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Sample records for aberrantly increased mrna

  1. Mammalian tissues defective in nonsense-mediated mRNA decay display highly aberrant splicing patterns

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    Weischenfeldt, Joachim Lütken; Waage, Johannes Eichler; Tian, Geng

    2012-01-01

    ABSTRACT: BACKGROUND: Nonsense-mediated mRNA decay (NMD) affects the outcome of alternative splicing by degrading mRNA isoforms with premature termination codons. Splicing regulators constitute important NMD targets; however, the extent to which loss of NMD causes extensive deregulation...... of alternative splicing has not previously been assayed in a global, unbiased manner. Here, we combine mouse genetics and RNA-seq to provide the first in vivo analysis of the global impact of NMD on splicing patterns in two primary mouse tissues ablated for the NMD factor UPF2. RESULTS: We developed...... importance, the latter events are associated with high intronic conservation. CONCLUSIONS: Our data demonstrate that NMD regulates alternative splicing outcomes through an intricate web of splicing regulators and that its loss leads to the deregulation of a panoply of splicing events, providing novel...

  2. Aberrant mRNA processing of the maize Rp1-D rust resistance gene in wheat and barley.

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    Ayliffe, Michael A; Steinau, Martin; Park, Robert F; Rooke, Lee; Pacheco, Maria G; Hulbert, Scot H; Trick, Harold N; Pryor, Anthony J

    2004-08-01

    The maize Rp1-D gene confers race-specific resistance against Puccinia sorghi (common leaf rust) isolates containing a corresponding avrRp1-D avirulence gene. An Rp1-D genomic clone and a similar Rp1-D transgene regulated by the maize ubiquitin promoter were transformed independently into susceptible maize lines and shown to confer Rp1-D resistance, demonstrating that this resistance can be transferred as a single gene. Transfer of these functional transgenes into wheat and barley did not result in novel resistances when these plants were challenged with isolates of wheat stem rust (P. graminis), wheat leaf rust (P. triticina), or barley leaf rust (P. hordei). Regardless of the promoter employed, low levels of gene expression were observed. When constitutive promoters were used for transgene expression, a majority of Rp1-D transcripts were truncated in the nucleotide binding site-encoding region by premature polyadenylation. This aberrant mRNA processing was unrelated to gene function because an inactive version of the gene also generated such transcripts. These data demonstrate that resistance gene transfer between species may not be limited only by divergence of signaling effector molecules and pathogen avirulence ligands, but potentially also by more fundamental gene expression and transcript processing limitations.

  3. Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis

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    Krakauer, Martin; Sorensen, P; Khademi, M

    2008-01-01

    BACKGROUND: Interferon (IFN)-beta therapy in multiple sclerosis (MS) has been suggested to promote a deviation from T lymphocyte production of pathogenic Th1 cytokines to less detrimental Th2 cytokines, but this is still controversial. We studied patterns of in vivo blood mononuclear cell (MNC...... of any Th1 or Th2 cytokines. The largest changes in cytokine mRNA levels occurred early (~9-12 h) after an IFN-beta injection. CONCLUSION: We found no evidence of a Th1- or Th2-mRNA-promoting effect of IFN-beta therapy. The therapeutic effect of IFN-beta is more likely attributable to the induction...

  4. Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis: interferon-beta treatment increases IL-10 mRNA expression while reducing IL-23 mRNA expression

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    Krakauer, M.; Sorensen, P.; Khademi, M.

    2008-01-01

    volunteers served to confirm initial findings. mRNA was analyzed by real-time reverse transcriptase polymerase chain reaction (PCR). RESULTS: We found elevated expression of interleukin (IL)-23 and IL-10 in untreated MS patients. IFN-beta therapy increased IL-10 and decreased IL-23 expression independently...... of the regulatory cytokine IL-10. The elevated IL-23 mRNA levels in MS patients are noteworthy in view of the newly discovered IL-23-driven Th17 T-cell subset, which is crucial in animal models of MS. Since IFN-beta therapy resulted in decreased IL-23 mRNA levels, the Th17 axis could be another target of IFN...

  5. Post-transcriptional regulation tends to attenuate the mRNA noise and to increase the mRNA gain

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    Shi, Changhong; Wang, Shuqiang; Zhou, Tianshou; Jiang, Yiguo

    2015-10-01

    Post-transcriptional regulation is ubiquitous in prokaryotic and eukaryotic cells, but how it impacts gene expression remains to be fully explored. Here, we analyze a simple gene model in which we assume that mRNAs are produced in a constitutive manner but are regulated post-transcriptionally by a decapping enzyme that switches between the active state and the inactive state. We derive the analytical mRNA distribution governed by a chemical master equation, which can be well used to analyze the mechanism of how post-transcription regulation influences the mRNA expression level including the mRNA noise. We demonstrate that the mean mRNA level in the stochastic case is always higher than that in the deterministic case due to the stochastic effect of the enzyme, but the size of the increased part depends mainly on the switching rates between two enzyme states. More interesting is that we find that in contrast to transcriptional regulation, post-transcriptional regulation tends to attenuate noise in mRNA. Our results provide insight into the role of post-transcriptional regulation in controlling the transcriptional noise.

  6. Identification of submicroscopic chromosomal aberrations in fetuses with increased

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    Leung, Tak Yeung; Vogel, Ida; Lau, Tze Kin

    2011-01-01

    known non-pathogenic variants and after validation with multiplex ligation-dependent probe amplification (MLPA) or Real-Time Quantitative PCR (RT-qPCR). The prevalence of pathogenic CNVs is reported and the association with NT and other ultrasound findings described. Results: CNVs were reported in 6....../48 (12.5%) cases by aCGH and the microdeletions or microduplications ranging from 1.07Mb to 7.80Mb. Five of these were validated by MLPA/RT-qPCR and four (9.5%) were considered to be pathogenic and clinical significant. The incidence of pathogenic CNV was 20% (2/10) among those cases with other...... sonographic anomalies, and 5.3% (2/38) among those without. Conclusions: aCGH allows detection of submicroscopic chromosomal abnormalities of which the prevalence may be increased in fetuses with NT>3.5mm and an apparently normal karyotype....

  7. Disruption of Maternal DNA Repair Increases Sperm-DerivedChromosomal Aberrations

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    Marchetti, Francesco; Essers, Jeroun; Kanaar, Roland; Wyrobek,Andrew J.

    2007-02-07

    The final weeks of male germ cell differentiation occur in aDNA repair-deficient environment and normal development depends on theability of the egg to repair DNA damage in the fertilizing sperm. Geneticdisruption of maternal DNA double-strand break repair pathways in micesignificantly increased the frequency of zygotes with chromosomalstructural aberrations after paternal exposure to ionizing radiation.These findings demonstrate that radiation-induced DNA sperm lesions arerepaired after fertilization by maternal factors and suggest that geneticvariation in maternal DNA repair can modulate the risk of early pregnancylosses and of children with chromosomal aberrations of paternalorigin.

  8. High throughput mRNA profiling highlights associations between myocardial infarction and aberrant expression of inflammatory molecules in blood cells

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    Wettinger, Stephanie Bezzina; Doggen, Catharina Jacoba Maria; Spek, C. Arnold; Rosendaal, Frits R.; Reitsma, Pieter H.

    2005-01-01

    Studies on the role of inflammation in cardiovascular disease focus on surrogate markers like plasma levels of C-reactive protein or interleukins that are affected by several factors. In this study we employ an approach in which the inflammatory mRNA profile of leucocytes is measured directly in a

  9. Severe subacute GM2 gangliosidosis caused by an apparently silent HEXA mutation (V324V) that results in aberrant splicing and reduced HEXA mRNA.

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    Wicklow, Brandy A; Ivanovich, Jennifer L; Plews, Margot M; Salo, Timothy J; Noetzel, Michael J; Lueder, Gregg T; Cartegni, Luca; Kaback, Michael M; Sandhoff, Konrad; Steiner, Robert D; Triggs-Raine, Barbara L

    2004-06-01

    We have characterized the molecular basis of beta-hexosaminidase A (HEX A) deficiency in a patient ascertained through an ophthalmologic examination that revealed cherry red spots on his retina. The absence of neurological deficit in this child until 3 3/4 years of age indicated residual HEX A must be present. Three HEXA mutations, 10T > C (S4P) and 972T > A (V324V) on the maternal allele, and 1A > T (M1L) on the paternal allele were identified. The effects of the amino acid substitutions on HEX A expressed in COS-7 cells were analyzed; as expected, no HEX A activity was associated with the M1L mutation but surprisingly, the S4P mutation resulted in 59% of the HEX A activity expressed by the wild type cDNA. The effect of the S4P change was much less than that of another HEXA mutation, G269S, associated with an adult onset form of G(M2) gangliosidosis. This indicated that the S4P change was not the cause of disease and suggested that one of the mutations on the maternal allele, 10T > C or 972T > A, had its effect at the mRNA level. This was confirmed by Northern blot analysis that showed only 7% of the normal level of HEXA mRNA in proband fibroblasts. Analysis of the residual mRNA by RT/PCR and sequencing revealed normal transcripts from both the maternal and paternal allele, as well as a low abundance aberrant transcript from the maternal allele. Sequencing of this aberrant transcript revealed a new exon 8 donor site created by the 972T > A mutation that resulted in a 17 bp deletion and destabilization of the resulting abnormal transcript. The remaining normal mRNA produced from the 972T > A allele must account for the delayed onset of clinical symptoms in this child. Copyright 2004 Wiley-Liss, Inc.

  10. Insertion of a T next to the donor splice site of intron 1 causes aberrantly spliced mRNA in a case of infantile GM1-gangliosidosis.

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    Morrone, A; Morreau, H; Zhou, X Y; Zammarchi, E; Kleijer, W J; Galjaard, H; d'Azzo, A

    1994-01-01

    The lysosomal storage disorders GM1-gangliosidosis and Morquio B syndrome are caused by a complete or partial deficiency of acid beta-galactosidase. Here, we have characterized the mutation segregating in a family with two siblings affected by the severe infantile form of GM1-gangliosidosis. In total mRNA preparations derived from the patients' fibroblasts at least two aberrantly spliced beta-galactosidase transcripts (1 and 2) have been identified. Both transcripts contain a 20 nucleotide (nt) insertion derived from the 5' end of intron 1 of the beta-galactosidase gene. Furthermore, in transcript 2 sequences encoded by exon II are deleted during the splicing process. Comparison of the 20-nt insertion with wild-type intronic sequences indicated that in the genomic DNA of the patients an extra T nucleotide is present immediately downstream of the conserved GT splice donor dinucleotide of intron 1. Both patients are homozygous for the T nucleotide insertion. We propose that this single base insertion is the mutation responsible for aberrant splicing of beta-galactosidase pre-mRNA, giving rise to transcripts that cannot encode a normal protein.

  11. Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.

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    Ruppenthal, Sabrina; Kleiner, Helga; Nolte, Florian; Fabarius, Alice; Hofmann, Wolf-Karsten; Nowak, Daniel; Seifarth, Wolfgang

    2018-01-01

    ESPL1/separase, a cysteine endopeptidase, is a key player in centrosome duplication and mitotic sister chromatid separation. Aberrant expression and/or altered separase proteolytic activity are associated with centrosome amplification, aneuploidy, tumorigenesis and disease progression. Since centrosome alterations are a common and early detectable feature in patients with myelodysplastic syndrome (MDS) and cytogenetic aberrations play an important role in disease risk stratification, we examined separase activity on single cell level in 67 bone marrow samples obtained from patients with MDS, secondary acute myeloid leukemia (sAML), de novo acute myeloid leukemia (AML) and healthy controls by a flow cytometric separase activity assay. The separase activity distribution (SAD) value, a calculated measure for the occurrence of cells with prominent separase activity within the analyzed sample, was tested for correlation with the centrosome, karyotype and gene mutation status. We found higher SAD values in bone marrow cells of sAML patients than in corresponding cells of MDS patients. This concurred with an increased incidence of aberrant centrosome phenotypes in sAML vs. MDS samples. No correlation was found between SAD values and the karyotype/gene mutation status. During follow-up of four MDS patients we observed increasing SAD values after transformation to sAML, in two patients SAD values decreased during azacitidine therapy. Cell culture experiments employing MDS-L cells as an in vitro model of MDS revealed that treatment with rigosertib, a PLK1 inhibitor and therapeutic drug known to induce G2/M arrest, results in decreased SAD values. In conclusion, the appearance of cells with unusual high separase activity levels, as indicated by increased SAD values, concurs with the transformation of MDS to sAML and may reflect separase dysregulation potentially contributing to clonal evolution during MDS progression. Separase activity measurement may therefore be useful as a

  12. Relative workload determines exercise-induced increases in PGC-1alpha mRNA

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    Nordsborg, Nikolai Baastrup; Lundby, Carsten; Leick, Lotte

    2010-01-01

    INTRODUCTION:: The hypothesis that brief intermittent exercise induced increases in human skeletal muscle metabolic mRNA is dependent on relative workload was investigated. METHODS:: Trained (n=10) and untrained (n=8) subjects performed exhaustive intermittent cycling exercise (4x4 min @ 85% of VO2...... peak, interspersed by 3 min). Trained subjects also performed the intermittent exercise at the same absolute workload as untrained, corresponding to 70% of VO2 peak (n=6). RESULTS:: Exercise at 85% of VO2 peak elevated (Ptrained...... after exercise at 85% of VO2 peak. Likewise, PDK4 and HKII mRNA expression were only increased (Ptrained subjects. HIF2alpha mRNA only increased (Ptrained, with no difference between the 70% and 85% of VO2 peak...

  13. Therapy-relevant aberrant expression of MRP3 and BCRP mRNA in TCC-/SCC-bladder cancer tissue of untreated patients.

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    Rady, Mona; Mostageer, Marwa; Rohde, Jan; Zaghloul, Ashraf; Knüchel-Clarke, Ruth; Saad, Shady; Attia, Deena; Mahran, Laila; Spahn-Langguth, Hilde

    2017-07-01

    Multidrug resistance (MDR) is a critical factor, which results in suboptimal outcomes in cancer chemotherapy. One principal mechanism of MDR is the increased expression of ATP-binding cassette (ABC) transporters. Of these, multidrug resistance-associated protein 3 (MRP3) and breast cancer resistance protein (BCRP) confer MDR when overexpressed in cancer cell lines. We measured the mRNA expression of MRP3 and BCRP in primary untreated bladder cancer specimens using reverse transcription-quantitative PCR (RT-qPCR) in comparison to normal bladder tissue. The MRP3 and BCRP expression in the two major histotypes of bladder cancer; transitional cell carcinoma (TCC; urothelial type of bladder cancer) and squamous cell carcinoma (SCC; 'Schistosoma-induced' bladder cancer) were compared. Furthermore, the association between MRP3 and BCRP expression and tumor grade and stage were investigated. MRP3 mRNA expression in bladder cancer specimens was increased ~13-fold on average compared to normal bladder tissue (n=36, PTCC showed significantly increased MRP3 mRNA expression compared to SCC of the bladder (PTCC and SCC of the bladder (P=0.1072). The increased MRP3 mRNA expression was not related to bladder tumor grade (P=0.3465) but was, however, significantly higher in superficial than in invasive bladder tumors (P=0.0173). The decreased expression of BCRP was not related to bladder tumor grade (P=0.1808) or stage (P=0.8016). The current data show that bladder cancer is associated with perturbed expression of MRP3 and BCRP. Representing drug resistance factors, determining the expression of these transporters in native tumors may be predictive of the outcome of chemotherapy based-treatment of bladder cancer.

  14. Increased IL-10 mRNA and IL-23 mRNA expression in multiple sclerosis: interferon-beta treatment increases IL-10 mRNA expression while reducing IL-23 mRNA expression

    DEFF Research Database (Denmark)

    Krakauer, M.; Sorensen, P.; Khademi, M.

    2008-01-01

    of the regulatory cytokine IL-10. The elevated IL-23 mRNA levels in MS patients are noteworthy in view of the newly discovered IL-23-driven Th17 T-cell subset, which is crucial in animal models of MS. Since IFN-beta therapy resulted in decreased IL-23 mRNA levels, the Th17 axis could be another target of IFN-beta......BACKGROUND: Interferon (IFN)-beta therapy in multiple sclerosis (MS) has been suggested to promote a deviation from T lymphocyte production of pathogenic Th1 cytokines to less detrimental Th2 cytokines, but this is still controversial. We studied patterns of in vivo blood mononuclear cell (MNC......) and whole blood cytokine and transcription factor mRNA expression before and during IFN-beta therapy in MS. METHODS: Twenty patients with relapsing-remitting MS were sampled before and after 3 months of treatment with IFN-beta along with 15 healthy volunteers. An additional 39 patients and 50 healthy...

  15. Peripheral Mononuclear Cell Resistin mRNA Expression Is Increased in Type 2 Diabetic Women

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    Panayoula C. Tsiotra

    2008-01-01

    Full Text Available Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P=.05. Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1β, TNF-α, and IL-6 were all significantly higher in DM2 compared to control women (P<.001. The corresponding plasma resistin levels were slightly, but not significantly, increased in DM2 women (P=.051, and overall, they correlated significantly with BMI (r=0.406, P=.010 and waist circumference (r=0.516, P=.003, but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1β, TNF-α, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients.

  16. Linear and non-linear dependencies between copy number aberrations and mRNA expression reveal distinct molecular pathways in breast cancer

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    Frigessi Arnoldo

    2011-05-01

    Full Text Available Abstract Background Elucidating the exact relationship between gene copy number and expression would enable identification of regulatory mechanisms of abnormal gene expression and biological pathways of regulation. Most current approaches either depend on linear correlation or on nonparametric tests of association that are insensitive to the exact shape of the relationship. Based on knowledge of enzyme kinetics and gene regulation, we would expect the functional shape of the relationship to be gene dependent and to be related to the gene regulatory mechanisms involved. Here, we propose a statistical approach to investigate and distinguish between linear and nonlinear dependences between DNA copy number alteration and mRNA expression. Results We applied the proposed method to DNA copy numbers derived from Illumina 109 K SNP-CGH arrays (using the log R values and expression data from Agilent 44 K mRNA arrays, focusing on commonly aberrated genomic loci in a collection of 102 breast tumors. Regression analysis was used to identify the type of relationship (linear or nonlinear, and subsequent pathway analysis revealed that genes displaying a linear relationship were overall associated with substantially different biological processes than genes displaying a nonlinear relationship. In the group of genes with a linear relationship, we found significant association to canonical pathways, including purine and pyrimidine metabolism (for both deletions and amplifications as well as estrogen metabolism (linear amplification and BRCA-related response to damage (linear deletion. In the group of genes displaying a nonlinear relationship, the top canonical pathways were specific pathways like PTEN and PI13K/AKT (nonlinear amplification and Wnt(B and IL-2 signalling (nonlinear deletion. Both amplifications and deletions pointed to the same affected pathways and identified cancer as the top significant disease and cell cycle, cell signaling and cellular

  17. Peripheral mononuclear cell resistin mRNA expression is increased in type 2 diabetic women.

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    Tsiotra, Panayoula C; Tsigos, Constantine; Anastasiou, Eleni; Yfanti, Eleni; Boutati, Eleni; Souvatzoglou, Emmanouil; Kyrou, Ioannis; Raptis, Sotirios A

    2008-01-01

    Resistin has been shown to cause insulin resistance and to impair glucose tolerance in rodents, but in humans its physiological role still remains elusive. The aim of this study was to examine whether resistin mRNA expression in human peripheral mononuclear cells (PBMCs) and its corresponding plasma levels are altered in type 2 diabetes. Resistin mRNA levels were easily detectable in human PBMC, and found to be higher in DM2 compared to healthy women (P = .05). Similarly, mononuclear mRNA levels of the proinflammatory cytokines IL-1beta, TNF-alpha, and IL-6 were all significantly higher in DM2 compared to control women (P DM2 women (P = .051), and overall, they correlated significantly with BMI (r = 0.406, P = .010) and waist circumference (r = 0.516, P = .003), but not with fasting insulin levels or HOMA-IR. Resistin mRNA expression is increased in PBMC from DM2 women, together with increased expression of the inflammatory cytokines IL-1beta, TNF-alpha, and IL-6, independent of obesity. These results suggest that resistin and cytokines might contribute to the low-grade inflammation and the increased atherogenic risk observed in these patients.

  18. X-ray-induced chromosome aberrations in Down lymphocytes: an explanation of their increased sensitivity

    International Nuclear Information System (INIS)

    Preston, R.J.

    1981-01-01

    Unstimulated lymphocytes from individuals with Down Syndrome (trisomy 21) are more sensitive to the induction of dicentric and ring aberrations by X rays than normal lymphocytes. Several explanations involving the more rapid rejoining of X-ray-induced lesions in Down cells have been offered. It is shown here that the repair of the DNA damage converted into chromosome aberrations is more rapid in Down cells than normal cells. This more rapid repair results in a higher probability of producing chromosome aberrations, and hence higher aberration frequencies in Down than normal cells

  19. X-ray-induced chromosome aberrations in Down lymphocytes: an explanation of their increased sensitivity

    International Nuclear Information System (INIS)

    Preston, R.J.

    1981-01-01

    Unstimulated lymphocytes from individuals with Down Syndrome (trisomy 21) are more sensitive to the induction of dicentric and ring aberrations by X rays than normal lymphocytes. Several explanations involving the more rapid rejoining of X-ray--induced lesions in Down cells have been offered. It is shown here that the repair of the DNA damage converted into chromosome aberrations is more rapid in Down cells than normal cells. This more rapid repair results in a higher probability of producing chromosomes aberrations, and hence higher aberration frequencies in Down than normal cells

  20. Increased CB2 mRNA and anandamide in human blood after cessation of cannabis abuse.

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    Muhl, Daniela; Kathmann, Markus; Hoyer, Carolin; Kranaster, Laura; Hellmich, Martin; Gerth, Christoph W; Faulhaber, Johannes; Schlicker, Eberhard; Leweke, F Markus

    2014-07-01

    In previous studies, long-term cannabis use led to alterations of the endocannabinoid system including an increase in CB1 and/or CB2 receptor messenger RNA (mRNA) in blood cells and an increase in the serum level of the endocannabinoid 2-arachidonoyl glycerol. However, in those studies, cannabis use was stopped only few days before testing or not interrupted at all. Therefore, one cannot decide whether the alterations are due to long-term cannabis abuse or are confounded by acute effects of cannabis. Blood was sampled from donors that had smoked marijuana ≥20 times in their lives but had abstained from cannabis for ≥6 months (high-frequency users, HFU) and from controls (cannabis use ≤5 times lifetime). CB1 and CB2 mRNA was determined in peripheral mononuclear blood cells using the reverse transcriptase polymerase chain reaction. Serum anandamide level was assayed using electrospray tandem mass spectrometry. CB2 mRNA was increased by 45 % in HFU when compared to controls, whereas CB1 mRNA did not differ. The anandamide level in HFU exceeded that in controls by 90 %. Tobacco smoking could be excluded as a confounding factor. In conclusion, marijuana users that had smoked marijuana ≥20 times in their lives and stopped cannabis use at least 6 months before the study show an increase in CB2 receptor mRNA in the blood and in serum anandamide level. These alterations resemble those obtained for marijuana smokers that had stopped cannabis use only few days before testing and may be implicated in the pathogenesis of disorders associated with long-term cannabis use.

  1. Stress rapidly increases alpha 1d adrenergic receptor mRNA in the rat dentate gyrus.

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    Campeau, Serge; Nyhuis, Tara J; Kryskow, Elisabeth M; Masini, Cher V; Babb, Jessica A; Sasse, Sarah K; Greenwood, Benjamin N; Fleshner, Monika; Day, Heidi E W

    2010-04-06

    The hippocampal formation is a highly plastic brain region that is sensitive to stress. It receives extensive noradrenergic projections, and noradrenaline is released in the hippocampus in response to stressor exposure. The hippocampus expresses particularly high levels of the alpha(1D) adrenergic receptor (ADR) and we have previously demonstrated that alpha(1d) ADR mRNA expression in the rat hippocampus is modulated by corticosterone. One of the defining features of a stress response is activation of the hypothalamic pituitary adrenal (HPA) axis, resulting in the release of corticosterone from the adrenal glands. However, the effect of stress on hippocampal expression of alpha(1d) ADR mRNA has not been determined. In this study, male rats were exposed to inescapable tail shock, loud noise or restraint, and the effect on alpha(1d) ADR mRNA expression in the hippocampus was determined by semi-quantitative in situ hybridization. All three stressors resulted in a rapid upregulation of alpha(1d) ADR mRNA in the dentate gyrus, with expression peaking at approximately 90min after the start of the stressor. Physical activity has previously been reported to counteract some of the effects of stress that occur within the dentate gyrus. However, 6weeks of voluntary wheel running in rats did not prevent the restraint stress-induced increase in alpha(1d) ADR mRNA expression in the dentate gyrus. Although the function of the alpha(1D) ADR in the dentate gyrus is not known, these data provide further evidence for a close interaction between stress and the noradrenergic system in the hippocampus. Copyright 2010 Elsevier B.V. All rights reserved.

  2. Increased Expression and Aberrant Localization of Mucin 13 in Metastatic Colon Cancer

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    Gupta, Brij K.; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Koch, Michael D.; Lynch, Douglas W.; Bohlmeyer, Teresa; Watanabe, Akira; Aburatani, Hiroyuki; Puumala, Susan E.; Jaggi, Meena

    2012-01-01

    MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (pcolon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (pcolon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer. PMID:22914648

  3. Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in human skeletal muscle.

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    Shearer, Jane; Wilson, Rhonda J; Battram, Danielle S; Richter, Erik A; Robinson, Deborah L; Bakovic, Marica; Graham, Terry E

    2005-09-01

    Glycogenin is the self-glycosylating protein primer that initiates glycogen granule formation. To examine the role of this protein during glycogen resynthesis, eight male subjects exercised to exhaustion on a cycle ergometer at 75% Vo2 max followed by five 30-s sprints at maximal capacity to further deplete glycogen stores. During recovery, carbohydrate (75 g/h) was supplied to promote rapid glycogen repletion, and muscle biopsies were obtained from the vastus lateralis at 0, 30, 120, and 300 min postexercise. At time 0, no free (deglycosylated) glycogenin was detected in muscle, indicating that all glycogenin was complexed to carbohydrate. Glycogenin activity, a measure of the glycosylating ability of the protein, increased at 30 min and remained elevated for the remainder of the study. Quantitative RT-PCR showed elevated glycogenin mRNA at 120 min followed by increases in protein levels at 300 min. Glycogenin specific activity (glycogenin activity/relative protein content) was also elevated at 120 min. Proglycogen increased at all time points, with the highest rate of resynthesis occurring between 0 and 30 min. In comparison, macroglycogen levels did not significantly increase until 300 min postexercise. Together, these results show that, during recovery from prolonged exhaustive exercise, glycogenin mRNA and protein content and activity increase in muscle. This may facilitate rapid glycogen resynthesis by providing the glycogenin backbone of proglycogen, the major component of glycogen synthesized in early recovery.

  4. Acute exercise induces biphasic increase in respiratory mRNA in skeletal muscle

    International Nuclear Information System (INIS)

    Ikeda, Shin-ichi; Kizaki, Takako; Haga, Shukoh; Ohno, Hideki; Takemasa, Tohru

    2008-01-01

    Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) promotes the expression of oxidative enzymes in skeletal muscle. We hypothesized that activation of the p38 MAPK (mitogen-activated protein kinase) in response to exercise was associated with exercise-induced PGC-1α and respiratory enzymes expression and aimed to demonstrate this under the physiological level. We subjected mice to a single bout of treadmill running and found that the exercise induced a biphasic increase in the expression of respiratory enzymes mRNA. The second phase of the increase was accompanied by an increase in PGC-1α protein, but the other was not. Administration of SB203580 (SB), an inhibitor of p38 MAPK, suppressed the increase in PGC-1α expression and respiratory enzymes mRNA in both phases. These data suggest that p38 MAPK is associated with the exercise-induced expression of PGC-1α and biphasic increase in respiratory enzyme mRNAs in mouse skeletal muscle under physiological conditions

  5. Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling.

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    Georg Kern

    Full Text Available Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the macrolide calcineurin inhibitor tacrolimus (FK-506 induced TGF-β-like effects, manifested by increased expression of NAD(PH-oxidase 4 (Nox4, transgelin, tropomyosin 1, and procollagen α1(V mRNA after three days. The macrolide mTOR inhibitor rapamycin had similar effects, while cyclosporine A did not induce fibrose-related genes. Concentration dependence curves were sigmoid, where mRNA expression was induced already at low nanomolar levels of tacrolimus, and reached saturation at 100-300 nM. The effects were independent of extracellular TGF-β as confirmed by the use of neutralizing antibodies, and thus most likely caused by aberrant TGF-β receptor signaling, where binding of tacrolimus to the regulatory FKBP12 protein results in a "leaky" TGF-β receptor. The myofibroblast marker α-smooth muscle actin was neither induced by tacrolimus nor by TGF-β1, indicating an incomplete activation of TK-173 fibroblasts under culture conditions. Tacrolimus- and TGF-β1-induced Nox4 protein upregulation was confirmed by Western blotting, and was accompanied by a rise in intracellular H2O2 concentration. Si-RNA mediated knock-down of Nox4 expression prevented up-regulation of procollagen α1(V mRNA in tacrolimus-treated cells, but induced procollagen α1(V expression in control cells. Nox4 knock-down had no significant effect on the other genes tested. TGF-β is a key molecule in fibrosis, and the constant activation of aberrant receptor signaling by tacrolimus might contribute to the long-term development of interstitial kidney fibrosis in immunosuppressed patients. Nox4 levels possibly play a regulatory role in these processes.

  6. Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in human skeletal muscle

    DEFF Research Database (Denmark)

    Shearer, Jane; Wilson, Rhonda J.; Battram, Danielle S.

    2005-01-01

    Glycogenin is the self-glycosylating protein primer that initiates glycogen granule formation. To examine the role of this protein during glycogen resynthesis, eight male subjects exercised to exhaustion on a cycle ergometer at 75% VO2 max followed by five 30-s sprints at maximal capacity...... to further deplete glycogen stores. During recovery, carbohydrate (75 g/h) was supplied to promote rapid glycogen repletion, and muscle biopsies were obtained from the vastus lateralis at 0, 30, 120, and 300 min postexercise. At time 0, no free (deglycosylated) glycogenin was detected in muscle, indicating...... min postexercise. Together, these results show that, during recovery from prolonged exhaustive exercise, glycogenin mRNA and protein content and activity increase in muscle. This may facilitate rapid glycogen resynthesis by providing the glycogenin backbone of proglycogen, the major component...

  7. Increased mRNA expression of cytochrome oxidase in dorsal raphe nucleus of depressive suicide victims

    Directory of Open Access Journals (Sweden)

    A Sanchez-Bahillo

    2008-04-01

    Full Text Available A Sanchez-Bahillo1, V Bautista-Hernandez1, Carlos Barcia Gonzalez1, R Bañon2, A Luna2, EC Hirsch3, Maria-Trinidad Herrero11Clinical and Experimental Neuroscience, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED; 2Department of Legal Medicine, Department of Human Anatomy, School of Medicine, University of Murcia, Campus de Espinardo, Murcia 30100, Spain; 3INSERM U679 Hôpital de la Salpêtrière, Boulevard de l’Hôpital, Paris, FranceAbstract: Suicidal behavior is a problem with important social repercussions. Some groups of the population show a higher risk of suicide; for example, depression, alcoholism, psychosis or drug abuse frequently precedes suicidal behavior. However, the relationship between metabolic alterations in the brain and premorbid clinical symptoms of suicide remains uncertain. The serotonergic and noradrenergic systems have frequently been, implicated in suicidal behavior and the amount of serotonin in the brain and CSF of suicide victims has been found to be low compared with normal subjects. However, there are contradictory results regarding the role of noradrenergic neurons in the mediation of suicide attempts, possibly reflecting the heterogeneity of conditions that lead to a common outcome. In the present work we focus on the subgroup of suicide victims that share a common diagnosis of major depression. Based on post-mortem studies analyzing mRNA expression by in situ hybridization, serotonergic neurons from the dorsal raphe nucleus (DRN from depressive suicide victims are seen to over-express cytochrome oxidase mRNA. However, no corresponding changes were found in the expression of tyrosine hydroxylase (TH mRNA in the noradrenergic neurons of the Locus Coeruleus (LC. These results suggest that, despite of the low levels of serotonin described in suicide victims, the activity of DRN neurons could increase in the suicidally depressed, probably due to the over activation of

  8. DNA methylation aberrations rather than polymorphisms of FZD3 gene increase the risk of spina bifida in a high-risk region for neural tube defects.

    Science.gov (United States)

    Shangguan, Shaofang; Wang, Li; Chang, Shaoyan; Lu, Xiaoling; Wang, Zhen; Wu, Lihua; Wang, Jianhua; Wang, Xiuwei; Guan, Zhen; Bao, Yihua; Zhao, Huizhi; Zou, Jizhen; Niu, Bo; Zhang, Ting

    2015-01-01

    Animal models of neural tube defects (NTDs) have indicated roles for the Fzd3 gene and the planar cell polarity signaling pathway in convergent extension. We investigated the involvement of FZD3 in genetic and epigenetic mechanisms associated with human NTDs, especially spina bifida. We explored the effects of variants spanning the FZD3 gene in NTDs and examined the role of aberrant methylation of the FZD3 promoter on gene expression in brain tissue in spina bifida. Six FZD3 single nucleotide polymorphisms were genotyped using a MassARRAY system in tissue from 165 NTD fetuses and 152 controls. DNA methylation aberrations in the FZD3 promoter region were detected using a MassARRAY EpiTYPER (17 CpG units from -500 to -2400 bp from the transcription start site) in brain tissue from 77 spina bifida and 74 control fetuses. None of the six single nucleotide polymorphisms evaluated were significantly associated with spina bifida, but the mean methylation level was significantly higher in spina bifida samples (13.70%) compared with control samples (10.91%) (p = 0.001). In terms of specific sites, DNA methylation levels were significantly higher in the spina bifida samples at 14 of the 17 CpG units, which mostly included in R2 region. FZD3 mRNA expression was negatively correlated with methylation of the FZD3 promoter region, especially the R2 region (R = 0.970; p = 0.001) in HeLa cells. The results of this study suggest that DNA methylation plays an important role in FZD3 gene expression regulation and may be associated with an increased risk of spina bifida. © 2014 Wiley Periodicals, Inc.

  9. Tau mRNA 3'UTR-to-CDS ratio is increased in Alzheimer disease.

    Science.gov (United States)

    García-Escudero, Vega; Gargini, Ricardo; Martín-Maestro, Patricia; García, Esther; García-Escudero, Ramón; Avila, Jesús

    2017-08-10

    Neurons frequently show an imbalance in expression of the 3' untranslated region (3'UTR) relative to the coding DNA sequence (CDS) region of mature messenger RNAs (mRNA). The ratio varies among different cells or parts of the brain. The Map2 protein levels per cell depend on the 3'UTR-to-CDS ratio rather than the total mRNA amount, which suggests powerful regulation of protein expression by 3'UTR sequences. Here we found that MAPT (the microtubule-associated protein tau gene) 3'UTR levels are particularly high with respect to other genes; indeed, the 3'UTR-to-CDS ratio of MAPT is balanced in healthy brain in mouse and human. The tau protein accumulates in Alzheimer diseased brain. We nonetheless observed that the levels of RNA encoding MAPT/tau were diminished in these patients' brains. To explain this apparently contradictory result, we studied MAPT mRNA stoichiometry in coding and non-coding regions, and found that the 3'UTR-to-CDS ratio was higher in the hippocampus of Alzheimer disease patients, with higher tau protein but lower total mRNA levels. Our data indicate that changes in the 3'UTR-to-CDS ratio have a regulatory role in the disease. Future research should thus consider not only mRNA levels, but also the ratios between coding and non-coding regions. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Gestational Protein Restriction Increases Cardiac Connexin 43 mRNA levels in male adult rat offspring.

    Science.gov (United States)

    Rossini, Kamila Fernanda; Oliveira, Camila Andrea de; Rebelato, Hércules Jonas; Esquisatto, Marcelo Augusto Marreto; Catisti, Rosana

    2017-07-01

    The dietary limitation during pregnancy influences the growth and development of the fetus and offspring and their health into adult life. The mechanisms underlying the adverse effects of gestational protein restriction (GPR) in the development of the offspring hearts are not well understood. The aim of this study was to evaluate the effects of GPR on cardiac structure in male rat offspring at day 60 after birth (d60). Pregnant Wistar rats were fed a normal-protein (NP, 17% casein) or low-protein (LP, 6% casein) diet. Blood pressure (BP) values from 60-day-old male offspring were measured by an indirect tail-cuff method using an electro sphygmomanometer. Hearts (d60) were collected for assessment of connexin 43 (Cx43) mRNA expression and morphological and morphometric analysis. LP offspring showed no difference in body weight, although they were born lighter than NP offspring. BP levels were significantly higher in the LP group. We observed a significant increase in the area occupied by collagen fibers, a decrease in the number of cardiomyocytes by 104 µm2, and an increase in cardiomyocyte area associated with an increased Cx43 expression. GPR changes myocardial levels of Cx43 mRNA in male young adult rats, suggesting that this mechanism aims to compensate the fibrotic process by the accumulation of collagen fibers in the heart interstitium. A limitação dietética durante a gravidez influencia o crescimento e desenvolvimento do feto e da prole e sua saúde na vida adulta. Os mecanismos subjacentes dos efeitos adversos da restrição proteica gestacional (RPG) no desenvolvimento dos corações da prole não são bem compreendidos. Avaliar os efeitos da RPG sobre a estrutura cardíaca em filhotes machos de ratas aos 60 dias após o nascimento (d60). Ratos fêmeas Wistar grávidas foram alimentadas com uma dieta de proteína normal (PN, 17% caseína) ou de baixa proteína (BP, caseína 6%). Os valores de pressão arterial (PA) de descendentes do sexo masculino de

  11. Increased thymidylate synthase mRNA concentration in blood leukocytes following an experimental stressor

    DEFF Research Database (Denmark)

    Ehrnrooth, Eva; Zacharia, Robert; Svendsen, Gunner

    2002-01-01

    BACKGROUND: While it is well documented that immune responses, e.g. proliferative responses, can be influenced by psychosocial factors, e.g. stress, less is known about the biological mechanisms mediating such influences. The aim of the present investigation was to study the effect...... experimental conditions at baseline in cortisol (p = 0.9) or TS mRNA levels (p = 0.1), significantly higher TS mRNA expression was found immediately after stress compared to pretreatment levels (p effect of the experimental stressor, with higher cortisol levels...... of an experimental stressor on mRNA levels in peripheral blood leukocytes of thymidylate synthase (TS), a gene necessary for cell division, while investigating possible individual differences in stress reactivity. METHODS: Fifteen healthy subjects were investigated under three experimental conditions: (1) exposure...

  12. Increased thymidylate synthase mRNA concentration in blood leukocytes following an experimental stressor

    DEFF Research Database (Denmark)

    Ehrnrooth, Eva; Zacharia, Robert; Svendsen, Gunner

    2002-01-01

    of an experimental stressor on mRNA levels in peripheral blood leukocytes of thymidylate synthase (TS), a gene necessary for cell division, while investigating possible individual differences in stress reactivity. METHODS: Fifteen healthy subjects were investigated under three experimental conditions: (1) exposure...... to a computerized mental stressor; (2) relaxation, and (3) control. Measurements included TS mRNA levels, total leukocyte number, leukocyte subtypes, and serum cortisol before (baseline), immediately after, and 1 h after each experimental condition. RESULTS: While no significant differences were found between...... in percentage of neutrophil cells after stress. CONCLUSION: The results suggest that TS mRNA levels in peripheral leukocytes may be sensitive to mental stress and confirm previous findings indicating that subjects scoring high on the personality trait of absorption exhibit greater physiological stress...

  13. IGF-II transgenic mice display increased aberrant colon crypt multiplicity and tumor volume after 1,2-dimethylhydrazine treatment

    Directory of Open Access Journals (Sweden)

    Oesterle Doris

    2006-01-01

    Full Text Available Abstract In colorectal cancer insulin-like growth factor II (IGF-II is frequently overexpressed. To evaluate, whether IGF-II affects different stages of tumorigenesis, we induced neoplastic alterations in the colon of wild-type and IGF-II transgenic mice using 1,2-dimethylhydrazine (DMH. Aberrant crypt foci (ACF served as markers of early lesions in the colonic mucosa, whereas adenomas and carcinomas characterized the endpoints of tumor development. DMH-treatment led initially to significantly more ACF in IGF-II transgenic than in wild-type mice. This increase in ACF was especially prominent for those consisting of ≥three aberrant crypts (AC. Nevertheless, adenomas and adenocarcinomas of the colon, present after 34 weeks in both genetic groups, were not found at different frequency. Tumor volumes, however, were significantly higher in IGF-II transgenic mice and correlated with serum IGF-II levels. Immunohistochemical staining for markers of proliferation and apoptosis revealed increased cell proliferation rates in tumors of IGF-II transgenic mice without significant affection of apoptosis. Increased proliferation was accompanied by elevated localization of β-catenin in the cytosol and cell nuclei and reduced appearance at the inner plasma membrane. In conclusion, we provide evidence that IGF-II, via activation of the β-catenin signaling cascade, promotes growth of ACF and tumors without affecting tumor numbers.

  14. Tributyltin (TBT) increases TNFα mRNA expression and induces apoptosis in the murine macrophage cell line in vitro.

    Science.gov (United States)

    Nakano, Ken; Tsunoda, Masashi; Konno, Nobuhiro

    2004-11-01

    Tributyltin (TBT) compounds have been widely used as antifouling agents for shipbottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1,in vitro. We examined tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) andc-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity. The mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1β was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently. The increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα andc-jun by TBT may be related to apoptosis in macrophages.

  15. Different loci and mRNA copy number of the increased serum survival gene of Escherichia coli.

    Science.gov (United States)

    Xu, Wang-Ye; Li, Yi-Jing; Fan, Chen

    2018-02-01

    The increased serum survival gene (iss) has been identified as a virulence trait associated with the virulence of Escherichia coli, causing colibacillosis in poultry. However, it remains unclear as to whether iss mRNA copy number and sequence affect virulence. To examine these influences, we assessed the presence of iss, sequence analysis, iss mRNA copy number, and serum resistance. The iss gene was detected in 88 (all) E. coli isolates from different sources, and sequencing identified 16 alleles (32 different loci) and 10 amino acid sequences (10 different loci). Nested polymerase chain reaction improved iss detection. The isolates from sick chickens had >68% livability in serum resistance tests and higher iss mRNA copy number. The iss mRNA copy number highly correlated with mortality and E. coli livability. Student's t tests confirmed the relationship between the different loci to iss transcription, serum resistance, and virulence. These data suggest that iss mRNA copy number and different loci affect the virulence and serum resistance. These findings could be useful in further studies on the prevalence of iss among E. coli isolates and other virulence factors.

  16. Toll-like receptor mRNA expression is selectively increased in the colonic mucosa of two animal models relevant to irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Declan P McKernan

    2009-12-01

    Full Text Available Irritable bowel syndrome (IBS is largely viewed as a stress-related disorder caused by aberrant brain-gut-immune communication and altered gastrointestinal (GI homeostasis. Accumulating evidence demonstrates that stress modulates innate immune responses; however, very little is known on the immunological effects of stress on the GI tract. Toll-like receptors (TLRs are critical pattern recognition molecules of the innate immune system. Activation of TLRs by bacterial and viral molecules leads to activation of NF-kB and an increase in inflammatory cytokine expression. It was our hypothesis that innate immune receptor expression may be changed in the gastrointestinal tract of animals with stress-induced IBS-like symptoms.In this study, our objective was to evaluate the TLR expression profile in the colonic mucosa of two rat strains that display colonic visceral hypersensitivity; the stress-sensitive Wistar-Kyoto (WKY rat and the maternally separated (MS rat. Quantitative PCR of TLR2-10 mRNA in both the proximal and distal colonic mucosae was carried out in adulthood. Significant increases are seen in the mRNA levels of TLR3, 4 & 5 in both the distal and proximal colonic mucosa of MS rats compared with controls. No significant differences were noted for TLR 2, 7, 9 & 10 while TLR 6 could not be detected in any samples in both rat strains. The WKY strain have increased levels of mRNA expression of TLR3, 4, 5, 7, 8, 9 & 10 in both the distal and proximal colonic mucosa compared to the control Sprague-Dawley strain. No significant differences in expression were found for TLR2 while as before TLR6 could not be detected in all samples in both strains.These data suggest that both early life stress (MS and a genetic predisposition (WKY to stress affect the expression of key sentinels of the innate immune system which may have direct relevance for the molecular pathophysiology of IBS.

