ELOA are complexes consisting of oleic acid and two homologous, yet functionally different, proteins with cytotoxic activities against mammalian cells, with HAMLET showing higher tumor cells specificity, possibly due to the difference in propensity for oleic acid binding, as HAMLET binds 5-8 oleic acid molecules per protein molecule and ELOA binds 11-48 oleic acids. HAMLET has been shown to possess bactericidal activity against a number of bacterial species, particularly those with a respiratory tropism, with Streptococcus pneumoniae displaying the greatest degree of sensitivity. We show here that ELOA also displays bactericidal activity against pneumococci, which at lower concentrations shows mechanistic similarities to HAMLET's bactericidal activity. ELOA binds to S. pneumoniae and causes perturbations of the plasma membrane, including depolarization and subsequent rupture, and activates an influx of calcium into the cells. Selective inhibition of calcium channels and sodium/calcium exchange activity significantly diminished ELOA's bactericidal activity, similar to what we have observed with HAMLET. Finally, ELOA-induced death was also accompanied by DNA fragmentation into high molecular weight fragments - an apoptosis-like morphological phenotype that is seen during HAMLET-induced death. Thus, in contrast to different mechanisms of eukaryote cell death induced by ELOA and HAMLET, these complexes are characterized by rather similar activities towards bacteria. Although the majority of these events could be mimicked using oleic acid alone, the concentrations of oleic acid required were significantly higher than those present in the ELOA complex, and for some assays, the results were not identical between oleic acid alone and the ELOA complex. This indicates that the lipid, as a common denominator in both complexes, is an important component for the complexes' bactericidal activities, while the proteins are required both to solubilize

  10. The impact of traffic noise on mental performance considering complexity of activities

    Directory of Open Access Journals (Sweden)

    I. Alimohammadi

    2015-12-01

      Conclusion: One of the most significant findings emerged from this study is that traffic noise seems to have no effect on the mentioned variables under simple activity condition. However, traffic noise has devastating effects on median reaction time, number of appeared stimuli and reactions under complex activity condition.

  11. Studies of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene in relation to insulin sensitivity among glucose tolerant caucasians

    DEFF Research Database (Denmark)

    Ek, J; Andersen, G; Urhammer, S A

    2001-01-01

    We examined whether the Pro12-Ala polymorphism of the human peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene was related to altered insulin sensitivity among glucose-tolerant subjects or a lower accumulated incidence or prevalence of IGT and Type II (non-insulin-dependent) dia......-insulin-dependent) diabetes mellitus among Scandinavian Caucasians....

  12. Effect of pregnancy-associated plasma protein-A (PAPP-A) single-nucleotide polymorphisms on the level and activity of PAPP-A and the hormone profile in fluid from normal human small antral follicles

    DEFF Research Database (Denmark)

    Bøtkjær, Jane Alrø; Borgbo, Tanni; Kløverpris, Søren

    2016-01-01

    Objective: To reveal a possible relationship between two single nucleotide polymorphisms (SNPs) in PAPP-A—1224 (rs7020782) and 327 (rs12375498)—and the level and activity of PAPP-A in follicular fluid (FF) of human small antral follicles, and to analyze the intrafollicular hormone levels. Design:...

  13. Synthesis, structures and urease inhibitory activity of cobalt(III) complexes with Schiff bases.

    Science.gov (United States)

    Jing, Changling; Wang, Cunfang; Yan, Kai; Zhao, Kedong; Sheng, Guihua; Qu, Dan; Niu, Fang; Zhu, Hailiang; You, Zhonglu

    2016-01-15

    A series of new cobalt(III) complexes were prepared. They are [CoL(1)(py)3]·NO3 (1), [CoL(2)(bipy)(N3)]·CH3OH (2), [CoL(3)(HL(3))(N3)]·NO3 (3), and [CoL(4)(MeOH)(N3)] (4), where L(1), L(2), L(3) and L(4) are the deprotonated form of N'-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide, N'-(2-hydroxybenzylidene)-3-hydroxylbenzohydrazide, 2-[(2-dimethylaminoethylimino)methyl]-4-methylphenol, and N,N'-bis(5-methylsalicylidene)-o-phenylenediamine, respectively, py is pyridine, and bipy is 2,2'-bipyridine. The complexes were characterized by infrared and UV-Vis spectra, and single crystal X-ray diffraction. The Co atoms in the complexes are in octahedral coordination. Complexes 1 and 4 show effective urease inhibitory activities, with IC50 values of 4.27 and 0.35 μmol L(-1), respectively. Complex 2 has medium activity against urease, with IC50 value of 68.7 μmol L(-1). While complex 3 has no activity against urease. Molecular docking study of the complexes with Helicobacter pylori urease was performed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria.

    Science.gov (United States)

    Popov-Celeketić, Dusan; Mapa, Koyeli; Neupert, Walter; Mokranjac, Dejana

    2008-05-21

    The TIM23 (translocase of the mitochondrial inner membrane) complex mediates translocation of preproteins across and their insertion into the mitochondrial inner membrane. How the translocase mediates sorting of preproteins into the two different subcompartments is poorly understood. In particular, it is not clear whether association of two operationally defined parts of the translocase, the membrane-integrated part and the import motor, depends on the activity state of the translocase. We established conditions to in vivo trap the TIM23 complex in different translocation modes. Membrane-integrated part of the complex and import motor were always found in one complex irrespective of whether an arrested preprotein was present or not. Instead, we detected different conformations of the complex in response to the presence and, importantly, the type of preprotein being translocated. Two non-essential subunits of the complex, Tim21 and Pam17, modulate its activity in an antagonistic manner. Our data demonstrate that the TIM23 complex acts as a single structural and functional entity that is actively remodelled to sort preproteins into different mitochondrial subcompartments.

  15. Interaction of single nucleotide polymorphisms in ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL with physical activity on the risk of type 2 diabetes mellitus and changes in characteristics of the metabolic syndrome

    DEFF Research Database (Denmark)

    Oskari Kilpeläinen, Tuomas; Lakka, Timo A; Laaksonen, David E

    2008-01-01

    Single nucleotide polymorphisms (SNPs) in the ADRB2, ADRB3, TNF, IL6, IGF1R, LIPC, LEPR, and GHRL genes were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes mellitus (T2D) in the Finnish Diabetes Prevention Study (DPS). In this study, we determined whether...... on the conversion to T2D was found. The Leu72Met (rs696217) polymorphism in GHRL modified the effect of moderate-to-vigorous PA on changes in weight and waist circumference, the -501A/C (rs26802) polymorphism in GHRL modified the effect of total and moderate-to-vigorous PA on change in high-density lipoprotein...... polymorphisms in these genes modified the effect of changes in physical activity (PA) on the risk of T2D in the DPS. Moreover, we assessed whether the polymorphisms modified the effect of changes in PA on changes in measures of body fat, serum lipids, and blood pressure during the first year of the follow...

  16. Synthesis, Characterization, and Thermal and Antimicrobial Activities of Some Novel Organotin(IV: Purine Base Complexes

    Directory of Open Access Journals (Sweden)

    Reena Jain

    2013-01-01

    Full Text Available A new series of organotin(IV complexes with purine bases theophylline (HL1 and theobromine (L2 of the types R3Sn(L1, R2Sn(L1Cl, R3Sn(L2Cl, and R2Sn(L2Cl2 (R = C6H5CH2–; p-ClC6H4CH2– have been synthesized in anhydrous THF. The complexes were characterized by elemental analysis, conductance measurements, molecular weight determinations, UV-vis, IR, 1H, 13C NMR, and mass spectral studies. Various kinetic and thermodynamic parameters of these complexes have also been determined using TG/DTA technique. The thermal decomposition techniques indicate the formation of SnO2 as a residue. The results show that the ligands act as bidentate, forming a five-member chelate ring. All the complexes are 1 : 1 metal-ligand complexes. In order to assess their antimicrobial activity, the ligands and their corresponding complexes have also been tested in vitro against bacteria (E. coli, S. aureus, and P. pyocyanea and fungi (Rhizopus oryzae and Aspergillus flavus. All the complexes exhibit remarkable activity, and the results provide evidence that the studied complexes might indeed be a potential source of antimicrobial agents.

  17. Isolation and structure–function characterization of a signaling-active rhodopsin–G protein complex

    Science.gov (United States)

    Gao, Yang; Westfield, Gerwin; Erickson, Jon W.; Cerione, Richard A.; Skiniotis, Georgios; Ramachandran, Sekar

    2017-01-01

    The visual photo-transduction cascade is a prototypical G protein–coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (GT). This results in the dissociation of GT into its component αT–GTP and β1γ1 subunit complex. Structural information for the Rho*–GT complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (GT*) comprising a GαT/Gαi1 chimera (αT*) and β1γ1. The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to GαT* is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one GT*. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β2-adrenergic receptor–GS complex, including a flexible αT* helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. PMID:28655769

  18. Isolation and structure-function characterization of a signaling-active rhodopsin-G protein complex.

    Science.gov (United States)

    Gao, Yang; Westfield, Gerwin; Erickson, Jon W; Cerione, Richard A; Skiniotis, Georgios; Ramachandran, Sekar

    2017-08-25

    The visual photo-transduction cascade is a prototypical G protein-coupled receptor (GPCR) signaling system, in which light-activated rhodopsin (Rho*) is the GPCR catalyzing the exchange of GDP for GTP on the heterotrimeric G protein transducin (G T ). This results in the dissociation of G T into its component α T -GTP and β 1 γ 1 subunit complex. Structural information for the Rho*-G T complex will be essential for understanding the molecular mechanism of visual photo-transduction. Moreover, it will shed light on how GPCRs selectively couple to and activate their G protein signaling partners. Here, we report on the preparation of a stable detergent-solubilized complex between Rho* and a heterotrimer (G T *) comprising a Gα T /Gα i1 chimera (α T *) and β 1 γ 1 The complex was formed on native rod outer segment membranes upon light activation, solubilized in lauryl maltose neopentyl glycol, and purified with a combination of affinity and size-exclusion chromatography. We found that the complex is fully functional and that the stoichiometry of Rho* to Gα T * is 1:1. The molecular weight of the complex was calculated from small-angle X-ray scattering data and was in good agreement with a model consisting of one Rho* and one G T *. The complex was visualized by negative-stain electron microscopy, which revealed an architecture similar to that of the β 2 -adrenergic receptor-G S complex, including a flexible α T * helical domain. The stability and high yield of the purified complex should allow for further efforts toward obtaining a high-resolution structure of this important signaling complex. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. The prevalence of 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene in central serous chorioretinopathy and its association with plasma PAI-1 levels.

    Science.gov (United States)

    Sogutlu Sari, Esin; Yazici, Alper; Eser, Betül; Erol, Muhammet Kazim; Kilic, Adil; Ermis, Sitki Samet; Koytak, Arif; Akşit, Hasan; Yakut, Tahsin

    2014-12-01

    Central serous chorioretinopathy (CSCR) is a poorly understood disease and the choroidal circulation abnormality induced by the plasminogen activator inhibitor type 1 (PAI-1) seems to be associated with the pathogenesis. There are many reports indicating that 4 G/5 G polymorphism of the PAI-1 gene is a risk factor for several diseases related to the elevated serum levels of PAI-1. To evaluate the 4 G/5 G polymorphism of the PAI-1 gene and its association with serum levels of PAI-1 in acute CSCR patients. Sixty CSCR patients and 50 healthy control patients were included. The PAI-1 4 G/5 G was genotyped using the polymerase chain reaction-restriction technique. Serum PAI-1 level was measured using enzyme-linked immunosorbent assay. Demographic data consisting of age, sex, body mass index (BMI) as well as genotype disturbances and serum PAI-1 levels were compared between the groups. Statistical significance for differences in the serum PAI-1 levels of each group with different genotypes was also analyzed. The CSCR group consisted of 40 male (66.7%) and 20 female (33.3%) patients with a mean age of 46.7 ± 8.39 years. The control group consisted of 32 male (64%) and 18 female (36%) healthy subjects with a mean age of 45.8 ± 8.39 years. There was no statistically significant difference between the groups in terms of age, sex and BMI. In the CSCR group the genotype frequencies were 4 G/4G: 30% (n = 18), 4G/5 G: 50% (n = 30), 5 G/5G: 20% (n = 12) and in the control group genotype frequencies were 34% (n = 17), 42% (n = 21) and 24% (n = 12), respectively. There was no statistically significant difference in the distribution of genotypes among the groups (chi-squared, p = 0.70). The CSCR group had a significantly higher serum PAI-1 concentration than the control group (p = 0.001). In both groups the mean plasma PAI-1 concentration did not vary significantly among the different genotypes (p > 0.05). Although our results demonstrated that the patients with acute CSCR have

  20. Polystyrene-Supported Acyclic Diaminocarbene Palladium Complexes in Sonogashira Cross-Coupling: Stability vs. Catalytic Activity

    Directory of Open Access Journals (Sweden)

    Vladimir N. Mikhaylov

    2018-04-01

    Full Text Available Two types of immobilized on the amino-functionalized polystyrene-supported acyclic diaminocarbene palladium complexes (ADC-PdII are investigated under Sonogashira cross-coupling conditions. Depending on substituents in the diaminocarbene fragment immobilized ADC-PdII, systems are found to have different catalytic activity and stability regarding Pd-leaching. PdII-diaminocarbenes possessing protons at both nitrogen atoms smoothly decompose into Pd0-containing species providing a catalytic “cocktail system” with high activity and ability to reuse within nine runs. Polymer-supported palladium (II complex bearing NBn–Ccarbene–NH-moiety exhibits greater stability while noticeably lower activity under Sonogashira cross-coupling. Four molecular ADC-PdII complexes are also synthesized and investigated with the aim of confirming proposed base-promoted pathway of ADC-PdII conversion through carbodiimide into an active Pd0 forms.

  1. Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites

    Science.gov (United States)

    Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas

    2017-01-01

    The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly. PMID:28949297

  2. Effect of mitochondrial complex I inhibition on Fe-S cluster protein activity

    Energy Technology Data Exchange (ETDEWEB)

    Mena, Natalia P. [Department of Biology, Faculty of Sciences, Universidad de Chile, Las Palmeras 3425, Santiago (Chile); Millennium Institute of Cell Dynamics and Biotechnology, Santiago (Chile); Bulteau, Anne Laure [UPMC Univ Paris 06, UMRS 975 - UMR 7725, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); Inserm, U 975, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); CNRS, UMR 7225, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, Paris 75013 (France); Salazar, Julio [Millennium Institute of Cell Dynamics and Biotechnology, Santiago (Chile); Hirsch, Etienne C. [UPMC Univ Paris 06, UMRS 975 - UMR 7725, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); Inserm, U 975, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); CNRS, UMR 7225, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, Paris 75013 (France); Nunez, Marco T., E-mail: mnunez@uchile.cl [Department of Biology, Faculty of Sciences, Universidad de Chile, Las Palmeras 3425, Santiago (Chile); Millennium Institute of Cell Dynamics and Biotechnology, Santiago (Chile)

    2011-06-03

    Highlights: {yields} Mitochondrial complex I inhibition resulted in decreased activity of Fe-S containing enzymes mitochondrial aconitase and cytoplasmic aconitase and xanthine oxidase. {yields} Complex I inhibition resulted in the loss of Fe-S clusters in cytoplasmic aconitase and of glutamine phosphoribosyl pyrophosphate amidotransferase. {yields} Consistent with loss of cytoplasmic aconitase activity, an increase in iron regulatory protein 1 activity was found. {yields} Complex I inhibition resulted in an increase in the labile cytoplasmic iron pool. -- Abstract: Iron-sulfur (Fe-S) clusters are small inorganic cofactors formed by tetrahedral coordination of iron atoms with sulfur groups. Present in numerous proteins, these clusters are involved in key biological processes such as electron transfer, metabolic and regulatory processes, DNA synthesis and repair and protein structure stabilization. Fe-S clusters are synthesized mainly in the mitochondrion, where they are directly incorporated into mitochondrial Fe-S cluster-containing proteins or exported for cytoplasmic and nuclear cluster-protein assembly. In this study, we tested the hypothesis that inhibition of mitochondrial complex I by rotenone decreases Fe-S cluster synthesis and cluster content and activity of Fe-S cluster-containing enzymes. Inhibition of complex I resulted in decreased activity of three Fe-S cluster-containing enzymes: mitochondrial and cytosolic aconitases and xanthine oxidase. In addition, the Fe-S cluster content of glutamine phosphoribosyl pyrophosphate amidotransferase and mitochondrial aconitase was dramatically decreased. The reduction in cytosolic aconitase activity was associated with an increase in iron regulatory protein (IRP) mRNA binding activity and with an increase in the cytoplasmic labile iron pool. Since IRP activity post-transcriptionally regulates the expression of iron import proteins, Fe-S cluster inhibition may result in a false iron deficiency signal. Given that

  3. Effect of mitochondrial complex I inhibition on Fe-S cluster protein activity

    International Nuclear Information System (INIS)

    Mena, Natalia P.; Bulteau, Anne Laure; Salazar, Julio; Hirsch, Etienne C.; Nunez, Marco T.

    2011-01-01

    Highlights: → Mitochondrial complex I inhibition resulted in decreased activity of Fe-S containing enzymes mitochondrial aconitase and cytoplasmic aconitase and xanthine oxidase. → Complex I inhibition resulted in the loss of Fe-S clusters in cytoplasmic aconitase and of glutamine phosphoribosyl pyrophosphate amidotransferase. → Consistent with loss of cytoplasmic aconitase activity, an increase in iron regulatory protein 1 activity was found. → Complex I inhibition resulted in an increase in the labile cytoplasmic iron pool. -- Abstract: Iron-sulfur (Fe-S) clusters are small inorganic cofactors formed by tetrahedral coordination of iron atoms with sulfur groups. Present in numerous proteins, these clusters are involved in key biological processes such as electron transfer, metabolic and regulatory processes, DNA synthesis and repair and protein structure stabilization. Fe-S clusters are synthesized mainly in the mitochondrion, where they are directly incorporated into mitochondrial Fe-S cluster-containing proteins or exported for cytoplasmic and nuclear cluster-protein assembly. In this study, we tested the hypothesis that inhibition of mitochondrial complex I by rotenone decreases Fe-S cluster synthesis and cluster content and activity of Fe-S cluster-containing enzymes. Inhibition of complex I resulted in decreased activity of three Fe-S cluster-containing enzymes: mitochondrial and cytosolic aconitases and xanthine oxidase. In addition, the Fe-S cluster content of glutamine phosphoribosyl pyrophosphate amidotransferase and mitochondrial aconitase was dramatically decreased. The reduction in cytosolic aconitase activity was associated with an increase in iron regulatory protein (IRP) mRNA binding activity and with an increase in the cytoplasmic labile iron pool. Since IRP activity post-transcriptionally regulates the expression of iron import proteins, Fe-S cluster inhibition may result in a false iron deficiency signal. Given that inhibition of complex

  4. Dependency of {gamma}-secretase complex activity on the structural integrity of the bilayer

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Hua, E-mail: hzhou2@lbl.gov [Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720 (United States); Zhou, Shuxia; Walian, Peter J.; Jap, Bing K. [Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA 94720 (United States)

    2010-11-12

    Research highlights: {yields} Partial solubilization of membranes with CHAPSO can increase {gamma}-secretase activity. {yields} Completely solubilized {gamma}-secretase is inactive. {yields} Purified {gamma}-secretase regains activity after reconstitution into lipid bilayers. {yields} A broad range of detergents can be used to successfully reconstitute {gamma}-secretase. -- Abstract: {gamma}-secretase is a membrane protein complex associated with the production of A{beta} peptides that are pathogenic in Alzheimer's disease. We have characterized the activity of {gamma}-secretase complexes under a variety of detergent solubilization and reconstitution conditions, and the structural state of proteoliposomes by electron microscopy. We found that {gamma}-secretase activity is highly dependent on the physical state or integrity of the membrane bilayer - partial solubilization may increase activity while complete solubilization will abolish it. The activity of well-solubilized {gamma}-secretase can be restored to near native levels when properly reconstituted into a lipid bilayer environment.

  5. DNA interaction, antioxidant activity, and bioactivity studies of two ruthenium(II) complexes

    Science.gov (United States)

    Han, Bing-Jie; Jiang, Guang-Bin; Yao, Jun-Hua; Li, Wei; Wang, Ji; Huang, Hong-Liang; Liu, Yun-Jun

    2015-01-01

    Two new ruthenium(II) polypyridyl complexes [Ru(dmb)2(dcdppz)](ClO4)2 (1) and [Ru(bpy)2(dcdppz)](ClO4)2 (2) were prepared and characterized. The crystal structure of the complex 2 was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P21/n with a = 12.9622(14) Å, b = 17.1619(19) Å, c = 22.7210(3) Å, β = 100.930(2)°, R = 0.0536, Rω = 0.1111. The DNA-binding constants for complexes 1 and 2 were determined to be 1.92 × 105 (s = 1.72) and 2.24 × 105 (s = 1.86) M-1, respectively. The DNA-binding behaviors showed that complexes 1 and 2 interact with DNA by intercalative mode. The antioxidant activities of the ligand and the complexes were performed. Ligand, dcdppz, has no cytotoxicity against the selected cell lines. Complex 1 shows higher cytotoxicity than complex 2, but lower than cisplatin toward selected cell lines. The apoptosis and cell cycle arrest were investigated, and the apoptotic mechanism of BEL-7402 cells was studied by reactive oxygen species (ROS), mitochondrial membrane potential and western blot analysis. Complex 1 induces apoptosis in BEL-7402 cells through ROS-mediated mitochondrial dysfunction pathway and by regulating the expression of Bcl-2 family proteins.

  6. Theoretical reflections on the structural polymorphism of the oxygen-evolving complex in the S2 state and the correlations to substrate water exchange and water oxidation mechanism in photosynthesis.

    Science.gov (United States)

    Guo, Yu; Li, Hui; He, Lan-Lan; Zhao, Dong-Xia; Gong, Li-Dong; Yang, Zhong-Zhi

    2017-10-01

    The structural polymorphism of the oxygen-evolving complex is of great significance to photosynthetic water oxidation. Employing density functional theory calculations, we have made further advisement on the interconversion mechanism of O5 transfer in the S 2 state, mainly focusing on the potentiality of multi-state reactivity and spin transitions. Then, O5 protonation is proven impossible in S 2 for irreversibility of the interconversion, which serves as an auxiliary judgment for the protonation state of O5 in S 1 . Besides, the structural polymorphism could also be archived by alternative mechanisms involving Mn3 ligand exchange, one of which with Mn3(III) makes sense to substrate water exchange in S 2 , although being irresponsible for the derivations of the observed EPR signals. During the water exchange, high-spin states would prevail to facilitate electron transfer between the ferromagnetically coupled Mn centers. In addition, water exchange in S 1 could account for the closed-cubane structure as the initial form entering S 2 at cryogenic temperatures. With regard to water oxidation, the structural flexibility and variability in both S 2 and S 3 guarantee smooth W2-O5 coupling in S 4 , according to the substrate assignments from water exchange kinetics. Within this theoretical framework, the new XFEL findings on S 1 -S 3 can be readily rationalized. Finally, an alternative mechanistic scenario for OO bond formation with ·OH radical near O4 is presented, followed by water binding to the pivot Mn4(III) from O4 side during S 4 -S 0 . This may diversify the substrate sources combined with the Ca channel in water delivery for the forthcoming S-cycle. Copyright © 2017. Published by Elsevier B.V.

  7. Polymorphism 4G/5G of the plasminogen activator inhibitor 1 gene as a risk factor for the development of allergic rhinitis symptoms in patients with asthma.

    Science.gov (United States)

    Lampalo, Marina; Jukic, Irena; Bingulac-Popovic, Jasna; Marunica, Ivona; Petlevski, Roberta; Pavlisa, Gordana; Popovic-Grle, Sanja

    2017-06-01

    Plasminogen activator inhibitor-1 (PAI-1) is a glycoprotein which has a role in tissue remodelling after inflammatory processes. The objective is to investigate the frequency of PAI-1 gene polymorphism (4G/5G) in patients with a lung ventilation dysfunction in asthma and allergic rhinitis. Genomic DNA was isolated and genotypes of polymorphism of PAI-1 4G/5G and ABO were determined using the methods of RT-PCR and PCR-SSP. Study group includes 145 adult patients diagnosed with chronic asthma, with all clinically relevant parameters and the laboratory markers of pO 2 , IgE and eosinophils in sputum and nasal swab. In the processing of data, appropriate statistical tests (Kolmogorov-Smirnov test, median, interquartile ranges, χ 2 and Mann-Whitney U tests) were used. Patients with symptoms of allergic rhinitis were significantly younger and had an almost four time higher levels of IgE (P = 0.001), higher pO 2 (P = 0.002) and PEF (P = 0.036), compared to those who do not have these symptoms. Genotype PAI 4G/4G is significantly more common in patients with allergic rhinitis (28.1% vs. 16.1%; P = 0.017) compared to the genotype 5G/5G. Carriers of the genotype 4G/5G also have a borderline statistical significance. There were no statistically significant difference in the incidence of allergic rhinitis in the carriers of any ABO genotypes. The frequency of PAI genotype 4G/4G is significantly more common in patients with allergic rhinitis. The results suggest that the carriers of at least one 4G allele are at a higher risk for developing symptoms of allergic rhinitis in asthma.

  8. Effects of Preretirement Work Complexity and Postretirement Leisure Activity on Cognitive Aging

    Science.gov (United States)

    Finkel, Deborah; Pedersen, Nancy L.

    2016-01-01

    Objectives: We examined the influence of postretirement leisure activity on longitudinal associations between work complexity in main lifetime occupation and trajectories of cognitive change before and after retirement. Methods: Information on complexity of work with data, people, and things, leisure activity participation in older adulthood, and four cognitive factors (verbal, spatial, memory, and speed) was available from 421 individuals in the longitudinal Swedish Adoption/Twin Study of Aging. Participants were followed for an average of 14.2 years (SD = 7.1 years) and up to 23 years across eight cognitive assessments. Most of the sample (88.6%) completed at least three cognitive assessments. Results: Results of growth curve analyses indicated that higher complexity of work with people significantly attenuated cognitive aging in verbal skills, memory, and speed of processing controlling for age, sex, and education. When leisure activity was added, greater cognitive and physical leisure activity was associated with reduced cognitive aging in verbal skills, speed of processing, and memory (for cognitive activity only). Discussion: Engagement in cognitive or physical leisure activities in older adulthood may compensate for cognitive disadvantage potentially imposed by working in occupations that offer fewer cognitive challenges. These results may provide a platform to encourage leisure activity participation in those retiring from less complex occupations. PMID:25975289

  9. Variation in antiviral 2',5'-oligoadenylate synthetase (2'5'AS) enzyme activity is controlled by a single-nucleotide polymorphism at a splice-acceptor site in the OAS1 gene

    DEFF Research Database (Denmark)

    Bonnevie-Nielsen, Vagn; Field, L Leigh; Lu, Shao

    2005-01-01

    It is likely that human genetic differences mediate susceptibility to viral infection and virus-triggered disorders. OAS genes encoding the antiviral enzyme 2',5'-oligoadenylate synthetase (2'5'AS) are critical components of the innate immune response to viruses. This enzyme uses adenosine......=.0044), but not spousal pairs, suggesting strong genetic control of basal activity. We next analyzed association between basal activity and 15 markers across the OAS gene cluster. Significant association was detected at multiple markers, the strongest being at an A/G single-nucleotide polymorphism...... at the exon 7 splice-acceptor site (AG or AA) of the OAS1 gene. At this unusual polymorphism, allele G had a higher gene frequency in persons with high enzyme activity than in those with low enzyme activity (0.44 vs. 0.20; P=3 x 10(-11)). Enzyme activity varied in a dose-dependent manner across the GG, GA...

  10. Investigating solvability and complexity of linear active networks by means of matroids

    DEFF Research Database (Denmark)

    Petersen, Bjørn

    1979-01-01

    The solvability and complexity problems of finear active network are approached from a purely combinatorial point of view, using the concepts of matroid theory. Since the method is purely combinatorial, we take into account the network topology alone. Under this assumption necessary and sufficient...... conditions are given for the unique solvablity of linear active networks. The complexity and the number of dc-eigenfrequencies are also given. The method enables.you to decide if degeneracies are due to the topology alone, or if they are caused by special relations among network parameter values....... If the network parameter values are taken into account, the complexity and number of dc-eigenfrequencies given by the method, are only upper and lower bounds, respectively. The above conditions are fairly easily checked, and the complexity and number of dc-elgenfrequencies are found, using polynomially bounded...