  17. Statins Activate Human PPAR Promoter and Increase PPAR mRNA Expression and Activation in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Makoto Seo

    2008-01-01

    Full Text Available Statins increase peroxisome proliferator-activated receptor (PPAR mRNA expression, but the mechanism of this increased PPAR production remains elusive. To examine the regulation of PPAR production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin on human PPAR promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1 Majority of statins enhanced PPAR promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPAR promoter. This enhancement may be mediated by statin-induced HNF-4. (2 PPAR mRNA expression was increased by statin treatment. (3 The PPAR levels in nuclear fractions were increased by statin treatment. (4 Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPAR/RXR expression vectors. In summary, these data demonstrate that PPAR production and activation are upregulated through the PPAR promoter activity by statin treatment.

  18. Aberrant lymphatic development in euploid fetuses with increased nuchal translucency including Noonan syndrome.

    NARCIS (Netherlands)

    Mooij, Y.M. de; Akker, N.M. van den; Bekker, M.N.; Bartelings, M.M.; Vugt, J.M.G. van; Gittenberger-de Groot, A.C.

    2011-01-01

    OBJECTIVE: Increased nuchal translucency in the human fetus is associated with aneuploidy, structural malformations and several syndromes such as Noonan syndrome. In 60-70% of the Noonan syndrome cases, a gene mutation can be demonstrated. Previous research showed that aneuploid fetuses with

  19. Non-thermal atmospheric pressure plasma increased mRNA expression of growth factors in human gingival fibroblasts.

    Science.gov (United States)

    Kwon, Jae-Sung; Kim, Yong Hee; Choi, Eun Ha; Kim, Chong-Kwan; Kim, Kyoung-Nam; Kim, Kwang-Mahn

    2016-09-01

    The aim of this in vitro study was to investigate the effects of a non-thermal atmospheric pressure plasma jet (NTAPPJ) on the cellular activity of human gingival fibroblasts (HGF) for possible non-surgical application of it during gingival wound healing. HGF cells were exposed with NTAPPJ for 1, 2, and 4 min and were investigated for cellular attachment, cell viability, morphology of attached cells, proliferation rate, and messenger ribonucleic acid (mRNA) expression of various growth factors. Also, scavengers for chemicals produced by NTAPPJ were used to identify the chemical species responsible for the effects. There was no significant change in the number of HGF cells attached or their proliferation following NTAPPJ exposure. Also, high cell viability resulted from exposure of all of HGF cells to NTAPPJ for 1, 2, and 4 min. However, cells were more stretched while the mRNA expressions of transforming growth factor and vascular endothelial growth factor were significantly increased following NTAPPJ exposure. Additionally, the scavenger test showed that nitric oxide is likely to be the chemical responsible for an increase of cellular activity. The results demonstrated that the NTAPPJ increased mRNA expressions of growth factors in human gingival fibroblasts. Application of NTAPPJ would be useful in gingival wound healing in clinics though additional studies confirming the effects would be needed.

  20. In situ hybridization of nucleus basalis neurons shows increased β-amyloid mRNA in Alzheimer disease

    International Nuclear Information System (INIS)

    Cohen, M.L.; Golde, T.E.; Usiak, M.F.; Younkin, L.H.; Younkin, S.G.

    1988-01-01

    To determine which cells within the brain produce β-amyloid mRNA and to assess expression of the β-amyloid gene in Alzheimer disease, the authors analyzed brain tissue from Alzheimer and control patients by in situ hybridization. The results demonstrate that β-amyloid mRNA is produced by neurons in the nucleus basalis of Meynert and cerebral cortex and that nuclues basalis perikarya from Alzheimer patients consistently hybridize more β-amyloid probe than those from controls. These observations support the hypothesis that increased expression of the β-amyloid gene plays an important role in the deposition of amyloid in the brains of patients with Alzheimer disease

  1. Chromosomal aberration

    International Nuclear Information System (INIS)

    Ishii, Yutaka

    1988-01-01

    Chromosomal aberrations are classified into two types, chromosome-type and chromatid-type. Chromosom-type aberrations include terminal deletion, dicentric, ring and interstitial deletion, and chromatid-type aberrations include achromatic lesion, chromatid deletion, isochromatid deletion and chromatid exchange. Clastogens which induce chromosomal aberration are divided into ''S-dependent'' agents and ''S-independent''. It might mean whether they can induce double strand breaks independent of the S phase or not. Double strand breaks may be the ultimate lesions to induce chromosomal aberrations. Caffeine added even in the G 2 phase appeared to modify the frequency of chromatid aberrations induced by X-rays and mitomycin C. Those might suggest that the G 2 phase involves in the chromatid aberration formation. The double strand breaks might be repaired by ''G 2 repair system'', the error of which might yield breakage types of chromatid aberrations and the by-pass of which might yield chromatid exchanges. Chromosome-type aberrations might be formed in the G 1 phase. (author)

  2. Spontaneous class switch recombination in B cell lymphopoiesis generates aberrant switch junctions and is increased after VDJ rearrangement.

    Science.gov (United States)

    Edry, Efrat; Koralov, Sergei B; Rajewsky, Klaus; Melamed, Doron

    2007-11-15

    Mature B cells replace the mu constant region of the H chain with a downstream isotype in a process of class switch recombination (CSR). Studies suggest that CSR induction is limited to activated mature B cells in the periphery. Recently, we have shown that CSR spontaneously occur in B lymphopoiesis. However, the mechanism and regulation of it have not been defined. In this study, we show that spontaneous CSR occurs at all stages of B cell development and generates aberrant joining of the switch junctions as revealed by: 1) increased load of somatic mutations around the CSR break points, 2) reduced sequence overlaps at the junctions, and 3) excessive switch region deletion. In addition, we found that incidence of spontaneous CSR is increased in cells carrying VDJ rearrangements. Our results reveal major differences between spontaneous CSR in developing B cells and CSR induced in mature B cells upon activation. These differences can be explained by deregulated expression or function of activation-induced cytidine deaminase early in B cell development.

  3. Miconia sp. Increases mRNA Levels of PPAR Gamma and Inhibits Alpha Amylase and Alpha Glucosidase

    Directory of Open Access Journals (Sweden)

    David Mizael Ortíz-Martinez

    2016-01-01

    Full Text Available Diabetes mellitus is a public health problem worldwide. For this reason, ethanolic extract of Miconia sp. from Oaxaca, Mexico, was selected in search of an alternative against this disease. The effect of Miconia sp. on mRNA expression of PPARγ on cell line 3T3-L1, its effect on alpha amylase and alpha glucosidase, lipid accumulation during adipogenesis, and cell viability on VERO cells were evaluated. The mRNA levels of PPARγ increased on 1.393±0.008 folds, lipid accumulation was increased by 29.55% with Miconia sp. extract and 34.57% with rosiglitazone, and α-amylase and α-glycosidase were inhibited with IC50 values from 28.23±2.15 μg/mL and 1.95±0.15 μg/mL, respectively; the IC50 on antiproliferative activity on VERO cells was 314.54±45.40 μg/mL. In case of α-amylase and α-glycosidase assays, IC50 (inhibitory concentration 50 refers to necessary extract amounts to inhibit 50% of enzymatic activity. On the other hand, on antiproliferative activity, IC50 (inhibitory concentration 50 refers to necessary extract amounts to inhibit 50% of cell proliferation. It was concluded that the compounds present in Miconia sp. ethanolic extract increase mRNA expression of PPARγ, inhibit α-amylase and α-glucosidase, and increase lipid accumulation. It constitutes an alternative as adjuvant in diabetes mellitus treatment; therefore, we recommend continuing identifying the compounds responsible for its promising in vivo antidiabetic activity.

  4. Increased skeletal muscle 11βHSD1 mRNA is associated with lower muscle strength in ageing.

    Directory of Open Access Journals (Sweden)

    Alixe H M Kilgour

    Full Text Available Sarcopenia, the loss of muscle mass and function with age, is associated with increased morbidity and mortality. Current understanding of the underlying mechanisms is limited. Glucocorticoids (GC in excess cause muscle weakness and atrophy. We hypothesized that GC may contribute to sarcopenia through elevated circulating levels or increased glucocorticoid receptor (GR signaling by increased expression of either GR or the GC-amplifying enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11βHSD1 in muscle.There were 82 participants; group 1 comprised 33 older men (mean age 70.2 years, SD 4.4 and 19 younger men (22.2 years, 1.7 and group 2 comprised 16 older men (79.1 years, 3.4 and 14 older women (80.1 years, 3.7. We measured muscle strength, mid-thigh cross-sectional area, fasting morning plasma cortisol, quadriceps muscle GR and 11βHSD1 mRNA, and urinary glucocorticoid metabolites. Data were analysed using multiple linear regression adjusting for age, gender and body size.Muscle strength and size were not associated with plasma cortisol, total urinary glucocorticoids or the ratio of urinary 5β-tetrahydrocortisol +5α-tetrahydrocortisol to tetrahydrocortisone (an index of systemic 11βHSD activity. Muscle strength was associated with 11βHSD1 mRNA levels (β -0.35, p = 0.04, but GR mRNA levels were not significantly associated with muscle strength or size.Although circulating levels of GC are not associated with muscle strength or size in either gender, increased cortisol generation within muscle by 11βHSD1 may contribute to loss of muscle strength with age, a key component of sarcopenia. Inhibition of 11βHSD1 may have therapeutic potential in sarcopenia.

  5. Introduction of enteral food increases plasma GLP-2 and decreases GLP-2 receptor mRNA abundance during pig development

    DEFF Research Database (Denmark)

    Petersen, Yvette M; Hartmann, Bolette; Holst, Jens Juul

    2003-01-01

    increased before birth, peaked in suckling 1-d-old pigs (87 +/- 14 pmol/L, P food intake resumed (81 +/- 9 pmol/L, P ... of the response was delayed in premature newborn pigs. Small intestinal GLP-2R mRNA abundance was highest at birth and decreased with enteral food intake in fetal, suckling and weaned pigs (P ... of colostrum in fetal pigs at 92% gestation compared with untreated controls (59 +/- 11 vs. 7 +/- 2 pmol/L, P time course...

  6. Improving the expression of recombinant pullulanase by increasing mRNA stability in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Tao Li

    2017-09-01

    Conclusion: The addition of the 5′ SD sequence at the 5′ UTR and a 3′ stem-loop structure at the 3′ UTR of the pulA gene is an effective approach to increase pulA gene expression and fermentation enzyme activity.

  7. Steady-state levels of aquaporin 1 mRNA expression are increased in idiopathic polyhydramnios.

    Science.gov (United States)

    Mann, Stephanie E; Dvorak, Natalia; Gilbert, Heather; Taylor, Robert N

    2006-03-01

    Polyhydramnios is a condition associated with significant perinatal morbidity. While the exact pathophysiology of this condition is unknown in the absence of obvious anatomic or organic etiologies, impaired intramembranous water transport has been shown. Previous studies from our laboratory have shown that the water channel aquaporin 1 (AQP1) is expressed in human fetal membranes from term pregnancies with normal amniotic fluid (AF) volume. Therefore, we hypothesized that in pregnancies with idiopathic polyhydramnios, AQP1 expression might be reduced in fetal membranes from pregnancies with this AF volume disorder. Placentas were collected from women at term (37-40 weeks) who presented with either polyhydramnios (amniotic fluid index [AFI] >24.0 cm) or normal AF volume (AFI 5.0-23.9 cm). Immediately after delivery, the membranes (amnion and chorion) directly overlying the placenta and the free-floating reflected membranes were sampled (total of 4 samples from each placenta). RNA was isolated from each sample and expression was quantified using real-time reverse transcriptase polymerase chain reaction (PCR) and relative quantification of gene expression. Relative to pregnancies with normal AF volume, there was an increase in expression of the water channel AQP1 in all regions of the fetal membranes. The greatest increase (33-fold) was seen in the reflected amnion. AQP1 expression is increased in polyhydramnios. This finding suggests that alterations in AQP1 expression may be a compensatory response to and not a cause of idiopathic polyhydramnios. We speculate that therapies focused on regulating AQP1 expression may be useful for treating this condition.

  8. No increase in radiation-induced chromosome aberration complexity detected by m-FISH after culture in the presence of 5'-bromodeoxyuridine

    International Nuclear Information System (INIS)

    Sumption, Natalia D.; Goodhead, Dudley T.; Anderson, Rhona M.

    2006-01-01

    The thymidine analogue, 5'-bromodeoxyuridine (BrdU), is a known mutagen that is routinely introduced into culture media for subsequent Harlequin stain analysis and determination of cell cycle status. Previously, we examined the induction of chromosome aberrations in human peripheral blood lymphocytes (PBL) known to be in their 1st cell division following exposure to a low dose (0.5 Gy, average one α-particle per cell) of high-LET α-particles. We found complex chromosome aberrations to be characteristic of exposure to high-LET radiation and suggested the features of complex exchange to reflect qualitatively the spatial deposition of this densely ionising radiation. To exclude the possibility that BrdU addition post-irradiation influenced the complexity of chromosomal damage observed by m-FISH, the effect of increasing BrdU concentration on aberration complexity was investigated. Comparisons between BrdU concentration (0, 10 and 40 μM) and between sham- and α-particle-irradiated PBL, were made both independently and in combination to enable discrimination between BrdU and high-LET radiation effects. Aberration type, size, complexity and completeness were assessed by m-FISH, and the relative progression through cell division was evaluated. We found no evidence of any qualitative difference in the complexity of damage as visualised by m-FISH but did observe an increase in the frequency of complex exchanges with increasing BrdU concentration indicative of altered cell cycle kinetics. The parameters measured here are consistent with findings from previous in vitro and in vivo work, indicating that each complex aberration visualised by m-FISH is characteristic of the structure of the high-LET α-particle track and the geometry of cell irradiated

  9. EGF receptor inhibitors increase ErbB3 mRNA and protein levels in breast cancer cells

    DEFF Research Database (Denmark)

    Grøvdal, Lene Melsæther; Kim, Jiyoung; Holst, Mikkel Roland

    2012-01-01

    The potential benefits of drugs directly targeting the ErbB receptors for cancer therapy have led to an extensive development within this field. However, the clinical effects of ErbB receptor-targeting drugs in cancer treatment are limited due to a high frequency of resistance. It has been reported...... that, when inhibiting the epidermal growth factor receptor (EGFR) with the tyrosine kinase inhibitor gefitinib, increased activation of ErbB3 via MET, or by re-localization of ErbB3 mediates cell survival. Here we show further evidence that members of the ErbB receptor family facilitate resistance...... to EGFR inhibitor treatment in ErbB2 overexpressing breast cancer cells. We found that gefitinib treatment increased ErbB3 expression, both at protein and mRNA levels. ErbB3 expression was upregulated not only by gefitinib but also by a panel of different EGFR inhibitors, suggesting that inhibition...

  10. Introduction of enteral food increases plasma GLP-2 and decreases GLP-2 receptor mRNA abundance during pig development

    DEFF Research Database (Denmark)

    Petersen, Yvette M; Hartmann, Bolette; Holst, Jens Juul

    2003-01-01

    in these pigs. We conclude that the introduction of enteral feeding transiently increases plasma GLP-2 concentrations and decreases small intestinal GLP-2R mRNA levels during pig development. GLP-2 may play a role in the growth of the small intestine around birth and weaning via a response to enteral nutrition....... transcription polymerase chain reaction) during pre- and postnatal development and the relationship between these variables and small intestinal growth in enterally and parenterally fed fetal and newborn pigs (premature and term-delivered, 92 and 100% gestation, respectively). Plasma GLP-2 concentrations...... increased before birth, peaked in suckling 1-d-old pigs (87 +/- 14 pmol/L, P enteral infusion...

  11. Increased mRNA expression of genes involved in pronociceptive inflammatory reactions in bladder tissue of interstitial cystitis.

    Science.gov (United States)

    Homma, Yukio; Nomiya, Akira; Tagaya, Mitsuhiro; Oyama, Tatsuya; Takagaki, Kazuchika; Nishimatsu, Hiroaki; Igawa, Yasuhiko

    2013-11-01

    We assayed mRNA expression of the TRP family of channels and ASIC1 in bladder tissue from patients with interstitial cystitis. Bladder biopsies of 1) nonclassic interstitial cystitis, 2) nonulcerative portions of classic interstitial cystitis, 3) ulcerative portions of classic interstitial cystitis and 4) noncancerous portions of bladder cancer as the control were placed immediately in ice-cold RNAlater® and subjected to real-time reverse transcriptase-polymerase chain reaction. We compared the mRNA expression of TRP channels, ASIC1, NGF, CXCL9 and UPK3A with that of controls, and correlated expression with symptom severity. We analyzed specimens from 17 patients with nonclassic interstitial cystitis, 22 with classic interstitial cystitis and 11 controls. In nonclassic interstitial cystitis samples TRPV2 and NGF showed significantly increased expression. In classic interstitial cystitis samples nonulcerative portions demonstrated a significant increase in the expression of TRPA1, TRPM2 and 8, TRPV1 and 2, ASIC1, NGF and CXCL9, and a significant decrease in UPK3A and TRPV4. Ulcerative portions showed similar changes for TRPM2, TRPV1, 2 and 4, CXCL9 and UPK3A. Increased expression of TRPM2, first noted in interstitial cystitis tissue, was the most pronounced one of the TRP family. All symptom measures correlated with TRPM2 and TRPV2 expression, and partially with that of the other genes. This study showed increased expression of the genes involved in pronociceptive inflammatory reactions in interstitial cystitis, including TRPV1, 2 and 4, ASIC1, NGF and CXCL9, and to our knowledge TRPM2 for the first time. The different expression patterns suggest distinct pathophysiologies for classic and nonclassic interstitial cystitis. The genes and their products are potential candidates for use as biomarkers or novel therapy targets. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  12. Increased shelterin mRNA expression in peripheral blood mononuclear cells and skeletal muscle following an ultra-long-distance running event

    DEFF Research Database (Denmark)

    Laye, Matthew J; Solomon, Thomas; Karstoft, Kristian

    2012-01-01

    Located at the end of chromosomes, telomeres are progressively shortened with each replication of DNA during aging. Integral to the regulation of telomere length is a group of proteins making up the shelterin complex, whose tissue-specific function during physiological stress is not well understood....... In this study, we examine the mRNA and protein levels of proteins within and associated with the shelterin complex in subjects (n = 8, mean age = 44 yr) who completed a physiological stress of seven marathons in 7 days. Twenty-two to 24 h after the last marathon, subjects had increased mRNA levels of DNA repair...... enzymes Ku70 and Ku80 (P muscle and peripheral blood mononuclear cells (PBMCs). Additionally, the PBMCs displayed an increment in three shelterin protein mRNA levels (TRF1, TRF2, and Pot-1, P

  13. Quality control systems for aberrant mRNAs induced by aberrant translation elongation and termination.

    Science.gov (United States)

    Inada, Toshifumi

    2013-01-01

    RNA processing is an essential gene expression step and plays a crucial role to achieve diversity of gene products in eukaryotes. Various aberrant mRNAs transiently produced during RNA processing reactions are recognized and eliminated by specific quality control systems. It has been demonstrated that these mRNA quality control systems stimulate the degradation of aberrant mRNA to prevent the potentially harmful products derived from aberrant mRNAs. Recent studies on quality control systems induced by abnormal translation elongation and termination have revealed that both aberrant mRNAs and proteins are subjected to rapid degradation. In NonStop Decay (NSD) quality control system, a poly(A) tail of nonstop mRNA is translated and the synthesis of poly-lysine sequence results in translation arrest followed by co-translational degradation of aberrant nonstop protein. In No-Go Decay (NGD) quality control system, the specific amino acid sequences of the nascent polypeptide induce ribosome stalling, and the arrest products are ubiquitinated and rapidly degraded by the proteasome. In Nonfunctional rRNA Decay (NRD) quality control system, aberrant ribosomes composed of nonfunctional ribosomal RNAs are also eliminated when aberrant translation elongation complexes are formed on mRNA. I describe recent progresses on the mechanisms of quality control systems and the relationships between quality control systems. This article is part of a Special issue entitled: RNA Decay mechanisms. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Serum IL8 and mRNA level of CD11b in circulating neutrophils are increased in clinically amyopathic dermatomyositis with active interstitial lung disease.

    Science.gov (United States)

    Zou, Jing; Chen, Jie; Yan, Qingran; Guo, Qiang; Bao, Chunde

    2016-01-01

    The objective of this study is to assess serum IL8 and the potential activity of circulating neutrophils on relative messenger RNA (mRNA) levels and their relationship with disease activity in clinically amyopathic dermatomyositis (CADM) associated with interstitial lung disease (ILD). We studied 18 CADM patients and compared them with 18 classic dermatomyositis (DM) patients and 18 healthy control subjects. Serum IL8 level and mRNA expressions of neutrophils (chemokine (C-X-C motif) receptor 1 (CXCR1), cluster of differentiation molecule 11b (CD11b), cluster of differentiation 64 (CD64), myeloid cell leukemia 1 (MCL1), interleukin-18 (IL18)) were detected. The overproduction of serum IL8 level was most significant in the CADM group with active period. The mRNA expressions of CD11b, IL18, and MCL1 were greatly increased in the neutrophils in patients with CADM compared with DM or healthy controls. Up-expressions of CD11b, IL18, and MCL1 were detected in the neutrophils in CADM patients of active period compared with remission period. A positive correlation was found between CD11b mRNA level and high-resolution computed tomography (HRCT) score, in CADM associated with ILD. Serum IL8 level and mRNA levels of CD11b, MCL1, and IL18 in circulating neutrophils are related with the disease activity of CADM-ILD. The mRNA level of CD11b is positively correlated with HRCT score in CADM-ILD.

  15. The sensitivity of adipose tissue visfatin mRNA expression to lipopolysaccharide-induced endotoxemia is increased by ovariectomy in female rats.

    Science.gov (United States)

    Iwasa, Takeshi; Matsuzaki, Toshiya; Matsui, Sumika; Tungalagsuvd, Altankhuu; Munkhzaya, Munkhsaikhan; Takiguchi, Eri; Kawakita, Takako; Kuwahara, Akira; Yasui, Toshiyuki; Irahara, Minoru

    2016-06-01

    Visfatin plays an important role in inflammatory and metabolic conditions. In this study, the effects of septic stress on the serum, white-adipose-tissue (WAT), and liver visfatin levels of male and female rats were examined. Both gonadally intact (sham) and ovariectomized (OVX) female rats were used in order to evaluate the effects of the gonadal hormonal milieu on visfatin responses. Under the saline-injected conditions, the serum visfatin levels and the hepatic, subcutaneous, and visceral WAT visfatin mRNA levels of the OVX and sham rats did not differ. The serum visfatin levels and the subcutaneous, visceral WAT, and hepatic visfatin mRNA levels of both male and female rats were increased by the injection of a septic dose (5mg/kg) of LPS. At 6h after the injection of LPS, the WAT visfatin mRNA levels of the OVX rats were higher than those of the sham rats, whereas the serum visfatin levels and hepatic visfatin mRNA levels of the two groups did not differ. In the cultured visceral WAT, visfatin antagonist (FK-866) attenuated the LPS-induced up-regulations of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). The pathophysiological roles of visfatin under septic conditions remain to be clarified. In addition, the precise mechanisms responsible for the increased WAT visfatin expression seen after ovariectomy and the effects of such changes should also be clarified. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. High BMI levels associate with reduced mRNA expression of IL10 and increased mRNA expression of iNOS (NOS2) in human frontal cortex

    DEFF Research Database (Denmark)

    Lauridsen, J K; Olesen, R H; Vendelbo, J

    2017-01-01

    analysis was performed with BMI as variable on data on IL10, IL1β, IL6, PTGS2 (COX2) and NOS2 (iNOS). Increasing BMI is associated with a decrease in the mRNA expression of IL10 (P=0.014) and an increase in the expression of NOS2 (iNOS; P=0.040). Expressions of IL10 and NOS2 (iNOS) were negatively...... correlated (PIL10 was mostly affected by individuals with BMI ⩾40. Multiple linear regression analyses with BMI, age, sex and race as variables were performed in order to identify potential confounders. In conclusion, increasing BMI could affect the IL10-mediated anti...

  17. Increased mRNA expression of peripheral glial cell markers in bipolar disorder: The effect of long-term lithium treatment.

    Science.gov (United States)

    Ferensztajn-Rochowiak, Ewa; Tarnowski, Maciej; Samochowiec, Jerzy; Michalak, Michal; Ratajczak, Mariusz Z; Rybakowski, Janusz K

    2016-09-01

    Neuroinflammation, with microglial activation as an important element, plays a role in the pathogenesis of bipolar disorder (BD). Also, in mood disorders, pathological changes have been demonstrated in macroglial cells, such as astrocyctes and oligodendrocytes. Postmortem brain studies of BD patients to assess glial cells, such as astrocytes and oligodendrocytes and their markers such as glial fibrillary acidic protein (GFAP), Olig1 and Olig2, produced controversial results. On the other hand, investigation of these markers in the peripheral blood of such patients has not been performed so far. In this study, we examined the mRNA levels of GFAP, Olig1 and Olig2, in the peripheral blood of three groups: 15 BD subjects with a duration of illness at least 10 years (mean 20±9 years) but never treated with lithium, 15 subjects with BD treated continuously with lithium for 8-40 years (mean 16±8 years), and 15 control subjects. The groups were age-and sex-matched. Expression of mRNA markers was measured by real-time quantitative reverse transcription PCR (RQ-PCR). We observed increased mRNA levels of the Olig1 and Olig 2 glial markers studied in the BD patients not taking lithium, compared with the control subjects and increased mRNA level of GFAP, compared with lithium-treated patients. In the lithium-treated BD patients GFAP and Olig1 expression was at similar levels to that in the control group. However, Olig 2 expression was even higher than in the BD patients not taking lithium. The possible mechanisms concerning the higher expression of peripheral mRNA markers in BD patients may involve ongoing inflammatory process, compensatory mechanisms and regenerative responses. The beneficial effect of lithium may be related to its anti-inflammatory properties. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  18. Virulence factors of Helicobacter pylori vacA increase markedly gastric mucosal TGF-β1 mRNA expression in gastritis patients.

    Science.gov (United States)

    Rahimian, Ghorbanali; Sanei, Mohammad Hosein; Shirzad, Hedayatollah; Azadegan-Dehkordi, Fatemeh; Taghikhani, Afshin; Salimzadeh, Loghman; Hashemzadeh-Chaleshtori, Morteza; Rafieian-Kopaei, Mahmoud; Bagheri, Nader

    2014-01-01

    Helicobacter pylori (H. pylori) infection is the main cause of gastric inflammation. Regulatory T cells (Treg cells) suppress the activation and proliferation of antigen-specific T cells and mediate immunologic tolerance. TGF-β1 was shown to be secreted in a subset of Treg cells known as 'Th3 cells'. These cells have not been sufficiently studied in context to H. pylori-induced inflammation in human gastric mucosa. In this study we therefore, aimed to investigate the expression of TGF-β1 in the context of H. pylori colonization in chronic gastritis, to examine the relationship between it and histopathologic findings and to compare it with virulence factors. Total RNA was extracted from gastric biopsies of 48 H. pylori-infected patients and 38 H. pylori-negative patients with gastritis. Mucosal TGF-β1 mRNA expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. Presence of vacA, cagA, iceA, babA2 and oipA virulence factors was evaluated using PCR. TGF-β1 mRNA expression was significantly increased in biopsies of H. pylori-infected patients compared to H. pylori-uninfected patients. There was association between virulence factors and TGF-β1 mRNA expression. TGF-β1 mRNA expression in mucosa was significantly higher in patients with vacA s1 and s1m1. TGF-β1 may play an important role in the inflammatory response and promote the chronic and persistent inflammatory changes in the gastric. This may ultimately influence the outcome of H. pylori-associated diseases that arise within the context of gastritis and vacA may suffice to induce expression of TGF-β1 mRNA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Ribonuclease II preserves chloroplast RNA homeostasis by increasing mRNA decay rates, and cooperates with polynucleotide phosphorylase in 3' end maturation.

    Science.gov (United States)

    Germain, Arnaud; Kim, Sang Hu; Gutierrez, Ryan; Stern, David B

    2012-12-01

    Ribonuclease R (RNR1) and polynucleotide phosphorylase (cpPNPase) are the two known 3'→5' exoribonucleases in Arabidopsis chloroplasts, and are involved in several aspects of rRNA and mRNA metabolism. In this work, we show that mutants lacking both RNR1 and cpPNPase exhibit embryo lethality, akin to the non-viability of the analogous double mutant in Escherichia coli. We were successful, however, in combining an rnr1 null mutation with weak pnp mutant alleles, and show that the resulting chlorotic plants display a global reduction in RNA abundance. Such a counterintuitive outcome following the loss of RNA degradation activity suggests a major importance of RNA maturation as a determinant of RNA stability. Detailed analysis of the double mutant demonstrates that the enzymes catalyze a two-step maturation of mRNA 3' ends, with RNR1 polishing 3' termini created by cpPNPase. The bulky quaternary structure of cpPNPase compared with RNR1 could explain this activity split between the two enzymes. In contrast to the double mutants, the rnr1 single mutant overaccumulates most mRNA species when compared with the wild type. The excess mRNAs in rnr1 are often present in non-polysomal fractions, and half-life measurements demonstrate a substantial increase in the stability of most mRNA species tested. Together, our data reveal the cooperative activity of two 3'→5' exoribonucleases in chloroplast mRNA 3' end maturation, and support the hypothesis that RNR1 plays a significant role in the destabilization of mRNAs unprotected by ribosomes. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  20. Diabetes Induces Aberrant DNA Methylation in the Proximal Tubules of the Kidney.

    Science.gov (United States)

    Marumo, Takeshi; Yagi, Shintaro; Kawarazaki, Wakako; Nishimoto, Mitsuhiro; Ayuzawa, Nobuhiro; Watanabe, Atsushi; Ueda, Kohei; Hirahashi, Junichi; Hishikawa, Keiichi; Sakurai, Hiroyuki; Shiota, Kunio; Fujita, Toshiro

    2015-10-01

    Epigenetic mechanisms may underlie the progression of diabetic kidney disease. Because the kidney is a heterogeneous organ with different cell types, we investigated DNA methylation status of the kidney in a cell type-specific manner. We first identified genes specifically demethylated in the normal proximal tubules obtained from control db/m mice, and next delineated the candidate disease-modifying genes bearing aberrant DNA methylation induced by diabetes using db/db mice. Genes involved in glucose metabolism, including Sglt2, Pck1, and G6pc, were selectively hypomethylated in the proximal tubules in control mice. Hnf4a, a transcription factor regulating transporters for reabsorption, was also selectively demethylated. In diabetic mice, aberrant hypomethylation of Agt, Abcc4, Cyp4a10, Glut5, and Met and hypermethylation of Kif20b, Cldn18, and Slco1a1 were observed. Time-dependent demethylation of Agt, a marker of diabetic kidney disease, was accompanied by histone modification changes. Furthermore, inhibition of DNA methyltransferase or histone deacetylase increased Agt mRNA in cultured human proximal tubular cells. Aberrant DNA methylation and concomitant changes in histone modifications and mRNA expression in the diabetic kidney were resistant to antidiabetic treatment with pioglitazone. These results suggest that an epigenetic switch involving aberrant DNA methylation causes persistent mRNA expression of select genes that may lead to phenotype changes of the proximal tubules in diabetic kidney disease. Copyright © 2015 by the American Society of Nephrology.

  1. Ribosome profiling-guided depletion of an mRNA increases cell growth rate and protein secretion

    DEFF Research Database (Denmark)

    Beuchert Kallehauge, Thomas; Li, Shangzhong; Pedersen, Lasse Ebdrup

    2017-01-01

    Recombinant protein production coopts the host cell machinery to provide high protein yields of industrial enzymes or biotherapeutics. However, since protein translation is energetically expensive and tightly controlled, it is unclear if highly expressed recombinant genes are translated as effici......Recombinant protein production coopts the host cell machinery to provide high protein yields of industrial enzymes or biotherapeutics. However, since protein translation is energetically expensive and tightly controlled, it is unclear if highly expressed recombinant genes are translated...... as efficiently as host genes. Furthermore, it is unclear how the high expression impacts global translation. Here, we present the first genome-wide view of protein translation in an IgG-producing CHO cell line, measured with ribosome profiling. Through this we found that our recombinant mRNAs were translated...... as efficiently as the host cell transcriptome, and sequestered up to 15% of the total ribosome occupancy. During cell culture, changes in recombinant mRNA translation were consistent with changes in transcription, demonstrating that transcript levels influence specific productivity. Using this information, we...

  2. Increasing cDNA yields from single-cell quantities of mRNA in standard laboratory reverse transcriptase reactions using acoustic microstreaming.

    Science.gov (United States)

    Boon, Wah Chin; Petkovic-Duran, Karolina; Zhu, Yonggang; Manasseh, Richard; Horne, Malcolm K; Aumann, Tim D

    2011-07-11

    Correlating gene expression with cell behavior is ideally done at the single-cell level. However, this is not easily achieved because the small amount of labile mRNA present in a single cell (1-5% of 1-50 pg total RNA, or 0.01-2.5 pg mRNA, per cell) mostly degrades before it can be reverse transcribed into a stable cDNA copy. For example, using standard laboratory reagents and hardware, only a small number of genes can be qualitatively assessed per cell. One way to increase the efficiency of standard laboratory reverse transcriptase (RT) reactions (i.e. standard reagents in microliter volumes) comprising single-cell amounts of mRNA would be to more rapidly mix the reagents so the mRNA can be converted to cDNA before it degrades. However this is not trivial because at microliter scales liquid flow is laminar, i.e. currently available methods of mixing (i.e. shaking, vortexing and trituration) fail to produce sufficient chaotic motion to effectively mix reagents. To solve this problem, micro-scale mixing techniques have to be used. A number of microfluidic-based mixing technologies have been developed which successfully increase RT reaction yields. However, microfluidics technologies require specialized hardware that is relatively expensive and not yet widely available. A cheaper, more convenient solution is desirable. The main objective of this study is to demonstrate how application of a novel "micromixing" technique to standard laboratory RT reactions comprising single-cell quantities of mRNA significantly increases their cDNA yields. We find cDNA yields increase by approximately 10-100-fold, which enables: greater numbers of genes to be analyzed per cell; more quantitative analysis of gene expression; and better detection of low-abundance genes in single cells. The micromixing is based on acoustic microstreaming, a phenomenon where sound waves propagating around a small obstacle create a mean flow near the obstacle. We have developed an acoustic microstreaming

  3. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    Directory of Open Access Journals (Sweden)

    Jungsuwadee Paiboon

    2011-02-01

    Full Text Available Abstract Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In addition, decreased levels of mRNA associated with T-cell signaling were found in the jejunum and ileum. Several members of the Solute Carrier (SLC and Adenosine Triphosphate Binding Cassette (ABC superfamilies of membrane transporters were found to be differentially expressed; these genes may play a role in differences in nutrient and xenobiotic absorption and disposition. mRNA expression of SLC39a4_predicted, a zinc transporter, was increased in all tissues, suggesting that it is involved in increased zinc uptake during lactation. Microarray data are available through GEO under GSE19175. Conclusions We detected differential expression of mRNA from several pathways in lactating dams, including upregulation of the cholesterol biosynthetic pathway in liver and intestine, consistent with Srebp activation. Differential T-Cell signaling in the two most distal regions of the small intestine (ileum and

  4. Aberrant REST-mediated transcriptional regulation in major depressive disorder.

    Science.gov (United States)

    Otsuki, Koji; Uchida, Shusaku; Wakabayashi, Yusuke; Matsubara, Toshio; Hobara, Teruyuki; Funato, Hiromasa; Watanabe, Yoshifumi

    2010-04-01

    There is growing evidence that aberrant transcriptional regulation is one of the key components of the pathophysiology of mood disorders. The repressor element-1 silencing transcription factor (REST) is a negative regulator of genes that contain the repressor element-1 (RE-1) binding site. REST has many target genes, including corticotropin releasing hormone (CRH), brain-derived neurotrophic factor, serotonin 1A receptor, which are suggested to be involved in the pathophysiology of depression and the action of antidepressants. However, a potential role for REST-mediated transcriptional regulation in mood disorders remains unclear. In this study, we examined the mRNA levels of REST and its known and putative target genes, using quantitative real-time PCR in peripheral blood cells of patients with major depressive and bipolar disorders in both a current depressive and a remissive state. We found reduced mRNA expression of REST and increased mRNA expression of CRH, adenylate cyclase 5, and the tumor necrosis factor superfamily, member 12-13 in patients with major depressive disorder in a current depressive state, but not in a remissive state. Altered expression of these mRNAs was not found in patients with bipolar disorder. Our results suggest that the aberrant REST-mediated transcriptional regulation of, at least, CRH, adenylate cyclase 5, and tumor necrosis factor superfamily, member 12-13, might be state-dependent and associated with the pathophysiology of major depression. Copyright 2009 Elsevier Ltd. All rights reserved.

  5. Antidepressant dose of taurine increases mRNA expression of GABAA receptor α2 subunit and BDNF in the hippocampus of diabetic rats.

    Science.gov (United States)

    Caletti, Greice; Almeida, Felipe Borges; Agnes, Grasiela; Nin, Maurício Schüler; Barros, Helena Maria Tannhauser; Gomez, Rosane

    2015-04-15

    Diabetes mellitus is a metabolic disorder associated with higher risk for depression. Diabetic rats present depressive-like behaviors and taurine, one of the most abundant free amino acids in the brain, reverses this depressive behaviors. Because taurine is a GABAA agonist modulator, we hypothesize that its antidepressant effect results from the interaction on this system by changing α2 GABAA receptor subunit expression, beside changes on BDNF mRNA, and memory in diabetic rats. Streptozotocin-diabetic and non-diabetic Wistar rats were daily injected with 100mg/kg of taurine or saline, intraperitoneally, for 30 days. At the end of the experiment, rats were exposed to the novel object recognition memory. Later they were euthanized, the brains were weighed, and the hippocampus was dissected for α2 GABAA subunit and BDNF mRNA expression. Real-time quantitative PCR (qPCR) showed that diabetic rats presented lower α2 GABAA subunit and BDNF mRNA expression than non-diabetic rats and taurine increased both parameters in these sick rats. Taurine also reversed the lower brain weight and improved the short-term memory in diabetic rats. Thus, the taurine antidepressant effect may be explained by interference with the GABA system, in line to its neuroprotective effect showed here by preventing brain weight loss and improving memory in diabetic rats. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Artesunate Reduces Serum Lipopolysaccharide in Cecal Ligation/Puncture Mice via Enhanced LPS Internalization by Macrophages through Increased mRNA Expression of Scavenger Receptors

    Directory of Open Access Journals (Sweden)

    Bin Li

    2014-01-01

    Full Text Available Innate immunity is the first line of defense in human beings against pathogen infection; monocytes/macrophages are the primary cells of the innate immune system. Recently, macrophages/monocytes have been discovered to participate in LPS clearance, and the clearance efficiency determines the magnitude of the inflammatory response and subsequent organ injury. Previously, we reported that artesunate (AS protected sepsis mice against heat-killed E. coli challenge. Herein, we further confirmed that AS protected cecal ligation/puncture (CLP sepsis mice. Its protection on sepsis mice was related to not only reduction of pro-inflammatory cytokines and serum LPS levels but also improvement of liver function. Based on the fact that AS did not directly bind and neutralize LPS, we hypothesized that the reduction of serum LPS level might be related to enhancement of LPS internalization and subsequent detoxification. Our results showed that AS increased FITC-LPS internalization by peritoneal macrophage and liver Kupffer cell, but enhancement of LPS internalization by AS was not related to the clathrin-dependent pathway. However, AS induced mRNA expression of important scavenger receptors (SRs; SR-A and MARCO mRNA expression was upregulated, suggesting that AS enhancement of LPS internalization and inhibition of pro-inflammatory cytokines was related to changes in mRNA expression of SRs.

  7. Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and thyroid hormone receptor β-1 in a fasting-adapted mammal.

    Science.gov (United States)

    Martinez, Bridget; Soñanez-Organis, José G; Vázquez-Medina, José Pablo; Viscarra, Jose A; MacKenzie, Duncan S; Crocker, Daniel E; Ortiz, Rudy M

    2013-12-15

    Food deprivation in mammals is typically associated with reduced thyroid hormone (TH) concentrations and deiodinase content and activity to suppress metabolism. However, in prolonged-fasted, metabolically active elephant seal pups, TH levels are maintained, if not elevated. The functional relevance of this apparent paradox is unknown and demonstrates variability in the regulation of TH levels, metabolism and function in food-deprived mammals. To address our hypothesis that cellular TH-mediated activity is upregulated with fasting duration, we quantified the mRNA expression and protein content of adipose and muscle deiodinase type I (DI1) and type II (DI2), and TH receptor beta-1 (THrβ-1) after 1, 3 and 7 weeks of fasting in northern elephant seal pups (N=5-7 per week). Fasting did not decrease the concentrations of plasma thyroid stimulating hormone, total triiodothyronine (tT3), free T3, total thyroxine (tT4) or free T4, suggesting that the hypothalamic-pituitary-thyroid axis is not suppressed, but rather maintained during fasting. Mean mRNA expression of adipose DI1 and DI2 increased threefold and fourfold, respectively, and 20- and 30-fold, respectively, in muscle. With the exception of adipose DI1, protein expression of adipose DI2 and muscle DI1 and DI2 increased twofold to fourfold. Fasting also increased adipose (fivefold) and muscle (fourfold) THrβ-1 mRNA expression, suggesting that the mechanisms mediating cellular TH activity are upregulated with prolonged fasting. The data demonstrate a unique, atypical mechanism of TH activity and regulation in mammals adapted to prolonged food deprivation in which the potential responsiveness of peripheral tissues and cellular TH activity are increased, which may contribute to their lipid-based metabolism.

  8. Colonic aberrant crypt formation accompanies an increase of opportunistic pathogenic bacteria in C57BL/6 mice fed a high-fat diet.

    Science.gov (United States)

    Zeng, Huawei; Ishaq, Suzanne L; Liu, Zhenhua; Bukowski, Michael R

    2018-04-01

    The increasing worldwide incidence of colon cancer has been linked to obesity and consumption of a high-fat Western diet. To test the hypothesis that a high-fat diet (HFD) promotes colonic aberrant crypt (AC) formation in a manner associated with gut bacterial dysbiosis, we examined the susceptibility to azoxymethane (AOM)-induced colonic AC and microbiome composition in C57/BL6 mice fed a modified AIN93G diet (AIN, 16% fat, energy) or an HFD (45% fat, energy) for 14 weeks. Mice receiving the HFD exhibited increased plasma leptin, body weight, body fat composition and inflammatory cell infiltration in the ileum compared with those in the AIN group. Consistent with the gut inflammatory phenotype, we observed an increase in colonic AC, plasma interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1 and inducible nitric oxide synthase in the ileum of the HFD-AOM group compared with the AIN-AOM group. Although the HFD and AIN groups did not differ in bacterial species number, the HFD and AIN diets resulted in different bacterial community structures in the colon. The abundance of certain short-chain fatty acid (SCFA) producing bacteria (e.g., Barnesiella) and fecal SCFA (e.g., acetic acid) content were lower in the HFD-AOM group compared with the AIN and AIN-AOM groups. Furthermore, we identified a high abundance of Anaeroplasma bacteria, an opportunistic pathogen in the HFD-AOM group. Collectively, we demonstrate that an HFD promotes AC formation concurrent with an increase of opportunistic pathogenic bacteria in the colon of C57BL/6 mice. Published by Elsevier Inc.

  9. Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation.