  11. Synthesis, Characterization, and Biological Activity of Nickel (II and Palladium (II Complex with Pyrrolidine Dithiocarbamate (PDTC

    Directory of Open Access Journals (Sweden)

    Sk Imadul Islam

    2016-01-01

    Full Text Available The synthesis of square planar Ni(II and Pd(II complexes with pyrrolidine dithiocarbamate (PDTC was characterized by elemental, physiochemical, and spectroscopic methods. Two complexes were prepared by the reaction of nickel acetate and palladium acetate with pyrrolidine dithiocarbamate (PDTC in 1 : 2 molar ratio. The bovine serum albumin (BSA interaction with complexes was examined by absorption and fluorescence spectroscopic techniques at pH 7.4. All the spectral data suggest that coordination of the pyrrolidine dithiocarbamate (PDTC takes place through the two sulphur atoms in a symmetrical bidentate fashion. All the synthesized compounds were screened for their antimicrobial activity against some species of pathogenic bacteria (Escherichia coli, Vibrio cholerae, Streptococcus pneumonia, and Bacillus cereus. It has been observed that complexes have higher activity than the free ligand.

  12. Synthesis, characterization and anticancer activities of two lanthanide(III) complexes with a nicotinohydrazone ligand

    Science.gov (United States)

    Xu, Zhou-Qin; Mao, Xian-Jie; Jia, Lei; Xu, Jun; Zhu, Tao-Feng; Cai, Hong-Xin; Bie, Hong-Yan; Chen, Ru-Hua; Ma, Tie-liang

    2015-12-01

    Two isostructural acylhydrazone based complexes, namely [Ce(penh)2(H2O)4](NO3)3·4H2O (1) and [Sm(penh)2(NO3)2](NO3)·C2H5OH (2) (penh = 2-acetylpyridine nicotinohydrazone), have been obtained and characterized by physico-chemical and spectroscopic methods. The ten-coordinated lanthanide metal ion in each complex is surrounded by two independent tridentate neutral acylhydrazones with two ON2 donor sets. The other four coordination oxygen atoms are from four water molecules and two bidentate nitrate anions for complexes 1 and 2, respectively, thus giving distorted bicapped square antiprism geometry. Both complexes have excellent antitumor activity towards human pancreatic cancer (PATU8988), human colorectal cancer (lovo) and human gastric cancer(SGC7901) cell line. Furthermore, the cell apoptosis of complex 1 is detected by AnnexinV/PI flow cytometry.

  13. Carbohydrate-Based Host-Guest Complexation of Hydrophobic Antibiotics for the Enhancement of Antibacterial Activity.

    Science.gov (United States)

    Jeong, Daham; Joo, Sang-Woo; Shinde, Vijay Vilas; Cho, Eunae; Jung, Seunho

    2017-08-08

    Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release.

  14. Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis.

    Directory of Open Access Journals (Sweden)

    Orion D Weiner

    2006-02-01

    Full Text Available Migrating cells need to make different actin assemblies at the cell's leading and trailing edges and to maintain physical separation of signals for these assemblies. This asymmetric control of activities represents one important form of cell polarity. There are significant gaps in our understanding of the components involved in generating and maintaining polarity during chemotaxis. Here we characterize a family of complexes (which we term leading edge complexes, scaffolded by hematopoietic protein 1 (Hem-1, that organize the neutrophil's leading edge. The Wiskott-Aldrich syndrome protein family Verprolin-homologous protein (WAVE2 complex, which mediates activation of actin polymerization by Rac, is only one member of this family. A subset of these leading edge complexes are biochemically separable from the WAVE2 complex and contain a diverse set of potential polarity-regulating proteins. RNA interference-mediated knockdown of Hem-1-containing complexes in neutrophil-like cells: (a dramatically impairs attractant-induced actin polymerization, polarity, and chemotaxis; (b substantially weakens Rac activation and phosphatidylinositol-(3,4,5-tris-phosphate production, disrupting the (phosphatidylinositol-(3,4,5-tris-phosphate/Rac/F-actin-mediated feedback circuit that organizes the leading edge; and (c prevents exclusion of activated myosin from the leading edge, perhaps by misregulating leading edge complexes that contain inhibitors of the Rho-actomyosin pathway. Taken together, these observations show that versatile Hem-1-containing complexes coordinate diverse regulatory signals at the leading edge of polarized neutrophils, including but not confined to those involving WAVE2-dependent actin polymerization.

  15. The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation

    OpenAIRE

    Malik, Sohail; Roeder, Robert G.

    2010-01-01

    The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action ...

  16. Polymorphic Embedding of DSLs

    DEFF Research Database (Denmark)

    Hofer, Christian; Ostermann, Klaus; Rendel, Tillmann

    2008-01-01

    propose polymorphic embedding of DSLs, where many different interpretations of a DSL can be provided as reusable components, and show how polymorphic embedding can be realized in the programming language Scala. With polymorphic embedding, the static type-safety, modularity, composability and rapid...

  17. Synthesis and photocatalytic activity of TiO2/conjugated polymer complex nanoparticles

    Institute of Scientific and Technical Information of China (English)

    Shi Xiong Min; Fang Wang; Lei Feng; Yong Chun Tong; Zi Rong Yang

    2008-01-01

    A photocatalyst of nanometer TiO2/conjugated polymer complex was successfully synthesized and characterized by spectroscopic methods and photocatalytic experiments. The complex photocatalyst could be activated by absorbing both ultraviolet and visible light (λ=190-800nm). Methylene blue (MB) could be degraded more efficiently on the complex photocatalyst than on the TiO2 under natural light. The conjugated polymer played a promoting role in the photocatalytic degradation of MB. The calcination temperature had an important effect in degradation of dye and could be summarized as 260℃>300℃>340℃>220℃>180℃.

  18. Synthesis, characterization, and biological activity of a new palladium(II) complex with deoxyalliin

    Energy Technology Data Exchange (ETDEWEB)

    Corbi, P.P.; Massabni, A.C. [Inst. de Quimica - UNESP, Dept., Dept. de Quimica Geral e Inoganica, Araraquara (Brazil)]. E-mail: pedrocorbi@yahoo.com; Moreira, A.G. [Inst. de Quimica - UNESP, Dept. de Quimica Geral e Inoganica, Araraquara (Brazil); Faculdade de Medicina de Ribeirao Preto - USP, Dept. de Bioquimica e Imunologia, Ribeirao Preto (Brazil); Medrano, F.J. [Laboratorio Nacional de Luz Sincrotron - LNLS, Campinas (Brazil); Jasiulionis, M.G. [Escola Paulista de Medicina - UNIFESP, Dept. de Micro-Imuno-Parasitologia, Sao Paulo (Brazil); Costa-Neto, C.M. [Faculdade de Medicina de Ribeirao Preto - USP, Dept. de Bioquimica e Imunologia, Ribeirao Preto (Brazil)

    2005-02-15

    Synthesis, characterization, and biological activity of a new water-soluble Pd(II)-deoxyalliin (S-allyl-L-cysteine) complex are described in this article. Elemental and thermal analysis for the complex are consistent with the formula [Pd(C{sub 6}H{sub 10}NO{sub 2}S){sub 2}]. {sup 13}C NMR, {sup 1}H NMR, and IR spectroscopy show coordination of the ligand to Pd(II) through S and N atoms in a square planar geometry. Final residue of the thermal treatment was identified as a mixture of PdO and metallic Pd. Antiproliferative assays using aqueous solutions of the complex against HeLa and TM5 tumor cells showed a pronounced activity of the complex even at low concentrations. After incubation for 24 h, the complex induced cytotoxic effect over HeLa cells when used at concentrations higher than 0.40 mmol/L. At lower concentrations, the complex was nontoxic, indicating its action is probably due to cell cycle arrest, rather than cell death. In agreement with these results, the flow cytometric analysis indicated that after incubation for 24 h at low concentrations of the complex cells are arrested in G0/G1. (author)

  19. Synthesis, characterization and biocidal activities of heterobimetallic complexes having tin(IV) as a padlock

    Science.gov (United States)

    Husain, Ahmad; Nami, Shahab A. A.; Siddiqi, K. S.

    2010-04-01

    A mononuclear precursor complex, [(CH 3) 2Sn(tpdtc)] and several of its heterobimetallic derivatives of the type, [(CH 3) 2Sn(tpdtc)]MCl 2 have been synthesized by the simple addition reaction of transition metal chlorides, MCl 2· nH 2O where tpdtc = tetraethylenepentamine bis(dithiocarbamate) anion, M = Fe(II), Co(II), Ni(II), Cu(II) and Zn(II). The synthesized complexes have been systematically characterized by the physicochemical and spectroscopic techniques. A square-pyramidal geometry has been proposed for all the transition metal atoms with chloride ions occupying the axial while the three nitrogen atoms occupying the equatorial positions. A symmetrical bidentate coordination has been observed for the dithiocarbamato moiety leading to the formation of 18 member cavity. The thermal studies reveal that the mononuclear complex decomposes in three stages while its heterobimetallic analog exhibits a simple two-stage profile. The conductivity measurement data (1 mmol solution) implies a non-electrolytic behavior for all the complexes as evident by their low conductivity values obtained at room temperature. The heterobimetallic complexes have also been tested against the bacterial ( Escherichia coli and Pseudomonas aeruginosa) and antifungal strains ( Aspergillus niger and Fusarium oxysporum). All the complexes were found to be active against the test organisms and maximum activity was found for [(CH 3) 2Sn(tpdtc)]CuCl 2 complex.

  20. Immobilized copper(II) macrocyclic complex on MWCNTs with antibacterial activity

    Energy Technology Data Exchange (ETDEWEB)

    Tarlani, Aliakbar, E-mail: Tarlani@ccerci.ac.ir [Inorganic Nanostructures and Catalysts Research Lab., Chemistry & Chemical Engineering Research Center of Iran, Pajoohesh Blvd., km 17, Karaj Hwy, Tehran 14968-13151 (Iran, Islamic Republic of); Narimani, Khashayar [Inorganic Nanostructures and Catalysts Research Lab., Chemistry & Chemical Engineering Research Center of Iran, Pajoohesh Blvd., km 17, Karaj Hwy, Tehran 14968-13151 (Iran, Islamic Republic of); Mohammadipanah, Fatemeh; Hamedi, Javad [Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, Tehran 14155-6455 (Iran, Islamic Republic of); University of Tehran Biocompound Collection (UTBC), Microbial Technology and Products Research Center, University of Tehran, Tehran (Iran, Islamic Republic of); Tahermansouri, Hasan [Department of Chemistry, Ayatollah Amoli Branch, Islamic Azad University, Amol (Iran, Islamic Republic of); Amini, Mostafa M. [Department of Chemistry, Shahid Behshti University, 1983963113, Tehran (Iran, Islamic Republic of)

    2015-06-30

    Graphical abstract: In an antibacterial test, grafted copper(II) macrocyclic complex on the surface of MWCNT showed higher antibacterial activity against Bacillus subtilis compared to the individual MWCNT-COOH and the complex. - Highlights: • Copper(II) tetraaza macrocyclic complex covalently bonded to modified MWCNT. • Grafting of the complex carried out via an interaction between −C(=O)Cl group and NH of the ligand. • The samples were subjected in an antibacterial assessment to compare their activity. • Immobilized complex showed higher antibacterial activity against Bacillus subtilis ATCC 6633 compared to separately MWCNT-C(C=O)-OH and CuTAM. - Abstract: In a new approach, a copper(II) tetraaza macrocyclic complex (CuTAM) was covalently bonded on modified multi-walled carbon nanotubes (MWCNTs). To achieve this purpose, MWCNTs were converted to MWCNT-COCl and then reacted to NH groups of TAM ligand. The prepared material was characterized by Fourier Transform Infrared (FT-IR), X-ray diffraction (XRD), Raman spectroscopy, thermal gravimetric analysis (TGA), and FESEM (field emission scanning electron microscopy). FT-IR and TGA demonstrated the presence of the organic moieties, and XRD proved that the structure of MWCNTs remained intact during the three modification steps. An increase in the I{sub D}/I{sub G} ratio in Raman spectra confirmed the surface modifications. Finally, the samples were subjected to an antibacterial assessment to compare their biological activity. The antibacterial test showed that the grafted complex on the surface of the nanotube (MWCNT-CO-CuTAM) has higher antibacterial activity against Bacillus subtilis ATCC 6633 than the MWCNT-COOH and CuTAM with 1000 and 2000 μg/mL.

  1. Cyclometalated Ruthenium(II) Anthraquinone Complexes Exhibit Strong Anticancer Activity in Hypoxic Tumor Cells.

    Science.gov (United States)

    Zeng, Leli; Chen, Yu; Huang, Huaiyi; Wang, Jinquan; Zhao, Donglei; Ji, Liangnian; Chao, Hui

    2015-10-19

    Hypoxia is the critical feature of the tumor microenvironment that is known to lead to resistance to many chemotherapeutic drugs. Six novel ruthenium(II) anthraquinone complexes were designed and synthesized; they exhibit similar or superior cytotoxicity compared to cisplatin in hypoxic HeLa, A549, and multidrug-resistant (A549R) tumor cell lines. Their anticancer activities are related to their lipophilicity and cellular uptake; therefore, these physicochemical properties of the complexes can be changed by modifying the ligands to obtain better anticancer candidates. Complex 1, the most potent member of the series, is highly active against hypoxic HeLa cancer cells (IC50 =0.53 μM). This complex likely has 46-fold better activity than cisplatin (IC50 =24.62 μM) in HeLa cells. This complex tends to accumulate in the mitochondria and the nucleus of hypoxic HeLa cells. Further mechanistic studies show that complex 1 induced cell apoptosis during hypoxia through multiple pathways, including those of DNA damage, mitochondrial dysfunction, and the inhibition of DNA replication and HIF-1α expression, making it an outstanding candidate for further in vivo studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Systemic activation of the immune system in HIV infection: The role of the immune complexes (hypothesis).

    Science.gov (United States)

    Korolevskaya, Larisa B; Shmagel, Konstantin V; Shmagel, Nadezhda G; Saidakova, Evgeniya V

    2016-03-01

    Currently, immune activation is proven to be the basis for the HIV infection pathogenesis and a strong predictor of the disease progression. Among the causes of systemic immune activation the virus and its products, related infectious agents, pro-inflammatory cytokines, and regulatory CD4+ T cells' decrease are considered. Recently microbial translocation (bacterial products yield into the bloodstream as a result of the gastrointestinal tract mucosal barrier integrity damage) became the most popular hypothesis. Previously, we have found an association between immune complexes present in the bloodstream of HIV infected patients and the T cell activation. On this basis, we propose a significantly modified hypothesis of immune activation in HIV infection. It is based on the immune complexes' participation in the immunocompetent cells' activation. Immune complexes are continuously formed in the chronic phase of the infection. Together with TLR-ligands (viral antigens, bacterial products coming from the damaged gut) present in the bloodstream they interact with macrophages. As a result macrophages are transformed into the type II activated forms. These macrophages block IL-12 production and start synthesizing IL-10. High level of this cytokine slows down the development of the full-scale Th1-response. The anti-viral reactions are shifted towards the serogenesis. Newly synthesized antibodies' binding to viral antigens leads to continuous formation of the immune complexes capable of interacting with antigen-presenting cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. ACTIVATION OF ACETYLENE BY COORDINATION TO BIS-TRIPHENYLPHOSPHINE COMPLEX OF Pt(0: DFT STUDY

    Directory of Open Access Journals (Sweden)

    N. N. Gorinchoy

    2009-06-01

    Full Text Available The present work is devoted to the theoretical study of the activation of the acetylene molecule coordinated in the [Pt(PPh32C2H2] complex. By means of DFT calculations it is shown that the geometrical and electronic characteristics of the C2H2 are essentially changed due to its coordination. The subsequent detailed analysis of the molecular orbitals (MO of the active valence zone of this complex allows one to make important conclusion that this activation is being realized mainly due to the orbital back donation of 5d-electronic density from one of the occupied MOs of the complex [Pt(PPh32] to the unoccupied antibonding π*-MO of C2H2.

  4. Carbonic anhydrase activity of integral-functional complexes of thylakoid membranes of spinach chloroplasts

    Directory of Open Access Journals (Sweden)

    A. V. Semenihin

    2015-06-01

    Full Text Available Isolated thylakoid membranes were disrupted by treatment with nonionic detergents digitonin or dodecyl maltoside. Solubilized polypeptide complexes were separated by native gel charge shift electrophoresis. The position of ATP-synthase complex and its isolated catalytic part (CF1 within gel was determined using the color reaction for ATPase activity. Due to the presence of cytochromes, the red band in unstained gels corresponded to the cytochrome b6f complex. Localization of the cytochrome b6f complex, ATP synthase and coupling CF1 in the native gel was confirmed by their subunit composition determined after SDS-electrophoretic analysis. Carbonic anhydrase (CA activity in polypeptide zones of PS II, cytochrome b6f complex, and ATP-synthase CF1 was identified in native gels using indicator bromothymol blue. CA activity of isolated CF1 in solution was determined by infrared gas analysis as the rate of bicarbonate dehydration. The water-soluble acetazolamide, an inhibitor of CA, unlike lipophilic ethoxyzolamide inhibited CA activity of CF1. Thus, it was shown for the first time that ATP-synthase has a component which is capable of catalyzing the interconversion of forms of carbonic acid associated with proton exchange. The data obtained suggest the presence of multiple forms of carbonic anhydrase in the thylakoid membranes of spinach chloroplasts and confirm their involvement in the proton transfer to the ATP synthase.

  5. Synthesis, characterization and biological activities of semicarbazones and their copper complexes.

    Science.gov (United States)

    Venkatachalam, Taracad K; Bernhardt, Paul V; Noble, Chris J; Fletcher, Nicholas; Pierens, Gregory K; Thurecht, Kris J; Reutens, David C

    2016-09-01

    Substituted semicarbazones/thiosemicarbazones and their copper complexes have been prepared and several single crystal structures examined. The copper complexes of these semicarbazone/thiosemicarbazones were prepared and several crystal structures examined. The single crystal X-ray structure of the pyridyl-substituted semicarbazone showed two types of copper complexes, a monomer and a dimer. We also found that the p-nitrophenyl semicarbazone formed a conventional 'magic lantern' acetate-bridged dimer. Electron Paramagnetic Resonance (EPR) of several of the copper complexes was consistent with the results of single crystal X-ray crystallography. The EPR spectra of the p-nitrophenyl semicarbazone copper complex in dimethylsulfoxide (DMSO) showed the presence of two species, confirming the structural information. Since thiosemicarbazones and semicarbazones have been reported to exhibit anticancer activity, we examined the anticancer activity of several of the derivatives reported in the present study and interestingly only the thiosemicarbazone showed activity while the semicarbazones were not active indicating that introduction of sulphur atom alters the biological profile of these thiosemicarbazones. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Structurally related hydrazone-based metal complexes with different antitumor activities variably induce apoptotic cell death.

    Science.gov (United States)

    Megger, Dominik A; Rosowski, Kristin; Radunsky, Christian; Kösters, Jutta; Sitek, Barbara; Müller, Jens

    2017-04-05

    Three new complexes bearing the tridentate hydrazone-based ligand 2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)pyridine (L) were synthesized and structurally characterized. Biological tests indicate that the Zn(ii) complex [ZnCl 2 (L)] is of low cytotoxicity against the hepatocellular carcinoma cell line HepG2. In contrast, the Cu(ii) and Mn(ii) complexes [CuCl 2 (L)] and [MnCl 2 (L)] are highly cytotoxic with EC 50 values of 1.25 ± 0.01 μM and 20 ± 1 μM, respectively. A quantitative proteome analysis reveals that treatment of the cells with the Cu(ii) complex leads to a significantly altered abundance of 102 apoptosis-related proteins, whereas 38 proteins were up- or down-regulated by the Mn(ii) complex. A closer inspection of those proteins regulated only by the Cu(ii) complex suggests that the superior cytotoxic activity of this complex is likely to be related to an initiation of the caspase-independent cell death (CICD). In addition, an increased generation of reactive oxygen species (ROS) and a strong up-regulation of proteins responsive to oxidative stress suggest that alterations of the cellular redox metabolism likely contribute to the cytotoxicity of the Cu(ii) complex.

  7. Newly Synthesized Doxorubicin Complexes with Selected Metals—Synthesis, Structure and Anti-Breast Cancer Activity

    Directory of Open Access Journals (Sweden)

    Agata Jabłońska-Trypuć

    2017-07-01

    Full Text Available Doxorubicin (DOX is very effective chemotherapeutic agent, however it has several major drawbacks. Therefore the motivation for developing novel drug complexes as anticancer agents with different mechanism of action has arisen. The aim of the present study was to evaluate the influence of newly synthesized DOX complexes with selected metals (Mg, Mn, Co, Ni, Fe, Cu, Zn on apoptosis, cell cycle, viability, proliferation and cytotoxicity in the breast cancer cell line MCF-7. Complexation of DOX with metals has likewise been the subject of our research. The current work showed that the tested bivalent metals at a given pH condition formed metal:DOX complexes in a ratio of 2:1, while iron complexes with DOX in a ratio of 3:1. The studies also showed that selected metal-DOX complexes (Mg-DOX, Mn-DOX, Ni-DOX at 0.5 µM concentration significantly decreased cell viability and proliferation, however they increased caspase 7 activity. Results also indicated that studied metal-DOX complexes showed high cytotoxicity in MCF-7 cells. Therefore they were chosen for cell cycle check-points and apoptosis/necrosis analysis studied by flow cytometry. Obtained results suggest that doxorubicin complexed by specified metals can be considered as a potential anti-breast cancer agent, which is characterized by a higher efficacy than a parent drug.

  8. Enzymatic activity of the cellulolytic complex produced by trichoderma reesei. Enzymatic hydrolysis of cellulose

    International Nuclear Information System (INIS)

    Alfonsel Jaen, M.; Negro, M.J.; Saez, R.; Martin Moreno, C.

    1986-01-01

    The enzymatic activity characterization of the cellulolytic complex obtained from Trichoderma reese QM 9414 and the influence of the enzymatic hydrolysis conditions on the hydrolysis yield are studied. Pure cellulose and native or alkali pretreated biomass from Onopordum nervosum have been used as substrates. The values of pH, temperature, substrate concentration and enzyme-substrate ratio for the optimum activity of that complex, evaluated as glucose and reducing sugars productions, have been selected. Previous studies on enzymatic hydrolysis of O. nervosum have shown a remarkable effect of the alkaline pretreatments on the final hydrolysis yield. (author). 10 figs.; 10 refs

  9. Synthesis and Antimicrobial Activity of Novel Ag-N-Hetero-cyclic Carbene Complexes

    Directory of Open Access Journals (Sweden)

    İlknur Özdemir

    2010-04-01

    Full Text Available A series of imidazolidinium ligand precursors are metallated with Ag2O to give silver(I N-heterocyclic carbene complexes. All compounds were fully characterized by elemental analyses, 1H-NMR, 13C-NMR and IR spectroscopy techniques. All compounds studied in this work were screened for their in vitro antimicrobial activities against the standard strains: Enterococcus faecalis (ATCC 29212, Staphylococcus aureus (ATCC 29213, Escherichia coli (ATCC 25922, Pseudomonas aeruginosa (ATCC 27853 and the fungi Candida albicans and Candida tropicalis. The new imidazolidin-2-ylidene silver complexes have been found to display effective antimicrobial activity against a series of bacteria and fungi.

  10. Modification of glomerular immune complex deposition in mice by activation of the reticuloendothelial system.

    OpenAIRE

    Barcelli, U; Rademacher, R; Ooi, Y M; Ooi, B S

    1981-01-01

    To determine the effect of activation of the reticuloendothelial system on the localization of immune complexes in the kidney, a model of passive serum sickness nephritis in the mouse was used, with activation of the reticuloendothelial system with Corynebacterium parvum. Groups of mice, control and C. parvum-treated animals, were injected with BSA-125I-anti-BSA complexes containing 3 mg 125I-anti-BSA. Blood was obtained at 5 min, at 3 h, and at 12 h, when the animals were killed. Blood conce...

  11. Enzymatic activity of the cellulolytic complex produced by Trichoderma reesei. Enzymatic hydrolysis of cellulose

    International Nuclear Information System (INIS)

    Alfonsel J, M.; Negro A, M. J.; Saez A, R.; Martin M, C.

    1986-01-01

    The enzymatic activity characterization of the cellulolytic complex obtained from Trichoderma reesei QM 9414 and the influence of the enzymatic hydrolysis conditions on the hydrolysis yield are studied. Pure cellulose and native or alkali pretreated biomass Onopordum nervosum have been used as substrates. The values of pH, temperature, substrate concentration and enzyme-substrate ratio for the optimum activity of that complex, evaluated as glucose and reducing sugars production, have been selected. Previous studies on enzymatic hydrolysis of 0. nervosum have shown a remarkable effect of the alkaline pretreatments on the final hydrolysis yield. (Author) 10 refs

  12. Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity Evaluation

    Directory of Open Access Journals (Sweden)

    Cristina Di Donato

    2016-12-01

    Full Text Available Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in the treatment of the colon, liver, and stomac cancers, the drug was complexed with alpha- and beta-cyclodextrin. The inclusion complexes were prepared in the solid state by kneading method and characterized by Fourier transform-infrared (FT-IR spectroscopy and X-ray powder diffractometry. In solution, the 1:1 stoichiometry for all the inclusion complexes was established by the Job plot method and the binding constants were determined at different pHs by UV-VIS titration. Furthermore, the cytotoxic activity of 5-fluorouracil and its complexation products were evaluated using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay on MCF-7 (breast cancer cell line, Hep G2 (hepatocyte carcinoma cell line, Caco-2 (colon adenocarcinoma cell line, and A-549 (alveolar basal epithelial carcinoma cell line. The results showed that both inclusion complexes increased the 5-fluorouracil capability of inhibiting cell growth. In particular, 5-fluorouracil complexed with beta-cyclodextrin had the highest cytotoxic activity on MCF-7; with alpha-cyclodextrin the highest cytotoxic activity was observed on A-549. The IC50 values were equal to 31 and 73 µM at 72 h, respectively. Our results underline the possibility of using these inclusion complexes in pharmaceutical formulations for improving 5-fluorouracil therapeutic efficacy.

  13. New bioactive silver(I) complexes: Synthesis, characterization, anticancer, antibacterial and anticarbonic anhydrase II activities

    Science.gov (United States)

    Ozdemir, Ummuhan O.; Ozbek, Neslihan; Genc, Zuhal Karagoz; İlbiz, Firdevs; Gündüzalp, Ayla Balaban

    2017-06-01

    Silver(I) complexes of alkyl sulfonic acide hydrazides were newly synthesized as homologous series. Methanesulfonic acide hydrazide (L1), ethanesulfonic acide hydrazide (L2), propanesulfonic acide hydrazide (L3) and butanesulfonic acide hydrazide (L4) were used for complexation with Ag(I) ions. The silver complexes obtained in the mol ratio of 1:2 have the structural formula as Ag(L1)2NO3 (I), Ag(L2)2NO3 (II), Ag(L3)2NO3(III), (Ag(L4)2NO3 (IV). The Ag(I) complexes exhibit distorted linear two-fold coordination in [AgL2]+ cations with uncoordinated nitrates. Ligands are chelated with silver(I) ions through unsubstituted primary nitrogen in hydrazide group. Ag(I) complexes were characterized by using elemental analysis, spectroscopic methods (FT-IR, LC-MS), magnetic susceptibility and conductivity measurements. Silver(I) complexes were optimized using PBEPBE/LanL2DZ/DEF2SV basic set performed by DFT method with the Gaussian 09 program package. The geometrical parameters, frontier molecular orbitals (HOMOs and LUMOs) and molecular electrostatic potential (MEP) mapped surfaces of the optimized geometries were also determined by this quantum set. The anticancer activities of silver(I) complexes on MCF-7 human breast cancer cell line were investigated by comparing IC50 values. The antibacterial activities of complexes were studied against Gram positive bacteria; S. aureus ATCC 6538, B. subtilis ATCC 6633, B. cereus NRRL-B-3711, E. faecalis ATCC 29212 and Gram negative bacteria; E. coli ATCC 11230, P. aeruginosa ATCC 15442, K. pneumonia ATCC 70063 by using disc diffusion method. The inhibition activities of Ag(I) complexes on carbonic anhydrase II enzyme (hCA II) were also investigated by comparing IC50 and Ki values. The biological activity screening shows that Ag(I) complex of butanesulfonicacidehydrazide (IV) has the highest activity against tested breast cancer cell lines MCF-7, Gram positive/Gram negative bacteria and carbonic anhydrase II (hCA II) isoenzyme.

  14. Unsymmetrical dizinc complexes as models for the active sites of phosphohydrolases.

    Science.gov (United States)

    Jarenmark, Martin; Csapó, Edit; Singh, Jyoti; Wöckel, Simone; Farkas, Etelka; Meyer, Franc; Haukka, Matti; Nordlander, Ebbe

    2010-09-21

    The unsymmetrical dinucleating ligand 2-(N-isopropyl-N-((2-pyridyl)methyl)aminomethyl)-6-(N-(carboxylmethyl)-N-((2-pyridyl)methyl)aminomethyl)-4-methylphenol (IPCPMP or L) has been synthesized to model the active site environment of dinuclear metallohydrolases. It has been isolated as the hexafluorophosphate salt H(4)IPCPMP(PF(6))(2) x 2 H(2)O (H(4)L), which has been structurally characterized, and has been used to form two different Zn(II) complexes, [{Zn(2)(IPCPMP)(OAc)}(2)][PF(6)](2) (2) and [{Zn(2)(IPCPMP)(Piv)}(2)][PF(6)](2) (3) (OAc = acetate; Piv = pivalate). The crystal structures of and show that they consist of tetranuclear complexes with very similar structures. Infrared spectroscopy and mass spectrometry indicate that the tetranuclear complexes dissociate into dinuclear complexes in solution. Potentiometric studies of the Zn(II):IPCPMP system in aqueous solution reveal that a mononuclear complex is surprisingly stable at low pH, even at a 2:1 Zn(II):L ratio, but a dinuclear complex dominates at high pH and transforms into a dihydroxido complex by a cooperative deprotonation of two, probably terminally coordinated, water molecules. A kinetic investigation indicates that one of these hydroxides is the active nucleophile in the hydrolysis of bis(2,4-dinitrophenyl)phosphate (BDNPP) enhanced by complex 2, and mechanistic proposals are presented for this reaction as well as the previously reported transesterification of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) promoted by Zn(II) complexes of IPCPMP.

  15. The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis.

    Directory of Open Access Journals (Sweden)

    Amalia Lamana

    Full Text Available BACKGROUND: The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. METHODOLOGY AND RESULTS: We studied 640 patients with early arthritis (76% women; median age, 52 years, recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28 as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044. Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162. After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. CONCLUSIONS: Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

  16. Characterization of gut microbiota profiles by disease activity in patients with Crohn's disease using data mining analysis of terminal restriction fragment length polymorphisms.

    Science.gov (United States)

    Andoh, Akira; Kobayashi, Toshio; Kuzuoka, Hiroyuki; Tsujikawa, Tomoyuki; Suzuki, Yasuo; Hirai, Fumihito; Matsui, Toshiyuki; Nakamura, Shiro; Matsumoto, Takayuki; Fujiyama, Yoshihide

    2014-05-01

    The gut microbiota plays a significant role in the pathogenesis of Crohn's disease (CD). In this study, we analyzed the disease activity and associated fecal microbiota profiles in 160 CD patients and 121 healthy individuals. Fecal samples from the CD patients were collected during three different clinical phases, the active (n=66), remission-achieved (n=51) and remission-maintained (n=43) phases. Terminal restriction fragment length polymorphism (T-RFLP) and data mining analysis using the Classification and Regression Tree (C&RT) approach were performed. Data mining provided a decision tree that clearly identified the various subject groups (nodes). The majority of the healthy individuals were divided into Node-5 and Node-8. Healthy subjects comprised 99% of Node-5 (91 of 92) and 84% of Node-8 (21 of 25 subjects). Node-3 was characterized by CD (136 of 160 CD subjects) and was divided into Node-6 and Node-7. Node-6 (n=103) was characterized by subjects in the active phase (n=48; 46%) and remission-achieved phase (n=39; 38%) and Node-7 was characterized by the remission-maintained phase (21 of 37 subjects; 57%). Finally, Node-6 was divided into Node-9 and Node-10. Node-9 (n=78) was characterized by subjects in the active phase (n=43; 55%) and Node-10 (n=25) was characterized by subjects in the remission-maintained phase (n=16; 64%). Differences in the gut microbiota associated with disease activity of CD patients were identified. Thus, data mining analysis appears to be an ideal tool for the characterization of the gut microbiota in inflammatory bowel disease.

  17. CAPSAICIN SUPPLEMENTATION FAILS TO MODULATE AUTONOMIC AND CARDIAC ELECTROPHYSIOLOGIC ACTIVITY DURING EXERCISE IN THE OBESE: WITH VARIANTS OF UCP2 AND UCP3 POLYMORPHISM

    Directory of Open Access Journals (Sweden)

    Ki Ok Shin

    2008-09-01

    Full Text Available We investigated the effects of capsaicin supplementation (150mg on alterations of autonomic nervous system (ANS activity associated with adverse effects of cardiac depolarization-repolarization intervals during aerobic exercise in obese humans. Nine obese males (26.1 ± 1.5 yrs volunteered between study designed. The cardiac ANS activities evaluated by means of heart rate variability of power spectral analysis and cardiac QT interval were continuously measured during 5-min rest and 30-min exercise at 50% of maximal ventilation threshold (50%VTmax on stationary ergometer with placebo (CON or capsaicin (CAP oral administration chosen at random. The uncoupling protein (UCP 2 and UCP 3 genetic variants of the subjects were analyzed by noninvasive genotyping method from collecting buccal mucosa cells. The results indicated that there were no significant differences in cardiac ANS activities during rest and exercise between CON and CAP trials. Although no significant difference, A/A allele of UCP2 polymorphism showed a reduced sympathetic nervous system (SNS index activity compared to G/G + G/A allele during exercise intervention in our subjects. On the other hand, the data on cardiac QT interval showed no significant difference, indicating that oral administration of capsaicin did not cause any adverse effect on cardiac depolarization-repolarization. In conclusion, our results suggest that capsaicin supplementation 1 h before exercise intervention has no effect on cardiac ANS activities and cardiac electrical stability during exercise in obese individuals. Further studies should also consider genetic variants for exercise efficacy against obesity

  18. The TT genotype of the STAT4 rs7574865 polymorphism is associated with high disease activity and disability in patients with early arthritis.

    Science.gov (United States)

    Lamana, Amalia; Balsa, Alejandro; Rueda, Blanca; Ortiz, Ana M; Nuño, Laura; Miranda-Carus, Maria Eugenia; Gonzalez-Escribano, Maria F; Lopez-Nevot, Miguel A; Pascual-Salcedo, Dora; Martin, Javier; González-Álvaro, Isidoro

    2012-01-01

    The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

  19. The functional polymorphism rs73598374:G>A (p.Asp8Asn) of the ADA gene is associated with telomerase activity and leukocyte telomere length.

    Science.gov (United States)

    Concetti, Fabio; Carpi, Francesco M; Nabissi, Massimo; Picciolini, Matteo; Santoni, Giorgio; Napolioni, Valerio

    2015-02-01

    Recent evidence demonstrated a relevant role of adenosine deaminase (ADA) in replicative senescence of T cells through its capacity to modulate telomerase activity (TA). Herein, we tested the impact of the functional polymorphism ADA rs73598374:G>A (c.22G>A, p.Asp8Asn) on telomere biology, by measuring TA and leukocyte telomere length (LTL) in healthy subjects selected according to rs73598374 genotype. rs73598374-A carriers showed lower TA (P=0.019) and shorter LTL (P=0.003), respectively, compared to G/G carriers. rs73598374-A carriers showed a stronger cross-sectional age reduction of LTL (r=-0.314, P=0.005) compared to G/G carriers (r=-0.243, P=0.022). The reduced ADA activity associated to rs73598374-A variant predisposes those carriers to display higher levels of adenosine compared to G/G carriers. Consequently, it may lead to an accelerated process of replicative senescence, causing a stronger reduction of TA and in turn shorter LTL. In conclusion, the crucial role played by replicative senescence of the immune system in several human diseases and in the aging process underscores the relevance of the present findings and also spurs interest into the possible involvement of rs73598374 in shaping the susceptibility to several age-related diseases.

  20. Thermal methods for evaluating polymorphic transitions in nifedipine

    International Nuclear Information System (INIS)

    Grooff, D.; De Villiers, M.M.; Liebenberg, W.

    2007-01-01

    The thermal behaviour of nifedipine was studied with the view to understand the various phase transitions between its polymorphs. The focus was on polymorph identification, accompanying morphological changes during crystallization and the nature of the phase transformations. These features were compared to the complexity of the crystallization mechanisms, studied by dynamic differential scanning calorimetry (DSC) heating techniques. DSC, thermogravimetry (TG) established the temperature limits for preparation of amorphous nifedipine from the melt. DSC studies identified that metastable form B, melting point ∼163 deg. C, was enantiotropically related to a third modification, form C, which existed at lower temperatures. Form C converted endothermically to form B at ∼56 deg. C on heating and was shown by hot stage microscopy (HSM) to be accompanied by morphological changes. Modulated temperature differential scanning calorimetry (MTDSC) showed discontinuities in the reversing heat flow signal during crystallization of amorphous nifedipine (from ∼92 deg. C) to form B, which suggested that a number of polymorphs may nucleate from the melt prior to form B formation. Identification of the number of nifedipine polymorphs included the use of combined DSC-powder X-ray diffraction (PXRD) and variable temperature powder X-ray diffraction (VTPXRD). The crystallization kinetics studied by dynamic DSC heating techniques followed by analysis using the Friedman isoconversion method where values of activation energy (E) and frequency factor (A) were estimated as a function of alpha or extent of conversion (α). The variations in E with α, from 0.05 to 0.9, for the amorphous to form B conversion could indicate the formation of intermediate polymorphs prior to form B. The form B to form A conversion showed a constancy in E on kinetic analysis from α 0.05 to 0.9, which suggested that a constant crystallization mechanism operated during formation of the thermodynamically stable

  1. Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in dutch Caucasians

    NARCIS (Netherlands)

    Meex, Steven J. R.; van Greevenbroek, Marleen M. J.; Ayoubi, Torik A.; Vlietinck, Robert; van Vliet-Ostaptchouk, Jana V.; Hofker, Martin H.; Vermeulen, Vicky M. M. -J.; Schalkwijk, Casper G.; Feskens, Edith J. M.; Boer, Jolanda M. A.; Stehouwer, Coen D. A.; van der Kallen, Carla J. H.; de Bruin, Tjerk W. A.

    Context: Activating transcription factor 6 (ATF6) is critical for initiation and full activation of the unfolded protein response. An association between genetic variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima Indians. Objectives: To investigate the broader significance of

  2. Synthesis, Spectral Characterization and Antioxidant Activity of Tin(II-Morin Complex

    Directory of Open Access Journals (Sweden)

    Shahabuddin Memon

    2012-12-01

    Full Text Available The study focuses on the interaction between morin and Tin(II and the resulting complex was characterized through various analytical techniques by comparing it with morin. The complexation was confirmed at first by UV-Vis study, which shows that addition of Tin(II to morin may produce bathochromic shifts indicative of complex formation. IR spectral studies indicated that carbonyl has involved in coordination with Tin(II. Moreover, 1H-NMR studies validated that in conjunction with carbonyl, 3-OH of morin is more appropriate to be involved in complexation by replacement of its proton. Scavenging activities of morin and its Tin(II complex on DPPH• radical showed the inhibitory rates of 65% and 49%, respectively. In addition, the reducing capacity of morin was outstanding at 0.5 and 2.0 mg/ml concentrations relative to Tin(II complex. Overall, the study potentially shows the strong impact in order to design the anticancer drugs jointly from its cytotoxic potential and antioxidant activities, thereby selectively targeting the cancerous cells in result increasing their therapeutic index as well as extra advantages over other anticancer drugs.

  3. Environment-dependent regulation of spliceosome activity by the LSM2-8 complex in Arabidopsis.

    Science.gov (United States)

    Carrasco-López, Cristian; Hernández-Verdeja, Tamara; Perea-Resa, Carlos; Abia, David; Catalá, Rafael; Salinas, Julio

    2017-07-07

    Spliceosome activity is tightly regulated to ensure adequate splicing in response to internal and external cues. It has been suggested that core components of the spliceosome, such as the snRNPs, would participate in the control of its activity. The experimental indications supporting this proposition, however, remain scarce, and the operating mechanisms poorly understood. Here, we present genetic and molecular evidence demonstrating that the LSM2-8 complex, the protein moiety of the U6 snRNP, regulates the spliceosome activity in Arabidopsis, and that this regulation is controlled by the environmental conditions. Our results show that the complex ensures the efficiency and accuracy of constitutive and alternative splicing of selected pre-mRNAs, depending on the conditions. Moreover, miss-splicing of most targeted pre-mRNAs leads to the generation of nonsense mediated decay signatures, indicating that the LSM2-8 complex also guarantees adequate levels of the corresponding functional transcripts. Interestingly, the selective role of the complex has relevant physiological implications since it is required for adequate plant adaptation to abiotic stresses. These findings unveil an unanticipated function for the LSM2-8 complex that represents a new layer of posttranscriptional regulation in response to external stimuli in eukaryotes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Spectroscopic characterization of metal complexes of novel Schiff base. Synthesis, thermal and biological activity studies

    Science.gov (United States)

    Omar, M. M.; Mohamed, Gehad G.; Ibrahim, Amr A.

    2009-07-01

    Novel Schiff base (HL) ligand is prepared via condensation of 4-aminoantipyrine and 2-aminobenzoic acid. The ligand is characterized based on elemental analysis, mass, IR and 1H NMR spectra. Metal complexes are reported and characterized based on elemental analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance and thermal analyses (TGA, DrTGA and DTA). The molar conductance data reveal that all the metal chelates are non-electrolytes. IR spectra show that HL is coordinated to the metal ions in a uninegatively tridentate manner with NNO donor sites of the azomethine N, amino N and deprotonated caroxylic-O. From the magnetic and solid reflectance spectra, it is found that the geometrical structures of these complexes are octahedral. The thermal behaviour of these chelates shows that the hydrated complexes losses water molecules of hydration in the first step followed immediately by decomposition of the anions and ligand molecules in the subsequent steps. The activation thermodynamic parameters, such as, E*, ΔH*, ΔS* and ΔG* are calculated from the DrTG curves using Coats-Redfern method. The synthesized ligands, in comparison to their metal complexes also were screened for their antibacterial activity against bacterial species, Escherichia Coli, Pseudomonas aeruginosa, Staphylococcus Pyogones and Fungi (Candida). The activity data show that the metal complexes to be more potent/antibacterial than the parent Shciff base ligand against one or more bacterial species.

  5. Anti-trypanosomal activity of cationic N-heterocyclic carbene gold(I) complexes.

    Science.gov (United States)

    Winter, Isabel; Lockhauserbäumer, Julia; Lallinger-Kube, Gertrud; Schobert, Rainer; Ersfeld, Klaus; Biersack, Bernhard

    2017-06-01

    Two gold(I) N-heterocyclic carbene complexes 1a and 1b were tested for their anti-trypanosomal activity against Trypanosoma brucei parasites. Both gold compounds exhibited excellent anti-trypanosomal activity (IC 50 =0.9-3.0nM). The effects of the gold complexes 1a and 1b on the T. b. brucei cytoskeleton were evaluated. Rapid detachment of the flagellum from the cell body occurred after treatment with the gold complexes. In addition, a quick and complete degeneration of the parasitic cytoskeleton was induced by the gold complexes, only the microtubules of the detached flagellum remained intact. Both gold compounds 1a and 1b feature selective anti-trypanosomal agents and were distinctly more active against T. b. brucei cells than against human HeLa cells. Thus, the gold complexes 1a and 1b feature promising drug candidates for the treatment of trypanosome infections such as sleeping sickness (human African Trypanosomiasis caused by Trypanosoma brucei parasites). Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Structure of the active form of human origin recognition complex and its ATPase motor module

    Energy Technology Data Exchange (ETDEWEB)

    Tocilj, Ante; On, Kin Fan; Yuan, Zuanning; Sun, Jingchuan; Elkayam, Elad; Li, Huilin; Stillman, Bruce; Joshua-Tor, Leemor

    2017-01-23

    Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double-layered shallow corkscrew, with the AAA+ and AAA+-like domains forming one layer, and the winged-helix domains (WHDs) forming a top layer. CDC6 fits easily between ORC1 and ORC2, completing the ring and the DNA-binding channel, forming an additional ATP hydrolysis site. Analysis of the ATPase activity of the complex provides a basis for understanding ORC activity as well as molecular defects observed in Meier-Gorlin Syndrome mutations.

  7. Trithiocyanurate Complexes of Iron, Manganese and Nickel and Their Anticholinesterase Activity

    Directory of Open Access Journals (Sweden)

    Pavel Kopel

    2014-04-01

    Full Text Available The complexes of Fe(II, Mn(II and Ni(II with a combination of a Schiff base, nitrogen-donor ligand or macrocyclic ligand and trithiocyanuric acid (ttcH3 were prepared and characterized by elemental analysis and spectroscopies. Crystal and molecular structures of the iron complex of composition [Fe(L1](ttcH2(ClO4·EtOH·H2O (1, where L1 is Schiff base derived from tris(2-aminoethylamine and 2-pyridinecarboxaldehyde, were solved. It was found that the Schiff base is coordinated to the central iron atom by six nitrogens forming deformed octahedral arrangement, whereas trithiocyanurate(1- anion, perchlorate and solvent molecules are not coordinated. The X-ray structure of the Schiff base sodium salt is also presented and compared with the iron complex. The anticholinesterase activity of the complexes was also studied.

  8. Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration

    International Nuclear Information System (INIS)

    Nadanaciva, Sashi; Dykens, James A.; Bernal, Autumn; Capaldi, Roderick A.; Will, Yvonne

    2007-01-01

    Mitochondrial impairment is increasingly implicated in the etiology of toxicity caused by some thiazolidinediones, fibrates, and statins. We examined the effects of members of these drug classes on respiration of isolated rat liver mitochondria using a phosphorescent oxygen sensitive probe and on the activity of individual oxidative phosphorylation (OXPHOS) complexes using a recently developed immunocapture technique. Of the six thiazolidinediones examined, ciglitazone, troglitazone, and darglitazone potently disrupted mitochondrial respiration. In accord with these data, ciglitazone and troglitazone were also potent inhibitors of Complexes II + III, IV, and V, while darglitazone predominantly inhibited Complex IV. Of the six statins evaluated, lovastatin, simvastatin, and cerivastatin impaired mitochondrial respiration the most, with simvastatin and lovastatin impairing multiple OXPHOS Complexes. Within the class of fibrates, gemfibrozil more potently impaired respiration than fenofibrate, clofibrate, or ciprofibrate. Gemfibrozil only modestly inhibited Complex I, fenofibrate inhibited Complexes I, II + III, and V, and clofibrate inhibited Complex V. Our findings with the two complementary methods indicate that (1) some members of each class impair mitochondrial respiration, whereas others have little or no effect, and (2) the rank order of mitochondrial impairment accords with clinical adverse events observed with these drugs. Since the statins are frequently co-prescribed with the fibrates or thiazolidinediones, various combinations of these three drug classes were also analyzed for their mitochondrial effects. In several cases, the combination additively uncoupled or inhibited respiration, suggesting that some combinations are more likely to yield clinically relevant drug-induced mitochondrial side effects than others

  9. Semantic Segmentation of Real-time Sensor Data Stream for Complex Activity Recognition

    OpenAIRE

    Triboan, Darpan; Chen, Liming; Chen, Feng; Wang, Zumin

    2016-01-01

    Department of Information Engineering, Dalian University, China The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Data segmentation plays a critical role in performing human activity recognition (HAR) in the ambient assistant living (AAL) systems. It is particularly important for complex activity recognition when the events occur in short bursts with attributes of multiple sub-tasks. Althou...

  10. Nonlinearly Activated Neural Network for Solving Time-Varying Complex Sylvester Equation.

    Science.gov (United States)

    Li, Shuai; Li, Yangming

    2013-10-28

    The Sylvester equation is often encountered in mathematics and control theory. For the general time-invariant Sylvester equation problem, which is defined in the domain of complex numbers, the Bartels-Stewart algorithm and its extensions are effective and widely used with an O(n³) time complexity. When applied to solving the time-varying Sylvester equation, the computation burden increases intensively with the decrease of sampling period and cannot satisfy continuous realtime calculation requirements. For the special case of the general Sylvester equation problem defined in the domain of real numbers, gradient-based recurrent neural networks are able to solve the time-varying Sylvester equation in real time, but there always exists an estimation error while a recently proposed recurrent neural network by Zhang et al [this type of neural network is called Zhang neural network (ZNN)] converges to the solution ideally. The advancements in complex-valued neural networks cast light to extend the existing real-valued ZNN for solving the time-varying real-valued Sylvester equation to its counterpart in the domain of complex numbers. In this paper, a complex-valued ZNN for solving the complex-valued Sylvester equation problem is investigated and the global convergence of the neural network is proven with the proposed nonlinear complex-valued activation functions. Moreover, a special type of activation function with a core function, called sign-bi-power function, is proven to enable the ZNN to converge in finite time, which further enhances its advantage in online processing. In this case, the upper bound of the convergence time is also derived analytically. Simulations are performed to evaluate and compare the performance of the neural network with different parameters and activation functions. Both theoretical analysis and numerical simulations validate the effectiveness of the proposed method.

  11. Modeling the complex activity of sickle cell and thalassemia specialist nurses in England.

    Science.gov (United States)

    Leary, Alison; Anionwu, Elizabeth N

    2014-01-01

    Specialist advanced practice nursing in hemoglobinopathies has a rich historical and descriptive literature. Subsequent work has shown that the role is valued by patients and families and also by other professionals. However, there is little empirical research on the complexity of activity of these services in terms of interventions offered. In addition, the work of clinical nurse specialists in England has been devalued through a perception of oversimplification. The purpose of this study was to understand the complexity of expert nursing practice in sickle cell and thalassemia. The approach taken to modeling complexity was used from common methods in mathematical modeling and computational mathematics. Knowledge discovery through data was the underpinning framework used in this study using a priori mined data. This allowed categorization of activity and articulation of complexity. In total, 8966 nursing events were captured over 1639 hours from a total of 22.8 whole time equivalents, and several data sources were mined. The work of specialist nurses in this area is complex in terms of the physical and psychosocial care they provide. The nurses also undertook case management activity such as utilizing a very large network of professionals, and others participated in admission avoidance work and education of patients' families and other staff. The work of nurses specializing in hemoglobinopathy care is complex and multidimensional and is likely to contribute to the quality of care in a cost-effective way. An understanding of this complexity can be used as an underpinning to establishing key performance indicators, optimum caseload calculations, and economic evaluation.

  12. Structural characterization and antimicrobial activities of transition metal complexes of a hydrazone ligand

    Science.gov (United States)

    Bakale, Raghavendra P.; Naik, Ganesh N.; Machakanur, Shrinath S.; Mangannavar, Chandrashekhar V.; Muchchandi, Iranna S.; Gudasi, Kalagouda B.

    2018-02-01

    A hydrazone ligand has been synthesized by the condensation of 2-nitrobenzaldehyde and hydralazine, and its Co(II), Ni(II), Cu(II) and Zn(II) complexes have been reported. Structural characterization of the ligand and its metal complexes has been performed by various spectroscopic [IR, NMR, UV-Vis, Mass], thermal and other physicochemical methods. The structure of the ligand and its Ni(II) complex has been characterized by single crystal X-ray diffraction studies. All the synthesized compounds have been screened for in vitro antimicrobial activity. The antibacterial activity is tested against Gram-positive strains Enterococcus faecalis, Streptococcus mutans and Staphylococcus aureus and Gram-negative strains Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae using ciprofloxacin as the reference standard. Antifungal activity is tested against Candida albicans, Aspergillus fumigatus and Aspergillus niger using ketoconazole as the reference standard. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standard. Ligand, Cu(II) and Zn(II) complexes have shown excellent activity against Candida albicans.

  13. Late Pleistocene and Holocene activity of the Atacazo-Ninahuilca Volcanic Complex (Ecuador)

    NARCIS (Netherlands)

    Hidalgo, Silvana; Monzier, Michel; Almeida, Eduardo; Chazot, Gilles; Eissen, Jean-Philippe; van der Plicht, Johannes; Hall, Minard L.

    2008-01-01

    The Atacazo-Ninahuilca Volcanic Complex (ANVC) is located in the Western Cordillera of Ecuador, 10 km southwest of Quito. At least six periods of Pleistocene to Holocene activity (N1 to N6) have been preserved in the geologic record as tephra fallouts and pyroclastic flow deposits. New field data,

  14. Generalization of the Activated Complex Theory of Reaction Rates. II. Classical Mechanical Treatment

    Science.gov (United States)

    Marcus, R. A.

    1964-01-01

    In its usual classical form activated complex theory assumes a particular expression for the kinetic energy of the reacting system -- one associated with a rectilinear motion along the reaction coordinate. The derivation of the rate expression given in the present paper is based on the general kinetic energy expression.

  15. Theoretical Investigations on the Mechanistic Aspects of O2 Activation by a Biomimetic Dinitrosyl Iron Complex

    NARCIS (Netherlands)

    Banerjee, Ambar; Sen, Souloke; Paul, Ankan

    2018-01-01

    Though dinitrosyl-iron complexes (DNICs) are largely believed to act as NO carriers, several experiments on model DNICs have suggested that they can also act as nitrating agents in presence of dioxygen. Oxygen activation by DNICs has been implicated as a possible route for protein tyrosine nitration

  16. Caspase cleaved presenilin-1 is part of active gamma-secretase complexes

    DEFF Research Database (Denmark)

    Hansson, Camilla A; Popescu, Bogdan O; Laudon, Hanna

    2006-01-01

    , and Abeta is believed to be central for the molecular pathogenesis of AD. Apoptosis has been implicated as one of the mechanisms behind the neuronal cell loss seen in AD. We have studied preservation and activity of the gamma-secretase complex during apoptosis in neuroblastoma cells (SH-SY5Y) exposed...

  17. Metal-containing Complexes of Lactams, Imidazoles, and Benzimidazoles and Their Biological Activity

    Science.gov (United States)

    Kukalenko, S. S.; Bovykin, B. A.; Shestakova, S. I.; Omel'chenko, A. M.

    1985-07-01

    The results of the latest investigations of the problem of the synthesis of metal-containing complexes of lactams, imidazoles, and benzimidazoles, their structure, and their stability in solutions are surveyed. Some data on their biological activity (pesticide and pharmacological) and the mechanism of their physiological action are presented. The bibliography includes 190 references.

  18. Detection of Molecular Chirality by Induced Resonance Raman Optical Activity in Europium Complexes

    Czech Academy of Sciences Publication Activity Database

    Yamamoto, Shigeki; Bouř, Petr

    2012-01-01

    Roč. 51, č. 44 (2012), s. 11058-11061 ISSN 1433-7851 R&D Projects: GA MŠk(CZ) LH11033; GA ČR GAP208/11/0105 Institutional support: RVO:61388963 Keywords : europium * complexes * raman optical activity * resonance Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 13.734, year: 2012

  19. Arp2/3 complex activity in filopodia of spreading cells

    Directory of Open Access Journals (Sweden)

    Mendes Paula M

    2008-12-01

    Full Text Available Abstract Background Cells use filopodia to explore their environment and to form new adhesion contacts for motility and spreading. The Arp2/3 complex has been implicated in lamellipodial actin assembly as a major nucleator of new actin filaments in branched networks. The interplay between filopodial and lamellipodial protrusions is an area of much interest as it is thought to be a key determinant of how cells make motility choices. Results We find that Arp2/3 complex localises to dynamic puncta in filopodia as well as lamellipodia of spreading cells. Arp2/3 complex spots do not appear to depend on local adhesion or on microtubules for their localisation but their inclusion in filopodia or lamellipodia depends on the activity of the small GTPase Rac1. Arp2/3 complex spots in filopodia are capable of incorporating monomeric actin, suggesting the presence of available filament barbed ends for polymerisation. Arp2/3 complex in filopodia co-localises with lamellipodial proteins such as capping protein and cortactin. The dynamics of Arp2/3 complex puncta suggests that they are moving bi-directionally along the length of filopodia and that they may be regions of lamellipodial activity within the filopodia. Conclusion We suggest that filopodia of spreading cells have regions of lamellipodial activity and that this activity affects the morphology and movement of filopodia. Our work has implications for how we understand the interplay between lamellipodia and filopodia and for how actin networks are generated spatially in cells.