    Science.gov (United States)

    Hoffman, Ann N; Parga, Alejandro; Paode, Pooja R; Watterson, Lucas R; Nikulina, Ella M; Hammer, Ronald P; Conrad, Cheryl D

    2015-04-01

    The chronically stressed brain may present a vulnerability to develop maladaptive fear-related behaviors in response to a traumatic event. In rodents, chronic stress leads to amygdala hyperresponsivity and dendritic hypertrophy and produces a post traumatic stress disorder (PTSD)-like phenotype that includes exaggerated fear learning following Pavlovian fear conditioning and resistance to extinction. It is unknown whether chronic stress-induced enhanced fear memories are vulnerable to disruption via reconsolidation blockade, as a novel therapeutic approach for attenuating exaggerated fear memories. We used a chronic stress procedure in a rat model (wire mesh restraint for 6h/d/21d) to create a vulnerable brain that leads to a PTSD-like phenotype. We then examined freezing behavior during acquisition, reactivation and after post-reactivation rapamycin administration (i.p., 40mg/kg) in a Pavlovian fear conditioning paradigm to determine its effects on reconsolidation as well as the subsequent functional activation of limbic structures using zif268 mRNA. Chronic stress increased amygdala zif268 mRNA during fear memory retrieval at reactivation. Moreover, these enhanced fear memories were unaffected by post reactivation rapamycin to disrupt long-term fear memory. Also, post-reactivation long term memory processing was also associated with increased amygdala (LA and BA), and decreased hippocampal CA1 zif268 mRNA expression. These results suggest potential challenges for reconsolidation blockade as an effective approach in treating exaggerated fear memories, as in PTSD. Our findings also support chronic stress manipulations combined with fear conditioning as a useful preclinical approach to study a PTSD-like phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Visfatin, TNF-alpha and IL-6 mRNA expression is increased in mononuclear cells from type 2 diabetic women.

    Science.gov (United States)

    Tsiotra, P C; Tsigos, C; Yfanti, E; Anastasiou, E; Vikentiou, M; Psarra, K; Papasteriades, C; Raptis, S A

    2007-10-01

    Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMIwomen (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (pDM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-alpha, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (pDM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.

  11. The number of preproghrelin mRNA expressing cells is increased in mice with activity-based anorexia.

    Science.gov (United States)

    François, Marie; Barde, Swapnali; Achamrah, Najate; Breton, Jonathan; do Rego, Jean-Claude; Coëffier, Moïse; Hökfelt, Tomas; Déchelotte, Pierre; Fetissov, Sergueï O

    2015-06-01

    Plasma levels of ghrelin, an orexigenic peptide, are increased during conditions of chronic starvation, such as in patients with anorexia nervosa. However, it is not known whether such increase can be related to the number of preproghrelin mRNA-expressing cells in the stomach, and if chronic starvation may activate a tentative central ghrelin production. In this work, in situ hybridization technique was used to analyze the presence and number of preproghrelin mRNA-expressing cells in the stomach and the hypothalamus of mice with activity-based anorexia (ABA) induced by the combination of running wheel activity with progressive, during 10 days, feeding-time restriction (FTR) and compared with sedentary FTR, ABA pair-fed (PF) and ad libitum-fed control mice. All food-restricted mice lost more than 20% of body weight. Body weight loss was similar in ABA and PF mice, but it was more pronounced than in FTR mice. Food intake was also lower in ABA than in FTR mice. Preproghrelin mRNA-expressing cells in the stomach were increased proportionally to the body weight loss in all food-restricted groups with the highest number in ABA mice. No preproghrelin mRNA-producing cells were detectable in the hypothalamus of either control or food-restricted mice. Thus, the increased number of gastric preproghrelin mRNA-producing cells during chronic starvation proportionally to the body weight loss and reduced food intake may underlie increased plasma ghrelin. Hyperactivity-induced anorexia appears to further increase the number of preproghrelin mRNA-producing cells in the stomach. No evidence was found for ghrelin expression in the hypothalamus, not even in any of the present experimental models. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Passive Repetitive Stretching for a Short Duration within a Week Increases Myogenic Regulatory Factors and Myosin Heavy Chain mRNA in Rats' Skeletal Muscles

    Directory of Open Access Journals (Sweden)

    Yurie Kamikawa

    2013-01-01

    Full Text Available Stretching is a stimulation of muscle growth. Stretching for hours or days has an effect on muscle hypertrophy. However, differences of continuous stretching and repetitive stretching to affect muscle growth are not well known. To clarify the difference of continuous and repetitive stretching within a short duration, we investigated the gene expression of muscle-related genes on stretched skeletal muscles. We used 8-week-old male Wistar rats ( for this study. Animals medial gastrocnemius muscle was stretched continuously or repetitively for 15 min daily and 4 times/week under anesthesia. After stretching, muscles were removed and total RNA was extracted. Then, reverse transcriptional quantitative real-time PCR was done to evaluate the mRNA expression of MyoD, myogenin, and embryonic myosin heavy chain (MyHC. Muscles, either stretched continuously or repetitively, increased mRNA expression of MyoD, myogenin, and embryonic MyHC more than unstretched muscles. Notably, repetitive stretching resulted in more substantial effects on embryonic MyHC gene expression than continuous stretching. In conclusion, passive stretching for a short duration within a week is effective in increasing myogenic factor expression, and repetitive stretching had more effects than continuous stretching for skeletal muscle on muscle growth. These findings are applicable in clinical muscle-strengthening therapy.

  13. Frequently increased epidermal growth factor receptor (EGFR copy numbers and decreased BRCA1 mRNA expression in Japanese triple-negative breast cancers

    Directory of Open Access Journals (Sweden)

    Sugiura Hiroshi

    2008-10-01

    Full Text Available Abstract Background Triple-negative breast cancer (estrogen receptor-, progesterone receptor-, and HER2-negative (TNBC is a high risk breast cancer that lacks specific therapy targeting these proteins. Methods We studied 969 consecutive Japanese patients diagnosed with invasive breast cancer from January 1981 to December 2003, and selected TNBCs based on the immunohistochemical data. Analyses of epidermal growth factor receptor (EGFR gene mutations and amplification, and BRCA1 mRNA expression were performed on these samples using TaqMan PCR assays. The prognostic significance of TNBCs was also explored. Median follow-up was 8.3 years. Results A total of 110 (11.3% patients had TNBCs in our series. Genotyping of the EGFR gene was performed to detect 14 known EGFR mutations, but none was identified. However, EGFR gene copy number was increased in 21% of TNBCs, while only 2% of ER- and PgR-positive, HER2-negative tumors showed slightly increased EGFR gene copy numbers. Thirty-one percent of TNBCs stained positive for EGFR protein by immunohistochemistry. BRCA1 mRNA expression was also decreased in TNBCs compared with controls. Triple negativity was significantly associated with grade 3 tumors, TP53 protein accumulation, and high Ki67 expression. TNBC patients had shorter disease-free survival than non-TNBC in node-negative breast cancers. Conclusion TNBCs have an aggressive clinical course, and EGFR and BRCA1 might be candidate therapeutic targets in this disease.

  14. Passive repetitive stretching for a short duration within a week increases myogenic regulatory factors and myosin heavy chain mRNA in rats' skeletal muscles.

    Science.gov (United States)

    Kamikawa, Yurie; Ikeda, Satoshi; Harada, Katsuhiro; Ohwatashi, Akihiko; Yoshida, Akira

    2013-01-01

    Stretching is a stimulation of muscle growth. Stretching for hours or days has an effect on muscle hypertrophy. However, differences of continuous stretching and repetitive stretching to affect muscle growth are not well known. To clarify the difference of continuous and repetitive stretching within a short duration, we investigated the gene expression of muscle-related genes on stretched skeletal muscles. We used 8-week-old male Wistar rats (N = 28) for this study. Animals medial gastrocnemius muscle was stretched continuously or repetitively for 15 min daily and 4 times/week under anesthesia. After stretching, muscles were removed and total RNA was extracted. Then, reverse transcriptional quantitative real-time PCR was done to evaluate the mRNA expression of MyoD, myogenin, and embryonic myosin heavy chain (MyHC). Muscles, either stretched continuously or repetitively, increased mRNA expression of MyoD, myogenin, and embryonic MyHC more than unstretched muscles. Notably, repetitive stretching resulted in more substantial effects on embryonic MyHC gene expression than continuous stretching. In conclusion, passive stretching for a short duration within a week is effective in increasing myogenic factor expression, and repetitive stretching had more effects than continuous stretching for skeletal muscle on muscle growth. These findings are applicable in clinical muscle-strengthening therapy.

  15. Sodium bicarbonate ingestion augments the increase in PGC-1α mRNA expression during recovery from intense interval exercise in human skeletal muscle.

    Science.gov (United States)

    Percival, Michael E; Martin, Brian J; Gillen, Jenna B; Skelly, Lauren E; MacInnis, Martin J; Green, Alex E; Tarnopolsky, Mark A; Gibala, Martin J

    2015-12-01

    We tested the hypothesis that ingestion of sodium bicarbonate (NaHCO3) prior to an acute session of high-intensity interval training (HIIT) would augment signaling cascades and gene expression linked to mitochondrial biogenesis in human skeletal muscle. On two occasions separated by ∼1 wk, nine men (mean ± SD: age 22 ± 2 yr, weight 78 ± 13 kg, V̇O(2 peak) 48 ± 8 ml·kg(-1)·min(-1)) performed 10 × 60-s cycling efforts at an intensity eliciting ∼90% of maximal heart rate (263 ± 40 W), interspersed with 60 s of recovery. In a double-blind, crossover manner, subjects ingested a total of 0.4 g/kg body weight NaHCO3 before exercise (BICARB) or an equimolar amount of a placebo, sodium chloride (PLAC). Venous blood bicarbonate and pH were elevated at all time points after ingestion (P 0.05). However, the increase in PGC-1α mRNA expression after 3 h of recovery was higher in BICARB vs. PLAC (approximately sevenfold vs. fivefold compared with rest, P < 0.05). We conclude that NaHCO3 before HIIT alters the mRNA expression of this key regulatory protein associated with mitochondrial biogenesis. The elevated PGC-1α mRNA response provides a putative mechanism to explain the enhanced mitochondrial adaptation observed after chronic HIIT supplemented with NaHCO3 in rats. Copyright © 2015 the American Physiological Society.

  16. Deregulation of cap-dependent mRNA translation increases tumour radiosensitivity through reduction of the hypoxic fraction

    International Nuclear Information System (INIS)

    Rouschop, Kasper M.A.; Dubois, Ludwig; Schaaf, Marco B.E.; Beucken, Twan van den; Lieuwes, Natasja; Keulers, Tom G.H.; Savelkouls, Kim G.M.; Bussink, Johan; Kogel, Albert J. van der; Koritzinsky, Marianne; Wouters, Bradly G.

    2011-01-01

    Background and purpose: Tumour hypoxia is an important limiting factor in the successful treatment of cancer. Adaptation to hypoxia includes inhibition of mTOR, causing scavenging of eukaryotic initiation factor 4E (eIF4E), the rate-limiting factor for cap-dependent translation. The aim of this study was to determine the effect of preventing mTOR-dependent translation inhibition on hypoxic cell survival and tumour sensitivity towards irradiation. Material and methods: The effect of eIF4E-overexpression on cell proliferation, hypoxia-tolerance, and radiation sensitivity was assessed using isogenic, inducible U373 and HCT116 cells. Results: We found that eIF4E-overexpression significantly enhanced proliferation of cells under normal conditions, but not during hypoxia, caused by increased cell death during hypoxia. Furthermore, eIF4E-overexpression stimulated overall rates of tumour growth, but resulted in selective loss of hypoxic cells in established tumours and increased levels of necrosis. This markedly increased overall tumour sensitivity to irradiation. Conclusions: Our results demonstrate that hypoxia induced inhibition of translational control through regulation of eIF4E is an important mediator of hypoxia tolerance and radioresistance of tumours. These data also demonstrate that deregulation of metabolic pathways such as mTOR can influence the proliferation and survival of tumour cells experiencing metabolic stress in opposite ways of nutrient replete cells.

  17. Increased Set1 binding at the promoter induces aberrant epigenetic alterations and up-regulates cyclic adenosine 5'-monophosphate response element modulator alpha in systemic lupus erythematosus.

    Science.gov (United States)

    Zhang, Qing; Ding, Shu; Zhang, Huilin; Long, Hai; Wu, Haijing; Zhao, Ming; Chan, Vera; Lau, Chak-Sing; Lu, Qianjin

    2016-01-01

    Up-regulated cyclic adenosine 5'-monophosphate response element modulator α (CREMα) which can inhibit IL-2 and induce IL-17A in T cells plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE). This research aimed to investigate the mechanisms regulating CREMα expression in SLE. From the chromatin immunoprecipitation (ChIP) microarray data, we found a sharply increased H3 lysine 4 trimethylation (H3K4me3) amount at the CREMα promoter in SLE CD4+ T cells compared to controls. Then, by ChIP and real-time PCR, we confirmed this result. Moreover, H3K4me3 amount at the promoter was positively correlated with CREMα mRNA level in SLE CD4+ T cells. In addition, a striking increase was observed in SET domain containing 1 (Set1) enrichment, but no marked change in mixed-lineage leukemia 1 (MLL1) enrichment at the CREMα promoter in SLE CD4+ T cells. We also proved Set1 enrichment was positively correlated with both H3K4me3 amount at the CREMα promoter and CREMα mRNA level in SLE CD4+ T cells. Knocking down Set1 with siRNA in SLE CD4+ T cells decreased Set1 and H3K4me3 enrichments, and elevated the levels of DNMT3a and DNA methylation, while the amounts of H3 acetylation (H3ac) and H4 acetylation (H4ac) didn't alter greatly at the CREMα promoter. All these changes inhibited the expression of CREMα, then augmented IL-2 and down-modulated IL-17A productions. Subsequently, we observed that DNA methyltransferase (DNMT) 3a enrichment at the CREMα promoter was down-regulated significantly in SLE CD4+ T cells, and H3K4me3 amount was negatively correlated with both DNA methylation level and DNMT3a enrichment at the CREMα promoter in SLE CD4+ T cells. In SLE CD4+ T cells, increased Set1 enrichment up-regulates H3K4me3 amount at the CREMα promoter, which antagonizes DNMT3a and suppresses DNA methylation within this region. All these factors induce CREMα overexpression, consequently result in IL-2 under-expression and IL-17A overproduction, and

  18. Muscle glycogen depletion following 75-km of cycling is not linked to increased muscle IL-6, IL-8, and MCP-1 mRNA expression and protein content

    Directory of Open Access Journals (Sweden)

    David Christopher Nieman

    2016-09-01

    Full Text Available The cytokine response to heavy exertion varies widely for unknown reasons, and this study evaluated the relative importance of glycogen depletion, muscle damage, and stress hormone changes on blood and muscle cytokine measures. Cyclists (N=20 participated in a 75-km cycling time trial (168±26.0 min, with blood and vastus lateralis muscle samples collected before and after. Muscle glycogen decreased 77.2±17.4%, muscle IL-6, IL-8, and MCP-1 mRNA increased 18.5±2.8-, 45.3±7.8-, and 8.25±1.75-fold, and muscle IL-6, IL-8, and MCP-1 protein increased 70.5±14.1%, 347±68.1%, and 148±21.3%, respectively (all, P<0.001. Serum myoglobin and cortisol increased 32.1±3.3 to 242±48.3 mg/mL, and 295±27.6 to 784±63.5 nmol/L, respectively (both P<0.001. Plasma IL-6, IL-8, and MCP-1 increased 0.42±0.07 to 18.5±3.8, 4.07±0.37 to 17.0±1.8, and 96.5±3.7 to 240±21.6 pg/mL, respectively (all P<0.001. Increases in muscle IL-6, IL-8, and MCP-1 mRNA were unrelated to any of the outcome measures. Muscle glycogen depletion was related to change in plasma IL-6 (r=0.462, P=0.040, with change in myoglobin related to plasma IL-8 (r=0.582, P=0.007 and plasma MCP-1 (r=0.457, P=0.043, and muscle MCP-1 protein (r=0.588, P=0.017; cortisol was related to plasma IL-8 (r=0.613, P=0.004, muscle IL-8 protein (r=0.681, P=0.004, and plasma MCP-1 (r=0.442, P=0.050. In summary, this study showed that muscle IL-6, IL-8, and MCP-1 mRNA expression after 75-km cycling was unrelated to glycogen depletion and muscle damage, with change in muscle glycogen related to plasma IL-6, and changes in serum myoglobin and cortisol related to the chemotactic cytokines IL-8 and MCP-1.

  19. PTEN mutation cooperates with EGFR activation in human glioblastoma cells to increase VEGF mRNA levels by transactivating an element in the proximal promoter

    International Nuclear Information System (INIS)

    Maity, A.; Pore, N.; Haas-Kogan, D.A.; O'Rourke, D.M.

    2001-01-01

    Purpose: Glioblastomas often express high levels of vascular endothelial growth factor (VEGF), even under normoxic conditions. Genetic alterations that commonly occur in these tumors, including PTEN mutations and epidermal growth factor receptor (EGFR) overexpression, may contribute to this increased VEGF expression. Our previous work showed that, compared to parental U87MG human glioblastoma cells, VEGF mRNA levels are decreased in U87/T691, a derivative line in which EGFR signaling is inhibited by introduction of a truncated p185Neu protein (Cancer Research 60: 5879-5886, 2000). In that study, we also showed that the effect of EGFR activation on VEGF was mediated at the level of transcription via a PI3K dependent pathway. The purpose of the current study was to assess the role of PTEN, a negative regulator of PI3K, and its interaction with EGFR activation in regulating VEGF expression. Materials and Methods: Protein lysates were obtained from U87MG and U87/T691 cells for use in Western blotting for phosphorylated Akt. U87MG and U87/T691 cells were infected with adenovirus expressing either wildtype PTEN or phosphatase dead PTEN, then RNA was harvested for Northern blotting for VEGF. Nuclear extracts were also obtained from these cells for use in gel shift assays. Luciferase assays were performed with lysates of U87MG cells transfected with luciferase reporter constructs containing fragments of the VEGF promoter. Results: The level of phosphorylated Akt, a marker for PI3K activation, was lower in U87/T691 cells compared to U87MG cells, an expected result because of inhibition of the EGFR in the former. Treatment of U87/T691 cells with the PI3K inhibitor LY294002 further decreased the level of phosphorylated Akt and VEGF mRNA. Therefore, in spite of EGFR inhibition, U87/T691 cells contain residual PI3K activity that regulates VEGF expression. To determine whether the PTEN status of these cells influences VEGF mRNA levels, wildtype PTEN was introduced into U87MG and

  20. Combined whole-body vibration, resistance exercise, and sustained vascular occlusion increases PGC-1α and VEGF mRNA abundances.

    Science.gov (United States)

    Item, Flurin; Nocito, Antonio; Thöny, Sandra; Bächler, Thomas; Boutellier, Urs; Wenger, Roland H; Toigo, Marco

    2013-04-01

    We previously reported that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion (vibroX) markedly improves cycling endurance capacity, increases capillary-to-fibre ratio and skeletal muscle oxidative enzyme activity in untrained young women. These findings are intriguing, since increases in oxidative muscle phenotype and endurance capacity are typically induced by endurance but not heavy resistance exercise. Here, we tested the hypothesis that vibroX activates genes associated with mitochondrial biogenesis and angiogenesis. Eight healthy, recreationally resistance-trained young men performed either vibroX or resistance exercise (RES) in a randomised, cross-over design. Needle biopsies (M. vastus lateralis) were obtained at rest and 3 h post-exercise. Changes in relative gene expression levels were assessed by real-time quantitative PCR. After vibroX, vascular endothelial growth factor and peroxisome proliferator-activated receptor-γ coactivator 1α mRNA abundances increased to 2- and 4.4-fold, respectively, but did not significantly change above resting values after RES. Other genes involved in mitochondrial biogenesis were not affected by either exercise modality. While vibroX increased the expression of hexokinase II, xanthine dehydrogenase, and manganese superoxide dismutase mRNA, there were no changes in these transcripts after RES. This study demonstrates that high load resistance exercise with superimposed whole-body vibration and sustained vascular occlusion activates metabolic and angiogenic gene programs, which are usually activated after endurance but not resistance exercise. Thus, targeted modification of high load resistance exercise by vibration and vascular occlusion might represent a novel strategy to induce endurance-type muscle adaptations.

  1. Chromosomal aberration frequencies determined by conventinal methods: Parallel increases over time in the region of a petrochemical industry and throughout the Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Šrám, Radim; Rössner st., Pavel; Beskid, Olena; Bavorová, H.; Očadlíková, D.; Solanský, I.; Albertini, R. J.

    2007-01-01

    Roč. 166, 1-3 (2007), s. 239-244 ISSN 0009-2797 R&D Projects: GA MŽP SL/5/160/05; GA MŽP SL/740/5/03 Institutional research plan: CEZ:AV0Z50390512 Keywords : Gene expression * Cytogenetic analysis * Chromosomal aberrations Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.090, year: 2007

  2. Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor (ACTH-R) mRNA

    DEFF Research Database (Denmark)

    Carter, A M; Petersen, Y M; Towstoless, M

    2002-01-01

    ); and beta-actin. Ratios of mRNA expression to beta-actin mRNA expression (arbitrary units) were calculated to correct for differences in RNA quality between samples. The concentration (mean +/- SEM) of immunoreactive cortisol in fetal plasma was greater after ACTH infusion than after vehicle infusion (47...

  3. High ALK mRNA expression has a negative prognostic significance in rhabdomyosarcoma

    Science.gov (United States)

    Bonvini, P; Zin, A; Alaggio, R; Pawel, B; Bisogno, G; Rosolen, A

    2013-01-01

    Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in cancer, but its clinical and functional importance remain controversial. Mutation or amplification of ALK, as well as its expression levels assessed by conventional immunohistochemistry methods, has been linked to prognosis in cancer, although with potential bias because of the semi-quantitative approaches. Herein, we measured ALK mRNA expression in rhabdomyosarcoma (RMS) and determined its clinical impact on patients' stratification and outcome. Methods: Specimens were obtained from RMS patients and cell lines, and ALK expression was analysed by quantitative RT–PCR, western blotting, IHC, and copy number analysis. Results: High ALK mRNA expression was detected in the vast majority of PAX3/7-FOXO1-positive tumours, whereas PAX3/7-FOXO1-negative RMS displayed considerably lower amounts of both mRNA and protein. Notably, ALK mRNA distinguished unfavourable PAX3/7-FOXO1-positive tumours from PAX3/7-FOXO1-negative RMS (Ptumour size (PALK mRNA levels were of prognostic relevance by Cox univariate regression analysis and correlated with increased risk of relapse (P=0.001) and survival (P=0.01), whereas by multivariate analysis elevated ALK mRNA expression resulted a negative prognostic marker when clinical stage was not included. Conclusion: Quantitative assessment of ALK mRNA expression helps to improve risk stratification of RMS patients and identifies tumours with adverse biological characteristics and aggressive behaviour. PMID:24149177

  4. Flow cytogenetics: progress toward chromosomal aberration detection

    International Nuclear Information System (INIS)

    Carrano, A.V.; Gray, J.W.; Van Dilla, M.A.

    1977-01-01

    Using clonal derivatives of the Chinese hamster M3-1 cell line, we demonstrate the potential of flow systems to karyotype homogeneous aberrations (aberrations which are identical and present in every cell) and to detect heterogeneous aberrations (aberrations which occur randomly in a population and are not identical in every cell). Flow cytometry (FCM) of ethidium bromide stained isolated chromosomes from clone 650A of the M3-1 cells distinguishes nine chromosome types from the fourteen present in the actual karyotype. X-irradiation of this parent 650A clone produced two sub-clones with an altered flow karyotype, that is, their FCM distributions were characterized by the addition of new peaks and alterations in area under existing peaks. From the relative DNA content and area for each peak, as determined by computer analysis, we predicted that each clone had undergone a reciprocal translocation involving chromosomes from two peaks. This prediction was confirmed by Giemsa-banding the metaphase cells. Heterogeneous aberrations are reflected in the flow karyotype as an increase in background, that is, an increase in area underlying the chromosome peaks. This increase is dose dependent but, as yet, the sample variability has been too large for quantitative analysis. Flow sorting of the valleys between chromosome peaks produces enriched fractions of aberrant chromosomes for visual analysis. These approaches are potentially applicable to the analysis of chromsomal aberrations induced by environmental contaminants

  5. Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can occur without increased expression of ACTH receptor (ACTH-R) mRNA

    DEFF Research Database (Denmark)

    Carter, A M; Petersen, Y M; Towstoless, M

    2002-01-01

    thiocyanate method. Expression of specific mRNAs was determined by ribonuclease protection assay using cRNA probes directed against: ACTH-R; the steroid enzymes side-chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17apha-hydroxylase (P450c17) and 21beta-hydroxylase (P450c21......); and beta-actin. Ratios of mRNA expression to beta-actin mRNA expression (arbitrary units) were calculated to correct for differences in RNA quality between samples. The concentration (mean +/- SEM) of immunoreactive cortisol in fetal plasma was greater after ACTH infusion than after vehicle infusion (47...

  6. Increase in IL-8, IL-10, IL-13, and RANTES mRNA levels (in situ hybridization) in the nasal mucosa after nasal allergen provocation

    NARCIS (Netherlands)

    Kleinjan, A.; Dijkstra, M. D.; Boks, S. S.; Severijnen, L. A.; Mulder, P. G.; Fokkens, W. J.

    1999-01-01

    BACKGROUND: Allergic inflammation is regulated by the local production and release of several cytokines. OBJECTIVES: This study was designed to assess the changes in mRNA cytokine-positive cells after allergen provocation and to compare these cytokines with tissue eosinophilia as a marker of

  7. Increased levels of cell-free human placental lactogen mRNA at 28-32 gestational weeks in plasma of pregnant women with placenta previa and invasive placenta.

    Science.gov (United States)

    Kawashima, Akihiro; Sekizawa, Akihiko; Ventura, Walter; Koide, Keiko; Hori, Kyouko; Okai, Takashi; Masashi, Yoshida; Furuya, Kenichi; Mizumoto, Yoshifumi

    2014-02-01

    We compared the levels of cell-free human placental lactogen (hPL) messenger RNA (mRNA) in maternal plasma at 28 to 32 weeks of gestation between women with diagnosis of placenta previa or invasive placenta and women with an uneventful pregnancy. Sensitivity and specificity of hPL mRNA for the prediction of invasive placenta were further explored. Plasma hPL mRNA were quantified by real-time reverse-transcriptase polymerase chain reaction in women with placenta previa (n = 13), invasive placenta (n = 5), and normal pregnancies (n = 92). Median (range) hPL mRNA was significantly higher in women with placenta previa, 782 (10-2301) copies/mL of plasma, and in those with invasive placenta, 615 (522-2102) copies/mL of plasma, when compared to normal pregnancies, 90 (4-4407) copies/mL of plasma, P placenta among women with placenta previa. In conclusion, expression of hPL mRNA is increased in plasma of women with placenta previa and invasive placenta at 28 to 32 weeks of gestation.

  8. Reproductive Hazards Still Persist in the Microelectronics Industry: Increased Risk of Spontaneous Abortion and Menstrual Aberration among Female Workers in the Microelectronics Industry in South Korea.

    Directory of Open Access Journals (Sweden)

    Inah Kim

    Full Text Available Despite the global expansion of supply chains and changes to the production process, few studies since the mid-1990 s and 2000s have examined reproductive risks of the microelectronics industry; we examined the reproductive risks among female microelectronics workers in South Korea.Based on claim data from the National Health Insurance (2008-2012, we estimated age-specific rates of spontaneous abortion (SAB and menstrual aberration (MA among women aged 20 to 39 years. We compared data between microelectronics workers and three different control groups: economically inactive women, the working population as a whole, and workers employed in the bank industry. For an effect measure, age-stratified relative risks (RRs were estimated.Female workers in the microelectronics industry showed significantly higher risk for SAB and MA compared to control groups. The RRs for SAB with reference to economically inactive women, working population, and bank workers in their twenties were 1.57, 1.40, and 1.37, respectively, and the RRs for MA among females in their twenties were 1.54, 1.38, and 1.48, respectively. For women in their thirties, RRs for SAB were 1.58, 1.67, and 1.13, and those for MA were 1.25, 1.35, and 1.23 compared to the three control populations, respectively. All RRs were statistically significant at a level of 0.05, except for the SAB case comparison with bank workers in their thirties.Despite technical innovations and health and safety measures, female workers in microelectronics industry in South Korea have high rates of SAB and MA, suggesting continued exposure to reproductive hazards. Further etiologic studies based on primary data collection and careful surveillance are required to confirm these results.

  9. Reproductive Hazards Still Persist in the Microelectronics Industry: Increased Risk of Spontaneous Abortion and Menstrual Aberration among Female Workers in the Microelectronics Industry in South Korea.

    Science.gov (United States)

    Kim, Inah; Kim, Myoung-Hee; Lim, Sinye

    2015-01-01

    Despite the global expansion of supply chains and changes to the production process, few studies since the mid-1990 s and 2000s have examined reproductive risks of the microelectronics industry; we examined the reproductive risks among female microelectronics workers in South Korea. Based on claim data from the National Health Insurance (2008-2012), we estimated age-specific rates of spontaneous abortion (SAB) and menstrual aberration (MA) among women aged 20 to 39 years. We compared data between microelectronics workers and three different control groups: economically inactive women, the working population as a whole, and workers employed in the bank industry. For an effect measure, age-stratified relative risks (RRs) were estimated. Female workers in the microelectronics industry showed significantly higher risk for SAB and MA compared to control groups. The RRs for SAB with reference to economically inactive women, working population, and bank workers in their twenties were 1.57, 1.40, and 1.37, respectively, and the RRs for MA among females in their twenties were 1.54, 1.38, and 1.48, respectively. For women in their thirties, RRs for SAB were 1.58, 1.67, and 1.13, and those for MA were 1.25, 1.35, and 1.23 compared to the three control populations, respectively. All RRs were statistically significant at a level of 0.05, except for the SAB case comparison with bank workers in their thirties. Despite technical innovations and health and safety measures, female workers in microelectronics industry in South Korea have high rates of SAB and MA, suggesting continued exposure to reproductive hazards. Further etiologic studies based on primary data collection and careful surveillance are required to confirm these results.

  10. Low BMI is correlated with increased TGF-β and IL-10 mRNA levels in the peripheral blood of breast cancer patients.

    Science.gov (United States)

    Liu, Chao; Wang, Qian; Sun, Bing; Meng, Xiangying; Li, Lan; Yang, Liuchun; Cong, Yang; Liu, Jiannan; Xuan, Liang; Huang, Yan; Wu, Shikai

    2018-03-01

    Transforming growth factor-β (TGF-β), interleukin-10 (IL-10), and forkhead box P3 (Foxp3) have important roles in breast cancer development. Previous studies confirmed a correlation between these immune molecules and tumor characteristics, but their association with nutritional status in breast cancer is largely unknown. We aimed to investigate the association between body mass index (BMI), hemoglobin, total protein, albumin, globulin (GLB), albumin/GLB ratio (AGR), pre-albumin, prognostic nutritional index, and TGF-β, IL-10, and Foxp3 mRNA expression in patients with breast cancer. Quantitative real-time PCR was used to detect the mRNA expression of TGF-β, IL-10, and Foxp3 in the peripheral blood of 107 patients with breast cancer and 21 healthy controls. We found that TGF-β mRNA levels were 2.6-fold, 3.2-fold, and 2.3-fold higher in patients with low BMI (BMI (BMI BMI ≥ 25), respectively (P BMI, may strongly affect systematic immune function in patients with breast cancer. © 2018 IUBMB Life, 70(3):237-245, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

  11. Increased mRNA expression of a laminin-binding protein in human colon carcinoma: Complete sequence of a full-length cDNA encoding the protein

    International Nuclear Information System (INIS)

    Yow, Hsiukang; Wong, Jau Min; Chen, Hai Shiene; Lee, C.; Steele, G.D. Jr.; Chen, Lanbo

    1988-01-01

    Reliable markers to distinguish human colon carcinoma from normal colonic epithelium are needed particularly for poorly differentiated tumors where no useful marker is currently available. To search for markers the authors constructed cDNA libraries from human colon carcinoma cell lines and screened for clones that hybridize to a greater degree with mRNAs of colon carcinomas than with their normal counterparts. Here they report one such cDNA clone that hybridizes with a 1.2-kilobase (kb) mRNA, the level of which is ∼9-fold greater in colon carcinoma than in adjacent normal colonic epithelium. Blot hybridization of total RNA from a variety of human colon carcinoma cell lines shows that the level of this 1.2-kb mRNA in poorly differentiated colon carcinomas is as high as or higher than that in well-differentiated carcinomas. Molecular cloning and complete sequencing of cDNA corresponding to the full-length open reading frame of this 1.2-kb mRNA unexpectedly show it to contain all the partial cDNA sequence encoding 135 amino acid residues previously reported for a human laminin receptor. The deduced amino acid sequence suggests that this putative laminin-binding protein from human colon carcinomas consists of 295 amino acid residues with interesting features. There is an unusual C-terminal 70-amino acid segment, which is trypsin-resistant and highly negatively charged

  12. Increased FXYD1 and PGC-1α mRNA after blood flow-restricted running is related to fibre type-specific AMPK signalling and oxidative stress in human muscle

    DEFF Research Database (Denmark)

    Christiansen, Danny; Murphy, Robyn M; Bangsbo, Jens

    2018-01-01

    AIM: This study explored the effects of blood flow restriction (BFR) on mRNA responses of PGC-1α (total, 1α1, and 1α4) and Na+ ,K+ -ATPase isoforms (NKA; α1-3 , β1-3 , and FXYD1) to an interval running session, and determined if these effects were related to increased oxidative stress, hypoxia......). A muscle sample was collected before (Pre) and after exercise (+0h, +3h) to quantify mRNA, indicators of oxidative stress (HSP27 protein in type I and II fibres, and catalase and HSP70 mRNA), metabolites, and α-AMPK Thr172 /α-AMPK, ACC Ser221 /ACC, CaMKII Thr287 /CaMKII, and PLBSer16 /PLB ratios in type I...... of oxidative stress and type-I fibre ACC Ser221 /ACC ratio, but dissociated from muscle hypoxia, lactate, and CaMKII signalling. CONCLUSION: Blood flow restriction augmented exercise-induced increases in muscle FXYD1 and PGC-1α mRNA in men. This effect was related to increased oxidative stress and fibre type...

  13. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    genes and genetic signatures and for reducing dimensionally of gene expression data. Next, we have used machine-learning methods to predict survival and to assess important predictors based on these results. General application of a number of these methods has been implemented into two public query......Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  14. Study of ocular aberrations with age.

    Science.gov (United States)

    Athaide, Helaine Vinche Zampar; Campos, Mauro; Costa, Charles

    2009-01-01

    Aging has various effects on visual system. Vision deteriorate, contrast sensitivity decreases and ocular aberrations apparently make the optical quality worse across the years. To prospective evaluate ocular aberrations along the ages. Three hundred and fifteen patients were examined, 155 were male (39.36%) and 160 were female (60.63%). Ages ranged from 5 to 64 year-old, the study was performed from February to November, 2004. Patients were divided into 4 age-groups according to IBGE (Instituto Brasileiro de Geografia e Estatística) classification: 68 patients from 5 to 14 year-old, 55 patients from 15 to 24 year-old, 116 from 25 to 44 year-old and 76 from 45 to 67 year-old. All patients had the following characteristics: best corrected visual acuity > 20/25, emmetropia or spherical equivalent < 3.50 SD, refractive astigmatism < 1.75 CD on cycloplegic refraction, normal ophthalmologic exam and no previous ocular surgeries. This protocol was approved by Federal University of São Paulo Institutional Review Board. Total optical aberrations were measured by H-S sensor LadarWave Custom Cornea Wavefront System (Alcon Laboratories Inc, Orlando, FLA, USA) and were statistically analysed. Corneal aberrations were calculated using CT-View software Version 6.89 (Sarver and Associates, Celebration, FL, USA). Lens aberrations were calculated by subtraction. High-order (0.32 e 0.48 microm) and ocular spherical aberrations (0.02 e 0.26 microm) increased respectively in child and middle age groups. High order (0.27 microm) and corneal spherical aberrations (0.05 microm) did not show changes with age. Lens showed a statistically significant spherical aberration increase (from -0.02 to 0.22 microm). Vertical (from 0.10 to -0.07 microm) and horizontal coma (from 0.01 to -0.12 microm) presented progressively negative values with aging. High-order and spherical aberrations increased with age due to lens contribution. The cornea did not affect significantly changes observed on ocular

  15. Aberrant hepatic artery

    International Nuclear Information System (INIS)

    Konstam, M.A.; Novelline, R.A.; Athanasoulis, C.A.

    1979-01-01

    In a patient undergoing selective hepatic arteriography for suspected liver trauma, a nonopacified area of the liver, initially thought to represent a hepatic hematoma, was later discovered to be due to the presence of an accessory right hepatic artery arising from the superior mesenteric artery. This case illustrates the need for a search for aberrant vasculature whenever a liver hematoma is suspected on the basis of a selective hepatic arteriogram. (orig.) [de

  16. Increased induction of aberrant crypt foci by 1,2-dimethylhydrazine in rats fed diets containing purified genistein of genistein-rich soya protein

    NARCIS (Netherlands)

    Gee, J.M.; Noteborn, H.P.J.M.; Polley, A.C.J.; Johnson, I.T.

    2000-01-01

    The isoflavonoid genistein inhibits mitosis and increases apoptosis in a variety of tumour cell lines in vitro, and may exert anticarcinogenic effects in vivo. To assess its effects on the colon, rats were fed a semi-synthetic control diet, or similar diets enriched with genistein (0.25 g/kg),

  17. Effects of chalazion excision on ocular aberrations.

    Science.gov (United States)

    Sabermoghaddam, Ali A; Zarei-Ghanavati, Siamak; Abrishami, Mojtaba

    2013-06-01

    The goal of this study was to compare higher-order aberrations before and after upper lid chalazion excision. Fourteen eyes from 12 patients (8 females, mean age: 28.7 ± 2.7 years) with upper lid chalazion were enrolled in this prospective interventional case series. Chalazia were excised by standard transconjunctival vertical incision. Ocular aberrations were evaluated by aberrometry (ZyWave) before and 2 months after chalazion excision. Root mean square of total higher-order aberrations decreased from 0.67 ± 0.12 to 0.43 ± 0.15 μm (P = 0.012) after excision. The root mean square of Zernike orders in the vertical and horizontal trefoil and horizontal coma were decreased after excision. Orbscan IIz tomography showed a statistically significant decrease in 5 mm zone irregularity (P = 0.027) and an increase in minimum simulated keratometry after surgery (P = 0.046). Chalazion increases higher-order aberrations, as measured by the Hartmann-Shack aberrometer, which could affect the preoperative evaluation and results of refractive surgery, especially wavefront-guided approaches. Chalazion excision could reduce ocular aberrations and is recommended before refractive surgeries.

  18. Increased dopamine DRD4 receptor mRNA expression in lymphocytes of musicians and autistic individuals: bridging the music-autism connection.

    Science.gov (United States)

    Emanuele, Enzo; Boso, Marianna; Cassola, Francesco; Broglia, Davide; Bonoldi, Ilaria; Mancini, Lara; Marini, Mara; Politi, Pierluigi

    2010-01-01

    People with autistic spectrum disorder (ASD) are affected by a long-life disabling condition, characterized by communication deficits, severe impairments in social functioning, and stereotyped behaviors. Although ASD individuals display several problems in interactions, it has been reported that they may show a peculiar interest in music. Previous studies have suggested a pivotal role for the dopaminergic system in the psychobiology of reward, including the pleasure of music. In the present study, we sought to investigate dopamine DRD3 and DRD4 receptor expression in peripheral blood lymphocytes of adult healthy musicians and age- and gender-matched patients with ASD against the background hypothesis that the dopaminergic system may contribute a biological cause to the reward dimensions of the musical experience in both healthy and autistic individuals. ANOVA showed significant differences in DRD4 mRNA expression between the groups (P = 0.008). Post-hoc analysis showed significant differences between the control group and both musicians (P music and autism, possibly via mechanisms involving the reward system and the appraisal of emotions.

  19. Contraction-induced increases in Na+-K+-ATPase mRNA levels in human skeletal muscle are not amplified by activation of additional muscle mass

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai; Thomassen, Martin; Lundby, Carsten

    2005-01-01

    4, ß1, ß2, and ß3 mRNA in human skeletal muscle was investigated. On two occasions, eight subjects performed one-legged knee extension exercise (L) or combined one-legged knee extension and bilateral arm cranking (AL) for 5.00, 4.25, 3.50, 2.75, and 2.00 min separated by 3 min of rest. Leg exercise...... power output was the same in AL and L, but heart rate at the end of each exercise interval was higher in AL compared with L. One minute after exercise, arm venous blood lactate was higher in AL than in L. A higher level of blood epinephrine and norepinephrine was evident 3 min after exercise in AL...... compared with L. Nevertheless, none of the exercise-induced increases in a1, a2, ß1, and ß3 mRNA expression levels were higher in AL compared with L. The most abundant Na+-K+-ATPase subunit at the mRNA level was ß1, which was expressed 3.4 times than a2. Expression of a1, ß2, and ß3 was less than 5...

  20. Multiple Drug Treatments That Increase cAMP Signaling Restore Long-Term Memory and Aberrant Signaling in Fragile X Syndrome Models

    Science.gov (United States)

    Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Hinchey, Joseph; Rosenfelt, Cory; Gertner, Michael J.; Campbell, Sean R.; Emerson, Danielle; Hinchey, Paul; Kollaros, Maria; Ferrick, Neal J.; Chambers, Daniel B.; Langer, Steven; Sust, Steven; Malik, Aatika; Terlizzi, Allison M.; Liebelt, David A.; Ferreiro, David; Sharma, Ali; Koenigsberg, Eric; Choi, Richard J.; Louneva, Natalia; Arnold, Steven E.; Featherstone, Robert E.; Siegel, Steven J.; Zukin, R. Suzanne; McDonald, Thomas V.; Bolduc, Francois V.; Jongens, Thomas A.; McBride, Sean M. J.

    2016-01-01

    Fragile X is the most common monogenic disorder associated with intellectual disability (ID) and autism spectrum disorders (ASD). Additionally, many patients are afflicted with executive dysfunction, ADHD, seizure disorder and sleep disturbances. Fragile X is caused by loss of FMRP expression, which is encoded by the FMR1 gene. Both the fly and mouse models of fragile X are also based on having no functional protein expression of their respective FMR1 homologs. The fly model displays well defined cognitive impairments and structural brain defects and the mouse model, although having subtle behavioral defects, has robust electrophysiological phenotypes and provides a tool to do extensive biochemical analysis of select brain regions. Decreased cAMP signaling has been observed in samples from the fly and mouse models of fragile X as well as in samples derived from human patients. Indeed, we have previously demonstrated that strategies that increase cAMP signaling can rescue short term memory in the fly model and restore DHPG induced mGluR mediated long term depression (LTD) in the hippocampus to proper levels in the mouse model (McBride et al., 2005; Choi et al., 2011, 2015). Here, we demonstrate that the same three strategies used previously with the potential to be used clinically, lithium treatment, PDE-4 inhibitor treatment or mGluR antagonist treatment can rescue long term memory in the fly model and alter the cAMP signaling pathway in the hippocampus of the mouse model. PMID:27445731

  1. Chromosomal Aberrations in Monozygotic and Dizygotic Twins Versus Singletons in Denmark During 1968-2009

    DEFF Research Database (Denmark)

    Kristensen, Lone Krøldrup; Larsen, Lisbeth A; Fagerberg, Christina

    2017-01-01

    BACKGROUND: Hall (Embryologic development and monozygotic twinning. Acta Geneticae Medicae et Gemellologiae, Vol. 45, 1996, pp. 53-57) hypothesized that chromosomal aberrations can lead to monozygotic (MZ) twinning. However, twinning and chromosomal aberrations increase prenatal mortality and could...

  2. Increased CRF mRNA expression in the sexually dimorphic BNST of male but not female GAD67 mice and TMT predator odor stress effects upon spatial memory retrieval.