  20. A Rhodium(III) Complex as an Inhibitor of Neural Precursor Cell Expressed, Developmentally Down-Regulated 8-Activating Enzyme with in Vivo Activity against Inflammatory Bowel Disease.

    Science.gov (United States)

    Zhong, Hai-Jing; Wang, Wanhe; Kang, Tian-Shu; Yan, Hui; Yang, Yali; Xu, Lipeng; Wang, Yuqiang; Ma, Dik-Lung; Leung, Chung-Hang

    2017-01-12

    We report herein the identification of the rhodium(III) complex [Rh(phq) 2 (MOPIP)] + (1) as a potent and selective ATP-competitive neural precursor cell expressed, developmentally down-regulated 8 (NEDD8)-activating enzyme (NAE) inhibitor. Structure-activity relationship analysis indicated that the overall organometallic design of complex 1 was important for anti-inflammatory activity. Complex 1 showed promising anti-inflammatory activity in vivo for the potential treatment of inflammatory bowel disease.

  1. MECHANISMS OF THE COMPLEX FORMATION BY d-METALS ON POROUS SUPPORTS AND THE CATALYTIC ACTIVITY OF THE FORMED COMPLEXES IN REDOX REACTIONS

    Directory of Open Access Journals (Sweden)

    T. L. Rakitskaya

    2015-11-01

    Full Text Available The catalytic activity of supported complexes of d metals in redox reactions with participation of gaseous toxicants, PH3, CO, O3, and SO2, depends on their composition. Owing to the variety of physicochemical and structural-adsorption properties of available supports, their influence on complex formation processes, the composition and catalytic activity of metal complexes anchored on them varies over a wide range. The metal complex formation on sup-ports with weak ion-exchanging properties is similar to that in aqueous solutions. In this case, the support role mainly adds up to the ability to reduce the activity of water adsorbed on them. The interaction between a metal complex and a support surface occurs through adsorbed water molecules. Such supports can also affect complex formation processes owing to protolytic reactions on account of acidic properties of sorbents used as supports. The catalytic activity of metal complexes supported on polyphase natural sorbents considerably depends on their phase relationship. In the case of supports with the nonsimple structure and pronounced ion-exchanging properties, for instance, zeolites and laminar silicates, it is necessary to take into account the variety of places where metal ions can be located. Such location places determine distinctions in the coordination environment of the metal ions and the strength of their bonding with surface adsorption sites and, therefore, the catalytic activity of surface complexes formed by theses metal ions. Because of the energy surface inhomogeneity, it is important to determine a relationship between the strength of a metal complex bonding with a support surface and its catalytic activity. For example, bimetallic complexes are catalytically active in the reactions of oxidation of the above gaseous toxicants. In particular, in the case of carbon monoxide oxidation, the most catalytic activity is shown by palladium-copper complexes in which copper(II is strongly

  2. Template synthesis, characterization and antimicrobial activity of some new complexes with isonicotinoyl hydrazone ligands

    Directory of Open Access Journals (Sweden)

    LIVIU MITU

    2009-09-01

    Full Text Available Complexes of Cu(II, Ni(II, Co(II with the 9-anthraldehyde iso-nicotinoyl hydrazone ligand (HL1 and the 3,5-di-tert-butyl-4-hydroxy-benzaldehyde isonicotinoyl hydrazone ligand (H2L2 were synthesized by the template method. The complexes were characterized by analytical analysis, IR, UV-Vis and ESR spectroscopy, magnetic measurements, conductometry and thermal analysis and the two ligands by 1H-NMR spectroscopy. From the elemental analysis, 1:2 (metal:ligand stoichiometry for the complexes of Cu(II, Ni(II with the ligands HL1 and H2L2 and 1:1 (metal:ligand stoichiometry for the complex of Co(II with the ligand HL1 are proposed. The molar conductance data showed that the complexes are non-electrolytes. The magnetic susceptibility results coupled with the electronic and ESR spectra suggested a distorted octahedral geometry for the complexes Ni(II/HL1, Ni(II/H2L2 and Cu(II/H2L2, a tetrahedral stereochemistry for the complex Cu/HL1 and a square-planar geometry for the complex Co/HL1. The IR spectra demonstrated the bidentate coordination of the ligands HL1 and H2L2 by the O=C amide oxygen and the azomethine nitrogen, as well as monodentate coordination of the ligand HL1 by the azomethine nitrogen in the Cu(IIcomplex. The antibacterial activity of the ligands and their metallic complexes were tested against Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae.

  3. The activity state of the branched-chain 2-oxo acid dehydrogenase complex in rat tissues.

    Science.gov (United States)

    Wagenmakers, A J; Schepens, J T; Veldhuizen, J A; Veerkamp, J H

    1984-05-15

    An assay is described to define the proportion of the branched-chain 2-oxo acid dehydrogenase complex that is present in the active state in rat tissues. Activities are measured in homogenates in two ways: actual activities, present in tissues, by blocking both the kinase and phosphatase of the enzyme complex during homogenization, preincubation, and incubation with 1-14C-labelled branched-chain 2-oxo acid, and total activities by blocking only the kinase during the 5 min preincubation (necessary for activation). The kinase is blocked by 5 mM-ADP and absence of Mg2+ and the phosphatase by the simultaneous presence of 50 mM-NaF. About 6% of the enzyme is active in skeletal muscle of fed rats, 7% in heart, 20% in diaphragm, 47% in kidney, 60% in brain and 98% in liver. An entirely different assay, which measures activities in crude tissue extracts before and after treatment with a broad-specificity protein phosphatase, gave similar results for heart, liver and kidney. Advantages of our assay with homogenates are the presence of intact mitochondria, the simplicity, the short duration and the high sensitivity. The actual activities measured indicate that the degradation of branched-chain 2-oxo acids predominantly occurs in liver and kidney and is limited in skeletal muscle in the fed state.

  4. Oxovanadium(IV) complexes of non-steroidal anti-inflammatory drugs: synthesis, spectroscopy, and antimicrobial activity

    International Nuclear Information System (INIS)

    Muhammad, N.; Ali, S.; Shahzadi, S.; Khan, A.N.

    2008-01-01

    Oxovanadium(IV) complexes with four different non-steroidal anti-inflammatory drugs have been synthesized. These complexes were characterized by different analytical techniques such as CHN, IR, UV-Vis spectroscopy, and mass spectrometry. The IR data show the bidentate nature of the ligands and reveal hexacoordinate geometry in the solid state. The complexes were tested for their biological activity against six different bacterial strains and plant pathogens, and all complexes showed good biological activity with few exceptions [ru

  5. Evaluating the biological activity of oil-polluted soils using a complex index

    Science.gov (United States)

    Kabirov, R. R.; Kireeva, N. A.; Kabirov, T. R.; Dubovik, I. Ye.; Yakupova, A. B.; Safiullina, L. M.

    2012-02-01

    A complex index characterizing the biological activity of soils (BAS) is suggested. It is based on an estimate of the level of activity of catalase; the number of heterotrophic and hydrocarbon oxidizing microorganisms, microscopic fungi, algae, and cyanobacteria; and the degree of development of higher plants and insects in the studied soil. The data on using the BAS coefficient for evaluating the efficiency of rehabilitation measures for oil-polluted soils are given. Such measures included introducing the following biological preparations: Lenoil based on a natural consortium of microorganisms Bacillus brevis and Arthrobacter sp.; the Azolen biofertilizer with complex action based on Azotobacter vinelandii; the Belvitamil biopreparation, which is the active silt of pulp and paper production; and a ready-mixed industrial association of aerobic and anaerobic microorganisms that contains hydrocarbon oxidizing microorganisms of the Arthrobacter, Bacillus, Candida, Desulfovibrio, and Pseudomonas genera.

  6. The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation.

    Science.gov (United States)

    Malik, Sohail; Roeder, Robert G

    2010-11-01

    The Mediator is an evolutionarily conserved, multiprotein complex that is a key regulator of protein-coding genes. In metazoan cells, multiple pathways that are responsible for homeostasis, cell growth and differentiation converge on the Mediator through transcriptional activators and repressors that target one or more of the almost 30 subunits of this complex. Besides interacting directly with RNA polymerase II, Mediator has multiple functions and can interact with and coordinate the action of numerous other co-activators and co-repressors, including those acting at the level of chromatin. These interactions ultimately allow the Mediator to deliver outputs that range from maximal activation of genes to modulation of basal transcription to long-term epigenetic silencing.

  7. Structure-activity relationships of mononuclear metal-thiosemicarbazone complexes endowed with potent antiplasmodial and antiamoebic activities.

    Science.gov (United States)

    Bahl, Deepa; Athar, Fareeda; Soares, Milena Botelho Pereira; de Sá, Matheus Santos; Moreira, Diogo Rodrigo Magalhães; Srivastava, Rajendra Mohan; Leite, Ana Cristina Lima; Azam, Amir

    2010-09-15

    A useful concept for the rational design of antiparasitic drug candidates is the complexation of bioactive ligands with transition metals. In view of this, an investigation was conducted into a new set of metal complexes as potential antiplasmodium and antiamoebic agents, in order to examine the importance of metallic atoms, as well as the kind of sphere of co-ordination, in these biological properties. Four functionalized furyl-thiosemicarbazones (NT1-4) treated with divalent metals (Cu, Co, Pt, and Pd) to form the mononuclear metallic complexes of formula [M(L)2Cl2] or [M(L)Cl2] were examined. The pharmacological characterization, including assays against Plasmodium falciparum and Entamoeba histolytica, cytotoxicity to mammalian cells, and interaction with pBR 322 plasmid DNA was performed. Structure-activity relationship data revealed that the metallic complexation plays an essential role in antiprotozoal activity, rather than the simple presence of the ligand or metal alone. Important steps towards identification of novel antiplasmodium (NT1Cu, IC50 of 4.6 microM) and antiamoebic (NT2Pd, IC50 of 0.6 microM) drug prototypes were achieved. Of particular relevance to this work, these prototypes were able to reduce the proliferation of these parasites at concentrations that are not cytotoxic to mammalian cells. Copyright (c) 2010. Published by Elsevier Ltd.

  8. Screening of Peroxisome Proliferator-Activated Receptors (PPARs) α, γ and α Gene Polymorphisms for Obesity and Metabolic Syndrome Association in the Multi-Ethnic Malaysian Population.

    Science.gov (United States)

    Chia, Phee-Phee; Fan, Sook-Ha; Say, Yee-How

    2015-11-05

    This study aimed to investigate the association of peroxisome proliferator-activated receptor (PPAR) genes PPARα L162V, PPARγ2 C161T and PPARδ T294C single nucleotide polymorphisms (SNPs) with obesity and metabolic syndrome (Met-S) in a multi-ethnic population in Kampar, Malaysia. Socio-demographic data, anthropometric and biochemical measurements (plasma lipid profile, adiponectin and interleukin-6 [IL-6] levels) were taken from 307 participants (124 males; 180 obese; 249 Met-S; 97 Malays, 85 ethnic Chinese, 55 ethnic Indians). The overall minor allele frequencies were .08, .22 and .30 for PPAR α L162V, γ C161T, δ T294C, respectively. All SNPs were not associated with obesity, Met-S and obesity with/without Met-S by χ(2) analysis, ethnicity-stratified and logistic regression analyses. Nevertheless, participants with V162 allele of PPARα had significantly higher IL-6, while those with T161 allele of PPARγ2 had significantly lower HOMA-IR. All PPAR SNPs were not associated with obesity and Met-S in the suburban population of Kampar, Malaysia, where only PPARα V162 and PPARγ2 T161 alleles were associated with plasma IL-6 and HOMA-IR, respectively.

  9. Extraction of an urease-active organo-complex from soil.

    Science.gov (United States)

    Burns, R. G.; El-Sayed, M. H.; Mclaren, A. D.

    1972-01-01

    Description of an extraction from a Dublin clay loam soil of a colloidal organic matter complex that is urease active and, by X-ray analysis, free of clays. Urease activity in the clay-free precipitates, as in the soil, was not destroyed by the activity of an added proteolytic enzyme, pronase. This is attributed to the circumstance that native soil urease resides in organic colloidal particles with pores large enough for water, urea, ammonia, and carbon dioxide to pass freely, but nevertheless small enough to exclude pronase.

  10. Functional effects of polymorphisms on glucocorticoid receptor modulation of human anxiogenic substance-P gene promoter activity in primary amygdala neurones.

    Science.gov (United States)

    Hay, Colin W; Shanley, Lynne; Davidson, Scott; Cowie, Philip; Lear, Marissa; McGuffin, Peter; Riedel, Gernot; McEwan, Iain J; MacKenzie, Alasdair

    2014-09-01

    Expression or introduction of the neuropeptide substance-P (SP; encoded by the TAC1 gene in humans and Tac1 in rodents) in the amygdala induces anxiety related behaviour in rodents. In addition, pharmacological antagonism of the main receptor of SP in humans; NK1, is anxiolytic. In the current study, we show that the Tac1 locus is up-regulated in primary rat amygdala neurones in response to activation of the glucocorticoid receptor (GR); a classic component of the stress response. Using a combination of bioinformatics, electrophoretic mobility shift assays (EMSA) and reporter plasmid magnetofection into rat primary amygdala neurones we identified a highly conserved GR response sequence (2GR) in the human TAC1 promoter that binds GR in response to dexamethasone (Dex) or forskolin. We also identified a second GR binding site in the human promoter that was polymorphic and whose T-allele is only found in Japanese and Chinese populations. We present evidence that the T-allele of SNPGR increases the activity of the TAC1 promoter through de-sequestration or de-repression of 2GR. The identification of Dex/forskolin response elements in the TAC1 promoter in amygdala neurones suggests a possible link in the chain of molecular events connecting GR activation and anxiety. In addition, the discovery of a SNP which can alter this response may have implications for our understanding of the role of regulatory variation in susceptibility to stress in specific populations. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. PF4-HIT antibody (KKO) complexes activate broad innate immune and inflammatory responses.

    Science.gov (United States)

    Haile, Lydia A; Rao, Roshni; Polumuri, Swamy K; Arepally, Gowthami M; Keire, David A; Verthelyi, Daniela; Sommers, Cynthia D

    2017-11-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin anticoagulation therapy resulting in thrombocytopenia frequently accompanied by thrombosis. Current evidence suggests that HIT is associated with antibodies developed in response to multi-molecular complexes formed by platelet factor 4 (PF4) bound to heparin or cell surface glycosaminoglycans. These antibody complexes activate platelets and monocytes typically through FcγRIIA receptors increasing the production of PF4, inflammatory mediators, tissue factor and thrombin. The influence of underlying events in HIT including complex-induced pro-inflammatory cell activation and structural determinants leading to local inflammatory responses are not fully understood. The stoichiometry and complex component requirements were determined by incubating fresh peripheral blood mononuclear cells (PBMC) with different concentrations of unfractionated heparin (H), low molecular weight heparin (LMWH), PF4- and anti-PF4-H complex antibodies (KKO). Cytokine mRNA or protein were measured by qRT-PCR or Meso Scale Discovery technology, respectively. Gene expression profile analysis for 594 genes was performed using Nanostring technology and analyzed using Ingenuity Pathway Analysis software. The data show that antibodies magnify immune responses induced in PBMCs by PF4 alone or in complex with heparin or LMWH. We propose that following induction of HIT antibodies by heparin-PF4 complexes, binding of the antibodies to PF4 is sufficient to induce a local pro-inflammatory response which may play a role in the progression of HIT. In vitro assays using PBMCs may be useful in characterizing local inflammatory and innate immune responses induced by HIT antibodies in the presence of PF4 and different sources of heparins. The findings and conclusions in this article are solely the responsibility of the authors and are not being formally disseminated by the Food and Drug Administration. Thus, they should not be

  12. CSK regulatory polymorphism is associated with systemic lupus erythematosus and influences B-cell signaling and activation

    NARCIS (Netherlands)

    Manjarrez-Orduno, N.; Marasco, E.; Chung, S.A.; Katz, M.S.; Kiridly, J.F.; Simpfendorfer, K.R.; Freudenberg, J.; Ballard, D.H.; Nashi, E.; Hopkins, T.J.; Cunninghame Graham, D.S.; Lee, A.T.; Coenen, M.J.H.; Franke, B.; Swinkels, D.W.; Graham, R.R.; Kimberly, R.P.; Gaffney, P.M.; Vyse, T.J.; Behrens, T.W.; Criswell, L.A.; Diamond, B.; Gregersen, P.K.

    2012-01-01

    The c-Src tyrosine kinase, Csk, physically interacts with the intracellular phosphatase Lyp (encoded by PTPN22) and can modify the activation state of downstream Src kinases, such as Lyn, in lymphocytes. We identified an association of CSK with systemic lupus erythematosus (SLE) and refined its

  13. Peroxisome proliferator-activated receptor-gamma (PPARgamma) Pro12Ala polymorphism and risk for pediatric obesity

    NARCIS (Netherlands)

    Dedoussis, George V; Vidra, Nikoleta; Butler, Johannah; Papoutsakis, Constantina; Yannakoulia, Mary; Hirschhorn, Joel N; Lyon, Helen N; Vidra, Nikoletta

    BACKGROUND: Variation in the peroxisome-proliferator-activated receptor gamma (PPARgamma) gene has been reported to alter the risk for adiposity in adults. METHODS: We investigated the gender related association between the Pro12Ala variant (rs1801282) in obesity and insulin resistance traits in 794

  14. Microwave synthesis, spectral, thermal, and antimicrobial activities of some transition metal complexes involving 5-bromosalicylaldehyde moiety

    Directory of Open Access Journals (Sweden)

    Rajendra K. Jain

    2012-07-01

    Full Text Available The coordination complexes of Co(II, Ni(II and Cu(II derived from 5-bromosalicylidene-3,4-dimethylaniline (BSMA and 5-bromosalicylidene-3,4-dichloroaniline (BSCA have been synthesized by conventional as well as microwave methods. These compounds have been characterized by elemental analysis, FT-IR, molar conductance, electronic spectra, 1H-NMR, FAB-mass, ESR, magnetic susceptibility, electrical conductivity and thermal analysis. The complexes are coloured and stable in air. Analytical data revealed that all the complexes exhibited 1:2 (metal: ligand ratio with coordination number 4 or 6. IR data shows that the ligand coordinates with the metal ions in a bidentate manner through the phenolic oxygen and azomethine nitrogen. FAB-mass and thermal data show degradation pattern of the complexes. Solid state electrical conductivity studies reflect semiconducting nature of the complexes. The Schiff base and metal complexes show a good activity against the Gram-positive bacteria; Staphylococcus aureus and Gram-negative bacteria; Escherichia coli and fungi Aspergillus niger and Candida albicans.

  15. Template synthesis and characterization of biologically active transition metal complexes comprising 14-membered tetraazamacrocyclic ligand

    Directory of Open Access Journals (Sweden)

    DHARMPAL SINGH

    2010-02-01

    Full Text Available A novel series of complexes of the type [M(C28H24N4X2], whereM = Co(II, Ni(II, Cu(II, Zn(II and Cd(II, X = Cl–, NO3–, CH3COO– and (C28H24N4 corresponds to the tetradentate macrocyclic ligand, were synthe¬sized by template condensation of 1,8-diaminonaphthalene and diacetyl in the presence of divalent metal salts in methanolic medium. The complexes were characterized by elemental analyses, conductance and magnetic measurements, as well as by UV/Vis, NMR, IR and MS spectroscopy. The low values of the molar conductance indicate non-electrolyte type of complexes. Based on these spectral data, a distorted octahedral geometry may be proposed for all of these complexes. All the synthesized macrocyclic complexes were tested for in vitro antibacterial activity against some pathogenic bacterial strains, viz Bacillus cereus, Salmonella typhi, Escherichia coli and Staphylococcus aureus. The MIC values shown by the complexes against these bacterial strains were compared with the MIC shown by the standard antibiotics linezolid and cefaclor.

  16. Effects of nanosuspension and inclusion complex techniques on the in vitro protease inhibitory activity of naproxen

    Energy Technology Data Exchange (ETDEWEB)

    Dharmalingam, Senthil Rajan; Chidambaram, Kumarappan; Srinivasan, Ramamurthy; Nadaraju, Shamala, E-mail: dsenthilrajan@yahoo.co.in [School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur (Malaysia)

    2014-01-15

    This study investigated the effects of nanosuspension and inclusion complex techniques on in vitro trypsin inhibitory activity of naproxen—a member of the propionic acid derivatives, which are a group of antipyretic, analgesic, and non-steroidal anti-inflammatory drugs. Nanosuspension and inclusion complex techniques were used to increase the solubility and anti-inflammatory efficacy of naproxen. The evaporative precipitation into aqueous solution (EPAS) technique and the kneading methods were used to prepare the nanosuspension and inclusion complex of naproxen, respectively. We also used an in vitro protease inhibitory assay to investigate the anti-inflammatory effect of modified naproxen formulations. Physiochemical properties of modified naproxen formulations were analyzed using UV, IR spectra, and solubility studies. Beta-cyclodextrin inclusion complex of naproxen was found to have a lower percentage of antitryptic activity than a pure nanosuspension of naproxen did. In conclusion, nanosuspension of naproxen has a greater anti-inflammatory effect than the other two tested formulations. This is because the nanosuspension formulation reduces the particle size of naproxen. Based on these results, the antitryptic activity of naproxen nanosuspension was noteworthy; therefore, this formulation can be used for the management of inflammatory disorders. (author)

  17. Differential patterns of cortical activation as a function of fluid reasoning complexity.

    Science.gov (United States)

    Perfetti, Bernardo; Saggino, Aristide; Ferretti, Antonio; Caulo, Massimo; Romani, Gian Luca; Onofrj, Marco

    2009-02-01

    Fluid intelligence (gf) refers to abstract reasoning and problem solving abilities. It is considered a human higher cognitive factor central to general intelligence (g). The regions of the cortex supporting gf have been revealed by recent bioimaging studies and valuable hypothesis on the neural correlates of individual differences have been proposed. However, little is known about the interaction between individual variability in gf and variation in cortical activity following task complexity increase. To further investigate this, two samples of participants (high-IQ, N = 8; low-IQ, N = 10) with significant differences in gf underwent two reasoning (moderate and complex) tasks and a control task adapted from the Raven progressive matrices. Functional magnetic resonance was used and the recorded signal analyzed between and within the groups. The present study revealed two opposite patterns of neural activity variation which were probably a reflection of the overall differences in cognitive resource modulation: when complexity increased, high-IQ subjects showed a signal enhancement in some frontal and parietal regions, whereas low-IQ subjects revealed a decreased activity in the same areas. Moreover, a direct comparison between the groups' activation patterns revealed a greater neural activity in the low-IQ sample when conducting moderate task, with a strong involvement of medial and lateral frontal regions thus suggesting that the recruitment of executive functioning might be different between the groups. This study provides evidence for neural differences in facing reasoning complexity among subjects with different gf level that are mediated by specific patterns of activation of the underlying fronto-parietal network.

  18. Adsorption of some metal complexes derived from acetyl acetone on activated carbon and purolite S-930

    Directory of Open Access Journals (Sweden)

    Salam A.H. Al-Ameri

    2014-12-01

    Full Text Available A new Schiff base (HL derived from condensation of p-anisidine and acetyl acetone has been prepared and used as a chelating ligand to prepare Cr(III, Mn(II, Co(II, Ni(II and Cu(II complexes. The study of the nature of these complexes formed in ethanol solution following the mole ratio method (2:1, L:M gave results which were compared successfully with these obtained from isolated solid state studies. These studies revealed that the complexes having square planner geometry of the type (ML2, M = Co(II, Ni(II and Cu(II, and octahedral geometry of the type [CrIIIL2(H2O2]Cl and [MNIIL2(H2O2]. The adsorption studies of three complexes Cr(III, Mn(II, and Co(II on activated carbon, H and Na-forms of purolite S-930 resin show high adsorption percentage for Cr(III on purolite S-930 due to ion exchange interaction compared with high adsorption of neutral Mn(II, Co(II complexes on activated charcoal. Linear plot of log Qe versus log Ce showed that the adsorption isotherm of these three complexes on activated carbon, H and Na-forms of purolite S-930 surface obeys Freundlich isotherm and was similar to S-curve type according to Giles classification which investigates heterogeneous adsorption. The regression values indicate that the adsorption data for these complexes fitted well within the Freundlich isothermal plots for the concentration studied. The accuracy and precision of the concentration measurements of these complexes were determined by preparing standard laboratory samples, the results show relative error ranging from ±1.08 to 5.31, ±1.04 to 4.82 and ±0.28 to 3.09 and the relative standard deviation did not exceed ±6.23, ±2.77 and ±4.38% for A1, A2 and A3 complexes, respectively.

  19. In vitro and in vivo anti-inflammatory active copper(II-lawsone complexes.

    Directory of Open Access Journals (Sweden)

    Ján Vančo

    Full Text Available We report in vitro and in vivo anti-inflammatory activities of a series of copper(II-lawsone complexes of the general composition [Cu(Law2(LNx(H2O(2-x]·yH2O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when LN = pyridine (1 and 2-aminopyridine (3 and x = 2 when LN = imidazole (2, 3-aminopyridine (4, 4-aminopyridine (5, 3-hydroxypyridine (6, and 3,5-dimethylpyrazole (7. The compounds were thoroughly characterized by physical techniques, including single crystal X-ray analysis of complex 2. Some of the complexes showed the ability to suppress significantly the activation of nuclear factor κB (NF-κB both by lipopolysaccharide (LPS and TNF-alpha (complexes 3-7 at 100 nM level in the similar manner as the reference drug prednisone (at 1 μM level. On the other hand, all the complexes 1-7 decreased significantly the levels of the secreted TNF-alpha after the LPS activation of THP-1 cells, thus showing the anti-inflammatory potential via both NF-κB moderation and by other mechanisms, such as influence on TNF-alpha transcription and/or translation and/or secretion. In addition, a strong intracellular pro-oxidative effect of all the complexes has been found at 100 nM dose in vitro. The ability to suppress the inflammatory response, caused by the subcutaneous application of λ-carrageenan, has been determined by in vivo testing in hind-paw edema model on rats. The most active complexes 1-3 (applied in a dose corresponding to 40 μmol Cu/kg, diminished the formation of edema simalarly as the reference drug indomethacine (applied in 10 mg/kg dose. The overall effect of the complexes, dominantly 1-3, shows similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular pro-oxidative effects.

  20. Studies on chalcone derivatives: Complex formation, thermal behavior, stability constant and antioxidant activity

    Science.gov (United States)

    El-Sayed, Yusif S.; Gaber, M.

    2015-02-01

    The chalcone 3-[4‧-dimethylaminophenyl]-1-(2-pyridyl) prop-2-en-1-one (DMAPP) and 3-(4‧-diethylaminophenyl)-1-(2-pyridinyl) prop-2-en-1-one abbreviated as DEAPP have been synthesized and characterized with IR, 1H NMR, 13C NMR spectroscopic techniques as described previously (El-Daly et al., 2008; Gaber et al., 2009; El-Sayed, 2013). By using UV visible spectroscopy method the mole fraction ratio for copper with DMAPP and DEAPP complexes were determined and it was found to be 1:1. The stability constants of this complex have been determined by Job's method. The stability constant (Kf) of copper with DMAPP and DEAPP complexes in universal buffer pH = 3.2 was determined to be 9.9 × 104 and 5.2 × 104 respectively. The effect of Cu(II) ion on the emission spectrum of the free chalcone is also assigned. Adherence to Beer's law and Ringbom optimum concentration ranges are determined. The thermal decomposition of the metal complexes is studied by TGA technique. The kinetic parameters like activation energy, pre-exponential factor and entropy of activation are estimated. The structure of complexes was energetically optimized through molecular mechanics applying MM+ force field coupled with molecular dynamics simulation. The bond lengths and bond angles have been calculated to confirm the geometry of the ligands and their Cu(II) complexes. The mode of interaction of the chalcone to copper nanoparticles was studied. The apparent association constants of the colloidal copper nanoparticles:chalcone complexes in solution were evaluated using the spectral method and compared with the formation constant of the Cu(II) chalcone complexes. Antioxidant activity of these chalcones was evaluated by using 1,1‧-diphenyl-2-picrylhydrazyl (DPPHrad) radicals scavenging method, which showed that the antioxidant activity of DMAPP has higher value than the DEAPP. Semi-empirical study results showed that DMAPP have higher dipole moment than DEAPP [1].