    Science.gov (United States)

    Janitzky, K; Peine, A; Kröber, A; Yanagawa, Y; Schwegler, H; Roskoden, T

    2014-10-01

    The bed nucleus of the stria terminalis (BNST) is an important region for 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) predator odor-induced stress responses in mice. It is sexually dimorphic and a region for corticotropin-releasing factor (CRF)-enhanced stress responses. Dense GABAergic and CRF input from the amygdala to the BNST gives point to relevant interactions between CRF and GABA activity in these brain regions. Hence, to investigate sexual dimorphism of stress-induced neuronal changes, we studied effects of acute TMT exposure on CRF mRNA expression in stress-related brain regions in male and female GAD67 mice and their wild-type littermates. In GAD67 mice, heterozygous knock-in of GFP in GABAergic neurons caused a 50% decrease of GAD67 protein level in the brain [91,99]. Results show higher CRF mRNA levels in the BNST of male but not female GAD67 mice after TMT and control odor exposure. While CRF neurons in the BNST are predominantly GABAergic and CRF enhances GABAergic transmission in the BNST [20,51], the deficit in GABAergic transmission in GAD67 mice could induce a compensatory CRF increase. Sexual dimorphism of the BNST with greater density of GABA-ir neurons in females could explain the differences in CRF mRNA levels between male and female GAD67 mice. Effects of odor exposure were studied in a radial arm maze (RAM) task. Results show impaired retrieval of spatial memory after acute TMT exposure in both sexes and genotypes. However, only GAD67 mice show increased working memory errors after control odor exposure. Our work elicits GAD67 mice as a model to further study interactions of GABA and CRF in the BNST for a better understanding of how sex-specific characteristics of the brain may contribute to differences in anxiety- and stress-related psychological disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Increased expression of cyclin B1 mRNA coincides with diminished G{sub 2}-phase arrest in irradiated HeLa cells treated with staurosporine or caffeine

    Energy Technology Data Exchange (ETDEWEB)

    Bernhard, E.J.; Maity, A.; McKenna, W.G.; Muschel, R.J. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)

    1994-12-01

    The irradiation of cells results in delayed progression through the G{sub 2} phase of the cell cycle. Treatment of irradiated HeLa cells with caffeine greatly reduces the G{sub 2}-phase delay, while caffeine does not alter progression of cells through the cell cycle in unirradiated cells. In this report we demonstrate that treatment of HeLa cells with the kinase inhibitor staurosporine, but not with the inhibitor H7, also results in a reduction of the G{sub 2}-phase arrest after irradiation. Cell cycle progression in unirradiated cells is unaffected by 4.4 nM (2ng/ml) staurosporine, which releases the radiation-induced G{sub 2}-phase arrest. In HeLa cells, the G{sub 2}-phase delay after irradiation in S phase is accompanied by decreased expression of cyclin B1 mRNA. Coincident with the reduction in G{sub 2}-phase delay, we observed an increase in cyclin B1 mRNA accumulation in irradiated, staurosporine-treated cells compared to cells treated with irradiation alone. Caffeine treatment of irradiated HeLa cells also resulted in an elevation in the levels of cyclin B1 message. These results support the hypothesis that diminished cyclin B1 mRNA levels influence G{sub 2}-phase arrest to some degree. The findings that both staurosporine and caffeine treatments reverse the depression in cyclin B1 expression suggest that these two compounds may act on a common pathway of cell cycle control in response to radiation injury. 33 refs., 6 figs.

  4. Functional Integration of mRNA Translational Control Programs

    Directory of Open Access Journals (Sweden)

    Melanie C. MacNicol

    2015-07-01

    Full Text Available Regulated mRNA translation plays a key role in control of cell cycle progression in a variety of physiological and pathological processes, including in the self-renewal and survival of stem cells and cancer stem cells. While targeting mRNA translation presents an attractive strategy for control of aberrant cell cycle progression, mRNA translation is an underdeveloped therapeutic target. Regulated mRNAs are typically controlled through interaction with multiple RNA binding proteins (RBPs but the mechanisms by which the functions of distinct RBPs bound to a common target mRNA are coordinated are poorly understood. The challenge now is to gain insight into these mechanisms of coordination and to identify the molecular mediators that integrate multiple, often conflicting, inputs. A first step includes the identification of altered mRNA ribonucleoprotein complex components that assemble on mRNAs bound by multiple, distinct RBPs compared to those recruited by individual RBPs. This review builds upon our knowledge of combinatorial control of mRNA translation during the maturation of oocytes from Xenopus laevis, to address molecular strategies that may mediate RBP diplomacy and conflict resolution for coordinated control of mRNA translational output. Continued study of regulated ribonucleoprotein complex dynamics promises valuable new insights into mRNA translational control and may suggest novel therapeutic strategies for the treatment of disease.

  5. The suppression of aberrant crypt multiplicity in colonic tissue of 1,2-dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes.

    Science.gov (United States)

    Winkelmann, Isabel; Diehl, Daniela; Oesterle, Doris; Daniel, Hannelore; Wenzel, Uwe

    2007-07-01

    Colorectal cancer is the second leading cause of cancer deaths worldwide with diet playing a prominent role in disease initiation and progression. Flavonoids are secondary plant compounds that are suggested as protective ingredients of a diet rich in fruits and vegetables. We here tested whether flavone, a flavonoid that proved to be an effective apoptosis inducer in colon cancer cells in culture, can affect the development of aberrant crypt foci (ACFs) in C57BL/6J mice in vivo when preneoplastic lesions were induced by the carcinogen 1,2-dimethylhydrazine (DMH). Flavone applied at either a low dose (15 mg/kg body wt per day) or a high dose (400 mg/kg body wt per day) reduced the numbers of ACFs significantly, independent of whether it was supplied simultaneously with the carcinogen (blocking group) or subsequent to the tumor induction phase (suppressing group). Proteome analysis performed in colonic tissue samples revealed that flavone treatment increased the expression of a number of Krebs cycle enzymes in the suppressing group and this was associated with reduced crypt multiplicity. It suggests that mitochondrial substrate oxidation is increased by flavone in colonic cells in vivo as already observed in HT-29 cells in vitro as the prime mechanism underlying tumor cell apoptosis induction by flavone. In conclusion, flavone reduces the number of ACFs in DMH-treated mice at doses that can be achieved for flavonoids by a diet rich in fruits and vegetables. Moreover, reduction in crypt multiplicity by flavone is most probably due to the preservation of a normal oxidative metabolism.

  6. IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM.

    Science.gov (United States)

    Henness, Sheridan; van Thoor, Eveline; Ge, Qi; Armour, Carol L; Hughes, J Margaret; Ammit, Alaina J

    2006-06-01

    Human airway smooth muscle (ASM) plays an immunomodulatory role in asthma. Recently, IL-17A has become of increasing interest in asthma, being found at elevated levels in asthmatic airways and emerging as playing an important role in airway neutrophilia. IL-17A predominantly exerts its neutrophil orchestrating role indirectly via the induction of cytokines by resident airway structural cells. Here, we perform an in vitro study to show that although IL-17A did not induce secretion of the CXC chemokine IL-8 from ASM cells, IL-17A significantly potentiates TNF-alpha-induced IL-8 protein secretion and gene expression in a concentration- and time-dependent manner (P ASM cells, acting via a p38 MAPK-dependent posttranscriptional pathway to augment TNF-alpha-induced secretion of the potent neutrophil chemoattractant IL-8 from ASM cells.

  7. Rats prone to obesity under a high-carbohydrate diet have increased post-meal CCK mRNA expression and characteristics of rats fed a high-glycemic index diet

    Directory of Open Access Journals (Sweden)

    Catherine eChaumontet

    2015-07-01

    Full Text Available We previously reported that rats prone to obesity exhibit an exaggerated increase in glucose oxidation and an exaggerated decline in lipid oxidation under a low-fat high-carbohydrate (LF/HC diet. The aim of the present study was to investigate the mechanisms involved in these metabolic dysregulations. After a one week adaptation to laboratory conditions, 48 male Wistar rats were fed a LF/HC diet for 3 weeks. During weeks 2 and 3, glucose tolerance tests (GTT, insulin tolerance tests (ITT and meal tolerance tests (MTT were performed to evaluate blood glucose, plasma and insulin. Glucose and lipid oxidation were also assayed during the GTT. At the end of the study, body composition was measured in all the rats, and they were classified as carbohydrate resistant (CR or carbohydrate sensitive (CS according to their adiposity. Before sacrifice, 24 of the 48 rats received a calibrated LF/HC meal. Liver, muscle and intestine tissue samples were taken to measure mRNA expression of key genes involved in glucose, lipid and protein metabolism. ITT, GTT and MTT showed that CS rats were neither insulin resistant nor glucose intolerant, but mRNA expression of CCK in the duodenum was higher and that of CPT1, PPARα and PGC1α in liver were lower than in CR rats. From these results, we make the hypothesis that in CS rats, CCK increased pancreatic secretion which may favor a quicker absorption of carbohydrates and consequently induces an enhanced inhibition of lipid oxidation in the liver leading to a progressive accumulation of fat preferentially in visceral deposits. Such a mechanism may explain why CS rats share many characteristics observed in rats fed a high glycemic index diet.

  8. Corneal versus ocular aberrations after overnight orthokeratology.

    Science.gov (United States)

    Gifford, Paul; Li, Melanie; Lu, Helen; Miu, Jonathan; Panjaya, Monica; Swarbrick, Helen A

    2013-05-01

    To investigate relationships between changes to corneal and ocular aberrations induced by orthokeratology (OK) and their influence on visual function. Eighteen subjects (aged 20 to 23 years) were fitted with OK lenses (BE Enterprises Pty Ltd, Australia), manufactured in Boston XO material (Bausch & Lomb Boston, Wilmington, MA), and worn overnight for seven nights. Corneal and ocular aberrations were simultaneously captured (Discovery, Innovative Visual Systems, Elmhurst, IL), and contrast sensitivity function was measured on days 1 and 7, within 2 and 8 hours after lens removal on waking. Data from the eye achieving the higher myopic correction were analyzed for changes over time. There was a significant refractive effect at all visits. Orthokeratology induced an increase in corneal and ocular root mean square higher order aberrations (HOAs) and a positive shift in spherical aberration (SA) on day 1, with further increases by day 7. Increases in root mean square coma became significant by day 7. Changes to corneal and ocular SA were similar on day 1; however, by day 7, there was a greater increase in corneal than ocular SA, indicating a change in internal SA. Orthokeratology led to an overall decrease in contrast sensitivity function, which was isolated to spatial frequency changes on day 1 at 1 cycle per degree and on day 7 at 1 and 8 cycles per degree. A greater positive shift in corneal compared with ocular SA on day 7 suggests a negative shift in internal SA, which would be consistent with an increased accommodative response. Lack of any difference on day 1 indicates that this may be an ocular adaptation response toward neutralizing induced positive SA, rather than a direct effect of SA changes on the accommodation mechanism.

  9. Chromosome aberrations analysis of Serbia population from 1985 to 1995

    International Nuclear Information System (INIS)

    Jovicic, D.; Markovic, B.; Milacic, S.; Joksic, G.

    1996-01-01

    After the accident of NE Chernobyl in May 1986, Chernobyl's fallout with unhomogeneous dispersion of radioactive material in atmosphere caused the difference in contamination of the Serbia territory. The highest contamination was found to be in region Uzice, and the lowest in the region Nis. Two groups of population from these regions were undergone chromosome aberration analysis during 1987, 1988 and 1989. year. The results of our examination show increased frequency of structural chromosome aberrations/dicentrics, rings, peri centric inversions and acentric/ in the Uzice population, especially in the 1987. year. In 1985 and 1995 year have not been found chromosome aberrations. 2 refs.; 1 figs.; 2 tabs

  10. Aberrant CpG methylation of the TFAP2A gene constitutes a mechanism for loss of TFAP2A expression in human metastatic melanoma.

    Science.gov (United States)

    Hallberg, Andrea R; Vorrink, Sabine U; Hudachek, Danielle R; Cramer-Morales, Kimberly; Milhem, Mohammed M; Cornell, Robert A; Domann, Frederick E

    2014-12-01

    Metastatic melanoma is a deadly treatment-resistant form of skin cancer whose global incidence is on the rise. During melanocyte transformation and melanoma progression the expression profile of many genes changes. Among these, a gene implicated in several steps of melanocyte development, TFAP2A, is frequently silenced; however, the molecular mechanism of TFAP2A silencing in human melanoma remains unknown. In this study, we measured TFAP2A mRNA expression in primary human melanocytes compared to 11 human melanoma samples by quantitative real-time RT-PCR. In addition, we assessed CpG DNA methylation of the TFAP2A promoter in these samples using bisulfite sequencing. Compared to primary melanocytes, which showed high TFAP2A mRNA expression and no promoter methylation, human melanoma samples showed decreased TFAP2A mRNA expression and increased promoter methylation. We further show that increased CpG methylation correlates with decreased TFAP2A mRNA expression. Using The Cancer Genome Atlas, we further identified TFAP2A as a gene displaying among the most decreased expression in stage 4 melanomas vs. non-stage 4 melanomas, and whose CpG methylation was frequently associated with lack of mRNA expression. Based on our data, we conclude that TFAP2A expression in human melanomas can be silenced by aberrant CpG methylation of the TFAP2A promoter. We have identified aberrant CpG DNA methylation as an epigenetic mark associated with TFAP2A silencing in human melanoma that could have significant implications for the therapy of human melanoma using epigenetic modifying drugs.

  11. Aberrant PO2 values in proficiency testing.

    Science.gov (United States)

    Fonzi, C E; Clausen, J L; Mahoney, J

    1993-03-01

    We prospectively determined the frequency of aberrant vials of fluorocarbon/buffer used for proficiency testing of measurements of pH, PCO2, and PO2, using 20 duplicate vials from 12 lots of fluorocarbon/buffer and two arterial blood gas analyzers in eight reference laboratories. We defined aberrant vials as vials for which both duplicate measurements differed from the mean value of repeated measurements for the specific instrument (for each lot of testing materials) by > 0.04 for pH, > 10% of the mean or 3.0 mm Hg, whichever was greater, for PCO2; or > 10% of the mean or 6 mm Hg, whichever was greater, for PO2. Four of 1620 vials (0.25%) were aberrant, all based on PO2 measurements (range of mean values: pH, 7.181-7.631; PCO2, 12.7-65.9; PO2, 32.5-150.1) were 0.0055 for pH, 0.67 mm Hg for PCO2, and 1.65 mm Hg for PO2. Deliberate contamination of the fluorocarbon emulsion with room air, as might occur during sampling from the vial, indicated that only minor increases in PO2 (e.g., 1.0 mm Hg at PO2 of 56 mm Hg) occur when samples are aspirated. Larger increases in PO2 (mean 7.1 mm Hg at a PO2 of 66 mm Hg) occurred when the syringe samples were contaminated with room air. We conclude that isolated aberrant measurements of PO2 in blood gas proficiency testing attributable to vial contents can occur, but the frequency is very low.

  12. Spherical aberration in contact lens wear.

    Science.gov (United States)

    Lindskoog Pettersson, A; Jarkö, C; Alvin, A; Unsbo, P; Brautaset, R

    2008-08-01

    The aim of the present studies was to investigate the effect on spherical aberration of different non custom-made contact lenses, both with and without aberration control. A wavefront analyser (Zywave, Bausch & Lomb) was used to measure the aberrations in each subject's right eye uncorrected and with the different contact lenses. The first study evaluated residual spherical aberration with a standard lens (Focus Dailies Disposable, Ciba Vision) and with an aberration controlled contact lens (ACCL) (Definition AC, Optical Connection Inc.). The second study evaluated the residual spherical aberrations with a monthly disposable silicone hydrogel lens with aberration reduction (PureVision, Bausch & Lomb). Uncorrected spherical aberration was positive for all pupil sizes in both studies. In the first study, residual spherical aberration was close to zero with the standard lens for all pupil sizes whereas the ACCL over-corrected spherical aberration. The results of the second study showed that the monthly disposable lens also over-corrected the aberration making it negative. The changes in aberration were statistically significant (plenses. Since the amount of aberration varies individually we suggest that aberrations should be measured with lenses on the eye if the aim is to change spherical aberration in a certain direction.

  13. Chromosome Aberrations by Heavy Ions

    Science.gov (United States)

    Ballarini, Francesca; Ottolenghi, Andrea

    It is well known that mammalian cells exposed to ionizing radiation can show different types of chromosome aberrations (CAs) including dicentrics, translocations, rings, deletions and complex exchanges. Chromosome aberrations are a particularly relevant endpoint in radiobiology, because they play a fundamental role in the pathways leading either to cell death, or to cell conversion to malignancy. In particular, reciprocal translocations involving pairs of specific genes are strongly correlated (and probably also causally-related) with specific tumour types; a typical example is the BCR-ABL translocation for Chronic Myeloid Leukaemia. Furthermore, aberrations can be used for applications in biodosimetry and more generally as biomarkers of exposure and risk, that is the case for cancer patients monitored during Carbon-ion therapy and astronauts exposed to space radiation. Indeed hadron therapy and astronauts' exposure to space radiation represent two of the few scenarios where human beings can be exposed to heavy ions. After a brief introduction on the main general features of chromosome aberrations, in this work we will address key aspects of the current knowledge on chromosome aberration induction, both from an experimental and from a theoretical point of view. More specifically, in vitro data will be summarized and discussed, outlining important issues such as the role of interphase death/mitotic delay and that of complex-exchange scoring. Some available in vivo data on cancer patients and astronauts will be also reported, together with possible interpretation problems. Finally, two of the few available models of chromosome aberration induction by ionizing radiation (including heavy ions) will be described and compared, focusing on the different assumptions adopted by the authors and on how these models can deal with heavy ions.

  14. Low level dose induced chromosome aberrations in human blood lymphocytes

    International Nuclear Information System (INIS)

    Pohl-Rueling, J.

    1992-01-01

    Unstable structural aberrations in chromosomes of human blood lymphocytes cannot be used as biological dosemeters in the low dose range, when extrapolating from high doses using a linear dose response, as required by the original formula of the dual radiation action theory. A survey is given of experimental dose-response curves of chromosome aberrations, obtained in investigations not only by this institute, in cooperation with many other laboratories, but also by various authors in different areas of the world. The results are not compatible with the predicted linear dose relationships at in vivo dose ranges up to 30 mGy.y -1 . The aberration frequencies rise sharply with dose within the normal environmental exposure up to about twice that level. At higher doses, aberration frequencies increase less rapidly and reach a plateau. Some in vitro experiments of various authors with higher doses of low LET radiations, up to about 400 mGy have found dose responses with steps. (author)

  15. Aberrations of Genetic Material as Biomarkers of Ionizing Radiation Effects

    Energy Technology Data Exchange (ETDEWEB)

    Milacic, S.

    2004-07-01

    Ionizing radiation is the most powerful mutagen in environmental and working conditions. The result of genotoxic effect of radiation is the development of chromosome aberrations. The structural chromosome aberrations in peripheral blood lymphocytes are dicentric, ring, acentric fragment. The observation of chromosome aberration frequency in lymphocyte karyotype is the conclusive method to assess the absorbed dose of ionizing radiation. Our study compared the incidence of chromosome aberrations in occupationally exposed healthy medical workers and in non-exposed healthy population. We analyzed the effect of working place, dose by thermo luminescence personal dosimeter (TLD), duration of occupational exposure (DOE) and age to the sum of aberrant cells and aberrations. four-year study included 462 subjects, mean-aged 42.3 years, who were occupational exposed to ionizing radiation and 95 subjects, mean-aged 35,2 years, who were not exposed to ionizing radiation, during the same time period and from the same territory. All of them possess thermo luminescence personal dosimeter (TLD) which is read by scanner for thermo luminescence dosimeters. Modified Moorheard's micro method for peripheral blood lymphocytes and conventional cytogenetic technique of chromosome aberration analysis were used for analysis of chromosome aberrations. Stained preparations (Giemsa) are observed in immersion by light microscope. The karyotype of 200 lymphocytes in metaphase is analyzed the most characteristic aberration: dicentric, then the ring and acentric fragments. The increased incidence of chromosome aberrations was found to tbe 21.6% in the exposed group and 2.1% in the controls, while the findings within the limits (non-specific chromosome lesions-gaps breaks, elongations, and exchanges) were equal in both groups (22%). Among occupationally exposed medical workers, the highest incidence was found in nuclear medicine workers (42.6%), then in orthopedists (27.08%). There is highly

  16. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  17. The Art of Optical Aberrations

    Science.gov (United States)

    Wylde, Clarissa Eileen Kenney

    Art and optics are inseparable. Though seemingly opposite disciplines, the combination of art and optics has significantly impacted both culture and science as they are now known. As history has run its course, in the sciences, arts, and their fruitful combinations, optical aberrations have proved to be a problematic hindrance to progress. In an effort to eradicate aberrations the simple beauty of these aberrational forms has been labeled as undesirable and discarded. Here, rather than approach aberrations as erroneous, these beautiful forms are elevated to be the photographic subject in a new body of work, On the Bright Side. Though many recording methods could be utilized, this work was composed on classic, medium-format, photographic film using white-light, Michelson interferometry. The resulting images are both a representation of the true light rays that interacted on the distorted mirror surfaces (data) and the artist's compositional eye for what parts of the interferogram are chosen and displayed. A detailed description of the captivating interdisciplinary procedure is documented and presented alongside the final artwork, CCD digital reference images, and deformable mirror contour maps. This alluring marriage between the arts and sciences opens up a heretofore minimally explored aspect of the inextricable art-optics connection. It additionally provides a fascinating new conversation on the importance of light and optics in photographic composition.

  18. Origins and fundamentals of nodal aberration theory

    Science.gov (United States)

    Rogers, John R.

    2017-11-01

    Nodal Aberration Theory, developed by Kevin Thompson and Roland Shack, predicts several important aberration phenomena but remains poorly understood. To de-mystify the theory, we describe the origins and fundamental concepts of the theory.

  19. Effect of spherical aberration on scintillations of Gaussian beams in atmospheric turbulence

    International Nuclear Information System (INIS)

    Ji, Xiaoling; Deng, Jinping

    2014-01-01

    The effect of spherical aberration on scintillations of Gaussian beams in weak, moderate and strong turbulence is studied using numerical simulation method. It is found that the effect of the negative spherical aberration on the on-axis scintillation index is quite different from that of the positive spherical aberration. In weak turbulence, the positive spherical aberration results in a decrease of the on-axis scintillation index on propagation, but the negative spherical aberration results in an increase of the on-axis scintillation index when the propagation distance is not large. In particular, in weak turbulence the negative spherical aberration may cause peaks of the on-axis scintillation index, and the peaks disappear in moderate and strong turbulence, which is explained in physics. The strong turbulence leads to less discrepancy among scintillations of Gaussian beams with and without spherical aberration. - Highlights: • In weak turbulence scintillations can be suppressed using positive spherical aberration. • In weak turbulence scintillations may be very large due to negative spherical aberration. • The effect of spherical aberration on scintillations is less with increasing of turbulence

  20. Effect of spherical aberration on scintillations of Gaussian beams in atmospheric turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Xiaoling, E-mail: jiXL100@163.com; Deng, Jinping

    2014-07-18

    The effect of spherical aberration on scintillations of Gaussian beams in weak, moderate and strong turbulence is studied using numerical simulation method. It is found that the effect of the negative spherical aberration on the on-axis scintillation index is quite different from that of the positive spherical aberration. In weak turbulence, the positive spherical aberration results in a decrease of the on-axis scintillation index on propagation, but the negative spherical aberration results in an increase of the on-axis scintillation index when the propagation distance is not large. In particular, in weak turbulence the negative spherical aberration may cause peaks of the on-axis scintillation index, and the peaks disappear in moderate and strong turbulence, which is explained in physics. The strong turbulence leads to less discrepancy among scintillations of Gaussian beams with and without spherical aberration. - Highlights: • In weak turbulence scintillations can be suppressed using positive spherical aberration. • In weak turbulence scintillations may be very large due to negative spherical aberration. • The effect of spherical aberration on scintillations is less with increasing of turbulence.

  1. Pulse compressor with aberration correction

    Energy Technology Data Exchange (ETDEWEB)

    Mankos, Marian [Electron Optica, Inc., Palo Alto, CA (United States)

    2015-11-30

    In this SBIR project, Electron Optica, Inc. (EOI) is developing an electron mirror-based pulse compressor attachment to new and retrofitted dynamic transmission electron microscopes (DTEMs) and ultrafast electron diffraction (UED) cameras for improving the temporal resolution of these instruments from the characteristic range of a few picoseconds to a few nanoseconds and beyond, into the sub-100 femtosecond range. The improvement will enable electron microscopes and diffraction cameras to better resolve the dynamics of reactions in the areas of solid state physics, chemistry, and biology. EOI’s pulse compressor technology utilizes the combination of electron mirror optics and a magnetic beam separator to compress the electron pulse. The design exploits the symmetry inherent in reversing the electron trajectory in the mirror in order to compress the temporally broadened beam. This system also simultaneously corrects the chromatic and spherical aberration of the objective lens for improved spatial resolution. This correction will be found valuable as the source size is reduced with laser-triggered point source emitters. With such emitters, it might be possible to significantly reduce the illuminated area and carry out ultrafast diffraction experiments from small regions of the sample, e.g. from individual grains or nanoparticles. During phase I, EOI drafted a set of candidate pulse compressor architectures and evaluated the trade-offs between temporal resolution and electron bunch size to achieve the optimum design for two particular applications with market potential: increasing the temporal and spatial resolution of UEDs, and increasing the temporal and spatial resolution of DTEMs. Specialized software packages that have been developed by MEBS, Ltd. were used to calculate the electron optical properties of the key pulse compressor components: namely, the magnetic prism, the electron mirror, and the electron lenses. In the final step, these results were folded

  2. Freeform aberrations in phase space: an example.

    Science.gov (United States)

    Babington, James

    2017-06-01

    We consider how optical propagation and aberrations of freeform systems can be formulated in phase space. As an example system, a freeform prism is analyzed and discussed. Symmetry considerations and their group theory descriptions are given some importance. Numerical aberrations are also highlighted and put into the context of the underlying aberration theory.

  3. Nonsense-mediated mRNA decapping occurs on polyribosomes in Saccharomyces cerevisiae.

    Science.gov (United States)

    Hu, Wenqian; Petzold, Christine; Coller, Jeff; Baker, Kristian E

    2010-02-01

    Nonsense-mediated decay (NMD) degrades mRNA containing premature translation termination codons. In yeast, NMD substrates are decapped and digested exonucleolytically from the 5' end. Despite the requirement for translation in recognition, degradation of nonsense-containing mRNA is considered to occur in ribosome-free cytoplasmic P bodies. We show decapped nonsense-containing mRNA associate with polyribosomes, indicating that recognition and degradation are tightly coupled and that polyribosomes are major sites for degradation of aberrant mRNAs.

  4. CDH1 (E-cadherin) in testicular germ cell neoplasia: suppressed translation of mRNA in pre-invasive carcinoma in situ but increased protein levels in advanced tumours

    DEFF Research Database (Denmark)

    Sonne, Si B; Hoei-Hansen, Christina E; Nielsen, John E

    2006-01-01

    E-cadherin (CDH1) is a transmembrane glycoprotein involved in cellular adhesion. In our recent microarray studies of testicular germ cell tumours (TGCTs) and the common precursor carcinoma in situ (CIS), CDH1 mRNA was highly expressed in CIS and embryonal carcinoma. It has previously been reported...... higher levels in patients with advanced disease (stage II/III) when compared to healthy individuals and patients with stage I TGCT. In conclusion, despite high mRNA levels, the CDH1 protein is not expressed in CIS, suggesting translational suppression of CDH1 protein expression. CDH1 serum levels may...

  5. Pathophysiology of MDS: genomic aberrations.

    Science.gov (United States)

    Ichikawa, Motoshi

    2016-01-01

    Myelodysplastic syndromes (MDS) are characterized by clonal proliferation of hematopoietic stem/progenitor cells and their apoptosis, and show a propensity to progress to acute myelogenous leukemia (AML). Although MDS are recognized as neoplastic diseases caused by genomic aberrations of hematopoietic cells, the details of the genetic abnormalities underlying disease development have not as yet been fully elucidated due to difficulties in analyzing chromosomal abnormalities. Recent advances in comprehensive analyses of disease genomes including whole-genome sequencing technologies have revealed the genomic abnormalities in MDS. Surprisingly, gene mutations were found in approximately 80-90% of cases with MDS, and the novel mutations discovered with these technologies included previously unknown, MDS-specific, mutations such as those of the genes in the RNA-splicing machinery. It is anticipated that these recent studies will shed new light on the pathophysiology of MDS due to genomic aberrations.

  6. Volumetric optical coherence microscopy enabled by aberrated optics (Conference Presentation)

    Science.gov (United States)

    Mulligan, Jeffrey A.; Liu, Siyang; Adie, Steven G.

    2017-02-01

    Optical coherence microscopy (OCM) is an interferometric imaging technique that enables high resolution, non-invasive imaging of 3D cell cultures and biological tissues. Volumetric imaging with OCM suffers a trade-off between high transverse resolution and poor depth-of-field resulting from defocus, optical aberrations, and reduced signal collection away from the focal plane. While defocus and aberrations can be compensated with computational methods such as interferometric synthetic aperture microscopy (ISAM) or computational adaptive optics (CAO), reduced signal collection must be physically addressed through optical hardware. Axial scanning of the focus is one approach, but comes at the cost of longer acquisition times, larger datasets, and greater image reconstruction times. Given the capabilities of CAO to compensate for general phase aberrations, we present an alternative method to address the signal collection problem without axial scanning by using intentionally aberrated optical hardware. We demonstrate the use of an astigmatic spectral domain (SD-)OCM imaging system to enable single-acquisition volumetric OCM in 3D cell culture over an extended depth range, compared to a non-aberrated SD-OCM system. The transverse resolution of the non-aberrated and astigmatic imaging systems after application of CAO were 2 um and 2.2 um, respectively. The depth-range of effective signal collection about the nominal focal plane was increased from 100 um in the non-aberrated system to over 300 um in the astigmatic system, extending the range over which useful data may be acquired in a single OCM dataset. We anticipate that this method will enable high-throughput cellular-resolution imaging of dynamic biological systems over extended volumes.

  7. Study of wavefront aberration in DR patients with different degree of dry eye

    Directory of Open Access Journals (Sweden)

    Jin-Ran Fang

    2018-05-01

    Full Text Available AIM: To compare the changes of wavefront aberrations in patients with diabetic retinopathy(DRand with different degrees of dry eye and to explore the reasons of visual quality decline in them. METHODS: We randomly selected 40 eyes in our hospital for treatment with DR and varying degrees of dry eye, and 40 eyes of normal control group. Topcon KR-1W visual quality analyzer was used to record the mean square the total high order corneal aberration, spherical aberration, comatic aberration and trefoil aberration of cornea with pupil diameters of 4mm and 6mm. Analysis of variance were used to compare the wavefront aberrations and the aberration values in the control group and in patients with diabetic retinopathy and with different degrees of dry eye. RESULTS: For 4mm and 6mm pupil diameters, nondiabetic retinopathy(NDRwith dry eye group, the nonproliferative diabetic retinopathy(NPDRwith dry eye group and proliferative diabetic retinopathy(PDRdry eye group had significantly increased tHOA, coma and trefoil compared with the contrast group(PPCONCLUSION: Dry eye of diabetic retinopathy with different degrees is closely related to the increase of wavefront aberration. Increased wavefront aberration may be one of the reasons to reduced visual quality in patients with diabetic retinopathy and with dry eye, and provide the basis for the decline of visual function of diabetic patients with dry eye.

  8. Metaphase chromosome aberrations as markers of radiation exposure and dose

    Energy Technology Data Exchange (ETDEWEB)

    Brooks, A.L.; Khan, M.A.; Jostes, R.F.; Cross, F.T.

    1992-10-01

    Chromosome aberration frequency provides the most reliable biological marker of dose for detecting acute accidental radiation exposure. Significant radiation-induced changes in the frequency of chromosome aberrations can be detected at very low doses. Our paper provides information on using molecular chromosome probes paints'' to score chromosome damage and illustrates how technical advances make it possible to understand mechanisms involved during formation of chromosome aberrations. In animal studies chromosome aberrations provide a method to relate cellular damage to cellular dose. Using an In vivo/In vitro approach aberrations provided a biological marker of dose from radon progeny exposure which was used to convert WLM to dose in rat tracheal epithelial cells. Injection of Chinese hamsters with [sup 144]Ce which produced a low dose rate exposure of bone marrow to either low-LET radiation increased the sensitivity of the cells to subsequent external exposure to [sup 60]Co. These studies demonstrated the usefulness of chromosome damage as a biological marker of dose and cellular responsiveness.

  9. Metaphase chromosome aberrations as markers of radiation exposure and dose

    Energy Technology Data Exchange (ETDEWEB)

    Brooks, A.L.; Khan, M.A.; Jostes, R.F.; Cross, F.T.

    1992-10-01

    Chromosome aberration frequency provides the most reliable biological marker of dose for detecting acute accidental radiation exposure. Significant radiation-induced changes in the frequency of chromosome aberrations can be detected at very low doses. Our paper provides information on using molecular chromosome probes ``paints`` to score chromosome damage and illustrates how technical advances make it possible to understand mechanisms involved during formation of chromosome aberrations. In animal studies chromosome aberrations provide a method to relate cellular damage to cellular dose. Using an In vivo/In vitro approach aberrations provided a biological marker of dose from radon progeny exposure which was used to convert WLM to dose in rat tracheal epithelial cells. Injection of Chinese hamsters with {sup 144}Ce which produced a low dose rate exposure of bone marrow to either low-LET radiation increased the sensitivity of the cells to subsequent external exposure to {sup 60}Co. These studies demonstrated the usefulness of chromosome damage as a biological marker of dose and cellular responsiveness.

  10. Radiation-induced cellular reproductive death and chromosome aberrations

    International Nuclear Information System (INIS)

    Bedford, J.S.; Mitchell, J.B.; Griggs, H.G.; Bender, M.A.

    1978-01-01

    If a major mode of cell killing by ionizing radiation is the death of cells containing visible chromosomal aberrations, as for example from anaphase-bridge formation at mitosis, then cells bearing such aberrations should be selectively eliminated from the population, resulting in an increased survival potential for the population remaining at each succeeding cell generation. Using synchronized V79B Chinese hamster cells, we measured the aberration frequency and the colony-forming ability of mitotic cells at each of the first three generations following irradiation in G1. Cells were resynchronized by mechanial harvest at each succeeding mitosis after irradiation in order to avoid mixing of generations in the cell population at later sampling times. As anticipated, the chromosome aberration frequencies decreased markedly from the first to the second and from the second to the third mitosis. The surviving fraction, however, was virtually the same for plating assays carried out immediately after irradiation, at the first, or at the second mitosis. The surviving fraction was significantly higher for cells reaching the third postirradiation mitosis. Survival and aberration frequencies were assayed again at approximately the fourteenth postirradiation division, by which time the irradiated and control populations were not significantly different

  11. Metaphase chromosome aberrations as markers of radiation exposure and dose

    International Nuclear Information System (INIS)

    Brooks, A.L.; Khan, M.A.; Jostes, R.F.; Cross, F.T.

    1992-10-01

    Chromosome aberration frequency provides the most reliable biological marker of dose for detecting acute accidental radiation exposure. Significant radiation-induced changes in the frequency of chromosome aberrations can be detected at very low doses. Our paper provides information on using molecular chromosome probes ''paints'' to score chromosome damage and illustrates how technical advances make it possible to understand mechanisms involved during formation of chromosome aberrations. In animal studies chromosome aberrations provide a method to relate cellular damage to cellular dose. Using an In vivo/In vitro approach aberrations provided a biological marker of dose from radon progeny exposure which was used to convert WLM to dose in rat tracheal epithelial cells. Injection of Chinese hamsters with 144 Ce which produced a low dose rate exposure of bone marrow to either low-LET radiation increased the sensitivity of the cells to subsequent external exposure to 60 Co. These studies demonstrated the usefulness of chromosome damage as a biological marker of dose and cellular responsiveness

  12. Aberrant Myokine Signaling in Congenital Myotonic Dystrophy

    Directory of Open Access Journals (Sweden)

    Masayuki Nakamori

    2017-10-01

    Full Text Available Summary: Myotonic dystrophy types 1 (DM1 and 2 (DM2 are dominantly inherited neuromuscular disorders caused by a toxic gain of function of expanded CUG and CCUG repeats, respectively. Although both disorders are clinically similar, congenital myotonic dystrophy (CDM, a severe DM form, is found only in DM1. CDM is also characterized by muscle fiber immaturity not observed in adult DM, suggesting specific pathological mechanisms. Here, we revealed upregulation of the interleukin-6 (IL-6 myokine signaling pathway in CDM muscles. We also found a correlation between muscle immaturity and not only IL-6 expression but also expanded CTG repeat length and CpG methylation status upstream of the repeats. Aberrant CpG methylation was associated with transcriptional dysregulation at the repeat locus, increasing the toxic RNA burden that upregulates IL-6. Because the IL-6 pathway is involved in myocyte maturation and muscle atrophy, our results indicate that enhanced RNA toxicity contributes to severe CDM phenotypes through aberrant IL-6 signaling. : Congenital myotonic dystrophy (CDM manifests characteristic genetic (very large CTG repeat expansions, epigenetic (CpG hypermethylation upstream of the repeat, and phenotypic (muscle immaturity features not seen in adult DM. Nakamori et al. find phenotype-genotype and epigenotype correlation in CDM muscle and reveal involvement of the IL-6 myokine signaling pathway in the disease process. Keywords: CTCF, ER stress, IL-6, muscular dystrophy, NF-κB, trinucleotide, cytokine, splicing

  13. Vibration Induces BAFF Overexpression and Aberrant O-Glycosylation of IgA1 in Cultured Human Tonsillar Mononuclear Cells in IgA Nephropathy

    Directory of Open Access Journals (Sweden)

    Muyao Ye

    2016-01-01

    Full Text Available Objective. To investigate the influence of in vitro vibratory stimulation of human tonsillar mononuclear cells (TMCs. Methods. Fourteen IgA nephropathy (IgAN patients with chronic tonsillitis (CT and 12 CT patients with no renal pathology were enrolled. Group A TMCs were collected after 24 hours of culture and used to determine baseline levels. TMCs in groups B, C, D, E, and F were exposed to vibratory stimulation (60 Hz for 0 (as the control group, 1, 3, 5, and 10 minutes, respectively. Results. Baseline concentrations of B-cell-activation factor (BAFF and IgA1, BAFF mRNA expression, and aberrant O-glycosylation IgA1 level were higher in the IgAN group as compared to that in the CT group, and all increased after vibratory stimulation. Baseline mRNA expressions of core β1,3-galactosyltransferase (C1GALT1 and core β1,3GalT-specific molecular chaperone (Cosmc were lower in the IgAN group; the levels decreased further after vibratory stimulation. Conclusion. In patients with IgAN, vibratory stimulation of TMCs appears to induce IgA1 secretion through activation of BAFF release and to aberrant O-glycosylation IgA1 by suppressing C1GALT1 and Cosmc expression. In vitro vibratory stimulation of human TMCs mimics the vibratory simulation of palatine tonsils produced by vocal cords during phonation.

  14. Effects of cyclosporin A and FK506 on Fc epsilon receptor type I-initiated increases in cytokine mRNA in mouse bone marrow-derived progenitor mast cells: resistance to FK506 is associated with a deficiency in FK506-binding protein FKBP12.

    Science.gov (United States)

    Kaye, R E; Fruman, D A; Bierer, B E; Albers, M W; Zydowsky, L D; Ho, S I; Jin, Y J; Castells, M C; Schreiber, S L; Walsh, C T

    1992-09-15

    The inhibitory effects of cyclosporin A (CsA) and FK506 on Fc epsilon receptor type I-initiated increases in cytokine mRNA and the expression of their intracellular binding proteins were studied in interleukin 3 (IL-3)-dependent, mouse bone marrow-derived mast cells (BMMCs). In BMMCs sensitized with IgE anti-trinitrophenyl, CsA inhibited trinitrophenylated bovine serum albumin-induced increases in mRNA for IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 in a dose-related manner (IC50 values of 4, 65, and 130 nM, respectively). FK506 did not inhibit hapten-specific increases of mRNA for TNF-alpha or IL-6, and for IL-1 beta the IC50 was greater than 50-fold higher than that of CsA. Neither agent inhibited exocytosis of the endogenous secretory granule mediators beta-hexosaminidase and histamine at the IC50 values for inhibition of increases in cytokine mRNA. BMMCs expressed cyclophilin, and CsA inhibited the phosphatase activity of cellular calcineurin with an IC50 of approximately 8 nM. That CsA inhibited IL-1 beta mRNA accumulation in IgE-activated BMMCs with an IC50 similar to that for inhibition of calcineurin activity, whereas the IC50 values were approximately 20-fold higher for the inhibition of TNF-alpha and IL-6 mRNA, suggests that the induction of TNF-alpha and IL-6 is less dependent upon calcineurin activity than is the induction of IL-1 beta. BMMCs were deficient in the 12-kDa FK506-binding protein FKBP12, but not FKBP13, as assessed by RNA and protein blot analyses. FK506 did not inhibit calcineurin phosphatase activity in BMMCs, even at drug concentrations of 1000 nM. The resistance of BMMCs to inhibition of Fc epsilon receptor type I-mediated increases in cytokine mRNA by FK506 is most likely due to their deficiency of FKBP12 and the related inability to inhibit the activity of calcineurin.

  15. An electron microscope for the aberration-corrected era

    International Nuclear Information System (INIS)

    Krivanek, O.L.; Corbin, G.J.; Dellby, N.; Elston, B.F.; Keyse, R.J.; Murfitt, M.F.; Own, C.S.; Szilagyi, Z.S.; Woodruff, J.W.

    2008-01-01

    Improved resolution made possible by aberration correction has greatly increased the demands on the performance of all parts of high-end electron microscopes. In order to meet these demands, we have designed and built an entirely new scanning transmission electron microscope (STEM). The microscope includes a flexible illumination system that allows the properties of its probe to be changed on-the-fly, a third-generation aberration corrector which corrects all geometric aberrations up to fifth order, an ultra-responsive yet stable five-axis sample stage, and a flexible configuration of optimized detectors. The microscope features many innovations, such as a modular column assembled from building blocks that can be stacked in almost any order, in situ storage and cleaning facilities for up to five samples, computer-controlled loading of samples into the column, and self-diagnosing electronics. The microscope construction is described, and examples of its capabilities are shown

  16. Sonic Hedgehog Signaling Affected by Promoter Hypermethylation Induces Aberrant Gli2 Expression in Spina Bifida.

    Science.gov (United States)

    Lu, Xiao-Lin; Wang, Li; Chang, Shao-Yan; Shangguan, Shao-Fang; Wang, Zhen; Wu, Li-Hua; Zou, Ji-Zhen; Xiao, Ping; Li, Rui; Bao, Yi-Hua; Qiu, Z-Y; Zhang, Ting

    2016-10-01

    GLI2 is a key mediator of the sonic hedgehog (Shh) signaling pathway and plays an important role in neural tube development during vertebrate embryogenesis; however, the role of gli2 in human folate-related neural tube defects remains unclear. In this study, we compared methylation status and polymorphisms of gli2 between spina bifida patients and a control group to explore the underlying mechanisms related to folate deficiency in spina bifida. No single nucleotide polymorphism was found to be significantly different between the two groups, although gli2 methylation levels were significantly increased in spina bifida samples, accompanied by aberrant GLI2 expression. Moreover, a prominent negative correlation was found between the folate level in brain tissue and the gli2 methylation status (r = -0.41, P = 0.014), and gli2 hypermethylation increased the risk of spina bifida with an odds ratio of 12.45 (95 % confidence interval: 2.71-57.22, P = 0.001). In addition, we established a cell model to illustrate the effect of gli2 expression and the accessibility of chromatin affected by methylation. High gli2 and gli1 mRNA expression was detected in 5-Aza-treated cells, while gli2 hypermethylation resulted in chromatin inaccessibility and a reduced association with nuclear proteins containing transcriptional factors. More meaningful to the pathway, the effect gene of the Shh pathway, gli1, was found to have a reduced level of expression along with a decreased expression of gli2 in our cell model. Aberrant high methylation resulted in the low expression of gli2 in spina bifida, which was affected by the change in chromatin status and the capacity of transcription factor binding.

  17. Phase and birefringence aberration correction

    Science.gov (United States)

    Bowers, M.; Hankla, A.