  1. Synthesis of a Benzodiazepine-derived Rhodium NHC Complex by C-H Bond Activation

    Energy Technology Data Exchange (ETDEWEB)

    Bergman, Roberg G.; Gribble, Jr., Michael W.; Ellman, Jonathan A.

    2008-01-30

    The synthesis and characterization of a Rh(I)-NHC complex generated by C-H activation of 1,4-benzodiazepine heterocycle are reported. This complex constitutes a rare example of a carbene tautomer of a 1,4-benzodiazepine aldimine stabilized by transition metal coordination and demonstrates the ability of the catalytically relevant RhCl(PCy{sub 3}){sub 2} fragment to induce NHC-forming tautomerization of heterocycles possessing a single carbene-stabilizing heteroatom. Implications for the synthesis of benzodiazepines and related pharmacophores via C-H functionalization are discussed.

  2. Synthesis, characterization, DFT calculations and antibacterial activity of palladium(II) cyanide complexes with thioamides

    Science.gov (United States)

    Ahmad, Saeed; Nadeem, Shafqat; Anwar, Aneela; Hameed, Abdul; Tirmizi, Syed Ahmed; Zierkiewicz, Wiktor; Abbas, Azhar; Isab, Anvarhusein A.; Alotaibi, Mshari A.

    2017-08-01

    Palladium(II) cyanide complexes of thioamides (or thiones) having the general formula PdL2(CN)2, where L = Thiourea (Tu), Methylthiourea (Metu), N,N‧-Dimethylthiourea (Dmtu), Tetramethylthiourea (Tmtu), 2-Mercaptopyridine (Mpy) and 2-Mercaptopyrimidine (Mpm) were prepared by reacting K2[PdCl4] with potassium cyanide and thioamides in the molar ratio of 1:2:2. The complexes were characterized by elemental analysis, thermal and spectroscopic methods (IR, 1H and 13C NMR). The structures of three of the complexes were predicted by DFT calculations. The appearance of a band around 2100 cm-1 in IR and resonances around 120-130 ppm in the 13C NMR spectra indicated the coordination of cyanide to palladium(II). More than one resonances were observed for CN- carbon atoms in 13C NMR indicating the existence of equilibrium between different species in solution. DFT calculations revealed that in the case of the palladium(II) complex of Tmtu, the ionic dinuclear [Pd(Tmtu)4][Pd(CN)4] form was more stable than the dimer of mononuclear complex [Pd(Tmtu)2(CN)2] by 0.91 kcal mol-1, while for the complexes of Tu or Mpy ligands, the nonionic [Pd(L)2(CN)2] forms were more stable than the corresponding [Pd(L)4][Pd(CN)4] complexes by 1.26 and 6.49 kcal mol-1 for L = Tu and Mpy, respectively. The complexes were screened for antibacterial effects and some of them showed significant activities against both gram positive as well as gram negative bacteria.

  3. Can Different Complex Training Improve the Individual Phenomenon of Post-Activation Potentiation?

    Science.gov (United States)

    Chen, Zong-Rong; Lo, Shin-Liang; Wang, Min-Hsien; Yu, Ching-Fang; Peng, Hsien-Te

    2017-02-01

    The aims of the present study were (a) to determine whether the two types of complex training and vibration complex training would improve the individual phenomenon of post-activation potentiation (PAP) for every athlete in a team setting; and (b) to compare the acute effect of resistance and plyometric exercise, whole body vibration, complex training and vibration complex training on vertical jump performance. The participants were ten male division I college volleyball and basketball players. They were asked to perform three vertical jumps as a pre-test and were then randomly assigned to one of five PAP protocols, resistance exercise using half squat exercise, plyometric exercise using drop jumps with individualized drop height, whole body vibration using squats on a vibration plate, complex training combining resistance exercise with plyometric exercise, vibration complex training combining whole body vibration with plyometric exercise. Three vertical jumps were performed four minutes after the PAP protocol as a post-test. A two-way repeated-measures analysis of variance was used to examine the differences among the five PAP protocols and between the two testing times. Our results showed that the post-test results were significantly improved compared to the pre-test for the vertical jump height (p = .015) in all PAP protocols. There was, however, an individual phenomenon of PAP in the response to all PAP protocols. In conclusion, this study found that resistance and plyometric exercise, whole body vibration, complex training and vibration complex training induce similar group PAP benefits. However, some athletes decreased their performances in some of the exercises in the study. Therefore, it is not recommended for coaches to arrange the exercises in a team setting.

  4. Use of polyamfolit complexes of ethyl-amino-crotonate/acrylic acid with surface-active materials for radionuclide extraction

    International Nuclear Information System (INIS)

    Kabdyrakova, A.M.; Artem'ev, O.I.; Protskij, A.V.; Bimendina, L.A.; Yashkarova, M.G.; Orazzhanova, L.K.

    2005-01-01

    Pentifylline of betaine structure was synthesised on the basis of 3-aminocrotonate and acrylic acid. Polyamfolit composition and its complexes with anionic surface-active material (lauryl sulfate of sodium) were determined. It is revealed that complex formation occurs with [polyamfolit]:[surface active material]=1:1 ratio and is accompanied by significant reduce of system characteristics viscosity. The paper presents results of [polyamfolit]:[surface active material] complex apply experimental investigation for radionuclide directed migration in soil. (author)

  5. [The X+ chronic granulomatous disease as a fabulous model to study the NADPH oxidase complex activation].

    Science.gov (United States)

    Stasia, Marie-José

    2007-05-01

    Chronic granulomatous disease (CGD) is a rare inherited disorder in which phagocytes lack NADPH oxidase activity. Patients with CGD suffer from recurrent bacterial and fungal infections because of the absence of superoxide anions (O2- degrees ) generatingsystem. The NADPH oxidase complex is composed of a membranous cytochrome b558, cytosolic proteins p67phox, p47phox, p40phox and two small GTPases Rac2 and Rap1A. Cytochrome b558 consists of two sub-units gp91phox and p22phox. The most common form of CGD is due to mutations in CYBB gene encoding gp91phox. In some rare cases, the mutated gp91phox is normally expressed but is devoided of oxidase activity. These variants called X+ CGD, have provided interesting informations about oxidase activation mechanisms. However modelization of such variants is necessary to obtain enough biological material for studies at the molecular level. A cellular model (knock-out PLB-985 cells) has been developed for expressing recombinant mutated gp91phox for functional analysis of the oxidase complex. Recent works demonstrated that this cell line genetically deficient in gp91phox is a powerful tool for functional analysis of the NADPH oxidase complex activation.

  6. Complex of Key Instruments of Management of Operation Activity of a Small Business Trade Enterprise

    Directory of Open Access Journals (Sweden)

    Serdyuk Vira M.

    2013-11-01

    Full Text Available The article offers a complex of key instruments of management of operation activity of a small business trade enterprise, including: 1 budgeting of operation activity; 2 its accounting by norms and deviations from them; 3 monitoring of operational activity of an enterprise, which envisages analysis of revealed deviations. The article shows the most efficient way of realisation and practical use of the presented concept – application of the “standard-cost” scheme within the framework of which the following tasks are solved: 1 budgeting of income from operational activity; 2 establishment of standards of costs; 3 accumulation of data on factual income and expenditures; 4 analysis of deviations and reporting; and 5 introduction of necessary amendments. The article also offers an imitation model of analysis of dynamics of trade processes, which allows detection of key spheres of management of operation activity of a small trade enterprise and principles of carrying out an efficient and well thought over financial policy.

  7. Polymorphous computing fabric

    Science.gov (United States)

    Wolinski, Christophe Czeslaw [Los Alamos, NM; Gokhale, Maya B [Los Alamos, NM; McCabe, Kevin Peter [Los Alamos, NM

    2011-01-18

    Fabric-based computing systems and methods are disclosed. A fabric-based computing system can include a polymorphous computing fabric that can be customized on a per application basis and a host processor in communication with said polymorphous computing fabric. The polymorphous computing fabric includes a cellular architecture that can be highly parameterized to enable a customized synthesis of fabric instances for a variety of enhanced application performances thereof. A global memory concept can also be included that provides the host processor random access to all variables and instructions associated with the polymorphous computing fabric.

  8. X-Ray structure and cytotoxic activity of a picolinate ruthenium(II–arene complex

    Directory of Open Access Journals (Sweden)

    IVANKA IVANOVIĆ

    2011-01-01

    Full Text Available A ruthenium(II–arene complex with picolinic acid, [(η6-p-cymeneRuCl(pico]∙H2O, was prepared by the reaction of [(η6-p-cymeneRuCl2]2 with picolinic acid in a 1:2 molar ratio in 2-propanol. The compound was characterized by elemental analysis, and IR and NMR spectroscopy. X-ray diffraction analysis showed that the molecule adopts a “three-leg piano-stool” geometry, which is common for this type of complexes. The cytotoxic activity of the complex was tested in two human cancer cell lines HeLa (cervix and FemX (melanoma by MTT assay. The IC50 values were at 82.0 and 36.2 µmol dm-3 for HeLa and FemX cells, respectively.

  9. Synthesis of (2-[{sup 11}C]Methoxy)rotenone, a marker of mitochondrial complex I activity

    Energy Technology Data Exchange (ETDEWEB)

    Charalambous, A; Mangner, T J; Kilbourn, M R

    1995-01-01

    Recent studies suggest that defects in the function of the complexes of the electron transport chain might be involved in the pathology of neurological diseases such as mitochondrial encephalopathies, Parkinson's Huntington's and Alzheimer's disease. Rotenone is a potent reversible competitive inhibitor of complex I (NADH-CoQ reductase). To study the possible involvement of complex I in such diseases, we synthesized (2-[{sup 11}C]methoxy)rotenone by [{sup 11}C]alkylation of 2-O-desmethyl rotenone methyl enol ether followed by hydrolysis of the enol ether to the ketone using aqueous trifluoroacetic acid. (2-[{sup 11}C]Methoxy)rotenone was purified by high pressure liquid chromatography (silica gel) and was obtained in 7-10% yields decay corrected to end of bombardment in synthesis times typically shorter than 48 min. Radiochemical purities were over 95% and specific activities averaged 1000 Ci/mmol at end of synthesis.

  10. Antibacterial activity of Pd(II) complexes with salicylaldehyde-amino acids Schiff bases ligands.

    Science.gov (United States)

    Rîmbu, Cristina; Danac, Ramona; Pui, Aurel

    2014-01-01

    Palladium(II) complexes with Schiff bases ligands derived from salicylaldehyde and amino acids (Ala, Gly, Met, Ser, Val) have been synthesized and characterized by Fourier transform (FT)-IR, UV-Vis and (1)H-NMR spectroscopy. The electrospray mass spectrometry (ES-MS) spectrometry confirms the formation of palladium(II) complexes in 1/2 (M/L) molar ratio. All the Pd(II) complexes 1, [Pd(SalAla)2]Cl2; 2, [Pd(SalGly)2]Cl2; 3, [Pd(SalMet)2]Cl2; 4, [Pd(SalSer)2]Cl2; 5, [Pd(SalVal)2]Cl2; have shown antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Escherichia coli.

  11. Novel synthesis on poly (vinyl alcohol): characterization, complexation a biological activity

    International Nuclear Information System (INIS)

    El-Sawy, N.M.; Elassar, A.Z.; Al-Fulaij, O.

    2002-01-01

    Poly(vinyl alcohol), PVA, readily condensed with phenyl hydrazine and malononitrile in basic medium to give the hydrazone and pyran derivatives, respectively. PVA reacted with chloroacetonitrile, biuet and thiophene carbonyl chloride to give modified polymeric materials. While addition of PVA to acrylonitrile and phenyl isothiocyanate gives the ether and thiocarbamate ester derivatives, respectively. Hydroxylamine hydrochloride reacted with the modified, carbonitrile containing, polymer to give the amidoxime derivative. The amidoximated products of PVA and carbamate ester of polymeric material were complexed with CUCL2 solution. The complex materials were confirmed by using UV and ESDS measurements. The morphology of PVA and complex with CUII was observed by SEM. Biological activity of some of the prepared compounds was investigated toward bacteria and fungi

  12. Activity of Topotecan toward the DNA/Topoisomerase I Complex: A Theoretical Rationalization.

    Science.gov (United States)

    Bali, Semiha Kevser; Marion, Antoine; Ugur, Ilke; Dikmenli, Ayse Kumru; Catak, Saron; Aviyente, Viktorya

    2018-03-06

    Topotecan (TPT) is a nontoxic anticancer drug characterized by a pH-dependent lactone/carboxyl equilibrium. TPT acts on the covalently bonded DNA/topoisomerase I (DNA/TopoI) complex by intercalating between two DNA bases at the active site. This turns TopoI into a DNA-damaging agent and inhibits supercoil relaxation. Although only the lactone form of the drug is active and effectively inhibits TopoI, both forms have been co-crystallized at the same location within the DNA/TopoI complex. To gain further insights into the pH-dependent activity of TPT, the differences between two TPT:DNA/TopoI complexes presenting either the lactone (acidic pH) or the carboxyl (basic pH) form of TPT were studied by means of molecular dynamic simulations, quantum mechanical/molecular mechanical calculations, and topological analysis. We identified two specific amino acids that have a direct relationship with the activity of the drug, i.e., lysine 532 (K532) and asparagine 722 (N722). K532 forms a stable hydrogen bond bridge between TPT and DNA only when the drug is in its active lactone form. The presence of the active drug triggers the formation of an additional stable interaction between DNA and protein residues, where N722 acts as a bridge between the two fragments, thus increasing the binding affinity of DNA for TopoI and further slowing the release of DNA. Overall, our results provide a clear understanding of the activity of the TPT-like class of molecules and can help in the future design of new anticancer drugs targeting topoisomerase enzymes.

  13. Fat Mass and Obesity-Associated (FTO) Gene Polymorphisms Are Associated with Physical Activity, Food Intake, Eating Behaviors, Psychological Health, and Modeled Change in Body Mass Index in Overweight/Obese Caucasian Adults

    OpenAIRE

    Harbron, Janetta; Merwe, Lize van der; Zaahl, Monique; Kotze, Maritha; Senekal, Marjanne

    2014-01-01

    The fat mass and obesity-associated (FTO) gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085–rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed ...

  14. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    International Nuclear Information System (INIS)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P.

    1989-01-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO 4 /PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated 125 I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function

  15. High-level expression, purification and characterization of a constitutively active thromboxane A2 receptor polymorphic variant.

    Directory of Open Access Journals (Sweden)

    Bing Xu

    Full Text Available G protein-coupled receptors (GPCRs exhibit some level of basal signaling even in the absence of a bound agonist. This basal or constitutive signaling can have important pathophysiological roles. In the past few years, a number of high resolution crystal structures of GPCRs have been reported, including two crystal structures of constitutively active mutants (CAM of the dim-light receptor, rhodopsin. The structural characterizations of CAMs are impeded by the lack of proper expression systems. The thromboxane A2 receptor (TP is a GPCR that mediates vasoconstriction and promotes thrombosis in response to the binding of thromboxane. Here, we report on the expression and purification of a genetic variant and CAM in TP, namely A160T, using tetracycline-inducible HEK293S-TetR and HEK293S (GnTI¯-TetR cell lines. Expression of the TP and the A160T genes in these mammalian cell lines resulted in a 4-fold increase in expression to a level of 15.8 ±0.3 pmol of receptor/mg of membrane protein. The receptors expressed in the HEK293S (GnTI(--TetR cell line showed homogeneous glycosylation. The functional yield of the receptors using a single step affinity purification was 45 µg/10⁶ cells. Temperature- dependent secondary structure changes of the purified TP and A160T receptors were characterized using circular dichroism (CD spectropolarimetry. The CD spectra shows that the loss of activity or thermal sensitivity that was previously observed for the A160T mutant, is not owing to large unfolding of the protein but rather to a more subtle effect. This is the first study to report on the successful high-level expression, purification, and biophysical characterization of a naturally occurring, diffusible ligand activated GPCR CAM.

  16. 4G/5G plasminogen activator inhibitor-1 and -308 A/G tumor necrosis factor-α promoter gene polymorphisms in Argentinean lupus patients: focus on lupus nephritis.

    Science.gov (United States)

    Muñoz, Sebastián Andrés; Aranda, Federico; Allievi, Alberto; Orden, Alberto Omar; Perés Wingeyer, Silvia; Trobo, Rosana; Alvarez, Analía; Eimon, Alicia; Barreira, Juan Carlos; Schneeberger, Emilce; Dal Pra, Fernando; Sarano, Judith; Hofman, Julio; Chamorro, Julián; de Larrañaga, Gabriela

    2014-02-01

    We investigated the relationship between the 4G/5G plasminogen activator inhibitor (PAI-1) and -308 A/G tumor necrosis factor-α (TNF-α) polymorphisms and the clinical and biochemical features of systemic lupus erythematosus (SLE) in an Argentinean patient cohort. A total of 402 patients were studied, including 179 SLE patients and 223 healthy individuals. PCR-RLFP was used to determine the genotypes of the 4G/5G PAI-1 and -308 A/G TNF-α polymorphisms. SLE patients with lupus nephritis (LN) (n = 86) were compared with patients without LN (n = 93). Additionally, LN patients were divided into proliferative LN and non-proliferative LN groups according to the results of the renal biopsies. No significant differences were noted in the genotype distributions or allele frequencies of these TNF-α and PAI-1 polymorphisms between SLE patients and controls. There were higher numbers of criteria for SLE, more lupus flares and higher damage scores in LN patients, but there were similar frequencies of anti-phospholipid antibody (APA) positivity and anti-phospholipid syndrome. No significant difference was noted for any studied variable between the proliferative LN and non-proliferative LN groups except for the presence of APA. We found no significant differences in the TNF-α and PAI-1 genotype distributions or allele frequencies between groups. We found that the -308 A/G TNF-α and 4G/5G PAI-1 polymorphisms are not associated with susceptibility to SLE in an Argentinean population. We also did not find any association between the presence of any specific allele or genotype and the development of LN in SLE patients. Finally, no association was noted between either of the two polymorphisms and the severity of renal disease.

  17. An updated meta-analysis of the signal transducer and activator of transcription 4 (STAT4) rs7574865 G/T polymorphism and rheumatoid arthritis risk in an Asian population.

    Science.gov (United States)

    Jiang, X; Zhou, Z; Zhang, Y; Yang, H; Ren, K

    2014-01-01

    Signal transducer and activator of transcription 4 (STAT4) transmits signals induced by the cytokines interleukin (IL)-12, IL-23, and interferon (IFN)-γ, which play an important role in the development of rheumatoid arthritis (RA). Studies have shown conflicting results concerning the association between the rs7574865 G/T polymorphism in the STAT4 gene and RA in an Asian population. We have performed a meta-analysis to examine this relationship. We searched PubMed and WanFang databases for all papers published up to 5 October 2013. Eight case-control studies with 6029 cases and 4685 controls were retrieved based on the search criteria for RA susceptibility related to the STAT4 rs7574865 G/T polymorphism. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed using Begg's test. A significant association was found between the STAT4 rs7574865 G/T polymorphism and RA risk (e.g. GG+GT vs. TT: RR 0.96, 95% CI 0.95-0.97; GG+TT vs. GT: RR 0.94, 95% CI 0.91-0.97). Subgroup analysis of rheumatoid factor (RF) status revealed a protective relationship between the STAT4 rs7574865 G/T polymorphism and RF(+)/RF(-) RA risk. A similar relationship was detected in the anti-cyclic citrullinated peptide (CCP) status subgroup. No clear evidence of publication bias was detected in the overall analysis. Our study indicates that the STAT4 rs7574865 G/T polymorphism was significantly associated with a decreased RA risk in an Asian population.

  18. Natural single amino acid polymorphism (F19Y) in human galectin-8: detection of structural alterations and increased growth-regulatory activity on tumor cells.

    Science.gov (United States)

    Ruiz, Federico M; Scholz, Barbara A; Buzamet, Eliza; Kopitz, Jürgen; André, Sabine; Menéndez, Margarita; Romero, Antonio; Solís, Dolores; Gabius, Hans-Joachim

    2014-03-01

    Natural amino acid substitution by single-site nucleotide polymorphism can become a valuable tool for structure-activity correlations, especially if evidence for association to disease parameters exists. Focusing on the F19Y change in human galectin-8, connected clinically to rheumatoid arthritis, we here initiate the study of consequences of a single-site substitution in the carbohydrate recognition domain of this family of cellular effectors. We apply a strategically combined set of structural and cell biological techniques for comparing properties of the wild-type and variant proteins. The overall hydrodynamic behavior of the full-length protein and of the separate N-domain is not noticeably altered, but displacements in the F0 β-strand of the β-sandwich fold in the N-domain are induced, as evidenced by protein crystallography. Analysis of thermal stability by circular dichroism spectroscopy revealed perceptible differences for the full-length proteins, pointing to an impact of the substitution beyond the N-domain. In addition, small differences in thermodynamic parameters of carbohydrate binding are detected. On the level of two types of tumor cells, characteristics of binding appeared rather similar. In further comparison of the influence on proliferation, the variant proved to be more active as growth regulator in the six tested lines of neuroblastoma, erythroleukemia and colon adenocarcinoma. The seemingly subtle structural change identified here thus has functional implications in vitro, encouraging further analysis in autoimmune regulation and, in a broad context, in work with other natural single-site variants, using the documented combined strategy. The atomic coordinates and structure factors (codes 4BMB, 4BME) have been deposited in the Protein Data Bank. © 2014 FEBS.

  19. Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex.

    Science.gov (United States)

    Konermann, Silvana; Brigham, Mark D; Trevino, Alexandro E; Joung, Julia; Abudayyeh, Omar O; Barcena, Clea; Hsu, Patrick D; Habib, Naomi; Gootenberg, Jonathan S; Nishimasu, Hiroshi; Nureki, Osamu; Zhang, Feng

    2015-01-29

    Systematic interrogation of gene function requires the ability to perturb gene expression in a robust and generalizable manner. Here we describe structure-guided engineering of a CRISPR-Cas9 complex to mediate efficient transcriptional activation at endogenous genomic loci. We used these engineered Cas9 activation complexes to investigate single-guide RNA (sgRNA) targeting rules for effective transcriptional activation, to demonstrate multiplexed activation of ten genes simultaneously, and to upregulate long intergenic non-coding RNA (lincRNA) transcripts. We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. A gene expression signature based on the top screening hits correlated with markers of BRAF inhibitor resistance in cell lines and patient-derived samples. These results collectively demonstrate the potential of Cas9-based activators as a powerful genetic perturbation technology.

  20. A Cbx8-containing polycomb complex facilitates the transition to gene activation during ES cell differentiation.

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    Catherine Creppe

    2014-12-01

    Full Text Available Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Our project aimed to identify Cbx8 binding sites in differentiating mouse embryonic stem cells. Therefore, we used a genome-wide chromatin immunoprecipitation of endogenous Cbx8 coupled to direct massive parallel sequencing (ChIP-Seq. Our analysis identified 171 high confidence peaks. By crossing our data with previously published microarray analysis, we show that several differentiation genes transiently recruit Cbx8 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. Both interaction analysis, as well as chromatin immunoprecipitation experiments support the idea that activating Cbx8 acts in the context of an intact PRC1 complex. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3 and H2A ubiquitination. The composition of PRC1 is highly modular and changes when embryonic stem cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together, our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs.

  1. NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Sandford, Andrew J; Malhotra, Deepti; Boezen, H Marike; Siedlinski, Mateusz; Postma, Dirkje S; Wong, Vivien; Akhabir, Loubna; He, Jian-Qing; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Biswal, Shyam

    2012-08-01

    An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.

  2. 5-HTTLPR polymorphism impacts task-evoked and resting-state activities of the amygdala in Han Chinese.

    Science.gov (United States)

    Li, Sufang; Zou, Qihong; Li, Jun; Li, Jin; Wang, Deyi; Yan, Chaogan; Dong, Qi; Zang, Yu-Feng

    2012-01-01

    Prior research has shown that the amygdala of carriers of the short allele (s) of the serotonin transporter (5-HTT) gene (5-HTTLPR) have a larger response to negative emotional stimuli and higher spontaneous activity during the resting state than non-carriers. However, recent studies have suggested that the effects of 5-HTTLPR may be specific to different ethnic groups. Few studies have been conducted to address this issue. Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) was conducted on thirty-eight healthy Han Chinese subjects (l/l group, n = 19; s/s group, n = 19) during the resting state and during an emotional processing task. Compared with the s/s group, the l/l group showed significantly increased regional homogeneity or local synchronization in the right amygdala during the resting state (|t|>2.028, pemotional processing task. 5-HTTLPR can alter the spontaneous activity of the amygdala in Han Chinese. However, the effect of 5-HTTLPR on the amygdala both in task state and resting state in Asian population was no similar with Caucasians. They suggest that the effect of 5-HTTLPR on the amygdala may be modulated by ethnic differences.

  3. In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

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    Zelda de Lange

    Full Text Available Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT. We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009 but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central obesity was the biggest contributor to PAI-1act variance (12.5%. Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

  4. In black South Africans from rural and urban communities, the 4G/5G PAI-1 polymorphism influences PAI-1 activity, but not plasma clot lysis time.

    Science.gov (United States)

    de Lange, Zelda; Rijken, Dingeman C; Hoekstra, Tiny; Conradie, Karin R; Jerling, Johann C; Pieters, Marlien

    2013-01-01

    Data on genetic and environmental factors influencing PAI-1 levels and their consequent effect on clot lysis in black African populations are limited. We identified polymorphisms in the promoter area of the PAI-1 gene and determined their influence on PAI-1act levels and plasma clot lysis time (CLT). We also describe gene-environment interactions and the effect of urbanisation. Data from 2010 apparently healthy urban and rural black participants from the South African arm of the PURE study were cross-sectionally analysed. The 5G allele frequency of the 4G/5G polymorphism was 0.85. PAI-1act increased across genotypes in the urban subgroup (p = 0.009) but not significantly in the rural subgroup, while CLT did not differ across genotypes. Significant interaction terms were found between the 4G/5G polymorphism and BMI, waist circumference and triglycerides in determining PAI-1act, and between the 4G/5G polymorphism and fibrinogen and fibrinogen gamma prime in determining CLT. The C428T and G429A polymorphisms did not show direct relationships with PAI-1act or CLT but they did influence the association of other environmental factors with PAI-1act and CLT. Several of these interactions differed significantly between rural and urban subgroups, particularly in individuals harbouring the mutant alleles. In conclusion, although the 4G/5G polymorphism significantly affected PAI-1act, it contributed less than 1% to the PAI-1act variance. (Central) obesity was the biggest contributor to PAI-1act variance (12.5%). Urbanisation significantly influenced the effect of the 4G/5G polymorphism on PAI-1act as well as gene-environment interactions for the C428T and G429A genotypes in determining PAI-1act and CLT.

  5. Synthesis, DNA Cleavage Activity, Cytotoxicity, Acetylcholinesterase Inhibition, and Acute Murine Toxicity of Redox-Active Ruthenium(II) Polypyridyl Complexes.

    Science.gov (United States)

    Alatrash, Nagham; Narh, Eugenia S; Yadav, Abhishek; Kim, Mahn-Jong; Janaratne, Thamara; Gabriel, James; MacDonnell, Frederick M

    2017-07-06

    Four mononuclear [(L-L) 2 Ru(tatpp)] 2+ and two dinuclear [(L-L) 2 Ru(tatpp)Ru(L-L) 2 ] 4+ ruthenium(II) polypyridyl complexes (RPCs) containing the 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (tatpp) ligand were synthesized, in which L-L is a chelating diamine ligand such as 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me 4 phen) or 4,7-diphenyl-1,10-phenanthroline (Ph 2 phen). These Ru-tatpp analogues all undergo reduction reactions with modest reducing agents, such as glutathione (GSH), at pH 7. These, plus several structurally related but non-redox-active RPCs, were screened for DNA cleavage activity, cytotoxicity, acetylcholinesterase (AChE) inhibition, and acute mouse toxicity, and their activities were examined with respect to redox activity and lipophilicity. All of the redox-active RPCs show single-strand DNA cleavage in the presence of GSH, whereas none of the non-redox-active RPCs do. Low-micromolar cytotoxicity (IC 50 ) against malignant H358, CCL228, and MCF7 cultured cell lines was mainly restricted to the redox-active RPCs; however, they were substantially less toxic toward nonmalignant MCF10 cells. The IC 50 values for AChE inhibition in cell-free assays and the acute toxicity of RPCs in mice revealed that whereas most RPCs show potent inhibitory action against AChE (IC 50 values <15 μm), Ru-tatpp complexes as a class are surprisingly well tolerated in animals relative to other RPCs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Data in support of a central role of plasminogen activator inhibitor-2 polymorphism in recurrent cardiovascular disease risk in the setting of high HDL cholesterol and C-reactive protein using Bayesian network modeling

    Directory of Open Access Journals (Sweden)

    James P. Corsetti

    2016-09-01

    Full Text Available Data is presented that was utilized as the basis for Bayesian network modeling of influence pathways focusing on the central role of a polymorphism of plasminogen activator inhibitor-2 (PAI-2 on recurrent cardiovascular disease risk in patients with high levels of HDL cholesterol and C-reactive protein (CRP as a marker of inflammation, “Influences on Plasminogen Activator Inhibitor-2 Polymorphism-Associated Recurrent Cardiovascular Disease Risk in Patients with High HDL Cholesterol and Inflammation” (Corsetti et al., 2016; [1]. The data consist of occurrence of recurrent coronary events in 166 post myocardial infarction patients along with 1. clinical data on gender, race, age, and body mass index; 2. blood level data on 17 biomarkers; and 3. genotype data on 53 presumptive CVD-related single nucleotide polymorphisms. Additionally, a flow diagram of the Bayesian modeling procedure is presented along with Bayesian network subgraphs (root nodes to outcome events utilized as the data from which PAI-2 associated influence pathways were derived (Corsetti et al., 2016; [1]. Keywords: Recurrent cardiovascular disease risk, Pathophysiology, Plasminogen activator inhibitor-2, Bayesian network

  7. Fat Mass and Obesity-Associated (FTO Gene Polymorphisms Are Associated with Physical Activity, Food Intake, Eating Behaviors, Psychological Health, and Modeled Change in Body Mass Index in Overweight/Obese Caucasian Adults

    Directory of Open Access Journals (Sweden)

    Janetta Harbron

    2014-08-01

    Full Text Available The fat mass and obesity-associated (FTO gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085–rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed from whole blood samples. Weight and height was measured and a non-quantified food frequency questionnaire was completed to assess food group intake. Validated questionnaires were completed to assess physical activity (Baecke questionnaire, psychological health (General Health questionnaire, Rosenburg self-esteem scale and Beck Depression Inventory, and eating behavior (Three Factor Eating questionnaire. The risk alleles of the FTO polymorphisms were associated with poorer eating behaviors (higher hunger, internal locus for hunger, and emotional disinhibition scores, a higher intake of high fat foods and refined starches and more depressive symptoms. The modeled results indicate that interactions between the FTO polymorphisms or haplotypes and eating behavior, psychological health, and physical activity levels may be associated with BMI. The clinical significance of these results for implementation as part of weight management interventions needs further investigation.

  8. Studies on bis(halogeno) dioxomolybdenum(VI)-bipyridine complexes: synthesis and catalytic activity.

    Science.gov (United States)

    Günyar, Alev; Zhou, Ming-Dong; Drees, Markus; Baxter, Paul N W; Bassioni, Ghada; Herdtweck, Eberhardt; Kühn, Fritz E

    2009-10-28

    Dioxomolybdenum(VI) complexes with the general formula [MoO2Cl2L2] (L2=3,3'-dimethyl-2,2'-bipyridine, 5,5'-dimethyl-2,2'-bipyridine, 6,6'-dimethyl-2,2'-bipyridine, 4,4'-dibromo-2,2'-bipyridine, 5,5'-dibromo-2,2'-bipyridine, 5,5'-diamino-2,2'-bipyridine; 5,5'-dinitro-2,2'-bipyridine; 5,5'-di-ethoxycarbonyl-2,2'-bipyridine; 6-phenyl-2,2'-bipyridine; 2,2':6',2''-terpyridine) have been prepared and characterised. [MoO2Cl2(5,5'-di-ethoxycarbonyl-2,2'-bipyridine)] has been examined by single crystal X-ray analysis. The complexes were applied as homogenous catalysts for the epoxidation of cyclooctene with tert-butyl hydroperoxide (TBHP) as oxidising agent. The new compounds show an overall high activity and are highly selective catalysts in the epoxidation of cyclooctene. The stability of the complexes and differences in the catalytic activity can be clearly attributed to electronic contributions of the functional groups on bipyridine ligands and to steric restrictions. DFT calculations have assisted in a better understanding of the stability of the complexes and are in agreement with experiment. The influence of the terminal oxo ligands and the Lewis base ligands on the Mo center keep the compounds on quite a stable level of electron density.

  9. Evidence for Multiple Mediator Complexes in Yeast Independently Recruited by Activated Heat Shock Factor.

    Science.gov (United States)

    Anandhakumar, Jayamani; Moustafa, Yara W; Chowdhary, Surabhi; Kainth, Amoldeep S; Gross, David S

    2016-07-15

    Mediator is an evolutionarily conserved coactivator complex essential for RNA polymerase II transcription. Although it has been generally assumed that in Saccharomyces cerevisiae, Mediator is a stable trimodular complex, its structural state in vivo remains unclear. Using the "anchor away" (AA) technique to conditionally deplete select subunits within Mediator and its reversibly associated Cdk8 kinase module (CKM), we provide evidence that Mediator's tail module is highly dynamic and that a subcomplex consisting of Med2, Med3, and Med15 can be independently recruited to the regulatory regions of heat shock factor 1 (Hsf1)-activated genes. Fluorescence microscopy of a scaffold subunit (Med14)-anchored strain confirmed parallel cytoplasmic sequestration of core subunits located outside the tail triad. In addition, and contrary to current models, we provide evidence that Hsf1 can recruit the CKM independently of core Mediator and that core Mediator has a role in regulating postinitiation events. Collectively, our results suggest that yeast Mediator is not monolithic but potentially has a dynamic complexity heretofore unappreciated. Multiple species, including CKM-Mediator, the 21-subunit core complex, the Med2-Med3-Med15 tail triad, and the four-subunit CKM, can be independently recruited by activated Hsf1 to its target genes in AA strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. Structure and function of complex carbohydrates active in regulating plant-microbe interactions

    Energy Technology Data Exchange (ETDEWEB)

    Albersheim, P; Darvill, A G; McNeil, M

    1981-01-01

    A key regulatory role of complex carbohydrates in the interactions between plants and microbes has been established. The complex carbohydrates act as regulatory molecules or hormones in that the carbohydrates induce de novo protein synthesis in receptive cells. The first complex carbohydrate recognized to possess such regulatory properties is a polysaccharide (PS) present in the walls of fungi. Hormonal concentrations of this PS elicit plant cells to accumulate phytoalexins (antibiotics). More recently we have recognized that a PS in the walls of growing plant cells also elicits phytoalexin accumulation; microbes and viruses may cause the release of active fragments of this endogenous elicitor. Another PS in plant cell walls is the Proteinase Inhibitor Inducing Factor (PIIF). This hormone appears to protect plants by inducing synthesis in plants of proteins which specifically inhibit digestive enzymes of insects and bacteria. Glycoproteins secreted by incompatible races (races that do not infect the plant) of a fungal pathogen of soybeans protect seedlings from attack by compatible races. Glycoproteins from compatible races do not protect the seedlings. The acidic PS secreted by the nitrogen-fixing rhizobia appear to function in the infection of legumes by the rhizobia. W.D. Bauer and his co-workers have evidence that these PS are required for the development of root hairs capable of being infected by symbiont rhizobia. Current knowledge of the structures of these biologically active complex carbohydrates will be presented.

  11. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration.

    Science.gov (United States)

    Pollard, Amelia Kate; Craig, Emma Louise; Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70-71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions.

  12. Model of a ternary complex between activated factor VII, tissue factor and factor IX.

    Science.gov (United States)

    Chen, Shu-wen W; Pellequer, Jean-Luc; Schved, Jean-François; Giansily-Blaizot, Muriel

    2002-07-01

    Upon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.

  13. Synthesis, Spectroscopic Characterization and Biological Activities of Transition Metal Complexes Derived from a Tridentate Schiff Base

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    J. Senthil Kumaran

    2013-01-01

    Full Text Available A new series of Cu (II, Ni (II, Co (II and Zn (II complexes have been synthesized from the Schiff base derived from 4-hydroxy-3-methoxybenzylidine-4-aminoantipyrine and 2-aminophenol. The structural features have been determined from their elemental analysis, magnetic susceptibility, molar conductance, Mass, IR, UV-Vis, 1H-NMR, 13C-NMR and ESR spectral studies. The redox behavior of the copper complex has been studied by cyclic voltammetry. The data confirm that the complexes have composition of ML2 type. The electronic absorption spectral data of the complexes propose an octahedral geometry around the central metal ion. All the metal complexes with DNA structure were guided by the presence of inter-molecular C–H⋯O and C–H⋯N hydrogen bonds. The biological activity of the synthesized compounds were tested against the bacterial species such as Bacillus subtilis, Staphylococcus aureus, Proteus vulgaris and fungal species such as Candida albicans by the well-diffusion method.

  14. Regulation of the Stress-Activated Degradation of Mitochondrial Respiratory Complexes in Yeast

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    Alba Timón-Gómez

    2018-01-01

    Full Text Available Repair and removal of damaged mitochondria is a key process for eukaryotic cell homeostasis. Here we investigate in the yeast model how different protein complexes of the mitochondrial electron transport chain are subject to specific degradation upon high respiration load and organelle damage. We find that the turnover of subunits of the electron transport complex I equivalent and complex III is preferentially stimulated upon high respiration rates. Particular mitochondrial proteases, but not mitophagy, are involved in this activated degradation. Further mitochondrial damage by valinomycin treatment of yeast cells triggers the mitophagic removal of the same respiratory complexes. This selective protein degradation depends on the mitochondrial fusion and fission apparatus and the autophagy adaptor protein Atg11, but not on the mitochondrial mitophagy receptor Atg32. Loss of autophagosomal protein function leads to valinomycin sensitivity and an overproduction of reactive oxygen species upon mitochondrial damage. A specific event in this selective turnover of electron transport chain complexes seems to be the association of Atg11 with the mitochondrial network, which can be achieved by overexpression of the Atg11 protein even in the absence of Atg32. Furthermore, the interaction of various Atg11 molecules via the C-terminal coil domain is specifically and rapidly stimulated upon mitochondrial damage and could therefore be an early trigger of selective mitophagy in response to the organelles dysfunction. Our work indicates that autophagic quality control upon mitochondrial damage operates in a selective manner.

  15. Preparation, characterization, and anti-Helicobacter pylori activity of Bi3+-Hericium erinaceus polysaccharide complex.

    Science.gov (United States)

    Zhu, Yang; Chen, Yao; Li, Qian; Zhao, Ting; Zhang, Ming; Feng, Weiwei; Takase, Mohammed; Wu, Xueshan; Zhou, Zhaoxiang; Yang, Liuqing; Wu, Xiangyang

    2014-09-22

    Two new Bi3+-Hericium erinaceus polysaccharide (BiHEP) complexes were prepared using Bi3+ and two purified polysaccharides from H. erinaceus (HEPs), respectively. The complexes were characterized by elemental analysis, FT-IR, CD, SEM, AFM, XRD, and TG. The anti-Helicobacter pylori (Hp) activities in vitro by agar dilution assay of the complexes were evaluated. The molecular weights of HEPs were 197 and 20 kDa, respectively. All the analyses confirmed the formation of new BiHEP complexes with lower content of Bi3+ compared with colloidal bismuth subcitrate (CBS), the most utilized bismuth preparation clinically. Furthermore, HEPs themselves have definite inhibition effects on Hp, and BiHEP complexes have lower content of Bi exhibited strong inhibition effects on Hp (MIC=20 μg/mL), similar to that of CBS with higher content of Bi. The study provides a basis for further development of multiple treatments of Hp infection or new medicines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Spectroscopic properties and antimicrobial activity of dioxomolybdenum(VI complexes with heterocyclic S,S’-ligands

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    Sovilj Sofija P.

    2012-01-01

    Full Text Available Five new dioxomolybdenum(VI complexes of the general formula[MoO2(Rdtc2], 1-5, where Rdtc-refer to piperidine- (Pipdtc, 4-morpholine-(Morphdtc, 4-thiomorpholine-(Timdtc, piperazine- (Pzdtc or Nmethylpiperazine- (N-Mepzdtc dithiocarbamates, respectively, have been prepared. Elemental analysis, conductometric measurements, electronic, IR and NMR spectroscopy have been employed to characterize them. Complexes 1-5 contain a cis-MoO2 group and are of an octahedral geometry. Two dithiocarbamato ions join as bidentates with both the sulphur atoms to the molybdenum atom. The presence of different heteroatom in the piperidinо moiety influences the v(C----N and v(C----S vibrations, which decrease in the order of the complexes with: Pipdtc > N-Mepipdtc > Morphdtc > Pzdtc > Timdtc ligands. On the basis of spectral data, molecular structures of complexes 1-5 were optimized on semiempirical molecular-orbital level, and the geometries, as obtained from calculations, described. Antimicrobial activity was tested against nine different laboratory control strains of bacteria and two strains of yeast Candida albicans. All tested strains were sensitive. Complexes bearing heteroatom in position 4 of piperidine moiety are significantly more potent against bacteria tested comparing to corresponding ligands.

  17. Low-sensitivity active filter realization using a complex all-pass filter

    Science.gov (United States)

    Regalia, Phillip A.; Mitra, Sanjit K.

    1987-04-01

    A wide class of continuous-time transfer functions may be implemented as the parallel combination of two all-pass filters, including Butterworth, Chebyshev, and elliptic low-pass approximations of odd order. Here, the realization of even-order low-pass classical approximations is considered, and it is shown that they may be decomposed in terms of complex all-pass functions. A systematic realization approach, based on scattering domain simulation (i.e., wave active filters), allows for a low-sensitivity active filter implementation. Further insight into the low-sensitivity property is gained by connecting the insertion loss of doubly terminated antimetric networks with the imaginary return loss of complex lossless networks.

  18. Solution XAS Analysis for Exploring the Active Species in Homogeneous Vanadium Complex Catalysis

    Science.gov (United States)

    Nomura, Kotohiro; Mitsudome, Takato; Tsutsumi, Ken; Yamazoe, Seiji

    2018-06-01

    Selected examples in V K-edge X-ray Absorption Near Edge Structure (XANES) analysis of a series of vanadium complexes containing imido ligands (possessing metal-nitrogen double bond) in toluene solution have been introduced, and their pre-edge and the edge were affected by their structures and nature of ligands. Selected results in exploring the oxidation states of the active species in ethylene dimerization/polymerization using homogeneous vanadium catalysts [consisting of (imido)vanadium(V) complexes and Al cocatalysts] by X-ray absorption spectroscopy (XAS) analyses have been introduced. It has been demonstrated that the method should provide more clear information concerning the active species in situ, especially by combination with the other methods (NMR and ESR spectra, X-ray crystallographic analysis, and reaction chemistry), and should be powerful tool for study of catalysis mechanism as well as for the structural analysis in solution.

  19. Biological activity of Fe(III) aquo-complexes towards ferric chelate reductase (FCR).

    Science.gov (United States)

    Escudero, Rosa; Gómez-Gallego, Mar; Romano, Santiago; Fernández, Israel; Gutiérrez-Alonso, Ángel; Sierra, Miguel A; López-Rayo, Sandra; Nadal, Paloma; Lucena, Juan J

    2012-03-21

    In this study we have obtained experimental evidence that confirms the high activity of aquo complexes III and IV towards the enzyme FCR, responsible for the reduction of Fe(III) to Fe(II) in the process of iron acquisition by plants. The in vivo FCR assays in roots of stressed cucumber plants have shown a higher efficiency of the family of complexes III and a striking structure-activity relationship with the nature of the substituent placed in a phenyl group far away from the metal center. The results obtained in this work demonstrate that all the aquo compounds tested interact efficiently with the enzyme FCR and hence constitute a new concept of iron chelates that could be of great use in agronomy.

  20. Polymorphs and polymorphic cocrystals of temozolomide.

    Science.gov (United States)

    Babu, N Jagadeesh; Reddy, L Sreenivas; Aitipamula, Srinivasulu; Nangia, Ashwini

    2008-07-07

    Crystal polymorphism in the antitumor drug temozolomide (TMZ), cocrystals of TMZ with 4,4'-bipyridine-N,N'-dioxide (BPNO), and solid-state stability were studied. Apart from a known X-ray crystal structure of TMZ (form 1), two new crystalline modifications, forms 2 and 3, were obtained during attempted cocrystallization with carbamazepine and 3-hydroxypyridine-N-oxide. Conformers A and B of the drug molecule are stabilized by intramolecular amide N--HN(imidazole) and N--HN(tetrazine) interactions. The stable conformer A is present in forms 1 and 2, whereas both conformers crystallized in form 3. Preparation of polymorphic cocrystals I and II (TMZBPNO 1:0.5 and 2:1) were optimized by using solution crystallization and grinding methods. The metastable nature of polymorph 2 and cocrystal II is ascribed to unused hydrogen-bond donors/acceptors in the crystal structure. The intramolecularly bonded amide N-H donor in the less stable structure makes additional intermolecular bonds with the tetrazine C==O group and the imidazole N atom in stable polymorph 1 and cocrystal I, respectively. All available hydrogen-bond donors and acceptors are used to make intermolecular hydrogen bonds in the stable crystalline form. Synthon polymorphism and crystal stability are discussed in terms of hydrogen-bond reorganization.

  1. Radar observations of Taurid complex meteor showers in 2003: activity and mass distribution

    Czech Academy of Sciences Publication Activity Database

    Pecina, Petr; Pecinová, Drahomíra; Porubčan, V.; Toth, J.

    2005-01-01

    Roč. 95, 1-4 (2005), s. 681-688 ISSN 0167-9295. [Meteoroids 2004. London, Ontario, 16.08.2004-20.08.2004] R&D Projects: GA ČR GA205/03/1405 Institutional research plan: CEZ:AV0Z1003909 Keywords : Taurid complex * meteor showers * activity Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 0.975, year: 2005

  2. Calibration of a complex activated sludge model for the full-scale wastewater treatment plant

    OpenAIRE

    Liwarska-Bizukojc, Ewa; Olejnik, Dorota; Biernacki, Rafal; Ledakowicz, Stanislaw

    2011-01-01

    In this study, the results of the calibration of the complex activated sludge model implemented in BioWin software for the full-scale wastewater treatment plant are presented. Within the calibration of the model, sensitivity analysis of its parameters and the fractions of carbonaceous substrate were performed. In the steady-state and dynamic calibrations, a successful agreement between the measured and simulated values of the output variables was achieved. Sensitivity analysis revealed that u...

  3. The instrumental neutron-activation analysis of granites from the Bushveld Complex

    International Nuclear Information System (INIS)

    Watterson, J.I.W.

    1978-01-01

    Three methods of instrumental neutron-activation analysis, 14MeV, reactor thermal, and reactor epithermal, are compared for the analysis of granites form the Bushveld Complex. A total of 34 elements can be determined in the granites by these methods. Samples from the Zaaiplaats area were analysed by thermal neutron activation, and 22 elements were determined in all of them. These elements were used to distinguish between the mineralized Bobbejaankop and Lease granites and the Main granite by the use of multivariate statistics. The Bobbejaankop granite appears as a more-differentaited rock carrying greater amounts of the incompatible elements than does the Main granite [af

  4. Structural Analysis of the Bacterial Proteasome Activator Bpa in Complex with the 20S Proteasome.

    Science.gov (United States)

    Bolten, Marcel; Delley, Cyrille L; Leibundgut, Marc; Boehringer, Daniel; Ban, Nenad; Weber-Ban, Eilika

    2016-12-06

    Mycobacterium tuberculosis harbors proteasomes that recruit substrates for degradation through an ubiquitin-like modification pathway. Recently, a non-ATPase activator termed Bpa (bacterial proteasome activator) was shown to support an alternate proteasomal degradation pathway. Here, we present the cryo-electron microscopy (cryo-EM) structure of Bpa in complex with the 20S core particle (CP). For docking into the cryo-EM density, we solved the X-ray structure of Bpa, showing that it forms tight four-helix bundles arranged into a 12-membered ring with a 40 Å wide central pore and the C-terminal helix of each protomer protruding from the ring. The Bpa model was fitted into the cryo-EM map of the Bpa-CP complex, revealing its architecture and striking symmetry mismatch. The Bpa-CP interface was resolved to 3.5 Å, showing the interactions between the C-terminal GQYL motif of Bpa and the proteasome α-rings. This docking mode is related to the one observed for eukaryotic activators with features specific to the bacterial complex. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. ANTIBACTERIAL ACTIVITY OF BENZIMIDAZOLES 2-THIO, 2-AMINODERIVATIVES AND COMPLEXES OF BENZIMIDAZOLES WITH TRANSITIONAL METALS

    Directory of Open Access Journals (Sweden)

    E. I. Mayboroda

    2014-01-01

    Full Text Available The literature data about antibacterial properties of benzimidazole 2-thio-, 2-aminoderivatives and benzimidazole complexes have been generalized and systematized in the review. Today prevention and treatment of diseases caused by microorganisms is an actual problem of modern therapy. Therefore, the search for active molecules, the based on them development of some new, more effective antimicrobial agents is an important task of modern pharmaceutical chemistry. Promising compounds for solving these problems are benzimidazole derivatives. They are available, functionally capable, stable and have a wide spectrum of biological activities (antiviral, anthelmintic, antibacterial, anticancer, antidiabetic.The purpose of this paper is to generalize and systematize information about the antimicrobial action of 2-thio-, 2-amino-substituted benzimidazoles and benzimidazole derivatives complexes with transition metals.These compounds and their complexes with transition metals are active against pathogenic strains Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhimurium, Proteus vulgaris, Bacillus cereus, Micrococcus luteus, Helicobacter рylori and others.

  6. 4G/5G and A-844G Polymorphisms of Plasminogen Activator Inhibitor-1 Associated with Glioblastoma in Iran--a Case-Control Study.

    Science.gov (United States)

    Pooyan, Honari; Ahmad, Ebrahimi; Azadeh, Rakhshan

    2015-01-01

    Glioblastoma is a highly aggressive and malignant brain tumor. Risk factors are largely unknown however, although several biomarkers have been identified which may support development, angiogenesis and invasion of tumor cells. One of these biomarkers is PAI-1. 4G/5G and A-844G are two common polymorphisms in the gene promotor of PAI 1 that may be related to high transcription and expression of this gene. Studies have shown that the prevalence of the 4G and 844G allele is significantly higher in patients with some cancers and genetic disorders. We here assessed the association of 4G/5G and A-844G polymorphisms with glioblastoma cancer risk in Iranians in a case-control study. All 71 patients with clinically confirmed and 140 volunteers with no history and symptoms of glioblastoma as control group were screened for 4G/5G and A-844G polymorphisms of PAI-1, using ARMS-PCR. Genotype and allele frequencies of case and control groups were analyzed using the DeFinetti program. Our results showed significant associations between 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms of the PAI-1 gene with glioblastoma cancer risk in our Iranian population. The results of this study supporting an association of the PAI-1 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms with increasing glioblastoma cancer risk in Iranian patients.

  7. NLRC5 polymorphism is associated with susceptibility to chronic periodontitis.

    Science.gov (United States)

    Zupin, Luisa; Navarra, Chiara Ottavia; Robino, Antonietta; Bevilacqua, Lorenzo; Di Lenarda, Roberto; Gasparini, Paolo; Crovella, Sergio

    2017-05-01

    Periodontitis is a chronic oral pathology caused by impaired immune response against oral bacteria resulting in tissue inflammation and damage. Among the members of innate immune response, the first line of defence against pathogens, inflammasomes are macro-molecular protein complexes that can be activated by different stimuli, comprised bacteria infections. Different proteins are involved in inflammasoma formation; the most important are molecules belonging from the family of nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs). In this study, polymorphisms within 20 NLRs related genes were analysed in order to investigate their possible association with periodontitis susceptibility in a population from North-East Italy. One polymorphism, namely rs289723, in NLRC5 gene resulted associated with chronic slight and chronic localized periodontitis susceptibility, specifically A/A genotype was correlated with increased risk of disease development. Our study, for the first time, identified the possible involvement of a polymorphism within NLRC5 gene as a possible biomarker for periodontitis condition susceptibility among Italian individuals from genetic isolates. Copyright © 2017 Elsevier GmbH. All rights reserved.

  8. Complexation of trichlorosalicylic acids by alkaline and first row transition metals as a switch for their antibacterial activity

    KAUST Repository

    Kumar, Vijay; Chawla, Mohit; Cavallo, Luigi; Basit Wani, Abdul; Manhas, Anu; Kaur, Sukhmanpreet; Poater, Albert; Chadar, Hemlata; NirajUpadhyay

    2017-01-01

    3,5,6-trichlorosalicylic acid (TCSA) does not show a good antibacterial activity. In contrast, here metal complexes with TCSA have shown better antibacterial activity for selected bacterial strains with a good degree of selectivity. Amongst

  9. Some transition metal ions complexes of tricine (Tn and amino acids: pH-titration, synthesis and antimicrobial activity

    Directory of Open Access Journals (Sweden)

    M.E. Zayed

    2014-12-01

    Full Text Available Equilibrium studies have been carried out on complex formation of M(II (M = Co(II, Cu(II and Zn(II with tricine (Tn and L = amino acids in aqueous solution, at 25 °C and ionic strength of I = 0.1 M (NaNO3. The ternary complexes of amino acids are formed by simultaneous reactions. The concentration distribution of the complexes is evaluated. The solid complexes of [M(II–Tn–Histidine (Hist] have been synthesized and characterized by elemental analysis, infrared, magnetic and conductance measurements. The synthesized complexes have been screened for their antibacterial activities and the complexes show a significant antibacterial activity against four bacterial species: Staphylococcus aureus (Gram +ve, Streptococcus pyogenesr (Gram +ve, Serratia marcescens (Gram −ve and Escherichia coli (Gram −ve. The activity increases by increasing the concentration of the complexes.

  10. Integration of complex-wide mixed low-level waste activities for program acceleration and optimization

    International Nuclear Information System (INIS)

    McKenney, D.E.

    1998-01-01

    In July 1996, the US Department of Energy (DOE) chartered a contractor-led effort to develop a suite of technically defensible, integrated alternatives which would allow the Environmental Management program to accomplish its mission objectives in an accelerated fashion and at a reduced cost. These alternatives, or opportunities, could then be evaluated by DOE and stakeholders for possible implementation, given precursor requirements (regulatory changes, etc.) could be met and benefits to the Complex realized. This contractor effort initially focused on six waste types, one of which was Mixed Low-Level Waste (MLLW). Many opportunities were identified by the contractor team for integrating MLLW activities across the DOE Complex. These opportunities were further narrowed to six that had the most promise for implementation and savings to the DOE Complex. The opportunities include six items: (1) the consolidation of individual site analytical services procurement efforts, (2) the consolidation of individual site MLLW treatment services procurement efforts, (3) establishment of ''de minimus'' radioactivity levels, (4) standardization of characterization requirements, (5) increased utilization of existing DOE treatment facilities, and (6) using a combination of DOE and commercial MLLW disposal capacity. The results of the integration effort showed that by managing MLLW activities across the DOE Complex as a cohesive unit rather than as independent site efforts, the DOE could improve the rate of progress toward meeting its objectives and reduce its overall MLLW program costs. Savings potential for MLLW, if the identified opportunities could be implemented, could total $224 million or more. Implementation of the opportunities also could result in the acceleration of the MLLW ''work off schedule'' across the DOE Complex by five years

  11. Anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex in rats

    Directory of Open Access Journals (Sweden)

    L.H. Santos

    2004-08-01

    Full Text Available We investigated the anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex (5.5 or 11 mg/kg in male Wistar rats (180-300 g, N = 6 and compared it to free diclofenac (5 or 10 mg/kg and to the combination of diclofenac (5 or 10 mg/kg and zinc acetate (1.68 or 3.5 mg/kg. The carrageenin-induced paw edema and the cotton pellet-induced granulomatous tissue formation models were used to assess the anti-inflammatory activity, and the Hargreaves model of thermal hyperalgesia was used to assess the antinociceptive activity. To investigate the effect of orally or intraperitoneally (ip administered drugs on cold-induced gastric lesions, single doses were administered before exposing the animals to a freezer (-18ºC for 45 min in individual cages. We also evaluated the gastric lesions induced by multiple doses of the drugs. Diclofenac plus zinc complex had the same anti-inflammatory and antinociceptive effects as diclofenac alone. Gastric lesions induced by a single dose administered per os and ip were reduced in the group treated with zinc-diclofenac when compared to the groups treated with free diclofenac or diclofenac plus zinc acetate. In the multiple dose treatment, the complex induced a lower number of the most severe lesions when compared to free diclofenac and diclofenac plus zinc acetate. In conclusion, the present study demonstrates that the zinc-diclofenac complex may represent an important therapeutic alternative for the treatment of rheumatic and inflammatory conditions, as its use may be associated with a reduced incidence of gastric lesions.