    1996-07-09

    A Brillouin enhanced four wave mixing phase conjugate mirror corrects phase aberrations of a coherent electromagnetic beam and birefringence induced upon that beam. The stimulated Brillouin scattering (SBS) phase conjugation technique is augmented to include Brillouin enhanced four wave mixing (BEFWM). A seed beam is generated by a main oscillator which arrives at the phase conjugate cell before the signal beams in order to initiate the Brillouin effect. The signal beam which is being amplified through the amplifier chain is split into two perpendicularly polarized beams. One of the two beams is chosen to be the same polarization as some component of the seed beam, the other orthogonal to the first. The polarization of the orthogonal beam is then rotated 90{degree} such that it is parallel to the other signal beam. The three beams are then focused into cell containing a medium capable of Brillouin excitation. The two signal beams are focused such that they cross the seed beam path before their respective beam waists in order to achieve BEFWM or the two signal beams are focused to a point or points contained within the focused cone angle of the seed beam to achieve seeded SBS, and thus negate the effects of all birefringent and material aberrations in the system. 5 figs.

  18. Joint denoising, demosaicing, and chromatic aberration correction for UHD video

    Science.gov (United States)

    Jovanov, Ljubomir; Philips, Wilfried; Damstra, Klaas Jan; Ellenbroek, Frank

    2017-09-01

    High-resolution video capture is crucial for numerous applications such as surveillance, security, industrial inspection, medical imaging and digital entertainment. In the last two decades, we are witnessing a dramatic increase of the spatial resolution and the maximal frame rate of video capturing devices. In order to achieve further resolution increase, numerous challenges will be facing us. Due to the reduced size of the pixel, the amount of light also reduces, leading to the increased noise level. Moreover, the reduced pixel size makes the lens imprecisions more pronounced, which especially applies to chromatic aberrations. Even in the case when high quality lenses are used some chromatic aberration artefacts will remain. Next, noise level additionally increases due to the higher frame rates. To reduce the complexity and the price of the camera, one sensor captures all three colors, by relying on Color Filter Arrays. In order to obtain full resolution color image, missing color components have to be interpolated, i.e. demosaicked, which is more challenging than in the case of lower resolution, due to the increased noise and aberrations. In this paper, we propose a new method, which jointly performs chromatic aberration correction, denoising and demosaicking. By jointly performing the reduction of all artefacts, we are reducing the overall complexity of the system and the introduction of new artefacts. In order to reduce possible flicker we also perform temporal video enhancement. We evaluate the proposed method on a number of publicly available UHD sequences and on sequences recorded in our studio.

  19. Chromosomal aberrations in ore miners of Slovakia

    International Nuclear Information System (INIS)

    Beno, M.; Vladar, M.; Nikodemova, D.; Vicanova, M.; Durcik, M.

    1998-01-01

    A pilot study was performed in which the incidence of chromosomal aberrations in lymphocytes of miners in ore mines located in Central Slovakia was monitored and related to lifetime underground radon exposure and to lifetime smoking. The conclusions drawn from the results of the study were as follows: the counts of chromosomal aberrations in lymphocytes of miners were significantly higher than in an age matched control group of white-collar staff; the higher counts of chromosomal aberrations could be ascribed to underground exposure of miners and to smoking; a dependence of chromosomal aberration counts on the exposure to radon could not be assessed. (A.K.)

  20. Spherical aberration from trajectories in real and hard-edge ...

    Indian Academy of Sciences (India)

    Abstract. For analytical, real and hard-edge solenoidal axial magnetic fields, the low-energy electron trajectories are obtained using the third-order paraxial ray equation. Using the particle trajectories, it is shown that the spherical aberration in the hard-edge model is high and it increases monotonously with hard edginess, ...

  1. A selective splicing variant of hepcidin mRNA in hepatocellular carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Toki, Yasumichi [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido 078-8510 (Japan); Sasaki, Katsunori, E-mail: k-sasaki@asahikawa-med.ac.jp [Department of Gastrointestinal Immunology and Regenerative Medicine, Asahikawa Medical University, Hokkaido 078-8510 (Japan); Tanaka, Hiroki [Department of Legal Medicine, Asahikawa Medical University, Hokkaido 078-8510 (Japan); Yamamoto, Masayo; Hatayama, Mayumi; Ito, Satoshi; Ikuta, Katsuya; Shindo, Motohiro; Hasebe, Takumu; Nakajima, Shunsuke; Sawada, Koji; Fujiya, Mikihiro [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido 078-8510 (Japan); Torimoto, Yoshihiro [Oncology Center, Asahikawa Medical University Hospital, Hokkaido 078-8510 (Japan); Ohtake, Takaaki; Kohgo, Yutaka [Department of Gastroenterology, International University of Health and Welfare Hospital, Tochigi 329-2763 (Japan)

    2016-08-05

    Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. By RT-PCR/agarose gel electrophoresis of hepcidin mRNA in a hepatocellular carcinoma cell line HLF, a smaller mRNA band was shown in addition to the wild-type hepcidin mRNA. From sequencing analysis, this additional band was a selective splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene, producing the transcript that encodes truncated peptide lacking 20 amino acids at the middle of preprohepcidin. In the present study, we used the digital PCR, because such a small amount of variant mRNA was difficult to quantitate by the conventional RT-PCR amplification. Among seven hepatoma-derived cell lines, six cell lines have significant copy numbers of this variant mRNA, but not in one cell line. In the transient transfection analysis of variant-type hepcidin cDNA, truncated preprohepcidin has a different character comparing with native preprohepcidin: its product is insensitive to digestion, and secreted into the medium as a whole preprohepcidin form without maturation. Loss or reduction of function of HAMP gene by aberrantly splicing may be a suitable phenomenon to obtain the proliferating advantage of hepatoma cells. - Highlights: • An aberrant splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene. • Absolute quantification of hepcidin mRNA by digital PCR amplification. • Hepatoma-derived cell lines have significant copies of variant-type hepcidin mRNA. • Truncated preprohepcidin is secreted from cells without posttranslational cleavage.

  2. Possible mechanisms of chromosomal aberrations: VII. Comparative dynamics of sister chromatid disjunction and realization of radiation-induced chromosomal aberrations during mitosis

    International Nuclear Information System (INIS)

    Lebedeva, L.I.; Akhmamet'eva, E.M.

    1994-01-01

    An increase in radiation-induced chromosomal aberrations during c-metaphase sister chromatid disjunction was demonstrated in murine bone marrow cells exposed to a total γ-irradiation at 0.5 Gy. Caffeine (Cf) treatment during mitosis partially suppressed the chromatid disjunction rate and increased the number of radiation-induced aberrations in this mitosis. Nalidixic acid (NA) treatment of c-metaphase cells completely suppressed chromatid disjunction and the realization of induced aberrations. Topoisomerase 2 was assumed to be involved during mitosis in both processes

  3. Prognostic significance of CDH13 hypermethylation and mRNA in NSCLC

    Directory of Open Access Journals (Sweden)

    Xue R

    2014-10-01

    Full Text Available Ruilin Xue,1 Cuili Yang,1 Fang Zhao,2 Dejia Li1 1Global Health Institute, School of Public Health, 2Zhongnan Hospital, Wuhan University, Wuhan, People's Republic of ChinaAbstract: Aberrant methylation of CpG dinucleotides is a commonly observed epigenetic modification in human cancer. Thus, detection of aberrant gene promoter methylation as a tool for diagnosis of tumors or as a prognostic marker has been widely described for many types of cancers, including nonsmall cell lung cancer (NSCLC. Emerging evidence indicates that CDH13 is a candidate tumor suppressor in several types of human tumors, including NSCLC. However, the correlation between CDH13 hypermethylation and clinicopathological characteristics of NSCLC remains unclear. In the current study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of CDH13 hypermethylation on the incidence of NSCLC and clinicopathological characteristics. Final analysis of 803 NSCLC patients from eleven eligible studies was performed. CDH13 hypermethylation was observed to be significantly higher in NSCLC than in normal lung tissue, with the pooled odds ratio (OR from seven studies including 448 NSCLC and 345 normal lung tissue (OR, 7.85; 95% confidence interval, 5.12–12.03; P<0.00001. CDH13 hypermethylation was also associated with pathological types. The pooled OR was obtained from four studies, including 111 squamous cell carcinoma and 106 adenocarcinoma (OR, 0.35; 95% confidence interval, 0.19–0.66; P=0.001, which indicated that CDH13 hypermethylation plays a more important role in the pathogenesis of adenocarcinoma. NSCLC with CDH13 hypermethylation was found more frequently in poorly differentiated NSCLC patients. NSCLC patients with CDH13 hypermethylation had a lower survival rate than those without CDH13 hypermethylation. In addition, CDH13 mRNA high expression was found to correlate with better overall survival for all NSCLC patients followed for 20 years

  4. LIGHT ABERRATION IN OPTICAL ANISOTROPIC SINGLE-AXIS MEDIUM

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    V. M. Svishch

    2017-10-01

    Full Text Available The entrainment of the light flux by a uniaxial anisotropic medium and its influence on the measurement of stellar aberration are analyzed. The influence of the entrainment of the light flux by an isotropic medium on the measurement of stellar aberration was considered by Fresnel early. The absence of such influence was confirmed by Erie's experience when filling the telescope tube with water. The formula itself was perfectly confirmed by Fizeau's experiments with moving water and the repetition of this experiment with an increase in the accuracy of measurements by Michelson, Zeeman, and others. G.A. Lorentz already on the basis of the electromagnetic theory specified the formula with allowance for the frequency dispersion of the light flux. A. Einstein made an analysis of the schemes of experiments for determining the drag coefficient, covering all possible variants of similar experiments. As a result, he obtained Fresnel and Lorentz formulas, taking into account the frequency dispersion of light, starting from the theory of relativity. The entrainment of light and its influence on the measurement of stellar aberration by a uniaxial anisotropic medium have not been considered anywhere. An analysis of such influence is carried out. The results of the analysis indicate the possibility of measuring the current value of stellar aberration using a uniaxial anisotropic medium. The concept of active light aberration is introduced. The proposed schemes of experiments of using the entrainment of a light flux by an anisotropic substance for measuring the current value of stellar aberration are investigated. It is concluded that it is possible to study the determination of the current velocity of an inertial system relative to the light flux.

  5. Evaluation of residual aberration in fifth-order geometrical aberration correctors.

    Science.gov (United States)

    Morishita, Shigeyuki; Kohno, Yuji; Hosokawa, Fumio; Suenaga, Kazu; Sawada, Hidetaka

    2018-02-21

    Higher order geometrical aberration correctors for transmission electron microscopes are essential for atomic-resolution imaging, especially at low-accelerating voltages. We quantitatively calculated the residual aberrations of fifth-order aberration correctors to determine the dominant aberrations. The calculations showed that the sixth-order three-lobe aberration was dominant when fifth-order aberrations were corrected by using the double-hexapole or delta types of aberration correctors. It was also deduced that the sixth-order three-lobe aberration was generally smaller in the delta corrector than in the double-hexapole corrector. The sixth-order three-lobe aberration was counterbalanced with a finite amount of the fourth-order three-lobe aberration and 3-fold astigmatism. In the experiments, we used a low-voltage microscope equipped with delta correctors for probe- and image-forming systems. Residual aberrations in each system were evaluated using Ronchigrams and diffractogram tableaux, respectively. The counterbalanced aberration correction was applied to obtain high-resolution transmission electron microscopy images of graphene and WS2 samples at 60 and 15 kV, respectively.

  6. Ablation of the Stimulatory G Protein α-Subunit in Renal Proximal Tubules Leads to Parathyroid Hormone-Resistance With Increased Renal Cyp24a1 mRNA Abundance and Reduced Serum 1,25-Dihydroxyvitamin D.

    Science.gov (United States)

    Zhu, Yan; He, Qing; Aydin, Cumhur; Rubera, Isabelle; Tauc, Michel; Chen, Min; Weinstein, Lee S; Marshansky, Vladimir; Jüppner, Harald; Bastepe, Murat

    2016-02-01

    PTH regulates serum calcium, phosphate, and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels by acting on bone and kidney. In renal proximal tubules (PTs), PTH inhibits reabsorption of phosphate and stimulates the synthesis of 1,25(OH)2D. The PTH receptor couples to multiple G proteins. We here ablated the α-subunit of the stimulatory G protein (Gsα) in mouse PTs by using Cre recombinase driven by the promoter of type-2 sodium-glucose cotransporter (Gsα(Sglt2KO) mice). Gsα(Sglt2KO) mice were normophosphatemic but displayed, relative to controls, hypocalcemia (1.19 ±0.01 vs 1.23 ±0.01 mmol/L; P renal vitamin D 24-hydroxylase and bone fibroblast growth factor-23 (FGF23) mRNA abundance (∼3.4- and ∼11-fold over controls, respectively; P renal vitamin D 24-hydroxylase mRNA levels and for maintaining normal serum 1,25(OH)2D.

  7. Comparison of wavefront aberrations under cycloplegic, scotopic and photopic conditions using WaveScan

    Directory of Open Access Journals (Sweden)

    Rong Fan

    2012-04-01

    Full Text Available PURPOSE: To evaluate the differences of wavefront aberrations under cycloplegic, scotopic and photopic conditions. METHODS: A total of 174 eyes of 105 patients were measured using the wavefront sensor (WaveScan® 3.62 under different pupil conditions: cycloplegic 8.58 ± 0.54 mm (6.4 mm - 9.5 mm, scotopic 7.53 ± 0.69 mm (5.7 mm - 9.1 mm and photopic 6.08 ± 1.14 mm (4.1 mm - 8.8 mm. The pupil diameter, standard Zernike coefficients, root mean square of higher-order aberrations and dominant aberrations were compared between cycloplegic and scotopic conditions, and between scotopic and photopic conditions. RESULTS: The pupil diameter was 7.53 ± 0.69 mm under the scotopic condition, which reached the requirement of about 6.5 mm optical zone design in the wavefront-guided surgery and prevented measurement error due to the pupil centroid shift caused by mydriatics. Pharmacological pupil dilation induced increase of standard Zernike coefficients Z3-3, Z4(0 and Z5-5. The higher-order aberrations, third-order aberration, fourth-order aberration, fifth-order aberration, sixth-order aberration, and spherical aberration increased statistically significantly, compared to the scotopic condition (P<0.010. When the scotopic condition shifted to the photopic condition, the standard Zernike coefficients Z4(0, Z4², Z6-4, Z6-2, Z6² decreased and all the higher-order aberrations decreased statistically significantly (P<0.010, demonstrating that accommodative miosis can significantly improve vision under the photopic condition. Under the three conditions, the vertical coma aberration appears the most frequently within the dominant aberrations without significant effect by pupil size variance, and the proportion of spherical aberrations decreased with the decrease of the pupil size. CONCLUSIONS: The wavefront aberrations are significantly different under cycloplegic, scotopic and photopic conditions. Using the wavefront sensor (VISX WaveScan to measure scotopic

  8. Chromosome aberrations and cell survival in irradiated mammalian cells

    International Nuclear Information System (INIS)

    Tremp, J.

    1981-01-01

    A possible correlation between chromosome aberrations and reduced proliferation capacity or cell death was investigated. Synchronized Chinese hamster fibroblast cells were irradiated with 300 rad of x rays in early G 1 . Despite synchronization the cells reached the subsequent mitosis at different times. The frequency of chromosome aberrations was determined in the postirradiation division at 2-h intervals. The highest frequency occurred in cells with a first cell cycle of medium length. The colony-forming ability of mitotic cells was measured in parallel samples by following the progress of individual mitoses. The proportion of cells forming macrocolonies decreased with increasing cell cycle length, and the number of non-colony-forming cells increased. Irrespective of various first cell cycle lengths and different frequencies of chromosome aberrations, the number of cells forming microcolonies remained constant. A correlation was found between the absence of chromosome aberrations and the ability of cells to form macrocolonies. However, cells with a long first cell cycle formed fewer macrocolonies than expected

  9. Nodal aberration theory applied to freeform surfaces

    Science.gov (United States)

    Fuerschbach, Kyle; Rolland, Jannick P.; Thompson, Kevin P.

    2014-12-01

    When new three-dimensional packages are developed for imaging optical systems, the rotational symmetry of the optical system is often broken, changing its imaging behavior and making the optical performance worse. A method to restore the performance is to use freeform optical surfaces that compensate directly the aberrations introduced from tilting and decentering the optical surfaces. In order to effectively optimize the shape of a freeform surface to restore optical functionality, it is helpful to understand the aberration effect the surface may induce. Using nodal aberration theory the aberration fields induced by a freeform surface in an optical system are explored. These theoretical predications are experimentally validated with the design and implementation of an aberration generating telescope.

  10. Chromatin structure and ionizing-radiation-induced chromosome aberrations

    International Nuclear Information System (INIS)

    Muehlmann-Diaz, M.C.

    1993-01-01

    The possible influence of chromatic structure or activity on chromosomal radiosensitivity was studied. A cell line was isolated which contained some 10 5 copies of an amplified plasmid in a single large mosquito artificial chromosome (MAC). This chromosome was hypersensitive to DNase I. Its radiosensitivity was some three fold greater than normal mosquito chromosomes in the same cell. In cultured human cells irradiated during G 0 , the initial breakage frequency in chromosome 4, 19 and the euchromatic and heterochromatic portions of the Y chromosome were measured over a wide range of doses by inducing Premature Chromosome Condensation (PCC) immediately after irradiation with Cs-137 gamma rays. No evidence was seen that Y heterochromatin or large fragments of it remained unbroken. The only significant deviation from the expected initial breakage frequency per Gy per unit length of chromosome was that observed for the euchromatic portion of the Y chromosome, with breakage nearly twice that expected. The development of aberrations involving X and Y chromosomes at the first mitosis after irradation was also studied. Normal female cells sustained about twice the frequency of aberrations involving X chromosomes for a dose of 7.3 Gy than the corresponding male cells. Fibroblasts from individuals with supernumerary X chromosomes did not show any further increase in X aberrations for this dos. The frequency of aberrations involving the heterochromatic portion of the long arm of the Y chromosome was about what would be expected for a similar length of autosome, but the euchromatic portion of the Y was about 3 times more radiosensitive per unit length. 5-Azacytidine treatment of cultured human female fibroblasts or fibroblasts from a 49,XXXXY individual, reduced the methylation of cytosine residues in DNA, and resulted in an increased chromosomal radiosensitivity in general, but it did not increase the frequency of aberrations involving the X chromosomes

  11. Co-translational mRNA decay in Saccharomyces cerevisiae.

    Science.gov (United States)

    Hu, Wenqian; Sweet, Thomas J; Chamnongpol, Sangpen; Baker, Kristian E; Coller, Jeff

    2009-09-10

    The rates of RNA decay and transcription determine the steady-state levels of all messenger RNA and both can be subject to regulation. Although the details of transcriptional regulation are becoming increasingly understood, the mechanism(s) controlling mRNA decay remain unclear. In yeast, a major pathway of mRNA decay begins with deadenylation followed by decapping and 5'-3' exonuclease digestion. Importantly, it is hypothesized that ribosomes must be removed from mRNA before transcripts are destroyed. Contrary to this prediction, here we show that decay takes place while mRNAs are associated with actively translating ribosomes. The data indicate that dissociation of ribosomes from mRNA is not a prerequisite for decay and we suggest that the 5'-3' polarity of mRNA degradation has evolved to ensure that the last translocating ribosome can complete translation.

  12. Influence of coma aberration on aperture averaged scintillations in oceanic turbulence

    Science.gov (United States)

    Luo, Yujuan; Ji, Xiaoling; Yu, Hong

    2018-01-01

    The influence of coma aberration on aperture averaged scintillations in oceanic turbulence is studied in detail by using the numerical simulation method. In general, in weak oceanic turbulence, the aperture averaged scintillation can be effectively suppressed by means of the coma aberration, and the aperture averaged scintillation decreases as the coma aberration coefficient increases. However, in moderate and strong oceanic turbulence the influence of coma aberration on aperture averaged scintillations can be ignored. In addition, the aperture averaged scintillation dominated by salinity-induced turbulence is larger than that dominated by temperature-induced turbulence. In particular, it is shown that for coma-aberrated Gaussian beams, the behavior of aperture averaged scintillation index is quite different from the behavior of point scintillation index, and the aperture averaged scintillation index is more suitable for characterizing scintillations in practice.

  13. [Aberrant bodily self in schizophrenia].

    Science.gov (United States)

    Maeda, Takaki; Mimura, Masaru

    2014-04-01

    Patients with schizophrenia often experience aberrant bodily self including depersonalization and cenesthopathy, especially in its prodromal and early stage. These symptoms are regarded as the beginning of self-disturbances (i.e. the core psychopathology of the illness). Thus, an understanding of schizophrenic bodily experiences could provide insight into the pathophysiology of schizophrenia. Recently, in the field of cognitive neuroscience, research on self-awareness during intentional actions has focused on examining sense of body ownership (SoO) and sense of agency (SoA). The most critical factor for the emergence of those higher-order senses of self is subject's intention for actions. Intentional signals could integrate multiple bodily sensory feedbacks during actions, and lead to develop a coherent sense of self. Empirical studies using behavioral and neuroimaging experiments have demonstrated that schizophrenic patients exhibit specific patterns of abnormal SoO and SoA. Thus, from a clinical standpoint, the detection of specific nature of schizophrenic bodily experiences could provide evidence for early diagnosis and intervention for schizophrenia.

  14. Diagnostic radiation and chromosome aberrations

    International Nuclear Information System (INIS)

    Patil, S.R.; Hecht, F.; Lubs, H.A.; Kimberling, W.; Brown, J.; Gerald, P.S.; Summitt, R.L.

    1977-01-01

    Some evidence is presented suggesting that diagnostic X-rays may be important in the origin of a new chromosomal abnormality other than Down syndrome. Chromosome analyses have been carried out on 4342 children, seven or eight years old. Maternal diagnostic irradiation in the year before conception and up to third lunar month of the index pregnancy was recorded, before the chromosome study began, together with a large amount of family and clinical data. Information on X-ray exposure was supplied by the mothers, s o radiation dosage could not be estimated. 21 children (including a pair of twins and a pair of siblings) born to 19 mothers had chromosomal aberrations. The mothers of six children with inherited translocations, rearrangements and XYY karyotypes were excluded, and 3 (23%) of the remaining 13 mothers had received abdominal and pelvic X-ray exposures. In the whole sample, however, only 6% of the mothers had diagnostic irradiation. Two of these mothers, aged sixteen and twenty, gave birth to a child each with de-novo autosomal translocations, and the third mother, aged thirty-two, had a child with a complex mosaicism involving one X chromosome. Although the sample size of the mothers with chromosomally abnormal children is small, the results are significant. (U.K.)

  15. Multiple aberrations in shared inflammatory and oxidative & nitrosative stress (IO&NS) pathways explain the co-association of depression and cardiovascular disorder (CVD), and the increased risk for CVD and due mortality in depressed patients.

    Science.gov (United States)

    Maes, Michael; Ruckoanich, Piyanuj; Chang, Young Seun; Mahanonda, Nithi; Berk, Michael

    2011-04-29

    There is evidence that there is a bidirectional relationship between major depression and cardiovascular disorder (CVD): depressed patients are a population at risk for increased cardiac morbidity and mortality, and depression is more frequent in patients who suffer from CVD. There is also evidence that inflammatory and oxidative and nitrosative stress (IO&NS) pathways underpin the common pathophysiology of both CVD and major depression. Activation of these pathways may increase risk for both disorders and contribute to shared risk. The shared IO&NS pathways that may contribute to CVD and depression comprise the following: increased levels of pro-inflammatory cytokines, like interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α, and interferon-γ; T cell activation; increased acute phase proteins, like C-reactive protein, haptoglobin, fibrinogen and α1-antitrypsin; complement factors; increased LPS load through bacterial translocation and subsequent gut-derived inflammation; induction of indoleamine 2,3-dioxygenase with increased levels of tryptophan catabolites; decreased levels of antioxidants, like coenzyme Q10, zinc, vitamin E, glutathione and glutathione peroxidase; increased O&NS characterized by oxidative damage to low density lipoprotein (LDL) and phospholipid inositol, increased malondialdehyde, and damage to DNA and mitochondria; increased nitrosative stress; and decreased ω3 polyunsaturated fatty acids (PUFAs). The complex interplay between the abovementioned IO&NS pathways in depression results in pro-atherogenic effects and should be regarded as a risk factor to future clinical CVD and due mortality. We suggest that major depression should be added as a risk factor to the Charlson "comorbidity" index. It is advised that patients with (sub)chronic or recurrent major depression should routinely be assessed by serology tests to predict if they have an increased risk to cardiovascular disorders. Copyright © 2010 Elsevier Inc. All

  16. High ALK mRNA expression has a negative prognostic significance in rhabdomyosarcoma

    OpenAIRE

    Bonvini, P; Zin, A; Alaggio, R; Pawel, B; Bisogno, G; Rosolen, A

    2013-01-01

    Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in cancer, but its clinical and functional importance remain controversial. Mutation or amplification of ALK, as well as its expression levels assessed by conventional immunohistochemistry methods, has been linked to prognosis in cancer, although with potential bias because of the semi-quantitative approaches. Herein, we measured ALK mRNA expression in rhabdomyosarcoma (RMS) and determined its clin...

  17. Effects of SMILE and Trans-PRK on corneal higher order aberrations after myopic correction

    Directory of Open Access Journals (Sweden)

    Jiao Zhao

    2018-02-01

    Full Text Available AIM:To observe the effects of small incision lenticule extraction(SMILEand trans-epithelial photorefractive keratectomy(Trans-PRKon corneal horizontal coma, vertical coma, and spherical aberration and total higher order aberrations after refractive correction for myopia. METHODS: This was a prospective non-randomized cohort study. The cohort included 40 patients(80 eyeswith myopia, who received refraction correction surgery from December 2016 to February 2017 in Leshan Ophthalmic Center. Twenty patients(40 eyesreceived SMILE surgery and the other 20 patients(40 eyesreceived Trans-PRK surgery. Corneal aberrations were determined by a high-resolution Pentacam Scheimpflug camera before the surgery and at 1 and 3mo after the operation. Statistical analyses were performed using analysis of variance of repeated measures. RESULTS: At 1 and 3mo post-operation, the uncorrected visual acuity in both groups was better than or equal to the preoperative best corrected visual acuity. The preoperative corneal aberrations showed no significant difference between the two groups(P>0.05. Significantly higher aberration was found after the surgery in both groups(PP>0.05. Post-operation, horizontal and vertical coma had no significant difference between the two groups(P>0.05, while SMILE group showed lower spherical aberration and lower total higher order aberration than Trans-PRK group(PCONCLUSION: Both SMILE and Trans-PRK increase corneal aberration and their effects on horizontal and vertical coma are similar. However, SMILE has a minor influence on spherical aberration and total high order aberration than Trans-PRK.

  18. Chromosome aberration frequency in blood lymphocytes of animals with 239Pu lung burdens

    International Nuclear Information System (INIS)

    Brooks, A.L.; LaBauve, R.J.; McClellan, R.O.; Jensen, D.A.

    1976-01-01

    Other investigators have suggested a causal relationship between accidental 239 Pu exposures in man and the presence of chromosome aberrations in blood lymphocytes. For experimental assessment of this relationship, 16 rhesus monkeys and 171 Chinese hamsters were exposed to 239 PuO 2 aerosols and an additional five hamsters were injected with 239 Pu citrate, and the frequency of aberrations in blood lymphocyte was determined. Hamsters with the highest lung burden had a median survival time of about 80 days. No deaths occurred in any of the other treated hamsters or monkeys by 250 days after 239 Pu inhalation. Hamsters sacrificed at 30 days showed an increase in chromosome aberration frequency with increasing dose to lungs. By 120 days after inhalation, the aberration frequency in the controls was 0.012. The frequency in animals with doses that produced significant life shortening had decreased to 0.018 and to 0.032 aberration/cell in animals with lower doses. At 380 days after injection of 2 nCi of 239 Pu citrate per gram of body weight, hamster lymphocytes had an aberration frequency of 0.048 aberration/cell. The level of chromosome damage in the 239 PuO 2 -exposed monkeys at 30 and 90 days after inhalation was not different from that observed in controls. Possible reasons for differences between the experimental animal observations and findings in man are discussed

  19. Aberrant intestinal microbiota in individuals with prediabetes

    DEFF Research Database (Denmark)

    Allin, Kristine H.; Tremaroli, Valentina; Caesar, Robert

    2018-01-01

    with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log2 fold change −0.64 (SEM 0.23), padj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0...... individuals with prediabetes (mean log2 fold change −1.74 (SEM 0.41), padj = 2 × 10−3 and −1.65 (SEM 0.34), padj = 4 × 10−4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce...... impaired glucose regulation in recipient mice. Conclusions/interpretation: Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings...

  20. Retrospective chromosome aberration analysis of former uranium miners

    International Nuclear Information System (INIS)

    Meszaros, G.; Bognar, G.; Koeteles, G. J.

    2003-01-01

    In this paper we present our data collected in the period of 1981-1985 on 165 persons exposed by different radon concentrations expressed in working level month (WLM) units from 100 up to 600. Following the decommissioning of the uranium mine in Hungary in 1997 cytogenetic status of 131 persons were within a follow-up-study of their health conditions initiated by the Hungarian Academy of Science. The persons have terminated their underground activities 5 to 20 years before testing. The comparison of the two datasets suggest a long-term persistence of cytogenetic alterations above the population average values in large percentages of persons investigated. The frequency of chromosome aberrations of uranium miners was found increased in function of their exposure to radon. The comparison of the miner's categories 20 years ago and in the recent years demonstrated the long-term existence of aberrations for many years after completion of underground mining activities. (authors)

  1. Induction of chromosomal aberrations by neutron capture reactions

    International Nuclear Information System (INIS)

    Ikushima, Takaji

    1993-01-01

    Boron neutron capture reaction (B-NCR) has been practiced in the treatment of malignancies of the central nervous system and melanoma using a thermal neutron beam from the KUR. Because of the very large neutron absorption cross-section and high kinetic energy released, gadolinium (Gd-157) has been expected to be an another promising element for neutron capture therapy. The dose-response relationship was determined for the induction of chromosomal aberrations by neutron capture reactions by B-10 and Gd-157 in cultured mammalian cells. The cells were exposed to thermal neutron beam with and without B-10 enriched (97 atom %) boric acid or Gd-DTPA, and chromosome-type aberrations were analysed in the first metaphases following irradiation. The frequency of dicentrics and rings increased linearly with neutron fluence either in the presence or absence of B-10 boric acid, while the yield of chromosomal aberrations induced by Gd-NCR increased in a linear quadratic fashion as a function of dose as in γ-rayed cells. Survival curves for the cells exposed to thermal neutrons showed no shoulder irrespective of the loading of B-10, but Gd-NCR produced the survival curve with a small shoulder. The differential chromosomal response to B-NCR and Gd-NCR might reflect the difference in radiation quality generated from the two types of thermal neutron capture reaction. (J.P.N.)

  2. Corneal reshaping and wavefront aberrations during overnight orthokeratology.

    Science.gov (United States)

    Lian, Yan; Shen, Meixiao; Huang, Shenghai; Yuan, Yimin; Wang, Yaozeng; Zhu, Dexi; Jiang, Jun; Mao, Xinjie; Wang, Jianhua; Lu, Fan

    2014-05-01

    To investigate changes of corneal thickness at the vertical and horizontal meridians and of wavefront aberrations (WA) over a 30-day period of overnight myopia orthokeratology (OK) lens wear. Sixteen subjects (11 women, 5 men, 26.3±3.2 years) were enrolled and fitted for OK lenses. Long scan depth optical coherence tomography was used to measure corneal thickness profiles at both horizontal and vertical meridians at baseline and on days 1, 7, and 30 days. Corneal and ocular WA of a 6-mm pupil were measured and the root-mean-square (RMS) of the astigmatism, coma, spherical aberration (SA), and total higher-order aberrations (HOAs) were determined. During the 30-day period, the central cornea thinned in the horizontal and vertical meridians, whereas corneal thickening occurred in the temporal, nasal, and inferior mid-peripheries. In contrast, the cornea thinned in the mid-peripheral superior. There were significant increases in RMS for astigmatism, SA, coma, and positive horizontal coma during the study period. After OK, there were significant positive correlations between the midperipheral-central thickness change difference and the changes in corneal and ocular RMS of total HOAs and SA (r range: 0.281 to 0.492, POK caused unique changes in corneal thickness profiles at the vertical and horizontal meridians and increased corneal and ocular HOAs related to corneal reshaping.

  3. Population spherical aberration: associations with ametropia, age, corneal curvature, and image quality

    Directory of Open Access Journals (Sweden)

    Kingston AC

    2013-05-01

    Full Text Available Amanda C Kingston,1,2 Ian G Cox11Bausch + Lomb, Rochester, NY, USA; 2Department of Biomedical Engineering, University of Rochester, Rochester, NY, USAPurpose: The aim of this analysis was to determine the total ocular wavefront aberration values of a large phakic population of physiologically normal, ametropic eyes, gathered under the same clinical protocol using the same diagnostic wavefront sensor.Materials and methods: Studies were conducted at multiple sites in Asia, North America, Europe, and Australia. A Bausch + Lomb Zywave II Wavefront Aberrometer (Rochester, NY, USA was used to measure the lower and higher order aberrations of each eye. Data analysis was conducted using linear regression analysis to determine the relationship between total spherical aberration, ametropia, age, corneal curvature, and image quality.Results: Linear regression analysis showed no correlation (r = 0.0207, P = 0.4874 between degree of ametropia and the amount of spherical aberration. There was also no correlation when the population was stratified into myopic and hyperopic refractive groups (rm = 0.0529, Pm = 0.0804 and rh = 0.1572, Ph = 0.2754. There was a statistically significant and weak positive correlation (r = 0.1962, P < 0.001 between age and the amount of spherical aberration measured in the eye; spherical aberration became more positive with increasing age. Also, there was a statistically significant and moderately positive correlation (r = 0.3611, P < 0.001 with steepness of corneal curvature; spherical aberration became more positive with increasing power of the anterior corneal surface. Assessment of image quality using optical design software (Zemax™, Bellevue, WA, USA showed that there was an overall benefit in correcting the average spherical aberration of this population.Conclusion: Analysis of this dataset provides insights into the inherent spherical aberration of a typical phakic, pre-presbyopic, population and provides the ability to

  4. Chromosomal aberrations induced by alpha particles

    International Nuclear Information System (INIS)

    Guerrero C, C.; Brena V, M.

    2005-01-01

    The chromosomal aberrations produced by the ionizing radiation are commonly used when it is necessary to establish the exposure dose of an individual, it is a study that is used like complement of the traditional physical systems and its application is only in cases in that there is doubt about what indicates the conventional dosimetry. The biological dosimetry is based on the frequency of aberrations in the chromosomes of the lymphocytes of the individual in study and the dose is calculated taking like reference to the dose-response curves previously generated In vitro. A case of apparent over-exposure to alpha particles to which is practiced analysis of chromosomal aberrations to settle down if in fact there was exposure and as much as possible, to determine the presumed dose is presented. (Author)

  5. Electrostatic axisymmetric mirror with removable spherical aberration

    International Nuclear Information System (INIS)

    Birmuzaev, S.B.; Serikbaeva, G.S.; Hizirova, M.A.

    1999-01-01

    The electrostatic axisymmetric mirror, assembled from three coaxial cylinders with an equal diameter d and under the potential v1, v2 and v3, was computed. The proportions of geometrical and electric parameters of the mirror, with which the spherical 3-order aberration may be eliminated, were determined. The computation outcomes of the case, when the focal power of the mirror is enough large and the object plane in the focus is out of its field, are presented (Fig. 1 - potentials proportion that makes elimination of the spherical aberration possible; Fig. 2 - the focus coordinates when the spherical aberration is eliminated). The geometrical values are presented by d, and the electric ones are presented by v1. The figures on the curves present a length of the second (middle) electrode. The zero point is located in the middle of the gap between the first and second electrodes The investigated mirror may be used as a lens for the transmission electron microscope

  6. Chronic Nicotine Mitigates Aberrant Inhibitory Motor Learning Induced by Motor Experience under Dopamine Deficiency.

    Science.gov (United States)

    Koranda, Jessica L; Krok, Anne C; Xu, Jian; Contractor, Anis; McGehee, Daniel S; Beeler, Jeff A; Zhuang, Xiaoxi

    2016-05-11

    Although dopamine receptor antagonism has long been associated with impairments in motor performance, more recent studies have shown that dopamine D2 receptor (D2R) antagonism, paired with a motor task, not only impairs motor performance concomitant with the pharmacodynamics of the drug, but also impairs future motor performance once antagonism has been relieved. We have termed this phenomenon "aberrant motor learning" and have suggested that it may contribute to motor symptoms in movement disorders such as Parkinson's disease (PD). Here, we show that chronic nicotine (cNIC), but not acute nicotine, treatment mitigates the acquisition of D2R-antagonist-induced aberrant motor learning in mice. Although cNIC mitigates D2R-mediated aberrant motor learning, cNIC has no effect on D1R-mediated motor learning. β2-containing nicotinic receptors in dopamine neurons likely mediate the protective effect of cNIC against aberrant motor learning, because selective deletion of β2 nicotinic subunits in dopamine neurons reduced D2R-mediated aberrant motor learning. Finally, both cNIC treatment and β2 subunit deletion blunted postsynaptic responses to D2R antagonism. These results suggest that a chronic decrease in function or a downregulation of β2-containing nicotinic receptors protects the striatal network against aberrant plasticity and aberrant motor learning induced by motor experience under dopamine deficiency. Increasingly, aberrant plasticity and aberrant learning are recognized as contributing to the development and progression of movement disorders. Here, we show that chronic nicotine (cNIC) treatment or specific deletion of β2 nicotinic receptor subunits in dopamine neurons mitigates aberrant motor learning induced by dopamine D2 receptor (D2R) blockade in mice. Moreover, both manipulations also reduced striatal dopamine release and blunt postsynaptic responses to D2R antagonists. These results suggest that chronic downregulation of function and/or receptor

  7. Tumoral Environment Triggers Transcript Anomalies in Established Tumors: Induction of Altered Gene Expression and of Aberrant, Truncated and B2 Repeat-Containing Gene Transcripts

    Directory of Open Access Journals (Sweden)

    Pieter Rottiers

    1999-12-01

    Full Text Available In addition to eugenetic changes, cancerous cells exhibit extensive modifications in the expression levels of a variety of genes. The phenotypic switch observed after inoculation of T lymphoma cells into syngenic mice illustrates the active participation of tumoral environment in the induction of an aberrant gene expression pattern. To further substantiate this contribution, we performed polymerase chain reaction (PCR-based subtraction suppression hybridization (SSH to identify genes that are differentially expressed in tumor-derived EL4/13.3 cells compared to the same cells isolated from cultures. Besides a number of unknown genes, the subtracted library contained several known genes that have been reported to be expressed at increased levels in tumors and/or to contribute to carcinogenesis. Apart from clones representing translated transcripts, the subtracted library also contained a high number of clones representing B2 repeat elements, viz. short interspersed repetitive elements that are transcribed by RNA polymerase III. Northern blotting confirmed the induction of B2 transcripts in tumor tissue and also revealed induction of chimeric, B2 repeat-containing mRNA. The appearance of chimeric transcripts was accompanied by aberrant, shorter-than-full-length transcripts, specifically from upregulated genes. Accordingly, in addition to altered gene expression, tumoral environmental triggers constitute a potent mechanism to create an epigenetic diversity in cancers by inducing extensive transcript anomalies.

  8. Analysis of chromosome aberration data by hybrid-scale models

    International Nuclear Information System (INIS)

    Indrawati, Iwiq; Kumazawa, Shigeru

    2000-02-01

    This paper presents a new methodology for analyzing data of chromosome aberrations, which is useful to understand the characteristics of dose-response relationships and to construct the calibration curves for the biological dosimetry. The hybrid scale of linear and logarithmic scales brings a particular plotting paper, where the normal section paper, two types of semi-log papers and the log-log paper are continuously connected. The hybrid-hybrid plotting paper may contain nine kinds of linear relationships, and these are conveniently called hybrid scale models. One can systematically select the best-fit model among the nine models by among the conditions for a straight line of data points. A biological interpretation is possible with some hybrid-scale models. In this report, the hybrid scale models were applied to separately reported data on chromosome aberrations in human lymphocytes as well as on chromosome breaks in Tradescantia. The results proved that the proposed models fit the data better than the linear-quadratic model, despite the demerit of the increased number of model parameters. We showed that the hybrid-hybrid model (both variables of dose and response using the hybrid scale) provides the best-fit straight lines to be used as the reliable and readable calibration curves of chromosome aberrations. (author)

  9. Descriptive evaluation of chromosome aberrations in blood lymphocytes due to gamma-irradiation

    International Nuclear Information System (INIS)

    Medina III, F.S.; Gregorio, J.S.; Vinoya, P.C.; Panlaque, C.A.

    1983-01-01

    To induce and evaluate the effect of radiation among Filipinos, frequencies and types of ν-ray induced chromosome aberrations were studied with peripheral lymphocytes from 19 donors. Peripheral blood samples were irradiated at 0 Gray, 500 mGy, 1 Gy, 2 Gy, 3 Gy and 4 Gy. Irradiated blood samples were cultured by the same standard technique as that commonly used for human blood lymphocytes. Our observations showed that irradiation causes chromosomal aberration similar to effects observed in Caucasians. Our study confirm that irradiation causes an increase of the chromosome aberrations types normally found in the control (gaps, chromatid breaks and chromosome fragments) and can induce aberrations which are rarely observed in non-exposed individual (deletions, translocations, polycentrics, rings, and despiralizations). (author)

  10. Alternative splicing in the human cytochrome P450IIB6 gene generates a high level of aberrant messages

    Energy Technology Data Exchange (ETDEWEB)

    Miles, J.S.; McLaren, A.W.; Wolf, C.R. (Imperial Cancer Research Fund, Edinburgh (England))

    1989-10-25

    Polymorphisms within the human cytochrome P450 system can have severe clinical consequences and have been associated with adverse drug side effects and susceptibility to environmentally linked disease such as cancer. Aberrant splicing of cytochrome P450 mRNA has been proposed as a potential mechanism for these polymorphisms. The authors have isolated aberrantly, as well as normally, spliced mRNAs (cDNAs) from the human P450IIB6 gene which either contain part of intron 5 and lack exon 8 or which contain a 58-bp fragment (exon 8A) instead of exon 8. Sequence analysis of the P450IIB6 gene demonstrates the presence of cryptic splice sites in intron 8 which will account for the generation of exon 8A. The mRNAs were therefore generated by alternative splicing. These data gain significance as the mRNAs will not encode a functional P450 enzyme and appear to represent a high proportion of the P450IIB6 mRNA population. Analysis of mRNA from fifteen individual human livers and cDNA libraries constructed from a variety of human tissues using the polymerase chain reaction shows that the aberrant splicing occurs in all cells and all individuals tested. This suggests a high level of infidelity in the processing of P450IIB6 mRNAs and demonstrates that the presence of abnormal transcripts does not imply the presence of a functionally inactive gene.

  11. HLA-G allelic variants are associated with differences in the HLA-G mRNA isoform profile and HLA-G mRNA levels

    DEFF Research Database (Denmark)

    Hviid, Thomas Vauvert F; Hylenius, Sine; Rørbye, Christina

    2003-01-01

    During pregnancy, the human extra-villous trophoblast in the contact zone between maternal and fetal tissue in the placenta does not express the classical MHC class I and II molecules. Instead, HLA-G and -C, and possibly HLA-E, are expressed. HLA-G may modulate the immunological relationship...... between mother and fetus in several ways. Finally, the expression of membrane-bound HLA-G and soluble HLA-G has been proposed to influence the outcome of pregnancy, and an aberrant HLA-G expression in pre-eclamptic placentas and spontaneous abortions has been reported. Here, an association between certain...... HLA-G polymorphisms and the mRNA levels of the different alternatively spliced HLA-G isoforms in first trimester trophoblast cell populations is reported. Several alternatively spliced HLA-G mRNA isoforms, including a 14-bp polymorphism in the 3'UTR end (exon 8) of the HLA-G gene, are expressed...