  12. Effect of Cyclodextrin Complexation of Curcumin on its Solubility and Antiangiogenic and Anti-inflammatory Activity in Rat Colitis Model

    OpenAIRE

    Yadav, Vivek R.; Suresh, Sarasija; Devi, Kshama; Yadav, Seema

    2009-01-01

    The purpose of the study was to prepare and evaluate the anti-inflammatory activity of cyclodextrin (CD) complex of curcumin for the treatment of inflammatory bowel disease (IBD) in colitis-induced rat model. Inclusion complexes of curcumin were prepared by common solvent and kneading methods. These complexes were further evaluated for increase in solubility of poorly soluble curcumin. The inclusion complexes were characterized for enhancement in solubility, in vitro dissolution, surface morp...

  13. Do prion protein gene polymorphisms induce apoptosis in non

    Indian Academy of Sciences (India)

    To elucidate the relationship between the SNPs and apoptosis, TUNEL assays and active caspase-3 immunodetection techniques in brain sections of the polymorphic samples were performed. The results revealed that TUNEL-positive cells and active caspase-3-positive cells in the turtles with four polymorphisms were ...

  14. LIG1 polymorphisms: the Indian scenario

    Indian Academy of Sciences (India)

    Elucidation of the genetic diversity and relatedness of the subpopulations of India may provide a unique resource for future analysis of genetic association of several critical community-specific complex diseases.We performed a comprehensive exploration of single nucleotide polymorphisms (SNPs) within the gene DNA ...

  15. Silver(I) complexes of N-methylbenzothiazole-2-thione: Synthesis, structures and antibacterial activity

    Energy Technology Data Exchange (ETDEWEB)

    Aslanidis, P., E-mail: aslanidi@chem.auth.gr [Laboratory of Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki (Greece); Hatzidimitriou, A.G.; Andreadou, E.G. [Laboratory of Inorganic Chemistry, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki (Greece); Pantazaki, A.A., E-mail: natasa@chem.auth.gr [Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, GR-541 24 Thessaloniki (Greece); Voulgarakis, N. [Department of Logistics, Alexander Technological Educational Institute, GR-60100 Katerini (Greece)

    2015-05-01

    Three silver(I) complexes containing N-methylbenzothiazole-2-thione (mbtt) have been prepared and structurally characterized by X-ray single-crystal analysis. Silver(I) nitrate, and silver(I) triflate react with mbtt to give homoleptic complexes of formula [(mbtt){sub 2}Ag(μ-mbtt){sub 2}Ag(mbtt){sub 2}](NO{sub 3}){sub 2} (1) and [Ag(mbtt){sub 3}](CF{sub 3}SO{sub 3}) (2) respectively, while silver(I) chloride gives the binuclear halide-bridged [(mbtt){sub 2}Ag(μ{sub 2}-Cl){sub 2}Ag(mbtt){sub 2}] (3). In the binuclear complex 1 the two metal ions, separated by 3.73 Å from each other, are doubly bridged by the exocyclic S-atoms of two mbtt ligands, with the tetrahedral environment around each silver ion being completed by the S-atoms of two terminally bonded mbtt units. Compound 2 is mononuclear with the metal ion surrounded by the exocyclic S-atoms of three mbtt ligands in a nearly ideal trigonal planar arrangement. The new complexes showed significant in vitro antibacterial activity against certain Gram-positive and Gram-negative bacterial strains.

  16. Classification of Error Related Brain Activity in an Auditory Identification Task with Conditions of Varying Complexity

    Science.gov (United States)

    Kakkos, I.; Gkiatis, K.; Bromis, K.; Asvestas, P. A.; Karanasiou, I. S.; Ventouras, E. M.; Matsopoulos, G. K.

    2017-11-01

    The detection of an error is the cognitive evaluation of an action outcome that is considered undesired or mismatches an expected response. Brain activity during monitoring of correct and incorrect responses elicits Event Related Potentials (ERPs) revealing complex cerebral responses to deviant sensory stimuli. Development of accurate error detection systems is of great importance both concerning practical applications and in investigating the complex neural mechanisms of decision making. In this study, data are used from an audio identification experiment that was implemented with two levels of complexity in order to investigate neurophysiological error processing mechanisms in actors and observers. To examine and analyse the variations of the processing of erroneous sensory information for each level of complexity we employ Support Vector Machines (SVM) classifiers with various learning methods and kernels using characteristic ERP time-windowed features. For dimensionality reduction and to remove redundant features we implement a feature selection framework based on Sequential Forward Selection (SFS). The proposed method provided high accuracy in identifying correct and incorrect responses both for actors and for observers with mean accuracy of 93% and 91% respectively. Additionally, computational time was reduced and the effects of the nesting problem usually occurring in SFS of large feature sets were alleviated.

  17. Dynamical complexity detection in geomagnetic activity indices using wavelet transforms and Tsallis entropy

    Science.gov (United States)

    Balasis, G.; Daglis, I. A.; Papadimitriou, C.; Kalimeri, M.; Anastasiadis, A.; Eftaxias, K.

    2008-12-01

    Dynamical complexity detection for output time series of complex systems is one of the foremost problems in physics, biology, engineering, and economic sciences. Especially in magnetospheric physics, accurate detection of the dissimilarity between normal and abnormal states (e.g. pre-storm activity and magnetic storms) can vastly improve space weather diagnosis and, consequently, the mitigation of space weather hazards. Herein, we examine the fractal spectral properties of the Dst data using a wavelet analysis technique. We show that distinct changes in associated scaling parameters occur (i.e., transition from anti- persistent to persistent behavior) as an intense magnetic storm approaches. We then analyze Dst time series by introducing the non-extensive Tsallis entropy, Sq, as an appropriate complexity measure. The Tsallis entropy sensitively shows the complexity dissimilarity among different "physiological" (normal) and "pathological" states (intense magnetic storms). The Tsallis entropy implies the emergence of two distinct patterns: (i) a pattern associated with the intense magnetic storms, which is characterized by a higher degree of organization, and (ii) a pattern associated with normal periods, which is characterized by a lower degree of organization.

  18. Deficiency of PHB complex impairs respiratory supercomplex formation and activates mitochondrial flashes.

    Science.gov (United States)

    Jian, Chongshu; Xu, Fengli; Hou, Tingting; Sun, Tao; Li, Jinghang; Cheng, Heping; Wang, Xianhua

    2017-08-01

    Prohibitins (PHBs; prohibitin 1, PHB1 or PHB, and prohibitin 2, PHB2) are evolutionarily conserved and ubiquitously expressed mitochondrial proteins. PHBs form multimeric ring complexes acting as scaffolds in the inner mitochondrial membrane. Mitochondrial flashes (mitoflashes) are newly discovered mitochondrial signaling events that reflect electrical and chemical excitations of the organelle. Here, we investigate the possible roles of PHBs in the regulation of mitoflash signaling. Downregulation of PHBs increases mitoflash frequency by up to 5.4-fold due to elevated basal reactive oxygen species (ROS) production in the mitochondria. Mechanistically, PHB deficiency impairs the formation of mitochondrial respiratory supercomplexes (RSCs) without altering the abundance of individual respiratory complex subunits. These impairments induced by PHB deficiency are effectively rescued by co-expression of PHB1 and PHB2, indicating that the multimeric PHB complex acts as the functional unit. Furthermore, downregulating other RSC assembly factors, including SCAFI (also known as COX7A2L), RCF1a (HIGD1A), RCF1b (HIGD2A), UQCC3 and SLP2 (STOML2), all activate mitoflashes through elevating mitochondrial ROS production. Our findings identify the PHB complex as a new regulator of RSC formation and mitoflash signaling, and delineate a general relationship among RSC formation, basal ROS production and mitoflash biogenesis. © 2017. Published by The Company of Biologists Ltd.

  19. Tracking a Subset of Skeleton Joints: An Effective Approach towards Complex Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Muhammad Latif Anjum

    2017-01-01

    Full Text Available We present a robust algorithm for complex human activity recognition for natural human-robot interaction. The algorithm is based on tracking the position of selected joints in human skeleton. For any given activity, only a few skeleton joints are involved in performing the activity, so a subset of joints contributing the most towards the activity is selected. Our approach of tracking a subset of skeleton joints (instead of tracking the whole skeleton is computationally efficient and provides better recognition accuracy. We have developed both manual and automatic approaches for the selection of these joints. The position of the selected joints is tracked for the duration of the activity and is used to construct feature vectors for each activity. Once the feature vectors have been constructed, we use a Support Vector Machines (SVM multiclass classifier for training and testing the algorithm. The algorithm has been tested on a purposely built dataset of depth videos recorded using Kinect camera. The dataset consists of 250 videos of 10 different activities being performed by different users. Experimental results show classification accuracy of 83% when tracking all skeleton joints, 95% when using manual selection of subset joints, and 89% when using automatic selection of subset joints.

  20. Native gel electrophoresis of human telomerase distinguishes active complexes with or without dyskerin

    Science.gov (United States)

    Gardano, Laura; Holland, Linda; Oulton, Rena; Le Bihan, Thierry; Harrington, Lea

    2012-01-01

    Telomeres, the ends of linear chromosomes, safeguard against genome instability. The enzyme responsible for extension of the telomere 3′ terminus is the ribonucleoprotein telomerase. Whereas telomerase activity can be reconstituted in vitro with only the telomerase RNA (hTR) and telomerase reverse transcriptase (TERT), additional components are required in vivo for enzyme assembly, stability and telomere extension activity. One such associated protein, dyskerin, promotes hTR stability in vivo and is the only component to co-purify with active, endogenous human telomerase. We used oligonucleotide-based affinity purification of hTR followed by native gel electrophoresis and in-gel telomerase activity detection to query the composition of telomerase at different purification stringencies. At low salt concentrations (0.1 M NaCl), affinity-purified telomerase was ‘supershifted’ with an anti-dyskerin antibody, however the association with dyskerin was lost after purification at 0.6 M NaCl, despite the retention of telomerase activity and a comparable yield of hTR. The interaction of purified hTR and dyskerin in vitro displayed a similar salt-sensitive interaction. These results demonstrate that endogenous human telomerase, once assembled and active, does not require dyskerin for catalytic activity. Native gel electrophoresis may prove useful in the characterization of telomerase complexes under various physiological conditions. PMID:22187156

  1. Functional Requirements for Fab-7 Boundary Activity in the Bithorax Complex

    Science.gov (United States)

    Wolle, Daniel; Cleard, Fabienne; Aoki, Tsutomu; Deshpande, Girish; Karch, Francois

    2015-01-01

    Chromatin boundaries are architectural elements that determine the three-dimensional folding of the chromatin fiber and organize the chromosome into independent units of genetic activity. The Fab-7 boundary from the Drosophila bithorax complex (BX-C) is required for the parasegment-specific expression of the Abd-B gene. We have used a replacement strategy to identify sequences that are necessary and sufficient for Fab-7 boundary function in the BX-C. Fab-7 boundary activity is known to depend on factors that are stage specific, and we describe a novel ∼700-kDa complex, the late boundary complex (LBC), that binds to Fab-7 sequences that have insulator functions in late embryos and adults. We show that the LBC is enriched in nuclear extracts from late, but not early, embryos and that it contains three insulator proteins, GAF, Mod(mdg4), and E(y)2. Its DNA binding properties are unusual in that it requires a minimal sequence of >65 bp; however, other than a GAGA motif, the three Fab-7 LBC recognition elements display few sequence similarities. Finally, we show that mutations which abrogate LBC binding in vitro inactivate the Fab-7 boundary in the BX-C. PMID:26303531

  2. Synthesis, Characterization, Luminescence and Biological Activity of Two Lanthanide Complexes Involving Mixed Ligands

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Deyun; Guo, Haifu; Qin, Liang [Zhaoqing Univ., Zhaoqing (China); Xu, Jun [Jinan Univ., Guangzhou (China)

    2013-09-15

    Two new isostructural dinuclear complexes, Ln{sub 2}(4-cpa){sub 6}(bpy){sub 2} (Ln = Eu (1); Tb (2), 4-cpa = 4-chlorophenyl-acetate, bpy = 2,2'-bipyridine), have been hydrothermally synthesized and characterized by IR spectroscopy, elemental analysis, thermogravimetric analysis (TGA), powder X-ray diffraction and single-crystal X-ray diffraction. The lanthanide ions are bridged by two bidentate and two terdentate carboxylate groups to give centrosymmetric dimers with Ln···Ln separations of 3.967(2) and 3.956(3) A, respectively. Each metal atom is nine-coordinate and exhibits a distorted tricapped trigonal prismatic geometry. Three-dimensional fluorescence spectra show that both 1 and 2 emit bright red and green luminescence at room temperature, with long lifetimes of up to 0.369 ms (at 614 nm) and 0.432 ms (at 543 nm), respectively. Moreover, poor luminescence efficiency has been noted for complex 2. The 4-Hcpa ligand and complexes 1-2 have been screened for their phytogrowth-inhibitory activities against Brassica napus L. and Echinochloa crusgalli L., and the results are compared with the activity of quizalofop-P-ethyl.

  3. Functional Requirements for Fab-7 Boundary Activity in the Bithorax Complex.

    Science.gov (United States)

    Wolle, Daniel; Cleard, Fabienne; Aoki, Tsutomu; Deshpande, Girish; Schedl, Paul; Karch, Francois

    2015-11-01

    Chromatin boundaries are architectural elements that determine the three-dimensional folding of the chromatin fiber and organize the chromosome into independent units of genetic activity. The Fab-7 boundary from the Drosophila bithorax complex (BX-C) is required for the parasegment-specific expression of the Abd-B gene. We have used a replacement strategy to identify sequences that are necessary and sufficient for Fab-7 boundary function in the BX-C. Fab-7 boundary activity is known to depend on factors that are stage specific, and we describe a novel ∼700-kDa complex, the late boundary complex (LBC), that binds to Fab-7 sequences that have insulator functions in late embryos and adults. We show that the LBC is enriched in nuclear extracts from late, but not early, embryos and that it contains three insulator proteins, GAF, Mod(mdg4), and E(y)2. Its DNA binding properties are unusual in that it requires a minimal sequence of >65 bp; however, other than a GAGA motif, the three Fab-7 LBC recognition elements display few sequence similarities. Finally, we show that mutations which abrogate LBC binding in vitro inactivate the Fab-7 boundary in the BX-C. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. Hydrothermal activity in the Tulancingo-Acoculco Caldera Complex, central Mexico. Exploratory studies

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Hernandez, Aida [Gerencia de Proyectos Geotermoelectricos, CFE, Alejandro Volta 655, 58290 Morelia, Michoacan (Mexico); Centro de Geociencias, Universidad Nacional Autonoma de Mexico, Campus Juriquilla, Queretaro, Qro., 76230 (Mexico); Garcia-Estrada, Gerardo; Palma-Guzman, Hugo; Quijano-Leon, Jose L. [Gerencia de Proyectos Geotermoelectricos, CFE, Alejandro Volta 655, 58290 Morelia, Michoacan (Mexico); Aguirre-Diaz, Gerardo; Gonzalez-Partida, Eduardo [Centro de Geociencias, Universidad Nacional Autonoma de Mexico, Campus Juriquilla, Queretaro, Qro., 76230 (Mexico)

    2009-09-15

    Mineral alteration and fluid inclusion studies of drill cuttings and core samples indicate that the sedimentary basement rocks and the volcanic rocks associated with Tulancingo-Acoculco Caldera Complex have been the site of two distinct and major hydrothermal events. The complex, located in the eastern portion of the Trans-Mexican Volcanic Belt, is formed by the Pliocene Tulancingo Caldera and the younger (Pleistocene) Acoculco Caldera, which developed within the older depression. The volcanic rocks are underlain by Cretaceous sedimentary rocks of the Sierra Madre Oriental. The earliest important hydrothermal event occurred during the emplacement of Mid-Tertiary granitic intrusions that metamorphosed the sedimentary rocks; these intrusives are not exposed at the surface. However, granitic rocks were encountered at the bottom of exploratory borehole EAC-1, drilled within the Caldera Complex. The second main event occurred during the formation of the Tulancingo and Acoculco Calderas. Both episodes lead to secondary mineralization that reduced the permeability of the reservoir rocks. A possible third hydrothermal event may be associated with the recent magmatic activity within the Acoculco Caldera.Thermal logs from well EAC-1 display a conductive thermal gradient with maximum temperatures exceeding 300 C at 2000 m depth. Although there are no active thermal springs in the area, there is extensive fossil surface hydrothermal alteration and cold gas discharges with high He{sup 3}/He{sup 4} ratios. (author)

  5. Distinguishing Active Site Characteristics of Chlorite Dismutases with Their Cyanide Complexes.

    Science.gov (United States)

    Geeraerts, Zachary; Celis, Arianna I; Mayfield, Jeffery A; Lorenz, Megan; Rodgers, Kenton R; DuBois, Jennifer L; Lukat-Rodgers, Gudrun S

    2018-03-06

    O 2 -evolving chlorite dismutases (Clds) efficiently convert chlorite (ClO 2 - ) to O 2 and Cl - . Dechloromonas aromatica Cld ( DaCld) is a highly active chlorite-decomposing homopentameric enzyme, typical of Clds found in perchlorate- and chlorate-respiring bacteria. The Gram-negative, human pathogen Klebsiella pneumoniae contains a homodimeric Cld ( KpCld) that also decomposes ClO 2 - , albeit with an activity 10-fold lower and a turnover number lower than those of DaCld. The interactions between the distal pocket and heme ligand of the DaCld and KpCld active sites have been probed via kinetic, thermodynamic, and spectroscopic behaviors of their cyanide complexes for insight into active site characteristics that are deterministic for chlorite decomposition. At 4.7 × 10 -9 M, the K D for the KpCld-CN - complex is 2 orders of magnitude smaller than that of DaCld-CN - and indicates an affinity for CN - that is greater than that of most heme proteins. The difference in CN - affinity between Kp- and DaClds is predominantly due to differences in k off . The kinetics of binding of cyanide to DaCld, DaCld(R183Q), and KpCld between pH 4 and 8.5 corroborate the importance of distal Arg183 and a p K a of ∼7 in stabilizing complexes of anionic ligands, including the substrate. The Fe-C stretching and FeCN bending modes of the DaCld-CN - (ν Fe-C , 441 cm -1 ; δ FeCN , 396 cm -1 ) and KpCld-CN - (ν Fe-C , 441 cm -1 ; δ FeCN , 356 cm -1 ) complexes reveal differences in their FeCN angle, which suggest different distal pocket interactions with their bound cyanide. Conformational differences in their catalytic sites are also reported by the single ferrous KpCld carbonyl complex, which is in contrast to the two conformers observed for DaCld-CO.

  6. Mitochondria-targeting cyclometalated iridium(III)-PEG complexes with tunable photodynamic activity.

    Science.gov (United States)

    Li, Steve Po-Yam; Lau, Chris Tsan-Shing; Louie, Man-Wai; Lam, Yun-Wah; Cheng, Shuk Han; Lo, Kenneth Kam-Wing

    2013-10-01

    We present a new class of phosphorescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir(N(^)C)2(bpy-CONH-PEG)](PF6) (bpy-CONH-PEG = 4-(N-(2-(ω-methoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine, number average molecular weight (Mn) = 5272.23, weight average molecular weight (Mw) = 5317.38, polydispersity index (PDI) = 1.009; HN(^)C = 2-phenylpyridine, Hppy (1a), 2-((1,1'-biphenyl)-4-yl)pyridine, Hpppy (2a), 2-phenylquinoline, Hpq (3a), 2-phenylbenzothiazole, Hbt (4a), 2-(1-naphthyl)benzothiazole, Hbsn (5a)). The photophysical, photochemical, and biological properties of these complexes have been compared with those of their PEG-free counterparts [Ir(N(^)C)2(bpy-CONH-Et)](PF6) (bpy-CONH-Et = 4-(N-ethylaminocarbonyl)-4'-methyl-2,2'-bipyridine; HN(^)C = Hppy (1b), Hpppy (2b), Hpq (3b), Hbt (4b), Hbsn (5b)). Upon irradiation, all the complexes exhibited intense and long-lived green to orange-red emission under ambient conditions. The emission was phosphorescence in nature and can be quenched by O2 with the generation of singlet oxygen ((1)O2). The quantum yields for (1)O2 production of the complexes in aerated DMSO (0.24-0.83) were found to be dependent on the excited-state lifetimes of the complexes, which can be altered using different cyclometalating ligands (N(^)C). Cell-based assays indicated that the PEG complexes were noncytotoxic in the dark (IC50 > 300 μM); however, most of them became significantly cytotoxic upon irradiation (IC50 = 3.4 - 23.2 μM). Laser-scanning confocal microscopy images revealed localization of complex 3a in the mitochondrial region of HeLa cells and the induction of rapid necrotic cell death upon light activation. Additionally, the lack of dark toxicity and potential application of the PEG complexes as a visualizing reagent have been demonstrated using zebrafish (Danio rerio) as an animal model. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. The Raman and vibronic activity of intermolecular vibrations in aromatic-containing complexes and clusters

    International Nuclear Information System (INIS)

    Maxton, P.M.; Schaeffer, M.W.; Ohline, S.M.; Kim, W.; Venturo, V.A.; Felker, P.M.

    1994-01-01

    Theoretical and experimental results pertaining to the excitation of intermolecular vibrations in the Raman and vibronic spectra of aromatic-containing, weakly bound complexes and clusters are reported. The theoretical analysis of intermolecular Raman activity is based on the assumption that the polarizability tensor of a weakly bound species is given by the sum of the polarizability tensors of its constituent monomers. The analysis shows that the van der Waals bending fundamentals in aromatic--rare gas complexes may be expected to be strongly Raman active. More generally, it predicts strong Raman activity for intermolecular vibrations that involve the libration or internal rotation of monomer moieties having appreciable permanent polarizability anisotropies. The vibronic activity of intermolecular vibrations in aromatic-rare gas complexes is analyzed under the assumption that every vibronic band gains its strength from an aromatic-localized transition. It is found that intermolecular vibrational excitations can accompany aromatic-localized vibronic excitations by the usual Franck--Condon mechanism or by a mechanism dependent on the librational amplitude of the aromatic moiety during the course of the pertinent intermolecular vibration. The latter mechanism can impart appreciable intensity to bands that are forbidden by rigid-molecule symmetry selection rules. The applicability of such rules is therefore called into question. Finally, experimental spectra of intermolecular transitions, obtained by mass-selective, ionization-detected stimulated Raman spectroscopies, are reported for benzene--X (X=Ar, --Ar 2 , N 2 , HCl, CO 2 , and --fluorene), fluorobenzene--Ar and --Kr, aniline--Ar, and fluorene--Ar and --Ar 2 . The results support the conclusions of the theoretical analyses and provide further evidence for the value of Raman methods in characterizing intermolecular vibrational level structures

  8. Synthesis and antileishmanial activity of antimony (V) complexes of hydroxypyranone and hydroxypyridinone ligands.

    Science.gov (United States)

    Sheikhmoradi, Vafa; Saberi, Sedigheh; Saghaei, Lotfollah; Pestehchian, Nader; Fassihi, Afshin

    2018-04-01

    A novel series of antimony (V) complexes with the hydroxypyranone and hydroxypyridinone ligands were synthesized and characterized by 1 HNMR, FT-IR and electron spin ionization mass spectroscopic (ESI-MS) techniques. The synthesis process involved protection of hydroxyl group followed by the reaction of the intermediate with primary amines and finally deprotection. All compounds were evaluated for in vitro activities against the amastigote and promastigote forms of Leishmania major . Most of the synthesized compounds exhibited good antileishmanial activity against both forms of L. major . IC 50 values of the most active compounds; 9d , 9d and 9e , after 24, 48 and 72 h against amastigote model were 15, 12.5 and 5.5 μg/mL, respectively. 9e , 11 and 9e inhibited the promastigote form of parasite after 24, 48 and 72 h with IC 50 values of 10, 2 and 1 μg/mL, respectively.

  9. Effects of eHealth physical activity encouragement in adolescents with complex congenital heart disease

    DEFF Research Database (Denmark)

    Klausen, Susanne Hwiid; Andersen, Lars L; Søndergaard, Lars

    2016-01-01

    OBJECTIVE: To assess benefit and harms of adding an eHealth intervention to health education and individual counseling in adolescents with congenital heart disease. DESIGN: Randomized clinical trial. SETTING: Denmark. PATIENTS: A total of 158 adolescents aged 13-16years with no physical activity...... restrictions after repaired complex congenital heart disease. INTERVENTIONS: PReVaiL consisted of individually tailored eHealth encouragement physical activity for 52weeks. All patients received 45min of group-based health education and 15min of individual counseling involving patients' parents. OUTCOMES......·kg(-1)·min(-1) (95% CI -2.66 to 1.36). Between-group differences at 1year in physical activity, generic health-related quality of life, and disease-specific quality of life were not statistically significant. CONCLUSIONS: Adding a tailored eHealth intervention to health education and individual...

  10. Catalytic Water Oxidation by a Bio-inspired Nickel Complex with Redox Active Ligand

    Science.gov (United States)

    Wang, Dong; Bruner, Charlie O.

    2017-01-01

    The oxidation of water to dioxygen is important in natural photosynthesis. One of nature’s strategies for managing such multi-electron transfer reactions is to employ redox active metal-organic cofactor arrays. One prototype example is the copper-tyrosinate active site found in galactose oxidase. In this work, we have implemented such a strategy to develop a bio-inspired nickel-phenolate complex capable of catalyzing the oxidation of water to O2 electrochemically at neutral pH with a modest overpotential. The employment of the redox-active ligand turned out to be a useful strategy to avoid the formation of high-valent nickel intermediates while a reasonable turnover rate (0.15 s−1) is retained. PMID:29099176

  11. Catalytic Water Oxidation by a Bio-inspired Nickel Complex with a Redox-Active Ligand.

    Science.gov (United States)

    Wang, Dong; Bruner, Charlie O

    2017-11-20

    The oxidation of water (H 2 O) to dioxygen (O 2 ) is important in natural photosynthesis. One of nature's strategies for managing such multi-electron transfer reactions is to employ redox-active metal-organic cofactor arrays. One prototype example is the copper tyrosinate active site found in galactose oxidase. In this work, we have implemented such a strategy to develop a bio-inspired nickel phenolate complex capable of catalyzing the oxidation of H 2 O to O 2 electrochemically at neutral pH with a modest overpotential. Employment of the redox-active ligand turned out to be a useful strategy to avoid the formation of high-valent nickel intermediates while a reasonable turnover rate (0.15 s -1 ) is retained.

  12. Peroxisome proliferator-activated receptor gamma recruits the positive transcription elongation factor b complex to activate transcription and promote adipogenesis

    DEFF Research Database (Denmark)

    Iankova, Irena; Petersen, Rasmus K; Annicotte, Jean-Sébastien

    2006-01-01

    Positive transcription elongation factor b (P-TEFb) phosphorylates the C-terminal domain of RNA polymerase II, facilitating transcriptional elongation. In addition to its participation in general transcription, P-TEFb is recruited to specific promoters by some transcription factors such as c......-Myc or MyoD. The P-TEFb complex is composed of a cyclin-dependent kinase (cdk9) subunit and a regulatory partner (cyclin T1, cyclin T2, or cyclin K). Because cdk9 has been shown to participate in differentiation processes, such as muscle cell differentiation, we studied a possible role of cdk9...... with and phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma), which is the master regulator of this process, on the promoter of PPARgamma target genes. PPARgamma-cdk9 interaction results in increased transcriptional activity of PPARgamma and therefore increased adipogenesis....