  12. Chromosomal aberrations induced by Markhamia tomentosa (Benth ...

    African Journals Online (AJOL)

    Markhamia tomentosa (Benth.) K. Schum. Ex Engl. (Bignoniaceae) is used traditionally in the treatment of pain, oedema, pulmonary troubles and cancer. The genotoxic and cytotoxic effects of the ethanolic extract of the leaves of M. tomentosa was investigated using the Allium cepa root chromosomal aberration assay.

  13. Anti-forensics of chromatic aberration

    Science.gov (United States)

    Mayer, Owen; Stamm, Matthew C.

    2015-03-01

    Over the past decade, a number of information forensic techniques have been developed to identify digital image manipulation and falsification. Recent research has shown, however, that an intelligent forger can use anti-forensic countermeasures to disguise their forgeries. In this paper, an anti-forensic technique is proposed to falsify the lateral chromatic aberration present in a digital image. Lateral chromatic aberration corresponds to the relative contraction or expansion between an image's color channels that occurs due to a lens's inability to focus all wavelengths of light on the same point. Previous work has used localized inconsistencies in an image's chromatic aberration to expose cut-and-paste image forgeries. The anti-forensic technique presented in this paper operates by estimating the expected lateral chromatic aberration at an image location, then removing deviations from this estimate caused by tampering or falsification. Experimental results are presented that demonstrate that our anti-forensic technique can be used to effectively disguise evidence of an image forgery.

  14. The Aberrant Coronary Artery - The Management Approach.

    Science.gov (United States)

    King, Nina-Marie; Tian, David D; Munkholm-Larsen, Stine; Buttar, Sana N; Chow, Vincent; Yan, Tristan

    2017-07-03

    An aberrant coronary artery is a rare clinical occurrence with an incidence of 0.05-1.2%. Often it is an incidental finding detected on coronary angiography or at autopsy. However, symptomatic patients can experience angina, arrhythmia, sudden death or non-specific symptoms such as dyspnoea and syncope. At present, there are no guidelines or dedicated studies assessing the treatment of an aberrant coronary artery leaving management options for these patients controversial. Selected international cardiothoracic surgeons were surveyed electronically in November 2016 to determine whether consensus exists on different management aspects for patients with an aberrant coronary artery arising from the contralateral sinus with an interarterial course. For asymptomatic patients with either an aberrant left main coronary artery (ALMCA) arising from the contralateral sinus or an aberrant right main coronary artery (ARMCA) arising from the contralateral sinus, there was no consensus on surgical correction of the anomaly. If myocardial ischaemia was demonstrated on either coronary angiography with fractional flow reserve measurements and/or stress myocardial perfusion scan, surgical correction was the consensus between the surveyed surgeons. If surgery was deemed appropriate, coronary artery bypass surgery utilising the internal mammary artery was marginally preferred by the respondents in patients with an ALMCA whilst unroofing of the coronary ostium was preferred in patients with an ARMCA. Although no consensus was reached, a large proportion of respondents would not treat a patient over the age of 30 years differently compared to those under 30 years old. For symptomatic patients or if myocardial ischaemia is demonstrated on either coronary angiography with fractional flow reserve measurements and/or stress myocardial perfusion scan, surgical correction is indicated. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the

  15. Algorithm for sorting chromosomal aberrations

    DEFF Research Database (Denmark)

    Vogel, Ida; Lund, Najaaraq; Rasmussen, Steen

    2017-01-01

    Prenatal diagnostic methods and screening procedures change rapidly in these years. Years ago only karyotyping was performed prenatally, and we monitored only Down syndrome(1) . Since then the diagnostic possibilities have increased to QF-PCR, FISH, MLPA and chromosomal microarray....

  16. The Role of Aberrant Salience and Self-Concept Clarity in Psychotic-Like Experiences

    Science.gov (United States)

    Cicero, David C.; Becker, Theresa M.; Martin, Elizabeth A.; Docherty, Anna R.; Kerns, John G.

    2013-01-01

    Most theories of psychotic-like experiences posit the involvement of social-cognitive mechanisms. The current research examined the relations between psychotic-like experiences and two social-cognitive mechanisms, high aberrant salience and low self-concept clarity. In particular, we examined whether aberrant salience, or the incorrect assignment of importance to neutral stimuli, and low self-concept clarity interacted to predict psychotic-like experiences. The current research included three large samples (n = 667, 724, 744) of participants and over-sampled for increased schizotypal personality traits. In all three studies, an interaction between aberrant salience and self-concept clarity was found such that participants with high aberrant salience and low self-concept clarity had the highest levels of psychotic-like experiences. In addition, aberrant salience and self-concept clarity interacted to predict a supplemental measure of delusions in Study 2. In Study 3, in contrast to low self-concept clarity, neuroticism did not interact with aberrant salience to predict psychotic-like experiences, suggesting that the relation between low self-concept clarity and psychosis may not be due to neuroticism. Additionally, aberrant salience and self-concept clarity did not interact to predict to other schizotypal personality disorder criteria, social anhedonia or trait paranoia, which suggests the interaction is specific to psychotic-like experiences. Overall, our results are consistent with several social-cognitive models of psychosis suggesting that aberrant salience and self-concept clarity might be important mechanisms in the occurrence of psychotic-like symptoms. PMID:22452775

  17. The prediction of spherical aberration with schematic eyes.

    Science.gov (United States)

    Liou, H L; Brennan, N A

    1996-07-01

    Many model eyes have been proposed; they differ in optical characteristics and therefore have different aberrations and image quality. In predicting the visual performance of the eye, we are most concerned with the central foveal vision. Spherical aberration is the only on-axis monochromatic aberration and can be used as a criterion to assess the degree of resemblance of eye models to the human eye. We reviewed and compiled experimental values of the spherical aberration of the eye, calculated the spherical aberration of several different categories of model eyes and compared the calculated results to the experimental data. Results show an over-estimation of spherical aberration by all models, the finite schematic eyes predicting values of spherical aberration closest to the experimental data. Current model eyes do not predict the average experimental values of the spherical aberration of the eye. A new model eye satisfying this assessment criterion is required for investigations of the visual performance of the eye.

  18. Hyperthermic radiosensitization of synchronous Chinese hamster cells: relationship between lethality and chromosomal aberrations

    International Nuclear Information System (INIS)

    Dewey, W.C.; Sapareto, S.A.; Betten, D.A.

    1978-01-01

    Synchronous Chinese hamster cells in vitro were obtained by mitotic selection. The cells were heated at 45.5 0 C for 4 min in mitosis, 11 min in G 1 , or 7 min in S sphase and then x-irradiated immediately thereafter. Colony survival from heat alone was 0.30 to 0.45, and the frequency of chromosomal aberrations induced by heat was 0.00, 0.14, or 0.97 for heat treatments during M, G 1 , or S, respectively. As shown previously, lethality from hyperthermia alone is due to chromosomal aberrations only when the cells are heated during S phase. The log survival (D 0 /sup approximately/ = 80 rad) and aberration frequency curves for cells irradiated during mitosis were linear, and the only effect of hyperthermia was to shift the curves in accord with the effect from heat alone. Thus, hyperthermia did not radiosensitize the mitotic cells. The cells irradiated in G 1 were more resistant (D 0 /sup approximately/ = 100 rad) than those irradiated in mitosis, and the survival and aberration frequency curves both had shoulders. The primary effect of hyperthermia was to greatly reduce the shoulders of the curves and to increase the slopes by about 23%. The cells irradiated in S were the most resistant (D 0 /sup approximately/ = 140 rad), and the survival and aberration frequency curves both had large shoulders. For both end points of lethality and chromosomal aberrations, heat selectively radiosensitized S-phase cells relative to G 1 cells by removing most of the shoulder and increasing the slope by about 45%. For cells treated in G 1 or S, the increase in radiosensitization following hyperthermia can be accounted for by an increase in the frequency of chromosomal aberrations

  19. Aberrant Signaling Pathways in Glioma

    International Nuclear Information System (INIS)

    Nakada, Mitsutoshi; Kita, Daisuke; Watanabe, Takuya; Hayashi, Yutaka; Teng, Lei; Pyko, Ilya V.; Hamada, Jun-Ichiro

    2011-01-01

    Glioblastoma multiforme (GBM), a WHO grade IV malignant glioma, is the most common and lethal primary brain tumor in adults; few treatments are available. Median survival rates range from 12–15 months. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. This is mainly due to highly deregulated signaling pathways in the tumor. Studies of these signaling pathways have greatly increased our understanding of the biology and clinical behavior of GBM. An integrated view of signal transduction will provide a more useful approach in designing novel therapies for this devastating disease. In this review, we summarize the current understanding of GBM signaling pathways with a focus on potential molecular targets for anti-signaling molecular therapies

  20. Altered expression of MGMT in high-grade gliomas results from the combined effect of epigenetic and genetic aberrations.

    Directory of Open Access Journals (Sweden)

    João Ramalho-Carvalho

    Full Text Available MGMT downregulation in high-grade gliomas (HGG has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA. By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation and genetic (monosomy, locus deletion changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

  1. Altered Expression of MGMT in High-Grade Gliomas Results from the Combined Effect of Epigenetic and Genetic Aberrations

    Science.gov (United States)

    Ramalho-Carvalho, João; Pires, Malini; Lisboa, Susana; Graça, Inês; Rocha, Patrícia; Barros-Silva, João Diogo; Savva-Bordalo, Joana; Maurício, Joaquina; Resende, Mário; Teixeira, Manuel R.; Honavar, Mrinalini; Henrique, Rui; Jerónimo, Carmen

    2013-01-01

    MGMT downregulation in high-grade gliomas (HGG) has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP) or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA) and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA). By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation) and genetic (monosomy, locus deletion) changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy. PMID:23505468

  2. Expressions for third-order aberration theory for holographic images

    Indian Academy of Sciences (India)

    established aberration theory in the case of conventional optical elements. It was Meier. [1] who pioneered third-order aberration theory for applications in holography. There are reports in the literature contrary to Meier's results, e.g.,. (i) Smith [2] recalculated third-order aberration on the lines of Meier and tabulated his.

  3. Developmental trends of communicative skills in children with chromosome 14 aberrations.

    Science.gov (United States)

    Zampini, Laura; Zanchi, Paola; Rinaldi, Berardo; Novara, Francesca; Zuffardi, Orsetta

    2017-04-01

    Children with chromosome 14 aberrations usually show developmental delays, intellectual disability, neurological disorders and behaviour problems. The aim of the present study is to describe the developmental trajectories of the communicative skills of children with chromosome 14 aberrations, considering the possible relationships between the patterns of language development and the children's clinical characteristics (e.g., intellectual disability or autistic traits). Longitudinal data on five children (four with linear deletions and one with ring 14 syndrome) followed for 3 years are presented. Four out of five children showed profound intellectual disability, and three out of five showed autistic traits. A high individual variability was found in both vocal and gestural productions. However, only a modest increase in the children's communicative and symbolic skills was detected over time (e.g., in the quality of preverbal productions). The increase of communicative skills in children with chromosome 14 aberration is very slow. We need to consider the children's characteristics, in terms of type of chromosome aberration, level of intellectual disability and presence/absence of autistic traits, to predict their possible linguistic outcomes and to give a more realistic expectation to their parents. What is known: • The communicative skills of children with chromosome 14 aberrations are usually impaired. • The presence of autistic traits is frequent in these children. What is new: • The increase of communicative skills in children with chromosome 14 aberrations is very slow. • The level of intellectual disability and the presence/absence of autistic traits appeared to have a role in predicting the possible linguistic outcomes in children with chromosome 14 aberrations.

  4. [Chromosome aberrations in malformed newborns].

    Science.gov (United States)

    Centeno Malfaz, F; Beltrán Pérez, A; Ruiz Labarga, C; Centeno Robles, T; Macías Pardal, J; Martín Bermejo, M

    2001-06-01

    To determine the prevalence of chromosome abnormalities in malformed newborn infants and to analyze the distribution of the types of anomalies, and the variation in their frequency with maternal age. We used the data collected according to the Spanish Collaborative Study of Congenital Malformations (ECEMC) methodology from March 1982 -September 1996. Of 33,562 newborns (live and stillborn), 1,409(4.1%) malformed infants were identified. A total of 332 karyotypes were performed in peripheral blood, representing 23.5% of the newborns with congenital defects. Results The frequency at birth of chromosome abnormalities was 5.4% of malformed newborns. There were 59 infants with Down's syndrome, 6 with trisomy 18, 3 with Turner's syndrome, 2 with trisomy 13, 2 with "Triple X", 1 tetraploidy, 1 triploidy, 1 trisomy 9 p, and 1 infant with a complex XXY mosaicism. The prevalence of Down's syndrome in the general population is 0.17%. The mean age of mothers with Down's syndrome infants was 34.2 years and paternal age was 36 years, and a non-statistically significant diminishing trend in mean maternal age was observed during the course of the study. The prevalence of Down's syndrome was higher in mothers aged more than 35 years. A non-statistically significant increase of the prevalence of Down's syndrome in newborns with mothers aged between 31 and 34 years was observed with time. The mean number of previous pregnancies was 2.81. Among a total of 49 mothers and fathers, two chromosome alterations were found. The prevalence of chromosome abnormalities in newborns with birth defects was 5.4%. The frequency of Down's syndrome was higher. Down's syndrome was more prevalent in mothers aged more than 35 years. The mean maternal age of Down's syndrome infants gradually diminished, and accumulated between the ages of 31 and 34 years.

  5. Aberrant intestinal microbiota in individuals with prediabetes

    DEFF Research Database (Denmark)

    Allin, Kristine H.; Tremaroli, Valentina; Caesar, Robert

    2018-01-01

    Aims/hypothesis: Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut...... microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1–7.0 mmol/l or HbA1c of 42–48 mmol/mol [6.0–6.5%]) and a range of clinical biomarkers of poor metabolic health. Methods: In the present case–control study, we analysed the gut microbiota of 134 Danish adults...... impaired glucose regulation in recipient mice. Conclusions/interpretation: Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings...

  6. Osteoponin Promoter Controlled by DNA Methylation: Aberrant Methylation in Cloned Porcine Genome

    Directory of Open Access Journals (Sweden)

    Chih-Jie Shen

    2014-01-01

    Full Text Available Cloned animals usually exhibited many defects in physical characteristics or aberrant epigenetic reprogramming, especially in some important organ development. Osteoponin (OPN is an extracellular-matrix protein involved in heart and bone development and diseases. In this study, we investigated the correlation between OPN mRNA and its promoter methylation changes by the 5-aza-dc treatment in fibroblast cell and promoter assay. Aberrant methylation of porcine OPN was frequently found in different tissues of somatic nuclear transferred cloning pigs, and bisulfite sequence data suggested that the OPN promoter region −2615 to −2239 nucleotides (nt may be a crucial regulation DNA element. In pig ear fibroblast cell culture study, the demethylation of OPN promoter was found in dose-dependent response of 5-aza-dc treatment and followed the OPN mRNA reexpression. In cloned pig study, discrepant expression pattern was identified in several cloned pig tissues, especially in brain, heart, and ear. Promoter assay data revealed that four methylated CpG sites presenting in the −2615 to −2239 nt region cause significant downregulation of OPN promoter activity. These data suggested that methylation in the OPN promoter plays a crucial role in the regulation of OPN expression that we found in cloned pigs genome.

  7. Assessing the construct validity of aberrant salience

    Directory of Open Access Journals (Sweden)

    Kristin Schmidt

    2009-12-01

    Full Text Available We sought to validate the psychometric properties of a recently developed paradigm that aims to measure salience attribution processes proposed to contribute to positive psychotic symptoms, the Salience Attribution Test (SAT. The “aberrant salience” measure from the SAT showed good face validity in previous results, with elevated scores both in high-schizotypy individuals, and in patients with schizophrenia suffering from delusions. Exploring the construct validity of salience attribution variables derived from the SAT is important, since other factors, including latent inhibition/learned irrelevance, attention, probabilistic reward learning, sensitivity to probability, general cognitive ability and working memory could influence these measures. Fifty healthy participants completed schizotypy scales, the SAT, a learned irrelevance task, and a number of other cognitive tasks tapping into potentially confounding processes. Behavioural measures of interest from each task were entered into a principal components analysis, which yielded a five-factor structure accounting for ~75% percent of the variance in behaviour. Implicit aberrant salience was found to load onto its own factor, which was associated with elevated “Introvertive Anhedonia” schizotypy, replicating our previous finding. Learned irrelevance loaded onto a separate factor, which also included implicit adaptive salience, but was not associated with schizotypy. Explicit adaptive and aberrant salience, along with a measure of probabilistic learning, loaded onto a further factor, though this also did not correlate with schizotypy. These results suggest that the measures of learned irrelevance and implicit adaptive salience might be based on similar underlying processes, which are dissociable both from implicit aberrant salience and explicit measures of salience.

  8. The aberrant retroesophageal right subclavian artery.

    Science.gov (United States)

    Seres-Sturm, M; Maros, T N; Seres-Sturm, L

    1985-01-01

    Two cases with arteria lusoria were found at 278 routine dissections. These arteria arise as the last branches of the aortic arch and have a retroesophageal position. At the crossing point, the esophagus narrows due to the groove caused by the artery. The appearance of this malposition is the consequence of the perturbation in the organo-genesis of the right dorsal aorta and fourth branchial artery. The aberration can lead to disphagia lusoria.

  9. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Castanos-Velez Esmeralda

    2006-09-01

    Full Text Available Abstract Background Cancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression. Results We investigated genome-wide gene expression in colorectal carcinoma (CRC and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC. Conclusion An extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.

  10. RETRACTED — Orbital angular momentum entanglement states of Gaussian-Schell beam pumping in low-order non-Kolmogorov turbulent aberration channels

    Science.gov (United States)

    Chen, Hongmei; Sheng, Xueli; Zhao, Fengsheng; Zhang, Yixin

    2013-04-01

    Based on the Rytov approximation, we analyze the effect of the pump beam's space-coherence of parametric down-conversion on entangled orbital angular momentum (OAM) states propagation in slant low-order turbulence aberration channels. The detection probability of signal photon of entangled OAM states is modeled. Our numerical evaluation shows that the signal photon detection probability and the crosstalk probability decay nonlinearly with the increasing of the number of space coherent speckle and the OAM quantum number of signal photon in the channels of Z-tilt aberration, astigmatism aberration, defocus aberration and coma aberration declines. The OAM entanglement states of low spatial coherence are improper to be used for the carrier wave of the encoding of OAM. The signal photon detection probability decreases as the power-law exponent of non-Kolmogorov spectrum increases from 3 to 4, in the turbulence Z-tilt, astigmatism and coma aberrations channels.

  11. Adipose tissue interleukin-18 mRNA and plasma interleukin-18: effect of obesity and exercise

    DEFF Research Database (Denmark)

    Leick, Lotte; Lindegaard, Birgitte; Stensvold, Dorthe

    2007-01-01

    OBJECTIVES: Obesity and a physically inactive lifestyle are associated with increased risk of developing insulin resistance. The hypothesis that obesity is associated with increased adipose tissue (AT) interleukin (IL)-18 mRNA expression and that AT IL-18 mRNA expression is related to insulin...... of regular physical activity with improved insulin sensitivity.......: AT IL-18 mRNA content and plasma IL-18 concentration were higher (p insulin resistance. While acute exercise did not affect IL-18 mRNA expression...

  12. MiR-30e suppresses proliferation of hepatoma cells via targeting prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA

    International Nuclear Information System (INIS)

    Feng, Guoxing; Shi, Hui; Li, Jiong; Yang, Zhe; Fang, Runping; Ye, Lihong; Zhang, Weiying; Zhang, Xiaodong

    2016-01-01

    Aberrant microRNA expression has been shown to be characteristic of many cancers. It has been reported that the expression levels of miR-30e are decreased in liver cancer tissues. However, the role of miR-30e in hepatocellular carcinoma remains poorly understood. In the present study, we investigated the significance of miR-30e in hepatocarcinogenesis. Bioinformatics analysis reveals a putative target site of miR-30e in the 3′-untranslated region (3′UTR) of prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA. Moreover, luciferase reporter gene assays verified that miR-30e directly targeted 3′UTR of P4HA1 mRNA. Then, we demonstrated that miR-30e was able to reduce the expression of P4HA1 at the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blot analysis. Enforced expression of miR-30e suppressed proliferation of HepG2 cells by 5-ethynyl-2-deoxyuridine (EdU) assay and reduced colony formation of these cells by colony formation analysis. Conversely, anti-miR-30e enhanced the proliferation of hepatoma cells in vitro. Interestingly, the ectopic expression of P4HA1 could efficiently rescue the inhibition of cell proliferation mediated by miR-30e in HepG2 cells. Meanwhile, silencing of P4HA1 abolished the anti-miR-30e-induced proliferation of cells. Clinically, quantitative real-time PCR showed that miR-30e was down-regulated in liver tumor tissues relative to their peritumor tissues. The expression levels of miR-30e were negatively correlated to those of P4HA1 mRNA in clinical liver tumor tissues. Thus, we conclude that miR-30e suppresses proliferation of hepatoma cells through targeting P4HA1 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis. - Highlights: • P4HA1 is a novel target gene of miR-30e. • P4HA1 is increased in clinical HCC tissues. • MiR-30e is negatively correlated with P4HA1 in clinical HCC tissues. • MiR-30e suppresses the proliferation of HCC cells through

  13. MiR-30e suppresses proliferation of hepatoma cells via targeting prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Guoxing [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China); Shi, Hui [State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin (China); Li, Jiong; Yang, Zhe [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China); Fang, Runping; Ye, Lihong [State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin (China); Zhang, Weiying, E-mail: zhwybao@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China)

    2016-04-08

    Aberrant microRNA expression has been shown to be characteristic of many cancers. It has been reported that the expression levels of miR-30e are decreased in liver cancer tissues. However, the role of miR-30e in hepatocellular carcinoma remains poorly understood. In the present study, we investigated the significance of miR-30e in hepatocarcinogenesis. Bioinformatics analysis reveals a putative target site of miR-30e in the 3′-untranslated region (3′UTR) of prolyl 4-hydroxylase subunit alpha-1 (P4HA1) mRNA. Moreover, luciferase reporter gene assays verified that miR-30e directly targeted 3′UTR of P4HA1 mRNA. Then, we demonstrated that miR-30e was able to reduce the expression of P4HA1 at the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blot analysis. Enforced expression of miR-30e suppressed proliferation of HepG2 cells by 5-ethynyl-2-deoxyuridine (EdU) assay and reduced colony formation of these cells by colony formation analysis. Conversely, anti-miR-30e enhanced the proliferation of hepatoma cells in vitro. Interestingly, the ectopic expression of P4HA1 could efficiently rescue the inhibition of cell proliferation mediated by miR-30e in HepG2 cells. Meanwhile, silencing of P4HA1 abolished the anti-miR-30e-induced proliferation of cells. Clinically, quantitative real-time PCR showed that miR-30e was down-regulated in liver tumor tissues relative to their peritumor tissues. The expression levels of miR-30e were negatively correlated to those of P4HA1 mRNA in clinical liver tumor tissues. Thus, we conclude that miR-30e suppresses proliferation of hepatoma cells through targeting P4HA1 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis. - Highlights: • P4HA1 is a novel target gene of miR-30e. • P4HA1 is increased in clinical HCC tissues. • MiR-30e is negatively correlated with P4HA1 in clinical HCC tissues. • MiR-30e suppresses the proliferation of HCC cells through

  14. Aberrant phenotypes in peripheral T cell lymphomas.

    Science.gov (United States)

    Hastrup, N; Ralfkiaer, E; Pallesen, G

    1989-01-01

    Seventy six peripheral T cell lymphomas were examined immunohistologically to test their reactivity with a panel of monoclonal antibodies against 11 T cell associated antigens (CD1-8, CD27, UCHL1, and the T cell antigen receptor). Sixty two (82%) lymphomas showed aberrant phenotypes, and four main categories were distinguished as follows: (i) lack of one or several pan-T cell antigens (49, 64% of the cases); (ii) loss of both the CD4 and CD8 antigens (11, 15% of the cases); (iii) coexpression of the CD4 and CD8 antigens (13, 17% of the cases); and (iv) expression of the CD1 antigen (eight, 11% of the cases). No correlation was seen between the occurrence of aberrant phenotypes and the histological subtype. It is concluded that the demonstration of an aberrant phenotype is a valuable supplement to histological assessment in the diagnosis of peripheral T cell lymphomas. It is recommended that the panel of monoclonal antibodies against T cell differentiation antigens should be fairly large, as apparently any antigen may be lost in the process of malignant transformation. Images Figure PMID:2469701

  15. Study of radiation-induced chromosomal aberrations

    International Nuclear Information System (INIS)

    Wolfring, E.

    2004-06-01

    A method for determining chromosomal aberrations was established for the purpose of examining the relative biological effectiveness (RBE) of photon radiation with respect to mammary epithelium cells. Cells were exposed to 25 kV X-radiation and to 200 kV X-radiation for comparison and the resulting concentrations of chromosomal aberrations were compared. The RBE M value for radiation-induced fragmentation was found to be 4.2 ± 2.4, while the RBE M value for radiation-induced generation of dicentric chromosomes was found to be 0.5 ± 0.5. In addition to the evaluation of chromosomal aberrations the number of cell cycles undergone by the cells was monitored by means of BrDU staining. As expected, the proportion of cells which underwent more than one cell cycle following exposure to 5 Gy was very low in both cases, amounting to 1.9% (25 kV) and 3.2 (200 kV). Non-radiated cells yielded control values of 26.0% and 12.6%, suggesting variations in external conditions from day to day

  16. The effects of chalazion excision on corneal surface aberrations.

    Science.gov (United States)

    Park, Young Min; Lee, Jong Soo

    2014-10-01

    This study is the first to consider the effects of chalazion on corneal surface aberrations taking into account of corneal zones, and to establish the size standard for the excision of chalazion. Twenty three eyes from 23 patients with central upper eyelid chalazion larger than 3mm were recruited in this prospective study. The participants were classified into two groups, depending on size of the lesion: Group 1 with lesion size 3-5mm and Group 2 with lesion size >5mm Chalazion was excised by standard transconjunctival vertical incision. Corneal surface aberrations were measured using a Galilei™ analyzer and an auto-refractometer before and 2 months after the excision. Corneal astigmatism in all patients decreased significantly in both auto refractometer (P=0.012) and Galilei™ (P=0.020) measurements after chalazion excision. RMS of total HOAs decreased significantly in 6mm (P=0.043) and 3mm zone (P=0.051). The RMS of Zernike orders in the vertical and horizontal trefoil decreased significantly in 6mm (P=0.035) and 3mm (P=0.041) zone. Group 2 showed a significant decrease in corneal astigmatism in both auto refractometer (P=0.040) and Galilei™ (P=0.017) parameters after chalazion excision. Group 1 showed an insignificant decrease in corneal astigmatism. Unlike Group 1, the RMS of total HOAs and vertical and horizontal trefoil in 6mm zone decreased significantly in Group 2 (Pchalazion increases astigmatism and HOAs, especially at the peripheral cornea. Significantly induced astigmatism and HOAs are caused by chalazion >5mm in size. Thus, we recommend the surgical excision of chalazion >5mm in size to reduce corneal surface aberrations. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  17. Exaggerated translation causes synaptic and behavioural aberrations associated with autism.

    Science.gov (United States)

    Santini, Emanuela; Huynh, Thu N; MacAskill, Andrew F; Carter, Adam G; Pierre, Philippe; Ruggero, Davide; Kaphzan, Hanoch; Klann, Eric

    2013-01-17

    Autism spectrum disorders (ASDs) are an early onset, heterogeneous group of heritable neuropsychiatric disorders with symptoms that include deficits in social interaction skills, impaired communication abilities, and ritualistic-like repetitive behaviours. One of the hypotheses for a common molecular mechanism underlying ASDs is altered translational control resulting in exaggerated protein synthesis. Genetic variants in chromosome 4q, which contains the EIF4E locus, have been described in patients with autism. Importantly, a rare single nucleotide polymorphism has been identified in autism that is associated with increased promoter activity in the EIF4E gene. Here we show that genetically increasing the levels of eukaryotic translation initiation factor 4E (eIF4E) in mice results in exaggerated cap-dependent translation and aberrant behaviours reminiscent of autism, including repetitive and perseverative behaviours and social interaction deficits. Moreover, these autistic-like behaviours are accompanied by synaptic pathophysiology in the medial prefrontal cortex, striatum and hippocampus. The autistic-like behaviours displayed by the eIF4E-transgenic mice are corrected by intracerebroventricular infusions of the cap-dependent translation inhibitor 4EGI-1. Our findings demonstrate a causal relationship between exaggerated cap-dependent translation, synaptic dysfunction and aberrant behaviours associated with autism.

  18. Retinal image degradation by optical aberrations and light scatter in normal and albino chick eyes

    Science.gov (United States)

    Tian, Yibin; Shieh, Kevin; Wildsoet, Christine F.

    2007-02-01

    Comprehensive evaluation of retinal image quality requires that light scatter as well as optical aberrations be considered. In investigating how retinal image degradation affects eye growth in the chick model of myopia, we developed a simple method based on Shack-Hartmann images for evaluating the effects of both monochromatic aberrations and light scatter on retinal image quality. We further evaluated our method in the current study by applying it to data collected from both normal chick eyes and albino eyes that were expected to show increased intraocular light scatter. To analyze light scatter in our method, each Shack-Hartmann dot is treated as a local point spread function (PSF) that is the convolution of a local scatter PSF and a lenslet diffraction PSF. The local scatter PSF is obtained by de-convolution, and is fitted with a circularly symmetric Gaussian function using nonlinear regressions. A whole-eye scatter PSF also can be derived from the local scatter PSFs for the analyzed pupil. Aberrations are analyzed using OSA standard Zernike polynomials, and aberration-related PSF calculated from reconstructed wavefront using fast Fourier transform. Modulation transfer functions (MTFs) are computed separately for aberration and scatter PSFs, and a whole-eye MTF is derived as the product of the two. This method was applied to 4 normal and 4 albino eyes. Compared to normal eyes, albino eyes were more aberrated and showed greater light scatter. As a result, overall retinal image degradation was much greater in albino eyes than in normal eyes, with the relative contribution to retinal image degradation of light scatter compared to aberrations also being greater for albino eyes.

  19. Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA

    Directory of Open Access Journals (Sweden)

    Sharad Sawney

    2015-01-01

    Full Text Available One of the most frequent genetic aberrations in acute myeloid leukemia (AML is chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although patients with t(8;21 translocation have good prognosis, 5-year survival is observed only in 50% of the cases. AML1-ETO translocation is usually accompanied by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. We illustrate the potential use of esculetin on leukemic cell line, Kasumi-1, bearing t(8;21 translocation and mutated C-Kit gene. Esculetin decreases the expression of AML1-ETO at both protein and transcript level within 24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5 hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in esculetin treated cells. Esculetin also perturbed the expression of ectopically expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric gene was associated with increased expression of LAT1 and RUNX3 genes, targets of AML1. We envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application.

  20. Aberrant “Barbed-Wire” Nuclear Projections of Neutrophils in Trisomy 18 (Edwards Syndrome

    Directory of Open Access Journals (Sweden)

    Basil M. Kahwash

    2015-01-01

    Full Text Available We discuss the significance of neutrophils with increased, aberrant nuclear projections mimicking “barbed-wire” in a newborn child with trisomy 18 (T18. Increased, aberrant nuclear projections have been previously reported in trisomy of the D group of chromosomes (chromosomes 13, 14, and 15, and we report similar findings in a patient with T18. The peripheral blood smear showed relative neutrophilia with the majority (37% of neutrophils showing two or more thin, rod-shaped or spike-shaped, and often pedunculated aberrant nuclear projections. The number of projections ranged from 2 to 6 per cell, averaged 2 per affected neutrophil, and ranged in length from 0.22 μm to 0.83 μm. This case confirms that the morphologic finding described is not restricted to trisomy of one of the chromosomes in group D, as implied in the literature.

  1. Genome-wide identification of significant aberrations in cancer genome

    Directory of Open Access Journals (Sweden)

    Yuan Xiguo

    2012-07-01

    Full Text Available Abstract Background Somatic Copy Number Alterations (CNAs in human genomes are present in almost all human cancers. Systematic efforts to characterize such structural variants must effectively distinguish significant consensus events from random background aberrations. Here we introduce Significant Aberration in Cancer (SAIC, a new method for characterizing and assessing the statistical significance of recurrent CNA units. Three main features of SAIC include: (1 exploiting the intrinsic correlation among consecutive probes to assign a score to each CNA unit instead of single probes; (2 performing permutations on CNA units that preserve correlations inherent in the copy number data; and (3 iteratively detecting Significant Copy Number Aberrations (SCAs and estimating an unbiased null distribution by applying an SCA-exclusive permutation scheme. Results We test and compare the performance of SAIC against four peer methods (GISTIC, STAC, KC-SMART, CMDS on a large number of simulation datasets. Experimental results show that SAIC outperforms peer methods in terms of larger area under the Receiver Operating Characteristics curve and increased detection power. We then apply SAIC to analyze structural genomic aberrations acquired in four real cancer genome-wide copy number data sets (ovarian cancer, metastatic prostate cancer, lung adenocarcinoma, glioblastoma. When compared with previously reported results, SAIC successfully identifies most SCAs known to be of biological significance and associated with oncogenes (e.g., KRAS, CCNE1, and MYC or tumor suppressor genes (e.g., CDKN2A/B. Furthermore, SAIC identifies a number of novel SCAs in these copy number data that encompass tumor related genes and may warrant further studies. Conclusions Supported by a well-grounded theoretical framework, SAIC has been developed and used to identify SCAs in various cancer copy number data sets, providing useful information to study the landscape of cancer genomes

  2. Biomaterials for mRNA delivery.

    Science.gov (United States)

    Islam, Mohammad Ariful; Reesor, Emma K G; Xu, Yingjie; Zope, Harshal R; Zetter, Bruce R; Shi, Jinjun

    2015-12-01

    Messenger RNA (mRNA) has recently emerged with remarkable potential as an effective alternative to DNA-based therapies because of several unique advantages. mRNA does not require nuclear entry for transfection activity and has a negligible chance of integrating into the host genome which excludes the possibility of potentially detrimental genomic alternations. Chemical modification of mRNA has further enhanced its stability and decreased its activation of innate immune responses. Additionally, mRNA has been found to have rapid expression and predictable kinetics. Nevertheless, the ubiquitous application of mRNA remains challenging given its unfavorable attributes, such as large size, negative charge and susceptibility to enzymatic degradation. Further refinement of mRNA delivery modalities is therefore essential for its development as a therapeutic tool. This review provides an exclusive overview of current state-of-the-art biomaterials and nanotechnology platforms for mRNA delivery, and discusses future prospects to bring these exciting technologies into clinical practice.

  3. Short curcumin treatment modulates oxidative stress, arginase activity, aberrant crypt foci, and TGF-β1 and HES-1 transcripts in 1,2-dimethylhydrazine-colon carcinogenesis in mice

    International Nuclear Information System (INIS)

    Bounaama, Abdelkader; Djerdjouri, Bahia; Laroche-Clary, Audrey; Le Morvan, Valérie; Robert, Jacques

    2012-01-01

    Highlights: ► 1,2-Dimethylhydrazine (DMH) toxicity was driven by oxidative stress. ► Arginase activity correlated to aberrant crypt foci (ACF). ► Curcumin diet restored redox status and induced apoptosis of dysplastic ACF. ► Curcumin reduced arginase activity and up regulated TGF-β1 and HES-1 transcripts. -- Abstract: This study investigated the effect of short curcumin treatment, a natural antioxidant on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in mice. The incidence of aberrant crypt foci (ACF) was 100%, with 54 ± 6 per colon, 10 weeks after the first DMH injection and reached 67 ± 12 per colon after 12 weeks. A high level of undifferentiated goblet cells and a weak apoptotic activity were shown in dysplastic ACF. The morphological alterations of colonic mucosa were associated to severe oxidative stress ratio with 43% increase in malondialdehyde vs. 36% decrease in GSH. DMH also increased inducible nitric synthase (iNOS) mRNA transcripts (250%), nitrites level (240%) and arginase activity (296%), leading to nitrosative stress and cell proliferation. Curcumin treatment, starting at week 10 post-DMH injection for 14 days, reduced the number of ACF (40%), iNOS expression (25%) and arginase activity (73%), and improved redox status by approximately 46%, compared to DMH-treated mice. Moreover, curcumin induced apoptosis of dysplastic ACF cells without restoring goblet cells differentiation. Interestingly, curcumin induced a parallel increase in TGF-β1 and HES-1 transcripts (42% and 26%, respectively). In conclusion, the protective effect of curcumin was driven by the reduction of arginase activity and nitrosative stress. The up regulation of TGF-β1 and HES-1 expression by curcumin suggests for the first time, a potential interplay between these signalling pathways in the chemoprotective mechanism of curcumin.

  4. Demonstrating optical aberrations in the laboratory

    CSIR Research Space (South Africa)

    Naidoo, Darryl

    2009-07-01

    Full Text Available in the laboratory D. Naidoo1,2 , C. Mafusire1,2 and A. Forbes1,2 1 CSIR National Laser Centre 2 School of Physics, University of KwaZulu-Natal AN OPTICAL ABERRATION IS A DISTORTION OF AN IMAGE AS COMPARED TO THE OBJECT DUE TO DEFECTS IN AN OPTICAL SYSTEM TILT...Ne LASER COLLIMATING TELESCOPE MAGNIFICATION 8 TEST LENS SHACK-HARTMANN WAVEFRONT SENSOR FOCAL LENGTH Focal length from Defocus 750 850 950 1050 M e a s u r e d F o c a l L e n g t h ( m m ) Theoretical Experimental...

  5. Biological radiation dose estimation by chromosomal aberrations analysis in human peripheral blood (dose-effect curve)

    International Nuclear Information System (INIS)

    Al-Achkar, W.

    2001-09-01

    In order to draw a dose-effect curve, experimentally gamma ray induced chromosomal aberrations in human peripheral lymphocytes from eight healthy people were studied. Samples from 4 males and 4 females were irradiated in tubes with 0.15, 0.25, 0.5, 1, 1.5, 2, 2.5 gray of gamma ray (Co 60 at dose rate 0.3 Gy/min). Irradiated and control samples were incubated in 37 centigrade for 48 hours cell cultures. Cell cultures then were stopped and metaphases spread, Giemsa stained to score the induced chromosomal aberrations. Chromosomal aberrations from 67888 metaphases were scored. Curves from the total number of dicentrics, dicentrics + rings and total numbers of breaks in cell for each individual or for all people were drawn. An increase of all chromosomal aberrations types with the elevation of the doses was observed. The yield of chromosome aberrations is related to the dose used. These curves give a quick useful estimation of the accidentally radiation exposure. (author)

  6. A simulation study comparing aberration detection algorithms for syndromic surveillance

    Directory of Open Access Journals (Sweden)

    Painter Ian

    2007-03-01

    Full Text Available Abstract Background The usefulness of syndromic surveillance for early outbreak detection depends in part on effective statistical aberration detection. However, few published studies have compared different detection algorithms on identical data. In the largest simulation study conducted to date, we compared the performance of six aberration detection algorithms on simulated outbreaks superimposed on authentic syndromic surveillance data. Methods We compared three control-chart-based statistics, two exponential weighted moving averages, and a generalized linear model. We simulated 310 unique outbreak signals, and added these to actual daily counts of four syndromes monitored by Public Health – Seattle and King County's syndromic surveillance system. We compared the sensitivity of the six algorithms at detecting these simulated outbreaks at a fixed alert rate of 0.01. Results Stratified by baseline or by outbreak distribution, duration, or size, the generalized linear model was more sensitive than the other algorithms and detected 54% (95% CI = 52%–56% of the simulated epidemics when run at an alert rate of 0.01. However, all of the algorithms had poor sensitivity, particularly for outbreaks that did not begin with a surge of cases. Conclusion When tested on county-level data aggregated across age groups, these algorithms often did not perform well in detecting signals other than large, rapid increases in case counts relative to baseline levels.

  7. Prompt cytomolecular identification of chromosome aberration in irradiated blood cells

    Directory of Open Access Journals (Sweden)

    Seyed Akbar Moosavi

    2017-02-01

    Full Text Available Background: understanding the genomic alteration induced by ionizing radiation still remains to be a methodological challenge in genetic field. The energy released from this type of radiation can potentially causes structural and numerical alterations in lymphocytes, which in turn converts them into abnormal tumor cells. Chromosomal abnormalities associated with specific type of hematological malignancies are determinant factors in evaluation of radiation dose and its potential in harming the body. None the less early detection of chromosomal aberration (CA is crucial in prognosis and selection of therapy for the people exposed to irradiations. The aim of this study was to explore a swift and accurate genetic test that identifies CAs in radiologist exposed to X-rays. In addition synergistic effect of other clastogens in irradiated workers was also evaluated. Material and methods: thirty four heparinized blood samples were obtained from radiology workers exposed to X-rays. Blood samples were cultured in RPMI 1640 and F-10 Medias with and without PHA stimulation. Lymphocytes were harvested, separated and arrested at metaphase and their chromosomes were analyzed by solid and G-Banding techniques. Lymphocytic CA was also analyzed through whole chromosome painting FISH. Results: of the 37 blood sample from workers, 60% had various structural aberrations in which both the frequency and type of CAs were intensified among tobacco smokers. Conclusion: the results did not show any significant differences between the genders but other carcinogen like smoking can significantly increases the rate of CAs

  8. RBE of Energetic Iron Ions for the Induction of Early and Late Chromosome Aberrations in Different Cell Types

    Science.gov (United States)

    Zhang, Ye; Yeshitla, Samrawit; Hada, Megumi; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2015-01-01

    Numerous published studies have reported the Relative Biological Effectiveness (RBE) values for chromosome aberrations induced by charged particles of different LET. The RBE for chromosome aberrations in human lymphocytes exposed ex vivo has been suggested to show a similar relationship as the quality factor for cancer induction. Therefore, increased chromosome aberrations in the astronauts' white blood cells post long-duration missions are used to determine the biological doses from exposures to space radiation. However, the RBE value is known to be very different for different types of cancer. Previously, we reported that, even though the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions, the RBE was significantly reduced after multiple cell divisions post irradiation. To test the hypothesis that RBE values for chromosome aberrations are cell type dependent, and different between early and late damages, we exposed human lymphocytes ex vivo, and human mammary epithelial cells in vitro to various charged particles. Chromosome aberrations were quantified using the samples collected at first mitosis post irradiation for initial damages, and the samples collected after multiple generations for the remaining or late arising aberrations. Results of the study suggested that the effectiveness of high-LET charged particles for late chromosome aberrations may be cell type dependent, even though the RBE values are similar for early damages.

  9. Influence of Low-Dose Ionising Radiation on the Occurrence of Chromosomal Aberrations in Horse Lymphocytes after In vitro Irradiation

    International Nuclear Information System (INIS)

    Rukavina, D.; Hasanbasic, D.; Haveric, A.; Haveric, S.; Ajanovic, A.; Katica, A.

    2008-01-01

    It is well known that ionising radiation affect the chromosomal aberrations that have been used as a reliable criteria in biological dosimetry. Many studies confirm that the increase of radiation doses is related to the increase of mutation number and that even low doses could induce the mutations. Thus in this study we analysed the influence of low-dose ionising radiation to the occurrence of chromosomal aberrations in lymphocytes of peripheral blood of 12 horses after in vitro X-irradiation. To gain metaphase plates the method of cultivation periphery blood lymphocytes was employed. The observed aberrations were recorded and classified according to the International System of Cytogenetic Nomenclature (ISCN). The results showed that the percentage of chromosomal aberrations in irradiated blood (0.1 Gy and 0.2 Gy) was higher relative to the controlled samples of nonirradiated blood.(author)

  10. The enemy within: propagation of aberrant corticostriatal learning to cortical function in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Jeff A Beeler

    2013-09-01

    Full Text Available Motor dysfunction in Parkinson’s disease is believed to arise primarily from pathophysiology in the dorsal striatum and its related corticostriatal and thalamostriatal circuits during progressive dopamine denervation. One function of these circuits is to provide a filter that selectively facilitates or inhibits cortical activity to optimize cortical processing, making motor responses rapid and efficient. Corticostriatal synaptic plasticity mediates the learning that underlies this performance-optimizing filter. Under dopamine denervation, corticostriatal plasticity is altered, resulting in aberrant learning that induces inappropriate basal ganglia filtering that impedes rather than optimizes cortical processing. Human imaging suggests that increased cortical activity may compensate for striatal dysfunction in PD patients. In this Perspective article, we consider how aberrant learning at corticostriatal synapses may impair cortical processing and learning and undermine potential cortical compensatory mechanisms. Blocking or remediating aberrant corticostriatal plasticity may protect cortical function and support cortical compensatory mechanisms mitigating the functional decline associated with progressive dopamine denervation.