  13. Binding of the Ras activator son of sevenless to insulin receptor substrate-1 signaling complexes.

    Science.gov (United States)

    Baltensperger, K; Kozma, L M; Cherniack, A D; Klarlund, J K; Chawla, A; Banerjee, U; Czech, M P

    1993-06-25

    Signal transmission by insulin involves tyrosine phosphorylation of a major insulin receptor substrate (IRS-1) and exchange of Ras-bound guanosine diphosphate for guanosine triphosphate. Proteins containing Src homology 2 and 3 (SH2 and SH3) domains, such as the p85 regulatory subunit of phosphatidylinositol-3 kinase and growth factor receptor-bound protein 2 (GRB2), bind tyrosine phosphate sites on IRS-1 through their SH2 regions. Such complexes in COS cells were found to contain the heterologously expressed putative guanine nucleotide exchange factor encoded by the Drosophila son of sevenless gene (dSos). Thus, GRB2, p85, or other proteins with SH2-SH3 adapter sequences may link Sos proteins to IRS-1 signaling complexes as part of the mechanism by which insulin activates Ras.

  14. Research on Characteristics, Antioxidant and Antitumor Activities of Dihydroquercetin and Its Complexes

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2017-12-01

    Full Text Available Dihydroquercetin is a kind of dihydroflavonol compounds with antioxidant, antitumor, antivirus and radioresistance activities. This study attempted to produce the dihydroquercetin complexes with lecithin and β-cyclodextrin, and research their characteristics and bioactivities via ultraviolet spectrum (UV, infrared spectroscopy (IR, scanning electron microscope (SEM, differential scanning calorimetry (DSC, X-ray diffraction spectrum (XRD, and MTT assay. Results showed that the complexes with lecithin and β-cyclodextrin could improve the solubility and dissolution rate, and remove the characteristic endothermic peak of dihydroquercetin. IR spectra proved their interaction, and results of SEM and XRD showed the amorphous characteristics of the dihydroquercetin compounds. These results indicated that dihydroquercetin was combined by lecithin or β-cyclodextrin with better physical and chemical properties, which would effectively improve the application value in the food and drug industries.

  15. Novel ruthenium methylcyclopentadienyl complex bearing a bipyridine perfluorinated ligand shows strong activity towards colorectal cancer cells.

    Science.gov (United States)

    Teixeira, Ricardo G; Brás, Ana Rita; Côrte-Real, Leonor; Tatikonda, Rajendhraprasad; Sanches, Anabela; Robalo, M Paula; Avecilla, Fernando; Moreira, Tiago; Garcia, M Helena; Haukka, Matti; Preto, Ana; Valente, Andreia

    2018-01-01

    Three new compounds have been synthesized and completely characterized by analytical and spectroscopic techniques. The new bipyridine-perfluorinated ligand L1 and the new organometallic complex [Ru(η 5 -MeCp)(PPh 3 ) 2 Cl] (Ru1) crystalize in the centrosymmetric triclinic space group P1¯. Analysis of the phenotypic effects induced by both organometallic complexes Ru1 and [Ru(η 5 -MeCp)(PPh 3 )(L1)][CF 3 SO 3 ] (Ru2), on human colorectal cancer cells (SW480 and RKO) survival, showed that Ru2 has a potent anti-proliferative activity, 4-6 times higher than cisplatin, and induce apoptosis in these cells. Data obtained in a noncancerous cell line derived from normal colon epithelial cells (NCM460) revealed an intrinsic selectivity of Ru2 for malignant cells at low concentrations, showing the high potential of this compound as a selective anticancer agent. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. STAT4 gene polymorphism in patients after renal allograft transplantation

    OpenAIRE

    D?browska-?amojcin, Ewa; Dziedziejko, Violetta; Safranow, Krzysztof; Doma?ski, Leszek; S?uczanowska-G?abowska, Sylwia; Pawlik, Andrzej

    2016-01-01

    Introduction STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, we examined whether this polymorphism is associated with the early and late functions of renal allog...

  17. Using complexity theory to develop a student-directed interprofessional learning activity for 1220 healthcare students.

    Science.gov (United States)

    Jorm, Christine; Nisbet, Gillian; Roberts, Chris; Gordon, Christopher; Gentilcore, Stacey; Chen, Timothy F

    2016-08-08

    More and better interprofessional practice is predicated to be necessary to deliver good care to the patients of the future. However, universities struggle to create authentic learning activities that enable students to experience the dynamic interprofessional interactions common in healthcare and that can accommodate large interprofessional student cohorts. We investigated a large-scale mandatory interprofessional learning (IPL) activity for health professional students designed to promote social learning. A mixed methods research approach determined feasibility, acceptability and the extent to which student IPL outcomes were met. We developed an IPL activity founded in complexity theory to prepare students for future practice by engaging them in a self-directed (self-organised) learning activity with a diverse team, whose assessable products would be emergent creations. Complicated but authentic clinical cases (n = 12) were developed to challenge student teams (n = 5 or 6). Assessment consisted of a written management plan (academically marked) and a five-minute video (peer marked) designed to assess creative collaboration as well as provide evidence of integrated collective knowledge; the cohesive patient-centred management plan. All students (including the disciplines of diagnostic radiology, exercise physiology, medicine, nursing, occupational therapy, pharmacy, physiotherapy and speech pathology), completed all tasks successfully. Of the 26 % of students who completed the evaluation survey, 70 % agreed or strongly agreed that the IPL activity was worthwhile, and 87 % agreed or strongly agreed that their case study was relevant. Thematic analysis found overarching themes of engagement and collaboration-in-action suggesting that the IPL activity enabled students to achieve the intended learning objectives. Students recognised the contribution of others and described negotiation, collaboration and creation of new collective knowledge after working

  18. Cu(II AND Zn(II COMPLEX COMPOUNDS WITH BIGUANIDES AROMATIC DERIVATIVES. SYNTHESIS, CHARACTERIZATION, BIOLOGICAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    Ticuţa Negreanu-Pîrjol

    2011-05-01

    Full Text Available In this paper we report the synthesis, physical-chemical characterization and antimicrobial activity of some new complex compounds of hetero-aromatic biguanides ligands, chlorhexidine base (CHX and chlorhexidine diacetate (CHXac2 with metallic ions Cu(II and Zn(II, in different molar ratio. The synthesized complexes were characterized by elemental chemical analysis and differential thermal analysis. The stereochemistry of the metallic ions was determined by infrared spectra, UV-Vis, EPR spectroscopy and magnetic susceptibility in the aim to establish the complexes structures. The biological activity of the new complex compounds was identified in solid technique by measuring minimum inhibition diameter of bacterial and fungal culture, against three standard pathogen strains, Escherichia coli ATCC 25922, Staphilococcus aureus ATCC 25923 and Candida albicans ATCC 10231. The results show an increased specific antimicrobial activity for the complexes chlorhexidine:Cu(II 1:1 and 1:2 compared with the one of the Zn(II complexes.

  19. Protective effect of nonsteroidal anti-inflammatory drugs on colorectal adenomas is modified by a polymorphism in peroxisome proliferator-activated receptor [Delta

    NARCIS (Netherlands)

    Siezen, C.L.E.; Tijhuis, M.J.; Kram, N.R.; Soest, van E.M.; Jong, de D.J.; Fodde, R.; Kranen, H.J.; Kampman, E.

    2006-01-01

    OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a decreased risk of colorectal tumors. Single nucleotide polymorphisms (SNPs) in target genes of NSAID action, and their haplotypes, might modulate this protective effect. METHODS: A case-control study including 724 cases

  20. The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study

    DEFF Research Database (Denmark)

    Lindi, Virpi; Schwab, Ursula; Louheranta, Anne

    2007-01-01

    BACKGROUND AND AIMS: Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study...

  1. The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism

    DEFF Research Database (Denmark)

    Stefan, N; Vozarova, B; Del Parigi, A

    2002-01-01

    Leptin regulates body weight by its receptor-mediated anorectic, thermogenic and antisteatotic effects. Recently, lower leptin binding to the soluble form of the leptin receptor (LEPR) was shown in carriers of the Arg223-encoding allele of the Gln223Arg polymorphism of the LEPR. To investigate wh...

  2. Association of human liver bilirubin UDP-glucuronyltransferase activity with a polymorphism in the promoter region of the UGT1A1 gene

    NARCIS (Netherlands)

    Raijmakers, MTM; Jansen, PLM; Steegers, EAP; Peters, WHM

    Background/Aims: Gilbert's syndrome is a benign form of a deficiency in bilirubin glucuronidation. It is associated with a homozygous polymorphism, A(TA)(7)TAA instead of A(TA)(6)TAA, in the TATA-box of the promoter region of the bilirubin UDP-glucuronyltransferase gene. In this study the

  3. Functionalized granular activated carbon and surface complexation with chromates and bi-chromates in wastewater

    International Nuclear Information System (INIS)

    Singha, Somdutta; Sarkar, Ujjaini; Luharuka, Pallavi

    2013-01-01

    Cr(VI) is present in the aqueous medium as chromate (CrO 4 2− ) and bi-chromate (HCrO 4 − ). Functionalized granular activated carbons (FACs) are used as adsorbents in the treatment of wastewaters containing hexavalent chromium. The FACs are prepared by chemical modifications of granular activated carbons (GACs) using functionalizing agents like HNO 3 , HCl and HF. The Brunauer, Emmett and Teller surface areas of FAC-HCl (693.5 m 2 /g), FAC-HNO 3 (648.8 m 2 /g) and FAC-HF (726.2 m 2 /g) are comparable to the GAC (777.7 m 2 /g). But, the adsorption capacity of each of the FAC-HNO 3 , FAC-HCl and FAC-HF is found to be higher than the GAC. The functional groups play an important role in the adsorption process and pH has practically no role in this specific case. The FACs have hydrophilic protonated external surfaces in particular, along with the functional surface sites capable to make complexes with the CrO 4 2− and HCrO 4 − present. Surface complex formation is maximized in the order FAC-HNO 3 > FAC-HF > FAC-HCl, in proportion to the total surface acidity. This is also confirmed by the well-known pseudo second-order kinetic model. Physi-sorption equilibrium isotherms are parameterized by using standard Freundlich and Langmuir models. Langmuir fits better. The formation of surface complexes with the functional groups and hexavalent chromium is also revealed in the images of field emission scanning electron micrograph; energy dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy analysis after adsorption. The intra-particle diffusion is not the only rate-controlling factor. The Boyd's film diffusion model fits very well with R 2 as high as 98.1% for FAC-HNO 3 . This result demonstrates that the functionalization of the GAC by acid treatments would increase the diffusion rate, predominantly with a boundary layer diffusion effect. - Highlights: ► Physico-chemical adsorption using functionalized activated carbon (FACs) is applied. ► FACs

  4. INVESTMENT ACTIVITY OF AGRIBUSINESS IN THE AGROINDUSTRIAL COMPLEX REGION, AS ONE OF THE ELEMENTS OF THE FINANCIAL SECURITY OF THE AGRO-INDUSTRIAL COMPLEX OF THE STATE

    Directory of Open Access Journals (Sweden)

    Olga Nikolaevna Uglitskikh

    2015-09-01

    Full Text Available The developed economic-political situation around of Russia, specifies an indispensability of support of agricultural commodity producers as from their financial well-being, investment activity the financial security of agrarian and industrial complex of the state depends. Limitation of own financial resources at agrarians does not allow them to realize independently conceived projects. Studying of questions of formation and functioning of investment activity in agriculture of Stavropol Territory and an assessment of investment projects offered to reali-zation, have allowed to analyse investment activity of agrarian and industrial complex of region up to the introduction of Russia into WTO and in conditions of its membership. By results of the lead assessment the administrative areas of region showing the greatest investment activity, threats of a financial security of agrarian and industrial complex of region not putting by the activity have been revealed. It is drawn a conclusion on influence West-American sanctions on financial without-danger agra-rian and industrial complex of the state and the responsibility сельхозтоваропроизводителей about delivery of agricultural production in necessary volume and import substitution.

  5. Exquisite Modulation of the Active Site of Methanocaldococcus jannaschii Adenylosuccinate Synthetase in Forward Reaction Complexes.

    Science.gov (United States)

    Karnawat, Vishakha; Mehrotra, Sonali; Balaram, Hemalatha; Puranik, Mrinalini

    2016-05-03

    In enzymes that conduct complex reactions involving several substrates and chemical transformations, the active site must reorganize at each step to complement the transition state of that chemical step. Adenylosuccinate synthetase (ADSS) utilizes a molecule each of guanosine 5'-monophosphate (GTP) and aspartate to convert inosine 5'-monophosphate (IMP) into succinyl adenosine 5'-monophosphate (sAMP) through several kinetic intermediates. Here we followed catalysis by ADSS through high-resolution vibrational spectral fingerprints of each substrate and intermediate involved in the forward reaction. Vibrational spectra show differential ligand distortion at each step of catalysis, and band positions of substrates are influenced by binding of cosubstrates. We found that the bound IMP is distorted toward its N1-deprotonated form even in the absence of any other ligands. Several specific interactions between GTP and active-site amino acid residues result in large Raman shifts and contribute substantially to intrinsic binding energy. When both IMP and GTP are simultaneously bound to ADSS, IMP is converted into an intermediate 6-phosphoryl inosine 5'-monophosphate (6-pIMP). The 6-pIMP·ADSS complex was found to be stable upon binding of the third ligand, hadacidin (HDA), an analogue of l-aspartate. We find that in the absence of HDA, 6-pIMP is quickly released from ADSS, is unstable in solution, and converts back into IMP. HDA allosterically stabilizes ADSS through local conformational rearrangements. We captured this complex and determined the spectra and structure of 6-pIMP in its enzyme-bound state. These results provide important insights into the exquisite tuning of active-site interactions with changing substrate at each kinetic step of catalysis.

  6. Early-Late Heterobimetallic Complexes Linked by Phosphinoamide Ligands. Tuning Redox Potentials and Small Molecule Activation

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Christine M. [Brandeis Univ., Waltham, MA (United States)

    2015-08-01

    Recent attention in the chemical community has been focused on the energy efficient and environmentally benign conversion of abundant small molecules (CO2, H2O, etc.) to useful liquid fuels. This project addresses these goals by examining fundamental aspects of catalyst design to ultimately access small molecule activation processes under mild conditions. Specifically, Thomas and coworkers have targetted heterobimetallic complexes that feature metal centers with vastly different electronic properties, dictated both by their respective positions on the periodic table and their coordination environment. Unlike homobimetallic complexes featuring identical or similar metals, the bonds between metals in early/late heterobimetallics are more polarized, with the more electron-rich late metal center donating electron density to the more electron-deficient early metal center. While metal-metal bonds pose an interesting strategy for storing redox equivalents and stabilizing reactive metal fragments, the polar character of metal-metal bonds in heterobimetallic complexes renders these molecules ideally poised to react with small molecule substrates via cleavage of energy-rich single and double bonds. In addition, metal-metal interactions have been shown to dramatically affect redox potentials and promote multielectron redox activity, suggesting that metal-metal interactions may provide a mechanism to tune redox potentials and access substrate reduction/activation at mild overpotentials. This research project has provided a better fundamental understanding of how interactions between transition metals can be used as a strategy to promote and/or control chemical transformations related to the clean production of fuels. While this project focused on the study of homogeneous systems, it is anticipated that the broad conclusions drawn from these investigations will be applicable to heterogeneous catalysis as well, particularly on heterogeneous processes that occur at interfaces in

  7. Role of -675 4G/5G in the plasminogen activator inhibitor-1 gene and -308G/A tumor necrosis factor-α gene polymorphisms in obese Argentinean patients.

    Science.gov (United States)

    Wingeyer, Silvia D Perés; Graffigna, Mabel N; Belli, Susana H; Benetucci, Jorge; de Larrañaga, Gabriela F

    2012-05-01

    Plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor-α (TNF-α) are increased in the circulation of obese persons. Because a direct link between PAI-1 and TNF-α in obesity has been observed, they are candidate genes for the development of obesity. We sought to evaluate the relation between the genotypic and allelic frequencies of the -675 4G/5G PAI-1 and -308 G/A TNF-α polymorphisms and their association with the risk for obesity in an Argentinean population. A group of 110 consecutive obese persons and a group of 111 lean controls were recruited. Polymerase chain reaction was used to determine the frequency of PAI-1 and TNF-α polymorphisms; serum fasting glucose, insulin, and lipid levels were measured by standard methods. Insulin sensitivity was evaluated by using homeostasis model assessment. The -308 TNF-α and -675 4G/5G PAI-1 genotype distribution did not significantly differ between the groups (p=0.544 and p=0.327, respectively). Homeostasis model assessment was the only positive independent determinant of body mass index (R(2)=0.493; p<0.001). The -675 4G/5G PAI-1 and the -308 TNF-α polymorphism variants tested in this study, individually or combined, were not associated with obesity in an Argentinean population.

  8. Rs7574865 polymorphism in signal transducers and activators of transcription 4 gene and rheumatoid arthritis: an updated meta-analysis of 28 case-control comparisons.

    Science.gov (United States)

    Gu, EnPeng; Lu, Jun; Xing, Dan; Chen, XingRan; Xie, HaiBo; Liang, JinQian; Li, Lin

    2015-01-01

    The objective of the present meta-analysis was to investigate whether the combined evidence shows an association between the STAT4 rs7574865 polymorphism and RA. A systematic search of all relevant studies published through April 2013 was conducted using MEDLINE, EMBASE, OVID, and ScienceDirect. The observational studies that were related to an association between the STAT4 rs7574865 polymorphism and RA were identified. The association between the STAT4 rs7574865 polymorphism and RA susceptibility was assessed using genetic models. Seventeen case-control studies with a total of 28 comparisons (25 300 RA patients and 26 326 controls) met the inclusion criteria. A meta-analysis was conducted for genotype TT versus GT+GG, GT+TT versus GG, TT versus GG and T-allele. The meta-analysis showed an association between RA and the STAT4 rs7574865 TT genotype, GT+TT genotype and T-allele in all subjects. Stratification of RA patients according to ethnic group showed that the TT genotype, GT+TT genotype and T-allele were significantly associated with RA in Europeans, Asians, Africans and Latin Americans. A subgroup analysis according to the absence or presence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies revealed that the association between the STAT4 rs7574865 polymorphism and RA may be independent of the presence of RF and anti-CCP antibodies. This meta-analysis demonstrated that the STAT4 rs7574865 polymorphism confers susceptibility to RA in major ethnic groups. The association may not be dependent on the presence of RF and anti-CCP antibodies. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  9. Accurate and simple measurement method of complex decay schemes radionuclide activity

    International Nuclear Information System (INIS)

    Legrand, J.; Clement, C.; Bac, C.

    1975-01-01

    A simple method for the measurement of the activity is described. It consists of using a well-type sodium iodide crystal whose efficiency mith monoenergetic photon rays has been computed or measured. For each radionuclide with a complex decay scheme a total efficiency is computed; it is shown that the efficiency is very high, near 100%. The associated incertainty is low, in spite of the important uncertainties on the different parameters used in the computation. The method has been applied to the measurement of the 152 Eu primary reference [fr

  10. Low-cost sensor integrators for measuring the transmissivity of complex canopies to photosynthetically active radiation

    International Nuclear Information System (INIS)

    Newman, S.M.

    1985-01-01

    A system has been designed, tested and evaluated for measuring the transmissivities of complex canopies to photosynthetically active radiation (PAR). The system consists of filtered silicon photocells in cosine corrected mounts with outputs integrated by the use of chemical coulometers. The reading accumulated by the coulometers was taken electronically by the use of microcomputers. The low-cost sensor integrators, which do not require batteries, performed as expected and proved ideal for the study of agroforestry systems in remote areas. Information on the PAR transmissivity of a temperate agroforestry system in the form of an intercropped orchard is also presented. (author)

  11. The higher level of complexity of K-Ras4B activation at the membrane

    Science.gov (United States)

    Jang, Hyunbum; Banerjee, Avik; Chavan, Tanmay S.; Lu, Shaoyong; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2016-01-01

    Is nucleotide exchange sufficient to activate K-Ras4B? To signal, oncogenic rat sarcoma (Ras) anchors in the membrane and recruits effectors by exposing its effector lobe. With the use of NMR and molecular dynamics (MD) simulations, we observed that in solution, farnesylated guanosine 5′-diphosphate (GDP)-bound K-Ras4B is predominantly autoinhibited by its hypervariable region (HVR), whereas the GTP-bound state favors an activated, HVR-released state. On the anionic membrane, the catalytic domain adopts multiple orientations, including parallel (∼180°) and perpendicular (∼90°) alignments of the allosteric helices, with respect to the membrane surface direction. In the autoinhibited state, the HVR is sandwiched between the effector lobe and the membrane; in the active state, with membrane-anchored farnesyl and unrestrained HVR, the catalytic domain fluctuates reinlessly, exposing its effector-binding site. Dimerization and clustering can reduce the fluctuations. This achieves preorganized, productive conformations. Notably, we also observe HVR-autoinhibited K-Ras4B-GTP states, with GDP-bound-like orientations of the helices. Thus, we propose that the GDP/GTP exchange may not be sufficient for activation; instead, our results suggest that the GDP/GTP exchange, HVR sequestration, farnesyl insertion, and orientation/localization of the catalytic domain at the membrane conjointly determine the active or inactive state of K-Ras4B. Importantly, K-Ras4B-GTP can exist in active and inactive states; on its own, GTP binding may not compel K-Ras4B activation.—Jang, H., Banerjee, A., Chavan, T. S, Lu, S., Zhang, J., Gaponenko, V., Nussinov, R. The higher level of complexity of K-Ras4B activation at the membrane. PMID:26718888

  12. The higher level of complexity of K-Ras4B activation at the membrane.

    Science.gov (United States)

    Jang, Hyunbum; Banerjee, Avik; Chavan, Tanmay S; Lu, Shaoyong; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2016-04-01

    Is nucleotide exchange sufficient to activate K-Ras4B? To signal, oncogenic rat sarcoma (Ras) anchors in the membrane and recruits effectors by exposing its effector lobe. With the use of NMR and molecular dynamics (MD) simulations, we observed that in solution, farnesylated guanosine 5'-diphosphate (GDP)-bound K-Ras4B is predominantly autoinhibited by its hypervariable region (HVR), whereas the GTP-bound state favors an activated, HVR-released state. On the anionic membrane, the catalytic domain adopts multiple orientations, including parallel (∼180°) and perpendicular (∼90°) alignments of the allosteric helices, with respect to the membrane surface direction. In the autoinhibited state, the HVR is sandwiched between the effector lobe and the membrane; in the active state, with membrane-anchored farnesyl and unrestrained HVR, the catalytic domain fluctuates reinlessly, exposing its effector-binding site. Dimerization and clustering can reduce the fluctuations. This achieves preorganized, productive conformations. Notably, we also observe HVR-autoinhibited K-Ras4B-GTP states, with GDP-bound-like orientations of the helices. Thus, we propose that the GDP/GTP exchange may not be sufficient for activation; instead, our results suggest that the GDP/GTP exchange, HVR sequestration, farnesyl insertion, and orientation/localization of the catalytic domain at the membrane conjointly determine the active or inactive state of K-Ras4B. Importantly, K-Ras4B-GTP can exist in active and inactive states; on its own, GTP binding may not compel K-Ras4B activation.-Jang, H., Banerjee, A., Chavan, T. S, Lu, S., Zhang, J., Gaponenko, V., Nussinov, R. The higher level of complexity of K-Ras4B activation at the membrane. © FASEB.

  13. Human Retrotransposon Insertion Polymorphisms Are Associated with Health and Disease via Gene Regulatory Phenotypes

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2017-08-01

    Full Text Available The human genome hosts several active families of transposable elements (TEs, including the Alu, LINE-1, and SVA retrotransposons that are mobilized via reverse transcription of RNA intermediates. We evaluated how insertion polymorphisms generated by human retrotransposon activity may be related to common health and disease phenotypes that have been previously interrogated through genome-wide association studies (GWAS. To address this question, we performed a genome-wide screen for retrotransposon polymorphism disease associations that are linked to TE induced gene regulatory changes. Our screen first identified polymorphic retrotransposon insertions found in linkage disequilibrium (LD with single nucleotide polymorphisms that were previously associated with common complex diseases by GWAS. We further narrowed this set of candidate disease associated retrotransposon polymorphisms by identifying insertions that are located within tissue-specific enhancer elements. We then performed expression quantitative trait loci analysis on the remaining set of candidates in order to identify polymorphic retrotransposon insertions that are associated with gene expression changes in B-cells of the human immune system. This progressive and stringent screen yielded a list of six retrotransposon insertions as the strongest candidates for TE polymorphisms that lead to disease via enhancer-mediated changes in gene regulation. For example, we found an SVA insertion within a cell-type specific enhancer located in the second intron of the B4GALT1 gene. B4GALT1 encodes a glycosyltransferase that functions in the glycosylation of the Immunoglobulin G (IgG antibody in such a way as to convert its activity from pro- to anti-inflammatory. The disruption of the B4GALT1 enhancer by the SVA insertion is associated with down-regulation of the gene in B-cells, which would serve to keep the IgG molecule in a pro-inflammatory state. Consistent with this idea, the B4GALT1 enhancer

  14. Chemical diversity and antileishmanial activity of crude extracts of Laurencia complex (Ceramiales, Rhodophyta from Brazil

    Directory of Open Access Journals (Sweden)

    Fernanda L. da S. Machado

    Full Text Available Chemical profiles of extracts of four species from Laurencia complex (Ceramiales, Rhodophyta from different populations collected along Southeast Brazilian coast were assessed by High Performance Liquid Chromatography coupled with a Diode Array Detector in order to observe geographic chemical variability. Aiming to evaluate the impact of chemical diversity on potential pharmaceutical uses, the extracts were tested against the promastigote form of Leishmania amazonensis. The most active extracts were submitted to anti-amastigote and cytotoxicity assays. Principal Component Analysis of the chromatograms resulted in four major groups of chemical profiles according to the presence of leishmanicidal chamigranes (--elatol and obtusol. The existence of chemotypes, displaying variable pharmacological action, is proposed for the differences observed in L. dendroidea samples. Although all extracts were found active against promastigote form of L. amazonensis, their efficacy was remarkably different and not related to the variation of (--elatol and obtusol, which indicates the presence of additional compounds with antileishmanial activity. Moreover, the active extracts also displayed anti-amastigote activity and none of them were considered cytotoxic. The results highlight that the knowledge of chemical geographic variability can be valuable in the search of new antileishmanial compounds from marine sources.

  15. Antioxidant Activity of γ-Oryzanol: A Complex Network of Interactions

    Directory of Open Access Journals (Sweden)

    Igor Otavio Minatel

    2016-08-01

    Full Text Available γ-oryzanol (Orz, a steryl ferulate extracted from rice bran layer, exerts a wide spectrum of biological activities. In addition to its antioxidant activity, Orz is often associated with cholesterol-lowering, anti-inflammatory, anti-cancer and anti-diabetic effects. In recent years, the usefulness of Orz has been studied for the treatment of metabolic diseases, as it acts to ameliorate insulin activity, cholesterol metabolism, and associated chronic inflammation. Previous studies have shown the direct action of Orz when downregulating the expression of genes that encode proteins related to adiposity (CCAAT/enhancer binding proteins (C/EBPs, inflammatory responses (nuclear factor kappa-B (NF-κB, and metabolic syndrome (peroxisome proliferator-activated receptors (PPARs. It is likely that this wide range of beneficial activities results from a complex network of interactions and signals triggered, and/or inhibited by its antioxidant properties. This review focuses on the significance of Orz in metabolic disorders, which feature remarkable oxidative imbalance, such as impaired glucose metabolism, obesity, and inflammation.

  16. Antioxidant Activity of γ-Oryzanol: A Complex Network of Interactions.

    Science.gov (United States)

    Minatel, Igor Otavio; Francisqueti, Fabiane Valentini; Corrêa, Camila Renata; Lima, Giuseppina Pace Pereira

    2016-08-09

    γ-oryzanol (Orz), a steryl ferulate extracted from rice bran layer, exerts a wide spectrum of biological activities. In addition to its antioxidant activity, Orz is often associated with cholesterol-lowering, anti-inflammatory, anti-cancer and anti-diabetic effects. In recent years, the usefulness of Orz has been studied for the treatment of metabolic diseases, as it acts to ameliorate insulin activity, cholesterol