  11. Phase wavefront aberration modeling using Zernike and pseudo-Zernike polynomials.

    Science.gov (United States)

    Rahbar, Kambiz; Faez, Karim; Attaran Kakhki, Ebrahim

    2013-10-01

    Orthogonal polynomials can be used for representing complex surfaces on a specific domain. In optics, Zernike polynomials have widespread applications in testing optical instruments, measuring wavefront distributions, and aberration theory. This orthogonal set on the unit circle has an appropriate matching with the shape of optical system components, such as entrance and exit pupils. The existence of noise in the process of representation estimation of optical surfaces causes a reduction of precision in the process of estimation. Different strategies are developed to manage unwanted noise effects and to preserve the quality of the estimation. This article studies the modeling of phase wavefront aberrations in third-order optics by using a combination of Zernike and pseudo-Zernike polynomials and shows how this combination may increase the robustness of the estimation process of phase wavefront aberration distribution.

  12. Studies of chromosomal aberrations in occupationally coal exposed population (coal cutters)

    International Nuclear Information System (INIS)

    Vijender Reddy, V.; Rudrama Devi, K.

    1995-01-01

    A detailed study was carried out among the 235 coal mine workers (coal cutters) and 215 unexposed individuals (controls) on cytogenetic effect of coal in peripheral blood lymphocytes. The frequencies of chromosomal aberrations were studied in exposed coal mine workers as well as in the control groups . The confounding factors like smoking drinking and combination of both were taken into account. There was a significant increase in the total number of aberrations among exposed population subjected to different habits like smoking and alcoholism compared to that of the controls. (author). 14 refs., 1 tab

  13. Gamma induced chromosomal aberrations in meristem cells of cotton hybrids and their parental forms

    International Nuclear Information System (INIS)

    Kraevoj, S.Ya.; Akhmedova, M.M.; Amirkulov, D.

    1977-01-01

    The effect of gamma quanta on the first mitoses in the small roots of cotton hybrids and their parents results in different frequency of chromosome rearrangements in them. It has been proved that the frequency of chromosome aberrations is different in hybrids and different varieties of cotton. With increase in irradiation doses (from 10 to 30 kR) the frequency of chromosome aberrations goes up in all varieties and hybrids studies. The type of chromosome rearrangements in hybrids and their parents depends on the irradiation dose

  14. Effects of astigmatism on spectra and polarization of aberrant electromagnetic nonuniformly correlated beams in turbulent ocean.

    Science.gov (United States)

    Tang, Miaomiao; Zhao, Daomu

    2014-12-01

    Analytical formulas are derived, for the cross spectral density matrix of electromagnetic nonuniformly correlated (EMUNC) beams, with astigmatic aberration propagating through oceanic turbulence. We investigate the effects of astigmatism on the spectral density, and the spectral degree of polarization, in great detail. It can be seen that, unlike for an aberration-free case, the lateral shifted intensity maximum (of an astigmatic EMUNC beam) does not return back to the on-axis position, after propagating at sufficiently large distances in the turbulence. Furthermore, in the far-zone, the deviation of its maximum value (from the optical axis) gradually increases, in accordance with growing propagation distance.

  15. FREQUENCY OF CHROMOSOMAL ABERRATIONS AND MICRONUCLEI IN HORSE LYMPHOCYTES FOLLOWING IN VITRO EXPOSURE TO LOW DOSE IONISING RADIATION

    Directory of Open Access Journals (Sweden)

    Dunja Rukavina

    2012-07-01

    Full Text Available Ionising radiation is known to cause chromosomal instability, which is observed as increased frequency of chromosomal aberration and micronuclei. These are listed as reliable criteria in biological dosimetry. Numerous experiments conducted on both animal and plant models demonstrated that increase in radiation dosage is followed by increased mutation frequency, and that mutations occur even at the lowest exposure. We used horse blood in vitro irradiated by low doses of ionizing radiation. Cultivation of peripheral blood lymphocytes and micronucleus test were used as biomarkers of genetic damage. The observed aberrations were recorded and classified in accordance with the International System of Cytogenetic Nomenclature. Micronuclei were identified on the basis of criteria proposed by Fenech et al. (8. Analysis of chromosomal aberration showed increased frequency of aberrations in blood cultures exposed to 0,1 Gy and 0,2 Gy compared to the controls. Microscopic analysis of chromosomal damage in in vitro micronucleus test revealed that the applied radiation dose induced micronuclei while no binucleated cells with micronuclei were found in lymphocytes that were not irradiated. In this paper we analysed the influence of low dose ionising radiation on frequency of chromosomal aberration and micronuclei in horse lymphocytes following in vitro exposure to X-rays (0,1 Gy and 0,2 Gy. Key words: chromosomal aberrations, micronuclei, ionising radiation, horse lymphocytes

  16. Procedure Improvement in Blood Processing for Chromosome Aberration Analyst

    International Nuclear Information System (INIS)

    Noraisyah Mohd Yusof; Juliana Mahamad; Rahimah Abd Rahim; Yahaya Talib; Mohd Rodzi Ali

    2015-01-01

    Detection of chromosome at metaphase of the cell cycle is performed either manually or automatically. Procedure for slide preparation published by the IAEA does not guarantee that the quality of slide is suitable for automatic detection. The detection efficiency reduces if there is cells debris on slides. This paper describes the modifications made to the standard procedure. The period of hypotonic treatment to the cell was lengthened; the slides were pre-treated with RNase and the frequency of rinsing during the chromosomal coloring process was increased. Results show the metaphase images were better and clearer, and numbers of metaphase that can be detected automatically were also increased. In conclusion, modification to the current standard protocol helps to easy the process of chromosome aberration analysis at Nuclear Malaysia. (author)

  17. Annexin II mRNA expression in bovine oocytes during follicular development

    Directory of Open Access Journals (Sweden)

    Luis Fabiano Santos da Costa

    2006-01-01

    Full Text Available We investigated the expression of calcium-dependent phospholipid binding protein annexin-II (Ann-II messenger RNA (mRNA during preantral follicle development and in oocytes from antral follicles of different diameters ( 8 mm. The action of retinol on Ann-II mRNA expression in mature oocytes was also examined. Only oocytes from secondary preantral follicles expressed Ann-II mRNA and at the germinal vesicle stage expression by oocytes from follicles larger than 8 mm was significantly higher (p < 0.05 compared with oocytes from follicles smaller than 3 mm or between 5 and 8 mm. Ann-II mRNA expression by metaphase II oocytes from follicles larger than 8 mm was significantly higher (p < 0.05 than that from oocytes from follicles smaller than 3 mm, with oocytes from both these size-classes showing similar levels of Ann-II mRNA expression as oocytes recovered from 5-8 mm follicles. In the presence of retinol, Ann-II mRNA expression was higher than when retinol was absent (p < 0.05. Our data indicate that Ann-II mRNA expression is highest in competent oocytes and that retinol increases Ann-II mRNA and may be involved in the regulation of oocyte competence by decreasing the translation and/or degradation of Ann-II mRNA.

  18. Higher order aberrations of the eye: Part one

    Directory of Open Access Journals (Sweden)

    Marsha Oberholzer

    2016-03-01

    Full Text Available This article is the first in a series of two articles that provide a comprehensive literature review of higher order aberrations (HOAs of the eye. The present article mainly explains the general principles of such HOAs as well as HOAs of importance, and the measuring apparatus used to measure HOAs of the eye. The second article in the series discusses factors contributing to variable results in measurements of HOAs of the eye.Keywords: Higher order aberrations; wavefront aberrations; aberrometer

  19. Higher order monochromatic aberrations of the human infant eye

    OpenAIRE

    Wang, Jingyun; Candy, T. Rowan

    2005-01-01

    The monochromatic optical aberrations of the eye degrade retinal image quality. Any significant aberrations during postnatal development could contribute to infants’ immature visual performance and provide signals for the control of eye growth. Aberrations of human infant eyes from 5 to 7 weeks old were compared with those of adult subjects using a model of an adultlike infant eye that accounted for differences in both eye and pupil size. Data were collected using the COAS Shack-Hartmann wave...

  20. Higher order aberrations of the eye: Part one

    Directory of Open Access Journals (Sweden)

    Marsha Oberholzer

    2016-06-01

    Full Text Available This article is the first in a series of two articles that provide a comprehensive literature review of higher order aberrations (HOAs of the eye. The present article mainly explains the general principles of such HOAs as well as HOAs of importance, and the measuring apparatus used to measure HOAs of the eye. The second article in the series discusses factors contributing to variable results in measurements of HOAs of the eye. Keywords: Higher order aberrations; wavefront aberrations; aberrometer

  1. Chromosomal aberrations in peripheral blood lymphocytes of prostate cancer patients treated with IMRT and carbon ions

    International Nuclear Information System (INIS)

    Hartel, Carola; Nikoghosyan, Anna; Durante, Marco; Sommer, Sylwester; Nasonova, Elena; Fournier, Claudia; Lee, Ryonfa; Debus, Juergen; Schulz-Ertner, Daniela; Ritter, Sylvia

    2010-01-01

    Background and purpose: To investigate the cytogenetic damage in blood lymphocytes of patients treated for prostate cancer with different radiation qualities and target volumes. Materials and methods: Twenty patients receiving carbon-ion boost irradiation followed by IMRT or IMRT alone for the treatment of prostate cancer entered the study. Cytogenetic damage induced in peripheral blood lymphocytes of these patients was investigated at different times during the radiotherapy course using Giemsa staining and mFISH. A blood sample from each patient was taken before initiation of radiation therapy and irradiated in vitro to test for individual radiosensitivity. In addition, in vitro dose-effect curves for the induction of chromosomal exchanges by X-rays and carbon ions of different energies were measured. Results: The yield of chromosome aberrations increased during the therapy course, and the frequency was lower in patients irradiated with carbon ions as compared to patients treated with IMRT with similar target volumes. A higher frequency of aberrations was measured by increasing the target volume. In vitro, high-LET carbon ions were more effective than X-rays in inducing aberrations and yielded a higher fraction of complex exchanges. The yield of complex aberrations observed in vivo was very low. Conclusion: The investigation showed no higher aberration yield induced by treatment with a carbon-ion boost. In contrast, the reduced integral dose to the normal tissue is reflected in a lower chromosomal aberration yield when a carbon-ion boost is used instead of IMRT alone. No cytogenetic 'signature' of exposure to densely ionizing carbon ions could be detected in vivo.

  2. Prediction for the occurrence of clonal chromosome aberrations in human blood lymphocytes

    International Nuclear Information System (INIS)

    Nakano, M.; Kadama, Y.; Ohtaki, K.; Itoh, M.; Awa, A.; Cologne, J.; Nakamura, N.

    2003-01-01

    Full text: Identical chromosome aberrations among multiple blood lymphocytes in a blood sample (clonal aberrations) are encountered occasionally during cytogenetic examination of radiation-exposed people. Clonal aberrations are found primarily among high-dose exposed people but no systematic surveys were ever conducted. Therefore, the underlying mechanism is unknown. Here we conducted a large-scale screening for detecting clonal aberrations using FISH followed by Q-banding. Examinations of 500 cells from each of 513 A-bomb survivors led us to detect 96 clones. The clonal cell fraction (Cf) varied from 0.6% to 20% among the 500 cells. As the number of clonal event was inversely proportional to Cf, we hypothesized that the progenitor cells vary extensively in the number of offspring that they can produce and relative number of progenitor cells decreases as the increase of treatment, while other genes such as DNA repair proteinsnumber of progenitor cells capable to form clones (Cf >=0.6%) to be 2 (1 to 3) in non-exposed individuals. The number increased to up to 7 among the high-dose exposed survivors. Further, our preliminary results for the origins of 10 clones indicated that both hematopoietic stem cells (HSCs) and mature T cells contributed to the clone formation roughly equally. Thus, the estimated number of 2 in non-exposed individuals is shared as one HSC and one mature T cells. The model could neatly explain the frequency of clones in two reports. Our model predicts that clonal aberrations are rarely found but clonal expansion of T lymphocytes occurs commonly. In fact, clonal expansions of non-aberrant cells are reported using TCR gene rearrangement patterns as a marker. We now understand the rough structure of lymphocyte pool in humans and can predict the probability of detecting a clone if the individual frequency of non-clonal translocations and the number of cells scored are given

  3. Chromosome aberration analysis for biological dosimetry: a review

    International Nuclear Information System (INIS)

    Paul, S.F.D.; Venkatachalam, P.; Jeevanram, R.K.

    1996-01-01

    Among various biological dosimetry techniques, dicentric chromosome aberration method appears to be the method of choice in analysing accidental radiation exposure in most of the laboratories. The major advantage of this method is its sensitivity as the number of dicentric chromosomes present in control population is too small and more importantly radiation induces mainly dicentric chromosome aberration among unstable aberration. This report brings out the historical development of various cytogenetic methods, the basic structure of DNA, chromosomes and different forms of chromosome aberrations. It also highlights the construction of dose-response curve for dicentric chromosome and its use in the estimation of radiation dose. (author)

  4. Chromosome aberrations: plants to human and Feulgen to FISH

    International Nuclear Information System (INIS)

    Natarajan, A.T.

    2005-01-01

    Chromosome aberrations and their impact on human health have been recognized for a long time. In the 1950s, in India, studies on induced chromosome aberrations in plants were initiated by Swaminathan and his students. I trace here the impact of these initial studies on further developments in this field. The studies which were started in plants have been extended to mammals (including human) and the simple squash and solid staining have been improved by molecular cytogenetic techniques, thus enabling accurate identification and quantification of different types of chromosome aberrations. These studies have also thrown light on the mechanisms of chromosome aberration formation, especially following exposure to ionizing radiation. (author)

  5. Orthogonal polynomials describing polarization aberration for rotationally symmetric optical systems.

    Science.gov (United States)

    Xu, Xiangru; Huang, Wei; Xu, Mingfei

    2015-10-19

    Optical lithography has approached a regime of high numerical aperture and wide field, where the impact of polarization aberration on imaging quality turns to be serious. Most of the existing studies focused on the distribution rule of polarization aberration on the pupil, and little attention had been paid to the field. In this paper, a new orthonormal set of polynomials is established to describe the polarization aberration of rotationally symmetric optical systems. The polynomials can simultaneously reveal the distribution rules of polarization aberration on the exit pupil and the field. Two examples are given to verify the polynomials.

  6. Coordinated Regulations of mRNA Synthesis and Decay during Cold Acclimation in Arabidopsis Cells.

    KAUST Repository

    Arae, Toshihiro

    2017-04-18

    Plants possess a cold acclimation system to acquire freezing tolerance through pre-exposure to non-freezing low temperatures. The transcriptional cascade of C-repeat binding factors (CBFs)/dehydration response element-binding factors (DREBs) is considered a major transcriptional regulatory pathway during cold acclimation. However, little is known regarding the functional significance of mRNA stability regulation in the response of gene expression to cold stress. The actual level of individual mRNAs is determined by a balance between mRNA synthesis and degradation. Therefore, it is important to assess the regulatory steps to increase our understanding of gene regulation. Here, we analyzed temporal changes in mRNA amounts and half-lives in response to cold stress in Arabidopsis cell cultures based on genome-wide analysis. In this mRNA decay array method, mRNA half-life measurements and microarray analyses were combined. In addition, temporal changes in the integrated value of transcription rates were estimated from the above two parameters using a mathematical approach. Our results showed that several cold-responsive genes, including Cold-regulated 15a, were relatively destabilized, whereas the mRNA amounts were increased during cold treatment by accelerating the transcription rate to overcome the destabilization. Considering the kinetics of mRNA synthesis and degradation, this apparently contradictory result supports that mRNA destabilization is advantageous for the swift increase in CBF-responsive genes in response to cold stress.

  7. Frequency of chromosomal aberrations in rat myelocaryocytes during long-term repeated irradiation

    International Nuclear Information System (INIS)

    Uryadnitskaya, T.I.; Sukhodoev, V.V.; Muksinova, K.N.

    1977-01-01

    In the course of a long-term daily irradiation of rats (50R/day), the frequency of chromosome aberrations in the bone marrow cells increased disproportionally to a total radiation dose which was due to the reduced frequency of chromosome damage at the intervals between daily exposures. The rate of this reduction was mainly determined by myelocaryocyte proliferation

  8. Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes

    Directory of Open Access Journals (Sweden)

    Jinzi Wu

    2017-09-01

    Full Text Available It is well established that NADH/NAD+ redox balance is heavily perturbed in diabetes, and the NADH/NAD+ redox imbalance is a major source of oxidative stress in diabetic tissues. In mitochondria, complex I is the only site for NADH oxidation and NAD+ regeneration and is also a major site for production of mitochondrial reactive oxygen species (ROS. Yet how complex I responds to the NADH/NAD+ redox imbalance and any potential consequences of such response in diabetic pancreas have not been investigated. We report here that pancreatic mitochondrial complex I showed aberrant hyperactivity in either type 1 or type 2 diabetes. Further studies focusing on streptozotocin (STZ-induced diabetes indicate that complex I hyperactivity could be attenuated by metformin. Moreover, complex I hyperactivity was accompanied by increased activities of complexes II to IV, but not complex V, suggesting that overflow of NADH via complex I in diabetes could be diverted to ROS production. Indeed in diabetic pancreas, ROS production and oxidative stress increased and mitochondrial ATP production decreased, which can be attributed to impaired pancreatic mitochondrial membrane potential that is responsible for increased cell death. Additionally, cellular defense systems such as glucose 6-phosphate dehydrogenase, sirtuin 3, and NQO1 were found to be compromised in diabetic pancreas. Our findings point to the direction that complex I aberrant hyperactivity in pancreas could be a major source of oxidative stress and β cell failure in diabetes. Therefore, inhibiting pancreatic complex I hyperactivity and attenuating its ROS production by various means in diabetes might serve as a promising approach for anti-diabetic therapies.

  9. Effects of intraocular lenses with different diopters on chromatic aberrations in human eye models.

    Science.gov (United States)

    Song, Hui; Yuan, Xiaoyong; Tang, Xin

    2016-01-11

    In this study, the effects of intraocular lenses (IOLs) with different diopters (D) on chromatic aberration were investigated in human eye models, and the influences of the central thickness of IOLs on chromatic aberration were compared. A Liou-Brennan-based IOL eye model was constructed using ZEMAX optical design software. Spherical IOLs with different diopters (AR40e, AMO Company, USA) were implanted; modulation transfer function (MTF) values at 3 mm of pupil diameter and from 0 to out-of-focus blur were collected and graphed. MTF values, measured at 555 nm of monochromatic light under each spatial frequency, were significantly higher than the values measured at 470 to 650 nm of polychromatic light. The influences of chromatic aberration on MTF values decreased with the increase in IOL diopter when the spatial frequency was ≤12 c/d, while increased effects were observed when the spatial frequency was ≥15 c/d. The MTF values of each IOL eye model were significantly lower than the MTF values of the Liou-Brennan eye models when measured at 555 nm of monochromatic light and at 470 to 650 nm of polychromatic light. The MTF values were also found to be increased with the increase in IOL diopter. With higher diopters of IOLs, the central thickness increased accordingly, which could have created increased chromatic aberration and decreased the retinal image quality. To improve the postoperative visual quality, IOLs with lower chromatic aberration should be selected for patients with short axial lengths.

  10. Environmental Transmission Electron Microscopy in an Aberration-Corrected Environment

    DEFF Research Database (Denmark)

    Hansen, Thomas W.; Wagner, Jakob B.

    2012-01-01

    The increasing use of environmental transmission electron microscopy (ETEM) in materials science provides exciting new possibilities for investigating chemical reactions and understanding both the interaction of fast electrons with gas molecules and the effect of the presence of gas on high......-resolution imaging. A gaseous atmosphere in the pole-piece gap of the objective lens of the microscope alters both the incoming electron wave prior to interaction with the sample and the outgoing wave below the sample. Whereas conventional TEM samples are usually thin (below 100 nm), the gas in the environmental...... cell fills the entire gap between the pole pieces and is thus not spatially localized. By using an FEI Titan environmental transmission electron microscope equipped with a monochromator and an aberration corrector on the objective lens, we have investigated the effects on imaging and spectroscopy...

  11. Chromosome aberrations in peripheral blood lymphocytes of lung cancer patients exposed to radon and air pollution.

    Science.gov (United States)

    Minina, Varvara I; Sinitsky, Maxim Yu; Druzhinin, Vladimir G; Fucic, Aleksandra; Bakanova, Marina L; Ryzhkova, Anastasia V; Savchenko, Yana A; Timofeeva, Anna A; Titov, Ruslan A; Voronina, Elena N; Volobaev, Valentin P; Titov, Victor A

    2018-01-01

    Lung cancer is one of the most common forms of cancer. The aim of this study was to validate chromosome aberrations in peripheral blood lymphocytes of lung cancer patients living in a region with high air pollution and increased background radon levels as a biomarker of cancer risk. A total of 417 lung cancer patients and 468 control participants were analysed using a chromosome aberration assay in peripheral blood lymphocytes. The results showed that chromatid-type aberrations (2.26±1.58 vs. 1.60±1.58) and chromosome-type aberrations (CSAs) (0.96±1.36 vs. 0.42±0.70) in lung cancer patients were increased significantly in comparison with the controls. The most significant two-fold increase was detected for CSAs (nonsmoking patients: 0.84±1.54 vs. 0.41±0.73%, smoking patients: 0.99±1.31 vs. 0.44±0.67%). The frequency of dicentric and ring chromosomes, double minutes and rogue cells was significantly higher (P=0.002, 0.00002, 0.01, 0.0007) in the lung cancer patients. As both analysed groups lived in the same environment, our results show that increased radon levels were not the only source for the detected genome damage. Using binomial logistic regression, the estimated odds ratios and 95% confidence intervals adjusted for the main confounders (smoking, occupational exposure, age) were 1.31 (1.20-1.40) for chromatid-type aberrations, 1.28 (1.17-1.33), and 1.68 (1.49-1.88) for CSAs. It may be suggested that lung cancer patients show a significant increase in genome damage that may be caused by an interplay between exposure and individual low capacity of DNA repair, leading to genome instability.

  12. Digoxin up-regulates multidrug resistance transporter (MDR1) mRNA and simultaneously down-regulates steroid xenobiotic receptor mRNA.

    Science.gov (United States)

    Takara, Kohji; Takagi, Kentaro; Tsujimoto, Masayuki; Ohnishi, Noriaki; Yokoyama, Teruyoshi

    2003-06-20

    A steroid xenobiotic receptor (SXR) is involved in the induction of MDR1/P-glycoprotein. MDR1 up-regulation by digoxin was previously demonstrated in human colon adenocarcinoma Caco-2 cells, but the participation of SXR remains unclear. Herein, the participation of SXR in MDR1 up-regulation was examined using reverse transcription-polymerase chain reaction in Caco-2 cells, and digoxin-tolerant cells (Caco/DX) as well as human colon carcinoma LS180 cells, which expressed SXR. MDR1 mRNA expression in Caco-2 or LS180 cells was increased by exposure to 1 microM digoxin for 24h, in a concentration-dependent manner, but SXR mRNA decreased concentration-dependently and was undetectable or significantly lower at 1 microM digoxin, indicating antithetical changes in MDR1 and SXR mRNA expression. Moreover, the MDR1 mRNA level was higher in Caco/DX cells than Caco-2 cells, whereas the SXR mRNA level was lower in Caco/DX cells. Consequently, digoxin was demonstrated to up-regulate MDR1 mRNA and simultaneously down-regulate SXR mRNA expression.

  13. Aberrant laryngeal location of Onchocerca lupi in a dog.

    Science.gov (United States)

    Alho, Ana Margarida; Cruz, Luís; Coelho, Ana; Martinho, Filipe; Mansinho, Mário; Annoscia, Giada; Lia, Riccardo P; Giannelli, Alessio; Otranto, Domenico; de Carvalho, Luís Madeira

    2016-06-01

    Onchocerca lupi (Spirurida, Onchocercidae) is an emerging vector-borne helminth that causes nodular lesions associated with acute or chronic ocular disease in dogs and cats. Since its first description in dogs in 1991, this zoonotic filarioid has been increasingly reported in Europe and the United States. An 8-year-old outdoor mixed-breed female dog from the Algarve (southern Portugal) was presented with a history of severe dyspnoea. Cervical and thoracic radiographs revealed a slight reduction in the diameter of the cervical trachea and a moderate increase in radiopacity of the laryngeal soft tissue. An exploratory laryngoscopy was performed, revealing filiform worms associated with stenosis of the thyroid cartilage and a purulent necrotic tissue in the larynx lumen. A single sessile nodule, protruding from the dorsal wall of the laryngeal lumen caused a severe reduction of the glottis and tracheal diameter. Fragments of the worms were morphologically and molecularly identified as O. lupi. Histological examination of the nodule showed a granulomatous reaction with sections of coiled gravid female nematodes. Following laryngoscopy, a tracheostomy tube was inserted to relieve dyspnoea and ivermectin (300 μg/kg, once a week, for 8 weeks) combined with prednisolone was prescribed. The dog showed a complete recovery. Although O. lupi has been isolated in human patients from the spinal cord, this is the first report of an aberrant migration of O. lupi in a dog. The veterinary medical community should pay attention to aberrant location of O. lupi and consider onchocercosis as a differential diagnosis for airway obstruction in dogs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Aberrant expression of sonic hedgehog pathway in colon cancer and melanosis coli.

    Science.gov (United States)

    Wang, Zhong Chuan; Gao, Jun; Zi, Shu Ming; Yang, Ming; Du, Peng; Cui, Long

    2013-08-01

    To determine the hedgehog (Hh) signaling pathway correlated with the development of colon cancer and melanosis coli. Protein and mRNA levels of Hh signaling pathway components (sonic hedgehog [Shh], protein patched homolog 1 [Ptch 1], GLI family zinc finger 1 [Gli 1] and suppressor of fused homolog [Drosophila] [Sufu]) in 127 patients with colon cancer, 36 with melanosis coli and 20 adjacent normal mucosal tissues taken from surgical specimens were evaluated using antibody staining and quantitative real-time polymerase chain reaction. In adjacent normal tissue Shh and Ptch1, but not Gli1 or Sufu, were weakly expressed and mainly in the lining epithelium of the colonic mucosa. In cancerous tissues Shh and Gli1 were uniformly strong while Ptch1 was patchy and weak, and Sufu uniformly weak, which paralleled their levels of corresponding mRNA. Elevated protein levels of Shh and Ptch were significantly associated with mucinous colonic tissues. Elevated Sufu protein levels were positively correlated with the diameter and invasion of the tumor. In patients with melanosis coli, mRNA levels of Shh, Ptch1, Gli1 and Sufu were very low, which was similar to those of adjacent normal tissues; but protein levels of Shh, Ptch1 and Gli1, but not Sufu, were high, which was similar to those of cancerous tissues. The mRNA and protein levels of Hh pathway components are aberrantly elevated in colon cancer, which may be the potential molecular classification markers. Further studies are required to determine the role of melanosis coli in the colon tumorigenesis. © 2013 The Authors. Journal of Digestive Diseases © 2013 Wiley Publishing Asia Pty Ltd and Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine.

  15. Design of an aberration corrected low-voltage SEM

    NARCIS (Netherlands)

    Aken, R.H. van; Maas, D.J.; Hagen, C.W.; Barth, J.E.; Kruit, P.

    2010-01-01

    The low-voltage foil corrector is a novel type of foil aberration corrector that can correct for both the spherical and chromatic aberration simultaneously. In order to give a realistic example of the capabilities of this corrector, a design for a low-voltage scanning electron microscope with the

  16. Aberration analysis calculations for synchrotron radiation beamline design

    International Nuclear Information System (INIS)

    McKinney, W.R.; Howells, M.; Padmore, H.A.

    1997-09-01

    The application of ray deviation calculations based on aberration coefficients for a single optical surface for the design of beamline optical systems is reviewed. A systematic development is presented which allows insight into which aberration may be causing the rays to deviate from perfect focus. A new development allowing analytical calculation of line shape is presented

  17. An aberrant uterus: Case report | Ondieki | East African Medical ...

    African Journals Online (AJOL)

    A case of an aberrant uterus is presented and literature reviewed. The patient presented with abnormal uterine bleeding, left iliac fossa pain and was managed by excising the aberrant uterus. This case was an enigma as it didn't present in the classical way one with anomalies of the uterus would present. Despite ...

  18. Aberrant Breast in a Rare Site: A Case Report

    Directory of Open Access Journals (Sweden)

    Levent Yeniay

    2012-01-01

    Full Text Available Aberrant breast tissue is an anomaly in the embryogenesis of the breast that is found along the mammary ridge or out of that line. We report a case of a 71-year-old female patient with an abdominal aberrant breast tissue found incidentally in a piece of mesenteric biopsy. The histological features were consistent with breast tissue.

  19. [An aberrant course of the internal carotid artery].

    Science.gov (United States)

    Hittel, J P; Mertens, J

    2000-09-01

    Aberrant vascular courses of the A. carotis interna are extremely rare. They are usually combined with pulsatile symptoms. Missing symptoms are not proof of a non-existing aberration, though. A paracentesis in such a situation leads to an initially unstoppable bleeding from the tympanion and tuba. For this reason it is necessary to contemplate a vascular reason for the local findings preoperatively.

  20. Expressions for third-order aberration theory for holographic images

    Indian Academy of Sciences (India)

    Expressions for third-order aberration in the reconstructed wave front of point objects are established by Meier. But Smith, Neil Mohon, Sweatt independently reported that their results differ from that of Meier. We found that coefficients for spherical aberration, astigmatism, tally with Meier's while coefficients for distortion and ...

  1. Self-amplifying mRNA vaccines.

    Science.gov (United States)

    Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J

    2015-01-01

    This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. The study of the relationship between aberrant expression of hot shock protein 70 (HSP70) and spontaneous abortion.

    Science.gov (United States)

    Peng, Y-B; Liu, H; Huang, S-H; Lai, H; Zhou, Q; Luo, Y; Zhang, Z-Y; Xi, B-R; Ouyang, X

    2017-02-01

    The present study is aimed to explore the relationship between aberrant expression of heat shock protein 70 (HSP) and spontaneous abortion. 50 patients with spontaneous abortion and 50 patients with induced abortion were continuously selected based on the nearest matching principle, and the proportion of age and gestational age was 1:1. The decidual tissues were obtained, and the cell apoptosis was determined by TUNEL assay. Further, the expression of HSP70 was assayed by immune-histochemical staining, and the expression of HSP70 mRNA was detected by the RT-PCR approach. Apoptosis rate, HSP70 expression and HSP70 mRNA expression in the observation group were significantly higher than the control group. HSP70 might induce apoptosis so as to cause spontaneous abortion.

  3. Dose Assessment using Chromosome Aberration Analyses in Human Peripheral Blood Lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin-Hong; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    The healthy five donors were recruited to establish the dose-response calibration curve for chromosomal aberrations by ionizing radiation exposure. Our cytogenetic results revealed that the mean frequency of chromosome aberration increased with increasing radiation dose. In this study, dicentric assay and CBMN assay were compared considering the sensitivity and accuracy of dose estimation. Therefore, these chromosome aberration analyses will be the foundation for biological dosimetric analysis with additional research methods such as translocation and PCC assay. The conventional analysis of dicentric chromosomes in HPBL was suggested by Bender and Gooch in 1962. This assay has been for many years, the golden standard and the most specific method for ionizing radiation damage. The dicentric assay technique in HPBL has been shown as the most sensitive biological method and reliable bio-indicator of quantifying the radiation dose. In contrast, the micronucleus assay has advantages over the dicentric assay since it is rapid and requires less specialized expertise, and accordingly it can be applied to monitor a big population. The cytokinesis-block micronucleus (CBMN) assay is a suitable method for micronuceli measurement in cultured human as well as mammalian cells. The aim of our study was to establish the dose response curve of radiation-induced chromosome aberrations in HPBL by analyzing the frequency of dicentrics and micronuclei.

  4. Analysis of chromosomal aberrations frequency, haematological parameters and received doses by nuclear medicine professionals.

    Science.gov (United States)

    Djokovic-Davidovic, Jelena; Milovanovic, Andjela; Milovanovic, Jovica; Antic, Vojislav; Gajic, Milan

    2016-01-01

    The purpose of this article was to analyse the impact of low-dose ionizing radiation to nuclear medicine professionals of the Nuclear Medicine Centre of Serbia (NMCRS). Data from the previous/initial and the last medical check-ups, obtained from the medical records of 65 employees from NMCRS, were analysed. A typical checkup, haematological parameters analysis, as well as special cytogenetical analyses, such as unstable chromosomal aberrations and micronucleus test, were carried out. For analyses of chromosomal aberrations the modified Moorhead's micro method was applied to the culture of peripheral blood lymphocytes and conventional cytogenetic technique of chromosomal aberrations was applied. The received cumulative 5-year dose was measured by personal inactive thermoluminescent dosimeters (TLD) calibrated into personal doses equivalent Hp(10). An increased frequency of all unstable chromosomal aberration forms, such as acentric chromosomes and isochromatid lesions, was noticed in the last periodical check-up as compared to the previous/initial checkups (pNuclear medicine employees have increased health risks and there is a need to monitor their health condition by periodical check-ups for prevention from occupational diseases (carcinoma).

  5. Brown's TRANSPORT up to third order aberration by artificial intelligence

    International Nuclear Information System (INIS)

    Xia Jiawen; Xie Xi; Qiao Qingwen

    1991-01-01

    Brown's TRANSPORT is a first and second order matrix multiplication computer program intended for the design of accelerator beam transport systems, neglecting the third order aberration. Recently a new method was developed to derive analytically any order aberration coefficients of general charged particle optic system, applicable to any practical systems, such as accelerators, electron microscopes, lithographs, etc., including those unknown systems yet to be invented. An artificial intelligence program in Turbo Prolog was implemented on IBM-PC 286 or 386 machine to generate automatically the analytical expression of any order aberration coefficients of general charged particle optic system. Based on this new method and technique, Brown's TRANSPORT is extended beyond the second order aberration effects by artificial intelligence, outputing automatically all the analytical expressions up to the third order aberration coefficients

  6. Chromosome aberration analysis based on a beta-binomial distribution

    International Nuclear Information System (INIS)

    Otake, Masanori; Prentice, R.L.

    1983-10-01

    Analyses carried out here generalized on earlier studies of chromosomal aberrations in the populations of Hiroshima and Nagasaki, by allowing extra-binomial variation in aberrant cell counts corresponding to within-subject correlations in cell aberrations. Strong within-subject correlations were detected with corresponding standard errors for the average number of aberrant cells that were often substantially larger than was previously assumed. The extra-binomial variation is accomodated in the analysis in the present report, as described in the section on dose-response models, by using a beta-binomial (B-B) variance structure. It is emphasized that we have generally satisfactory agreement between the observed and the B-B fitted frequencies by city-dose category. The chromosomal aberration data considered here are not extensive enough to allow a precise discrimination between competing dose-response models. A quadratic gamma ray and linear neutron model, however, most closely fits the chromosome data. (author)

  7. Image based method for aberration measurement of lithographic tools

    Science.gov (United States)

    Xu, Shuang; Tao, Bo; Guo, Yongxing; Li, Gongfa

    2018-01-01

    Information of lens aberration of lithographic tools is important as it directly affects the intensity distribution in the image plane. Zernike polynomials are commonly used for a mathematical description of lens aberrations. Due to the advantage of lower cost and easier implementation of tools, image based measurement techniques have been widely used. Lithographic tools are typically partially coherent systems that can be described by a bilinear model, which entails time consuming calculations and does not lend a simple and intuitive relationship between lens aberrations and the resulted images. Previous methods for retrieving lens aberrations in such partially coherent systems involve through-focus image measurements and time-consuming iterative algorithms. In this work, we propose a method for aberration measurement in lithographic tools, which only requires measuring two images of intensity distribution. Two linear formulations are derived in matrix forms that directly relate the measured images to the unknown Zernike coefficients. Consequently, an efficient non-iterative solution is obtained.

  8. Brown's transport up to third order aberration by artificial intelligence

    International Nuclear Information System (INIS)

    Xia Jiawen; Xie Xi; Qiao Qingwen

    1992-01-01

    Brown's TRANSPORT is a first and second order matrix multiplication computer program intended for the design of accelerator beam transport systems, neglecting the third order aberration. Recently a new method was developed to derive analytically any order aberration coefficients of general charged particle optic system, applicable to any practical systems, such as accelerators, electron microscopes, lithographs, including those unknown systems yet to be invented. An artificial intelligence program in Turbo Prolog was implemented on IBM-PC 286 or 386 machine to generate automatically the analytical expression of any order aberration coefficients of general charged particle optic system. Based on this new method and technique, Brown's TRANSPORT is extended beyond the second order aberration effect by artificial intelligence, outputting automatically all the analytical expressions up to the third order aberration coefficients

  9. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.

    2015-01-01

    of these aberrations occur in normal hematopoietic stem and progenitor cells (HSCs/HPCs) before definitive leukemic transformation through additional acquisition of a few (that is, mostly 1 or 2) leukemia-promoting driver aberrations. NGS studies on sorted bone marrow (BM) populations of AML patients with a normal......Acute myeloid leukemia (AML) represents an aggressive cancer entity, whose malignant cells respond abnormally to regulatory stimuli and have lost the ability to differentiate and become fully mature blood cells.1, 2 AML evolves through accumulation of independent genetic aberrations, including...... karyotype have demonstrated the presence of prognostic driver aberrations (that is, NPM1, FLT3-ITD and FLT3-TKD) in committed HPCs but not in multipotent HSCs. However, the HSC populations lacking the prognostic driver aberrations contained preleukemic clones harboring a series of recurrent molecular...

  10. Adult-onset hypogonadotropic hypogonadism caused by aberrant expression of aromatase in an adrenocortical adenocarcinoma.

    Science.gov (United States)

    Advani, Andrew; Johnson, Sarah J; Nicol, Moira R; Papacleovoulou, Georgia; Evans, Dean B; Vaikkakara, Suresh; Mason, J Ian; Quinton, Richard

    2010-01-01

    Estrogen-secreting adrenal cancers are extremely rare, with feminizing symptoms attributed to aromatase expression in the adrenal tumor. We describe a case of hypogonadotropic hypogonadism as a consequence of aberrant aromatase expression in a patient with adrenocortical adenocarcinoma. A 54 year-old man presented with a two month history of gynecomastia and reduced libido. Endocrine biochemistry at presentation showed hypogonadotropic hypogonadism (LH 2.4 U/L, FSH E(1), 821 pmol/L) and estradiol (E(2), 797 pmol/L) and subclinical ACTH-independent hypercortisolism (serum cortisol post 1mg overnight dexamethasone suppression test, 291 nmol/L). A right adrenal mass was identified on CT scanning and the patient underwent an open adrenalectomy. Post-operative evaluation showed normalization of serum levels of E(1) (95 pmol/L), E(2 )(109 pmol/L), testosterone (11.4 nmol/L), LH (4.1 U/L) and FSH (5.9 IU/L), and of cortisol dynamics. Immunohistochemistry of the adrenal cancer confirmed aberrant expression of aromatase in most, although not all, carcinoma cells. Transcripts associated with utilization of promoters II, I.1 and I.3 were prominently represented in the tumor aromatase mRNA. This case highlights that clinical features of feminizing adrenocortical carcinomas can be secondary to estrogen production by aberrantly transcribed and translated aromatase within the tumor. Even in males, gonadotropin secretion is subject to predominantly estrogen-mediated feedback-inhibition. The diagnosis of adrenocortical adenocarcinoma should be considered in men presenting with low testosterone and gonadotropins, particularly in the presence of feminizing features.

  11. Internal ribosome entry site-mediated translation of a mammalian mRNA is regulated by amino acid availability

    NARCIS (Netherlands)

    Fernandez, J.; Yaman, I.; Mishra, R.; Merrick, W. C.; Snider, M. D.; Lamers, W. H.; Hatzoglou, M.

    2001-01-01

    The cationic amino acid transporter, Cat-1, facilitates the uptake of the essential amino acids arginine and lysine. Amino acid starvation causes accumulation and increased translation of cat-1 mRNA, resulting in a 58-fold increase in protein levels and increased arginine uptake. A bicistronic mRNA

  12. Spectrum of chromosomal aberrations in peripheral lymphocytes of hospital workers occupationally exposed to low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Maffei, Francesca; Angelini, Sabrina; Forti, Giorgio Cantelli; Violante, Francesco S.; Lodi, Vittorio; Mattioli, Stefano; Hrelia, Patrizia

    2004-01-01

    Chromosome aberrations frequency was estimated in peripheral lymphocytes from hospital workers occupationally exposed to low levels of ionizing radiation and controls. Chromosome aberrations yield was analyzed by considering the effects of dose equivalent of ionizing radiation over time, and of confounding factors, such as age, gender and smoking status. Frequencies of aberrant cells and chromosome breaks were higher in exposed workers than in controls (P=0.007, and P=0.001, respectively). Seven dicentric aberrations were detected in the exposed group and only three in controls, but the mean frequencies were not significantly different. The dose equivalent to whole body of ionizing radiation (Hwb) did appear to influence the spectrum of chromosomal aberrations when the exposed workers were subdivided by a cut off at 50 mSv. The frequencies of chromosome breaks in both subgroups of workers were significantly higher than in controls (≤50 mSv, P=0.041; >50 mSv, P=0.018). On the other hand, the frequency of chromatid breaks observed in workers with Hwb >50 mSv was significantly higher than in controls (P=0.015) or workers with Hwb ≤50 mSv (P=0.046). Regarding the influence of confounding factors on genetic damage, smoking status and female gender seem to influence the increase in chromosome aberration frequencies in the study population. Overall, these results suggested that chromosome breaks might provide a good marker for assessing genetic damage in populations exposed to low levels of ionizing radiation

  13. Peptide inhibitors of botulinum neurotoxin by mRNA display

    International Nuclear Information System (INIS)

    Yiadom, Kwabena P.A.B.; Muhie, Seid; Yang, David C.H.

    2005-01-01

    Botulinum neurotoxins (BoNTs) are extremely toxic. The metalloproteases associated with the toxins cleave proteins essential for neurotransmitter secretion. Inhibitors of the metalloprotease are currently sought to control the toxicity of BoNTs. Toward that goal, we produced a synthetic cDNA for the expression and purification of the metalloprotease of BoNT/A in Escherichia coli as a biotin-ubiquitin fusion protein, and constructed a combinatorial peptide library to screen for BoNT/A light chain inhibitors using mRNA display. A protease assay was developed using immobilized intact SNAP-25 as the substrate. The new peptide inhibitors showed a 10-fold increase in affinity to BoNT/A light chain than the parent peptide. Interestingly, the sequences of the new peptide inhibitors showed abundant hydrophobic residues but few hydrophilic residues. The results suggest that mRNA display may provide a general approach in developing peptide inhibitors of BoNTs

  14. The mRNA expression of XRCC repair genes in mice after γ-ray radiation

    International Nuclear Information System (INIS)

    Wang Qin; Yue Jingyin; Li Jin; Mu Chuanjie; Fan Feiyue

    2006-01-01

    Objective: To investigate the role of XRCC repair genes in radioresistance of IRM-2 inbred mice. Methods: Northern hybridization was used to measure mRNA expression of XRCC1 and XRCC5 genes in IRM-2 inbred mice. ICR/JCL and 615 after exposure to different doses of γ-ray radiation at different postirradiation time. Results: The levels of XRCC1 and XRCC5 mRNA expression in control IRM-2 mice were higher significantly than those in their control parental mice (P<0.01 and P<0.05). The mRNA expression of XRCC genes in ICR/JCL and 615 mice all increased to some extent after exposure 1, 2 and 4 Gy radiation. But the levels were significantly higher at 2h postirradiation (P<0.05) . The levels of XRCC mRNA expression in IRM-2 mice did not increase significnatly compared with the control mice after exposure 1 and 2 Gy radiation. But the levels of XRCC1 and XRCC5 mRNA expression increased markedly at 4Gy 1h postirradiation (P<0.05 and P<0.01). Conclusion: The basal levels of XRCC1 and XRCC5 mRNA expression in IRM-2 mice were high. The high level of XRCC5 mRNA expression was involved in the repair of DNA double strand breaks induced by higher dose radiation, which perhaps was one of radioresistance causes of IRM-2 mice. (authors)

  15. Higher-Order Wavefront Aberrations for Populations of Young Emmetropes and Myopes

    Directory of Open Access Journals (Sweden)

    Jinhua Bao

    2009-01-01

    Conclusions: Human eyes have systematical higher order aberrations in population, and factors that cause bilateral symmetry of wavefront aberrations between the right and left eyes made important contribution to the systematical aberrations.

  16. Failure of irradiated beef and ham to induce genetic aberrations of Drosophila

    International Nuclear Information System (INIS)

    Mittler, S.

    1979-01-01

    Ham that had been irradiated by electrons and beef which had been exposed to gamma rays from 60 Co were fed to Drosophila melanogaster to determine whether meat sterilized by these methods would induce genetic aberrations. The results showed that for yB/sc 8 y + Y males, fed on irradiated ham or beef, thermally preserved beef or frozen beef for their entire larval life, there was no significant increase in the loss of X or Y chromosomes or non-disjunction of these chromosomes; there was also no significant increase in any of the broods. Similarly for the Oregon R males, there was no significant increase in yield of sex-linked recessive lethals. Thus feeding of irradiated ham and beef to Drosophila males did not induce significant increases in genetic aberrations. The present findings are discussed in relation to the conflicting results of previous studies. (U.K.)

  17. Design and analysis of beam separator magnets for third generation aberration compensated PEEMs

    International Nuclear Information System (INIS)

    Wu, Y.K.; Robin, D.S.; Forest, E.; Schlueter, R.; Anders, S.; Feng, J.; Padmore, H.; Wei, D.H.

    2004-01-01

    A state of the art X-ray photoemission electron microscope (PEEM2) is operational at the Advanced Light Source at a resolution of typically 50 nm for a range of chemical and magnetic surface studies. A new microscope, PEEM3, is under development with an aim of achieving a resolution of 5 nm and more than an order of magnitude increase in transmission at the nominal resolution of PEEM2. The resolution and flux improvement is realized by providing geometric and chromatic aberration compensations in the system using an electron mirror and a beam separator magnet. The nearly aberration-free design of the beam separator is critical to the performance of third generation PEEMs. In this paper, we present the optics design model, optimal operation parameters, analyses of aberration impact, as well as the mechanical alignment tolerance for PEEM3 separator prototypes. In particular, we emphasize the importance of a new semi-analytical approach to design complex charged particle optics using the truncated power series algebra. Because of its ability to compute high-order aberrations, this approach allows systematic and comprehensive analyses of any charged particle optics systems with analytical electric and magnetic fields

  18. Third order aberration theory of double Wien filters

    Science.gov (United States)

    Ioanoviciu, D.; Tsuno, K.; Martinez, G.

    2004-11-01

    The second and the third order aberration theory for a double Wien filter have been analytically developed. A new second order aberration-free condition is found at the image plane of the second filter. This condition is met when b2=-1/4, e2=-1/2, and b3-e3=-1/8, where b2=B2R/B1, e2=E2R/E1, b3=B3R2/B1, and e3=E3R2/E1. Here, R is the cyclotron radius and E1, B1, E2, B2, E3, and B3 are the dipole, quadrupole, and hexapole components of electric and magnetic fields, respectively. This condition is different from the second order aberration-free condition for a single Wien filter, which is satisfied when b2=-3/4, e2=-1, and b3-e3=-3/8. The geometrical second order aberration-free condition has also been found, and requires that e3-b3=(m-1)/8, e2=-m/4, and b2=(1-m)/4. This last set is sufficient to satisfy the above two sets of conditions as well. Residual third order aberrations are calculated for various m. The third order aberrations at the second focus are very small when the new aberration-free condition is fulfilled.

  19. Chromosome aberrations in solid tumors have a stochastic nature

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Mauro A.A. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil) and Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil) and Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil) and Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil)]. E-mail: mauro@ufrgs.br; Onsten, Tor G.H. [Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil); Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil); Moreira, Jose C.F. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil); Almeida, Rita M.C. de [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil)

    2006-08-30

    An important question nowadays is whether chromosome aberrations are random events or arise from an internal deterministic mechanism, which leads to the delicate task of quantifying the degree of randomness. For this purpose, we have defined several Shannon information functions to evaluate disorder inside a tumor and between tumors of the same kind. We have considered 79 different kinds of solid tumors with 30 or more karyotypes retrieved from the Mitelman Database of Chromosome Aberrations in Cancer. The Kaplan-Meier cumulative survival was also obtained for each solid tumor type in order to correlate data with tumor malignance. The results here show that aberration spread is specific for each tumor type, with high degree of diversity for those tumor types with worst survival indices. Those tumor types with preferential variants (e.g. high proportion of a given karyotype) have shown better survival statistics, indicating that aberration recurrence is a good prognosis. Indeed, global spread of both numerical and structural abnormalities demonstrates the stochastic nature of chromosome aberrations by setting a signature of randomness associated to the production of disorder. These results also indicate that tumor malignancy correlates not only with karyotypic diversity taken from different tumor types but also taken from single tumors. Therefore, by quantifying aberration spread, we could confront diverse models and verify which of them points to the most likely outcome. Our results suggest that the generating process of chromosome aberrations is neither deterministic nor totally random, but produces variations that are distributed between these two boundaries.

  20. Chromosome aberrations of the peripheral lymphocytes in rabbits exposed to single and fractionated whole-body x-irradiations

    International Nuclear Information System (INIS)

    Tamura, Hiroaki; Sakurai, Masaharu; Sugahara, Tsutomu.

    1978-01-01

    The changes in the frequency of peripheral lymphocytes with chromosome aberrations were observed during or after irradiation of rabbits exposed to fractionated or single whole-body irradiations. In rabbits given daily fractionated whole-body irradiations the incidence of the aberrations showed a linear increase in the first week; however, the incidence decreased thereafter though exposures were repeated. The lymphocyte count tended to decrease as the number of irradiations increased. In rabbits exposed to a single dose of 250 R or 500 R the incidence of aberrations rapidly decreased over a period of 10 days following irradiation, and then showed a little change thereafter. The lymphocyte count in the peripheral blood reached a nadir 2 - 5 days after irradiation, and then started to increase gradually. It was speculated that there are two types of lymphocytes, long-lived and short-lived, in the peripheral blood of rabbits, both of which are PHA-committed. (auth.)

  1. FLT3-ITD and MLL-PTD influence the expression of MDR-1, MRP-1, and BCRP mRNA but not LRP mRNA assessed with RQ-PCR method in adult acute myeloid leukemia.

    Science.gov (United States)

    Nasilowska-Adamska, Barbara; Solarska, Iwona; Paluszewska, Monika; Malinowska, Iwona; Jedrzejczak, Wieslaw W; Warzocha, Krzysztof

    2014-04-01

    Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and mixed-lineage leukemia gene-partial tandem duplication (MLL-PTD) are aberrations associated with leukemia which indicate unsatisfactory prognosis. Downstream regulatory targets of FLT3-ITD and MLL-PTD are not well defined. We have analyzed the expression of MDR-1, multidrug resistant protein-1 (MRP-1), breast cancer resistance protein (BCRP), and lung resistance protein (LRP) messenger RNA (mRNA) in relation to the mutational status of FLT3-ITD and MLL-PTD in 185 acute myeloid leukemia (AML) adult patients. The real-time quantitative polymerase chain reaction method was performed to assess the expression of the MDR-1, MRP-1, BCRP, and LRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule. Significantly higher expressions of MDR-1 mRNA were found in patients who did not harbor FLT3-ITD (0.20 vs. 0.05; p = 0.0001) and MRP-1 mRNA in patients with this mutation (0.96 vs. 0.70; p = 0.002) and of BCRP mRNA in patients with MLL-PTD (0.61 vs. 0.38; p = 0.03). In univariate analysis, the high expression of MDR-1 mRNA (≥0.1317) negatively influenced the outcome of induction therapy (p = 0.05), whereas the high expression of BCRP mRNA (≥1.1487) was associated with a high relapse rate (RR) (p = 0.013). We found that the high expression of MDR-1 (≥0.1317), MRP-1 (≥0.8409), and BCRP mRNA (≥1.1487) significantly influenced disease-free survival (DFS; p = 0.059, 0.032, and 0.009, respectively) and overall survival (0.048, 0.014, and 0.059, respectively). Moreover, a high expression of BCRP mRNA (≥1.1487) proved to be an independent prognostic factor for RR (p = 0.01) and DFS (p = 0.002) in multivariate analysis. The significant correlation between the expression of MDR-1, MRP-1, and BCRP mRNA and FLT3-ITD or MLL-PTD in AML patients requires further investigation.

  2. Chromosome aberration studies and microdosimetry with radiations of varying quality

    International Nuclear Information System (INIS)

    Grillmaier, R.E.; Bihy, L.; Menzel, H.G.; Schuhmacher, H.

    1978-01-01

    To investigate the biological effectivity of complex irradiation fields encountered in radiation protection and high LET radiation therapy and to find meaningful specification of radiation quality closely related to the biological effectivity, correlated chromosome aberration studies and microdosimetric investigations have been carried out using cyclotron produced collimated fast neutrons. Human lymphocytes have been irradiated at different dose levels in the direct beam and in different positions in the penumbra and the rates of acentric fragments and dicentrics have been determined. In identical positions microdosimetric measurements have been performed. The dose relationship of aberration rates after irradiation in the direct beam, the aberration rates observed in the penumbra and the microdosimetric quantities ysub(D), ysub(F) and y* are presented and their relations are discussed. Furthermore the dose relationship of chromosome aberrations induced by 60 Co-γ-rays has been investigated and used to establish the RBE dose relationship of cyclotron neutrons

  3. Aberrant internal carotid artery in the middle ear

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Keun Tak; Kang, Hyun Koo [Dept. of Radiology, Seoul Veterans Hospital, Seoul (Korea, Republic of)

    2014-10-15

    The knowledge about the aberrant internal carotid artery (ICA) in the middle ear is essential for clinicians, because a misdiagnosis of the aberrant ICA could have serious consequences such as excessive aural bleeding during a middle ear surgery. A 38-year-old woman presented with tinnitus and hearing difficulties of the left ear that had started 5 years ago. During otoscopy, an anteroinferior bluish mass was seen in the tympanic space. Computed tomography and magnetic resonance imaging demonstrated a left-side aberrant ICA with bony dehiscence of the carotid canal in the middle ear and a reduced diameter of the tympanic ICA. Herein we report a case of an aberrant ICA in the middle ear. We also review the literature regarding this important vascular anomaly of the temporal bone which may lead to disastrous surgical complications.

  4. Aberrant internal carotid artery in the middle ear

    International Nuclear Information System (INIS)

    Roh, Keun Tak; Kang, Hyun Koo

    2014-01-01

    The knowledge about the aberrant internal carotid artery (ICA) in the middle ear is essential for clinicians, because a misdiagnosis of the aberrant ICA could have serious consequences such as excessive aural bleeding during a middle ear surgery. A 38-year-old woman presented with tinnitus and hearing difficulties of the left ear that had started 5 years ago. During otoscopy, an anteroinferior bluish mass was seen in the tympanic space. Computed tomography and magnetic resonance imaging demonstrated a left-side aberrant ICA with bony dehiscence of the carotid canal in the middle ear and a reduced diameter of the tympanic ICA. Herein we report a case of an aberrant ICA in the middle ear. We also review the literature regarding this important vascular anomaly of the temporal bone which may lead to disastrous surgical complications.

  5. Herpes,zoster with Wrist Drop and Aberrant Lesions

    Directory of Open Access Journals (Sweden)

    R K Dutta

    1987-01-01

    Full Text Available A patient having herpes zoster involving C6, 7, 8, Dl and 2 segments, developed ipsilateral wrist drop and aberrant lesions. Paralytic deformity preceded the skin eruption by one day.

  6. Aberrant Chromatin Modification as a Mechanism of Prostate Cancer Progression

    National Research Council Canada - National Science Library

    Chen, Hongwu

    2004-01-01

    .... However, the underlying mechanism is still unclear. The purpose of this study is to test the hypothesis that aberrant chromatin modification plays a critical role in prostate cancer progression...

  7. Impact of primary aberrations on coherent lidar performance

    DEFF Research Database (Denmark)

    Hu, Qi; Rodrigo, Peter John; Iversen, Theis Faber Quist

    2014-01-01

    of the lidar system using different optical transceiver configurations. A rotating belt is used as a hard target. Our study shows that the lidar weighting function suffers from both spatial broadening and shift in peak position in the presence of aberration. It is to our knowledge the first experimental......In this work we investigate the performance of a monostatic coherent lidar system in which the transmit beam is under the influence of primary phase aberrations: spherical aberration (SA) and astigmatism. The experimental investigation is realized by probing the spatial weighting function...... effciency, the optimum truncation of the transmit beam and the spatial sensitivity of a CW coherent lidar system. Under strong degree of aberration, the spatial confinement is significantly degraded. However for SA, the degradation of the spatial confinement can be reduced by tuning the truncation...

  8. Establishing working standards of chromosome aberrations analysis for biological dosimetry

    International Nuclear Information System (INIS)

    Bui Thi Kim Luyen; Tran Que; Pham Ngoc Duy; Nguyen Thi Kim Anh; Ha Thi Ngoc Lien

    2015-01-01

    Biological dosimetry is an dose assessment method using specify bio markers of radiation. IAEA (International Atomic Energy Agency) and ISO (International Organization for Standardization) defined that dicentric chromosome is specify for radiation, it is a gold standard for biodosimetry. Along with the documents published by IAEA, WHO, ISO and OECD, our results of study on the chromosome aberrations induced by radiation were organized systematically in nine standards that dealing with chromosome aberration test and micronucleus test in human peripheral blood lymphocytes in vitro. This standard addresses: the reference dose-effect for dose estimation, the minimum detection levels, cell culture, slide preparation, scoring procedure for chromosome aberrations use for biodosimetry, the criteria for converting aberration frequency into absorbed dose, reporting of results. Following these standards, the automatic analysis devices were calibrated for improving biological dosimetry method. This standard will be used to acquire and maintain accreditation of the Biological Dosimetry laboratory in Nuclear Research Institute. (author)

  9. Chromosome aberrations in pesticide-exposed greenhouse workers

    DEFF Research Database (Denmark)

    Lander, B F; Knudsen, Lisbeth E.; Gamborg, M O

    2000-01-01

    OBJECTIVES: The aim of this study was to investigate the possibility of subtoxic exposure to pesticides causing chromosome aberrations in greenhouse workers. METHODS: In a cross-sectional and prospective study design chromosome aberration frequencies in cultured lymphocytes were examined for 116...... greenhouse workers exposed to a complex mixture of almost 50 insecticides, fungicides, and growth regulators and also for 29 nonsmoking, nonpesticide-exposed referents. RESULTS: The preseason frequencies of chromosome aberrations were slightly but not statistically significantly elevated for the greenhouse...... workers when they were compared with the referents. After a summer season of pesticide spraying in the greenhouses, the total frequencies of cells with chromosome aberrations were significantly higher than in the preseason samples (P=0.02) and also higher than for the referents (P=0.05). This finding...

  10. Aberrant cervical thymus mimicking thyroid on ultrasonography: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Sub; Park, Ju Hyun; Kim, Bong Soo; Park, Ji Kang; Choi, Jae Hyuck [Jeju National Univ. Hospital/Jeju National Univ. School of Medicine, Jeju (Korea, Republic of)

    2012-10-15

    Aberrant cervical thymus is rarely reported in adults. We report a case of solid aberrant cervical thymus in a 27 year old female, which was found incidentally on ultrasonography for the evaluation of the thyroid cancer. On ultrasonography, the lesion was found between the left thyroid and common carotid artery without any remarkable interface echo, and had similar echogenicity to the thyroid. The lesion extended to the upper pole of the left thyroid.

  11. Adaptive optics enables 3D STED microscopy in aberrating specimens.

    Science.gov (United States)

    Gould, Travis J; Burke, Daniel; Bewersdorf, Joerg; Booth, Martin J

    2012-09-10

    Stimulated emission depletion (STED) microscopy allows fluorescence far-field imaging with diffraction-unlimited resolution. Unfortunately, extending this technique to three-dimensional (3D) imaging of thick specimens has been inhibited by sample-induced aberrations. Here we present the first implementation of adaptive optics in STED microscopy to allow 3D super-resolution imaging in strongly aberrated imaging conditions, such as those introduced by thick biological tissue.

  12. Adaptive optics enables 3D STED microscopy in aberrating specimens

    Science.gov (United States)

    Gould, Travis J.; Burke, Daniel; Bewersdorf, Joerg; Booth, Martin J.

    2012-01-01

    Stimulated emission depletion (STED) microscopy allows fluorescence far-field imaging with diffraction-unlimited resolution. Unfortunately, extending this technique to three-dimensional (3D) imaging of thick specimens has been inhibited by sample-induced aberrations. Here we present the first implementation of adaptive optics in STED microscopy to allow 3D super-resolution imaging in strongly aberrated imaging conditions, such as those introduced by thick biological tissue. PMID:23037223

  13. Moment aberrations in magneto-electrostatic plasma lenses (computer simulation)

    CERN Document Server

    Butenko, V I

    2001-01-01

    In this work moment aberrations in the plasma magneto-electrostatic lenses are considered in more detail with the use of the computer modeling. For solution of the problem we have developed a special computer code - the model of plasma optical focusing device, allowing to display the main parameters and operations of experimental sample of a lens, to simulate the moment and geometrical aberrations and give recommendations on their elimination.

  14. Higher-order aberrations and visual acuity after LASEK.

    Science.gov (United States)

    Urgancioglu, Berrak; Bilgihan, Kamil; Ozturk, Sertac

    2008-08-01

    To determine ocular higher-order aberrations (HOAs) in eyes with supernormal vision after myopic astigmatic laser subepithelial keratomileusis (LASEK) and to compare the findings with those in eyes with natural supernormal vision. Ocular HOAs were measured after LASEK in 20 eyes of 12 myopic astigmatic patients with postoperative uncorrected visual acuity (UCVA) of >20/16 (group 1). Patients who were included in the study had no visual symptoms like glare, halo or double vision. The measurements were taken 8.3 +/- 3 months after LASEK surgery. In group 2 ocular HOAs were examined in 20 eyes of 10 subjects with natural UCVA of >20/16 as a control. Measurements were taken across a pupil with a diameter of 4.0 mm and 6.0 mm. Root-mean-square (RMS) values of HOAs, Z(3)-1, Z(3)1, Z(4)0, Z(5)-1, Z(5)1 and Z(6)0 were analyzed. The mean RMS values for each order were higher in group 1 when compared with group 2 at 4.0 mm and 6.0 mm pupil diameters. There was no statistically significant difference between groups in spherical and coma aberrations (P > 0.05). Mean RMS values for total HOAs were 0.187 +/- 0.09 microm at 4.0 mm and 0.438 +/- 0.178 microm at 6.0 mm pupil in group 1 and 0.120 +/- 0.049 microm at 4.0 mm and 0.344 +/- 0.083 microm at 6.0 mm pupil in group 2. The difference between groups in total HOAs was statistically significant at 4.0 mm and 6.0 mm pupil diameters (P < 0.05). Ocular HOAs exist in eyes with supernormal vision. After LASEK, the amount of HOAs of the eye increases under both mesopic and photopic conditions. However the amount of HOA increase does not seem to be consistent with visual symptoms.

  15. Coherence and diffraction limited resolution in microscopic OCT by a unified approach for the correction of dispersion and aberrations

    Science.gov (United States)

    Schulz-Hildebrandt, H.; Münter, Michael; Ahrens, M.; Spahr, H.; Hillmann, D.; König, P.; Hüttmann, G.

    2018-03-01

    Optical coherence tomography (OCT) images scattering tissues with 5 to 15 μm resolution. This is usually not sufficient for a distinction of cellular and subcellular structures. Increasing axial and lateral resolution and compensation of artifacts caused by dispersion and aberrations is required to achieve cellular and subcellular resolution. This includes defocus which limit the usable depth of field at high lateral resolution. OCT gives access the phase of the scattered light and hence correction of dispersion and aberrations is possible by numerical algorithms. Here we present a unified dispersion/aberration correction which is based on a polynomial parameterization of the phase error and an optimization of the image quality using Shannon's entropy. For validation, a supercontinuum light sources and a costume-made spectrometer with 400 nm bandwidth were combined with a high NA microscope objective in a setup for tissue and small animal imaging. Using this setup and computation corrections, volumetric imaging at 1.5 μm resolution is possible. Cellular and near cellular resolution is demonstrated in porcine cornea and the drosophila larva, when computational correction of dispersion and aberrations is used. Due to the excellent correction of the used microscope objective, defocus was the main contribution to the aberrations. In addition, higher aberrations caused by the sample itself were successfully corrected. Dispersion and aberrations are closely related artifacts in microscopic OCT imaging. Hence they can be corrected in the same way by optimization of the image quality. This way microscopic resolution is easily achieved in OCT imaging of static biological tissues.

  16. RT-PCR analysis of dystrophin mRNA in DND/BMD patients

    Energy Technology Data Exchange (ETDEWEB)

    Ciafaloni, E.; Silva, H.A.R. de; Roses, A.D. [Duke Univ. Medical Center, Durham, NC (United States)

    1994-09-01

    Duchenne and Becker muscular dystrophies (DMD, BMD) are X-linked recessive disorders caused by mutations in the dystrophin (dys) gene. The majority of these mutations are intragenic deletions of duplications routinely detected by Southern biots and multiplex PCR. The remainder are very likely, smaller mutations, mostly point-mutations. Detection of these mutations is very difficult due to the size and complexity of the dys gene. We applied RT-PCR to analyse the entire dys mRNA of three DMD patients with no detectable genomic defect. In two unrelated patients, a duplication of the 62 bp exon 2 was identified. This causes a frameshift sufficient to explain the DMD phenotype. In the third patient, who had congenital DMD and severe mental retardation, a complex pattern of aberrant splicing at the 3-prime exons 67-79 was observed. Sural nerve biopsy in this patient showed the complete absence of Dp116. PCR-SSCP studies are presently in progress to identify the mutations responsible for the aberrant splicing patterns.

  17. El aumento de la expresión del ARNm de la enzima convertidora de angiotensina I homóloga (ECA-2 inducido por atorvastatina se asocia a menor fibrosis e hipertrofia ventricular izquierda en un modelo de cardiomiopatía diabética Atorvastatin induced increase in homologous angiotensin i converting enzyme (ACE2 mRNA is associated to decreased fibrosis and decreased left ventricular hypertrophy in a rat model of diabetic cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Cristian Aguilar

    2011-06-01

    content assay and genetic expressions of ACE and ACE2 mRNA. Results. Myocardial hypertrophy index and collagen deposition were increased in diabetic rats, but not in the treated-diabetic rats, without producing changes in cholesterol levels. Myocardial ACE mRNA levels were increased while ACE2 mRNA levels were decreased in diabetic rats. Atorvastatin administration attenuated overexpression of ACE mRNA and overexpression of ACE-2 mRNA in diabetic rats. Conclusions. Our results indicate that atorvastatin, independently of its cholesterol-lowering capacity, lowers the ACE/ACE2 ratio to normal values and attenuates the development of adverse remodeling in the diabetic heart.

  18. In silico evaluation of miRNA binding site in mutated 3'UTR mRNA of G6PD

    Science.gov (United States)

    Azmi, Syarifah Anis Wafa Binti Syed Mohd; Noorden, Mohd Shihabudin; Yusof, Nurul Yuziana Mohd; Ismail, Endom

    2015-09-01

    MicroRNAs (miRNAs) are small non coding RNA sized 21-25 nucleotide. It has the ability to bind to the 3'- untranslated regions (3'UTR) of their target genes. Consequently, the binding of miRNA in the 3'UTR of targeted mRNA will regulate the expression of this gene. Thus, changes in 3'UTR may affect miRNA binding to mRNA of their target gene, leading to aberrations in mRNA regulations or expression and likely contribute to the various phenotypic changes or clinical risk for certain diseases in man. Therefore, the aim of this study is to evaluate candidate miRNAs species involved during the regulation of glucose-6-phosphate dehydrogenase (G6PD) mRNA with and without a specific 3'UTR nucleotide change that was previously shown to be responsible for G6PD deficiency in a Negrito sub-group of the Malaysian Orang Asli. We have conducted in silico analysis using TargetScan, PITA, RegRNA 2.0 and miRanda platform. Our results indicate that three potential miRNAs may have a functional role towards the regulated expression of those bearing the 3'UTR mutation. The role of these eleven miRNA can be investigated in future in vitro expression studies in order to verify its miRNA:mRNA relationship.

  19. The follow-up study of chromosomal aberrations in Chernobyl clean-up workers

    International Nuclear Information System (INIS)

    Slozina, Natalia M.; Neronova, Elizaveta G.

    2016-01-01

    A cytogenetic study was carried out on 359 clean-up workers who worked at the Chernobyl station in 1986-1989. The investigation was performed 6-12 years after irradiation. Chromosome type damages, i.e. double fragments, dicentrics and rings were significantly increased in the clean-up workers compared to the control. Chromatid exchanges were found only in the clean-up workers. A temporal change of radiation makers was also investigated based on the data of 243 persons who worked at Chernobyl in 1986. The temporal variation of dicentric frequency shows an inexplicable tendency towards the increase of dicentrics rate for the period of 8-12 years after irradiation. The association between the frequency of different types of chromosomal aberrations and such variables as smoking habits, coffee, tea, alcohol consumption, etc. was also analysed using a stepwise multiple regression analysis. A statistically significant association was only observed between smoking and chromatid exchanges. This type of aberrations was significantly higher in the smoking subgroup than in the non-smoking subgroup of the clean-up workers. The fact of an increased level of unstable chromosomal aberrations in a remote period after irradiation allows us to suppose that other pathways of genomic burden may exist in addition to straight radiation action at the time of irradiation. (author)

  20. 60Co γ-irradiation enhances expression of GAP-43 mRNA in rat brain

    International Nuclear Information System (INIS)

    Su Bingyin; Cai Wenqin; Zhang Chenggang

    2001-01-01

    Objective: To study the relationship between the expression of GAP-43 mRNA and nerve regeneration in rat brain after 60 Co γ-irradiation. Methods: Wistar rats were subjected to whole-body irradiation with 8 Gy 60 Co γ-rays. The expression of GAP-43 was detected by in situ hybridization histochemistry using Dig-cRNA probe. Results: It was found that the expression of GAP-43 mRNA increased in the cerebral cortex, caudate, putamen, globus pallidum, thalamus and hypothalamus one week after 8 Gy 60 Co γ-irradiation. The peak of GAP-43 mRNA expression was observed in the fourth week and then began to decrease but still remained at a higher than normal level. However, it decreased to a low level after 7 weeks. Conclusion: Enhanced expression of GAP-43 mRNA after 60 Co γ-irradiation in rat brain is associated with nerve regeneration and reconstruction of synapse

  1. Adult hippocampal neurogenesis poststroke: More new granule cells but aberrant morphology and impaired spatial memory.

    Science.gov (United States)

    Woitke, Florus; Ceanga, Mihai; Rudolph, Max; Niv, Fanny; Witte, Otto W; Redecker, Christoph; Kunze, Albrecht; Keiner, Silke

    2017-01-01

    Stroke significantly stimulates neurogenesis in the adult dentate gyrus, though the functional role of this postlesional response is mostly unclear. Recent findings suggest that newborn neurons generated in the context of stroke may fail to correctly integrate into pre-existing networks. We hypothesized that increased neurogenesis in the dentate gyrus following stroke is associated with aberrant neurogenesis and impairment of hippocampus-dependent memory. To address these questions we used the middle cerebral artery occlusion model (MCAO) in mice. Animals were housed either under standard conditions or with free access to running wheels. Newborn granule cells were labelled with the thymidine analoque EdU and retroviral vectors. To assess memory performance, we employed a modified version of the Morris water maze (MWM) allowing differentiation between hippocampus dependent and independent learning strategies. Newborn neurons were morphologically analyzed using confocal microscopy and Neurolucida system at 7 weeks. We found that neurogenesis was significantly increased following MCAO. Animals with MCAO needed more time to localize the platform and employed less hippocampus-dependent search strategies in MWM versus controls. Confocal studies revealed an aberrant cell morphology with basal dendrites and an ectopic location (e.g. hilus) of new granule cells born in the ischemic brain. Running increased the number of new neurons but also enhanced aberrant neurogenesis. Running, did not improve the general performance in the MWM but slightly promoted the application of precise spatial search strategies. In conclusion, ischemic insults cause hippocampal-dependent memory deficits which are associated with aberrant neurogenesis in the dentate gyrus indicating ischemia-induced maladaptive plasticity in the hippocampus.

  2. Time-resolved measurement of thermally induced aberrations in a cryogenically cooled Yb:YAG slab with a wavefront sensor

    Science.gov (United States)

    Sikocinski, P.; Novak, O.; Smrz, M.; Pilar, J.; Jambunathan, V.; Jelínková, H.; Endo, A.; Lucianetti, A.; Mocek, T.

    2016-04-01

    The time-resolved measurements of thermally induced wavefront aberrations in a cryogenically cooled Yb:YAG crystal are presented in dependence on temperature in the range between 250 and 130 K under non-lasing condition. A wavefront sensor was utilized to determine the wavefront aberrations. The wavefront distortions were experimentally studied for a cryogenically cooled Yb:YAG crystal in detail for the first time. The wavefront aberrations were significantly reduced at cryogenic temperatures including defocus which was the dominant aberration and which was responsible for the so-called thermal lensing effect. We found that defocus aberration is caused not only by thermally induced effects (responsible for thermal lens), but also by electronically induced change in the refractive index due to excitation of ion activators which is responsible for the electronic lensing. Nevertheless, at pumping intensity of 6.3 kW/cm2 and repetition rate of 100 Hz thermal effects were the dominant one. In addition, an improvement in the Strehl ratio along with an increase in absorbed pump energy was observed while the temperature of the gain medium was decreased. The measurements clearly show the advantages of cryogenic cooling of laser-active media for beam quality improvement.

  3. Low aberration monolithic diffraction gratings for high performance optical spectrometers

    Science.gov (United States)

    Triebel, Peter; Moeller, Tobias; Diehl, Torsten; Gatto, Alexandre; Pesch, Alexander; Erdmann, Lars E.; Burkhardt, Matthias; Kalies, Alexander

    2017-09-01

    Gratings are the core element of the spectrometer. For imaging spectrometers beside the polarization sensitivity and efficiency the imaging quality of the diffraction grating is essential. Lenses and mirrors can be produced with lowest wavefront aberrations. Low aberration imaging quality of the grating is required not to limit the overall imaging quality of the instrument. Different types of spectrometers will lead to different requirements on the wavefront aberrations for their specific diffraction gratings. The wavefront aberration of an optical grating is a combination of the substrate wavefront and the grating wavefront. During the manufacturing process of the grating substrate different processes can be applied in order to minimize the wavefront aberrations. The imaging performance of the grating is also optimized due to the recording setup of the holography. This technology of holographically manufactured gratings is used for transmission and reflection gratings on different types of substrates like prisms, convex and concave spherical and aspherical surface shapes, free-form elements. All the manufactured gratings are monolithic and can be coated with high reflection and anti-reflection coatings. Prism substrates were used to manufacture monolithic GRISM elements for the UV to IR spectral range preferably working in transmission. Besides of transmission gratings, numerous spectrometer setups (e.g. Offner, Rowland circle, Czerny-Turner system layout) working on the optical design principles of reflection gratings. The present approach can be applied to manufacture high quality reflection gratings for the EUV to the IR. In this paper we report our latest results on manufacturing lowest wavefront aberration gratings based on holographic processes in order to enable at least diffraction limited complex spectrometric setups over certain wavelength ranges. Beside the results of low aberration gratings the latest achievements on improving efficiency together with

  4. Chromatic aberration, accommodation, and color preference in asthenopia.

    Science.gov (United States)

    Drew, Stefanie A; Borsting, Eric; Stark, Lawrence R; Chase, Chris

    2012-07-01

    Asthenopia is a common problem associated with near work and reports suggest that colored lenses or overlays may be applied to reduce symptoms. In this study, we examine the relationship between eyestrain, color preferences, and function of the accommodation and vergence system. Specifically, we examine whether symptomatic observers select colors that reduce accommodative demand based on longitudinal chromatic aberration (LCA). Forty-seven undergraduate students participated in this study. Visual discomfort symptoms were assessed using the Conlon survey. A Mark 2 Intuitive Colorimeter was used to obtain optimal colored light preferences. LCA was modeled using the Chromatic Eye and spectral power density data. A comprehensive evaluation of accommodation and vergence was performed following standard procedures. A significant negative correlation (r = -0.51) was found between eyestrain symptoms and the International Commission on Illumination (CIE) v' axis of colors preferences. Additionally, a significant negative correlation (r = -0.31) was found between eyestrain symptoms and LCA accommodation. Two thirds of the participants in the high discomfort group chose colors that decreased accommodative demand. Accommodative amplitude and vergence facility also correlated with LCA, accounting for 25% of the variance. The color preferences of individuals are systematically influenced by the functioning of their accommodation and vergence systems with increased symptomatology resulting in color selections that reduce LCA accommodative stimulus demand.

  5. Aberrant water homeostasis detected by stable isotope analysis.

    Directory of Open Access Journals (Sweden)

    Shannon P O'Grady

    Full Text Available While isotopes are frequently used as tracers in investigations of disease physiology (i.e., 14C labeled glucose, few studies have examined the impact that disease, and disease-related alterations in metabolism, may have on stable isotope ratios at natural abundance levels. The isotopic composition of body water is heavily influenced by water metabolism and dietary patterns and may provide a platform for disease detection. By utilizing a model of streptozotocin (STZ-induced diabetes as an index case of aberrant water homeostasis, we demonstrate that untreated diabetes mellitus results in distinct combinations, or signatures, of the hydrogen (delta2H and oxygen (delta18O isotope ratios in body water. Additionally, we show that the delta2H and delta18O values of body water are correlated with increased water flux, suggesting altered blood osmolality, due to hyperglycemia, as the mechanism behind this correlation. Further, we present a mathematical model describing the impact of water flux on the isotopic composition of body water and compare model predicted values with actual values. These data highlight the importance of factors such as water flux and energy expenditure on predictive models of body water and additionally provide a framework for using naturally occurring stable isotope ratios to monitor diseases that impact water homeostasis.

  6. mRNA quality control pathways in Saccharomyces cerevisiae

    Indian Academy of Sciences (India)

    2013-07-10

    Jul 10, 2013 ... THO components/maturing factors/mRNA-binding proteins are released from mRNA once the mRNA matures and become export competent. Similarly .... its coding sequence have remarkable influence on the stability of RPL30 mRNA ...... Lorentzen E, Basquin J and Conti E 2008 Structural organization of.

  7. Studying the action of Cadmium to classification and frequencies of chromosome aberrations induced in human lymphocytes exposed to gamma rays

    International Nuclear Information System (INIS)

    Tran Que; Hoang Hung Tien; Nguyen Thi Kim Anh; Thi Ngoc Lien; Trinh Dinh Dat; Do Le Thang; Nguyen Van Kinh

    2007-01-01

    In the effort to find the reasons lead to unstabilization of low radiation dose effects, the influence of the Persistent, Bioaccumulative and Toxic chemicals such as Arsenic, Cadmium and other heavy ion to chromosome aberrations in Human lymphocytes exposed to gamma rays was investigated. The presentation of the agents that prevented repair of DNA breaks by irradiation can induced more breaks than not. With a suggest that Cadmium is a factor that can cause damages in DNA molecular and inactivated repair enzyme also, the investigating chromosome aberrations induced in human lymphocytes by combined action of Cadmium and gamma rays is conducted with 4 groups: Cd; gamma; Cd/gamma and Gamma/Cd. Different with Arsenic, the observed results presented that Cadmium in the single concentrations 0.05 μg/ml and 0.10 μg/ml were not aspect to mitotic index and chromosome aberrations also. In the combined treatments, the difference on frequencies of Dicentric and Fragment in lymphocytes treated with variable Cadmium concentrations in the same group of gamma rays dose was clearly. Following the increasing of Cd concentrations in the combinations exposed to the same radiation dose, the frequencies of Dicentrics were decreasing but the frequencies of Fragments were increasing. The difference on frequencies of chromosome aberrations was not detected in the Cadmium concentrations 0.05 μg/ml and 0.10 μg/ml of the combinations of post-exposed to gamma rays, it means that Cadmium do not aspect to the induction of chromosome aberrations after repair time. We suggest that Cadmium is not directly causing chromosome aberrations but aspect to the DNA damage repair progress of lymphocytes. The Cadmium can induced the increasing fragments (blocking of cohensive free ends) by bound the blunt free-end of DSB or create near site DSB (unblunt free-end) that lead to difficulty in joint together.(author)

  8. Eliminating chromatic aberration of lens and recognition of thermal images with artificial intelligence applications

    Science.gov (United States)

    Fang, Yi-Chin; Wu, Bo-Wen; Lin, Wei-Tang; Jon, Jen-Liung

    2007-11-01

    Resolution and color are two main directions for measuring optical digital image, but it will be a hard work to integral improve the image quality of optical system, because there are many limits such as size, materials and environment of optical system design. Therefore, it is important to let blurred images as aberrations and noises or due to the characteristics of human vision as far distance and small targets to raise the capability of image recognition with artificial intelligence such as genetic algorithm and neural network in the condition that decreasing color aberration of optical system and not to increase complex calculation in the image processes. This study could achieve the goal of integral, economically and effectively to improve recognition and classification in low quality image from optical system and environment.

  9. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID during Inflammation-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tsutomu Chiba

    2011-06-01

    Full Text Available Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID, a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  10. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Atsushi; Marusawa, Hiroyuki, E-mail: maru@kuhp.kyoto-u.ac.jp; Chiba, Tsutomu [Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)

    2011-06-22

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  11. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    International Nuclear Information System (INIS)

    Takai, Atsushi; Marusawa, Hiroyuki; Chiba, Tsutomu

    2011-01-01

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis

  12. Chromosomal aberrations induced in mice bone marrow by treating with cisplatin and irradiation

    International Nuclear Information System (INIS)

    Wuerschmidt, F.; Molls, M.; Bardenheuer, M.J.; Mueller, W.U.

    2000-01-01

    Background: The aim of this study was to quantify the combined effect of cisplatin and radiation on chromosomal damage with emphasis on the time interval between cisplatin and radiation. Methods and materials: Bone marrow of female NMRI-nu(+)mice was taken as a model system for a highly proliferative tissue irradiated with cobalt-60 (1 to 4 Gy). Cisplatin was injected intraperitoneally (ip) at 1.1 to 36 mg/kg. Cisplatin was given at various time intervals before and after radiation. Bone marrow and metaphases were prepared according to standard procedures. Results: The percentage of aberrant metaphases after radiation or cisplatin alone increased in a dose-dependent manner (sigmoidal dose-response curve). Combining both modalities led to additive values at all time points for the percentage of aberrant metaphases. Borderline significant (p [de

  13. Impact of types of lymphocyte chromosomal aberrations on human cancer risk

    DEFF Research Database (Denmark)

    Hagmar, Lars; Strömberg, Ulf; Bonassi, Stefano

    2004-01-01

    The frequency of cells with structural chromosomal aberrations (CAs) in peripheral blood lymphocytes is the first genotoxicity biomarker that has shown an association with cancer risk. CAs are usually divided into chromosome-type (CSAs) and chromatid-type aberrations (CTAs), with different...... mechanisms of formation. From a mechanistic point of view, it is of interest to clarify whether the cancer predictivity of CAs is different with respect to CSAs and CTAs. We report here cancer risk for cytogenetically tested, healthy subjects with respect to frequency of CAs, CSAs, and CTAs in peripheral...... blood lymphocytes, using Nordic (1981 subjects with CA data, 1871 subjects with CSA/CTA data) and Italian (1573 subjects with CA data, 877 subjects with CTA/CSA data) cohorts, with a median follow-up of 17 years. High levels of CAs at test were clearly associated with increased total cancer incidence...

  14. Multiphoton fluorescence microscopy with GRIN objective aberration correction by low order adaptive optics.

    Science.gov (United States)

    Bortoletto, Favio; Bonoli, Carlotta; Panizzolo, Paolo; Ciubotaru, Catalin D; Mammano, Fabio

    2011-01-01

    Graded Index (GRIN) rod microlenses are increasingly employed in the assembly of optical probes for microendoscopy applications. Confocal, two-photon and optical coherence tomography (OCT) based on GRIN optical probes permit in-vivo imaging with penetration depths into tissue up to the centimeter range. However, insertion of the probe can be complicated by the need of several alignment and focusing mechanisms along the optical path. Furthermore, resolution values are generally not limited by diffraction, but rather by optical aberrations within the endoscope probe and feeding optics. Here we describe a multiphoton confocal fluorescence imaging system equipped with a compact objective that incorporates a GRIN probe and requires no adjustment mechanisms. We minimized the effects of aberrations with optical compensation provided by a low-order electrostatic membrane mirror (EMM) inserted in the optical path of the confocal architecture, resulting in greatly enhanced image quality.

  15. UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets

    Energy Technology Data Exchange (ETDEWEB)

    Dalgaard, Louise T., E-mail: ltd@ruc.dk [Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (United States); Department of Science, Systems and Models, Roskilde University (Denmark)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer UCP2 mRNA levels are decreased in islets of Langerhans from glucokinase deficient mice. Black-Right-Pointing-Pointer UCP2 mRNA up-regulation by glucose is dependent on glucokinase. Black-Right-Pointing-Pointer Absence of UCP2 increases GSIS of glucokinase heterozygous pancreatic islets. Black-Right-Pointing-Pointer This may protect glucokinase deficient mice from hyperglycemic damages. -- Abstract: Uncoupling Protein 2 (UCP2) is expressed in the pancreatic {beta}-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for UCP2 up-regulation in response to increased glucose is unknown. The aim was to examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression was reduced in GK+/- islets and GK heterozygosity prevented glucose-induced up-regulation of islet UCP2 mRNA. In contrast to UCP2 protein function UCP2 mRNA regulation was not dependent on superoxide generation, but rather on products of glucose metabolism, because MnTBAP, a superoxide dismutase mimetic, did not prevent the glucose-induced up-regulation of UCP2. Glucose-stimulated insulin secretion was increased in UCP2-/- and GK+/- islets compared with GK+/- islets and UCP2 deficiency improved glucose tolerance of GK+/- mice. Accordingly, UCP2 deficiency increased ATP-levels of GK+/- mice. Thus, the compensatory down-regulation of UCP2 is involved in preserving the insulin secretory capacity of GK mutant mice and might also be implicated in limiting disease progression in MODY2 patients.

  16. Studies on chromosome aberrations induced in human lymphocytes by very low-dose exposure to tritium

    International Nuclear Information System (INIS)

    Hori, T.; Moriya, Junko; Nakai, Sayaka

    1978-01-01

    Assessment of potential hazard from environmental tritium to man becomes very important with increasing the development of nuclear-power industry. However, little data are available as to the determination on the genetic effect of tritium especially at the low levels. The object of the present study is to obtain quantitative data for chromosome aberrations in human lymphocytes, as an indicator for genetic risk estimation, induced by tritium at very low dose levels. Leukocyte cultures of human peripheral blood were chronically exposed for 48h to tritiated water and 3 H-thymidine using a wide range of tritium doses, and aberrations in lymphocyte chromosomes at the first metaphases were examined. In the experimental conditions, the types of aberrations induced by radiation emitted from both tritiated water and 3 H-thymidine were mostly chromatid types, such as chromatid gaps and deletions. The dose-response relations for chromatid breaks per cell exhibited unusual dose-dependency in both cases. It was demonstrated that at higher dose range the yields of chromatid breaks increased linearly with dose, while those at lower dose range were significantly higher than would be expected by a downward extraporation from the linear relation. Partial-hit or partial-target kinetics events appeared at very low dose exposure. (author)

  17. Cell inactivation and chromosomal aberrations induced by X-rays and fast neutrons in cells of the Chinese hamster. 1

    International Nuclear Information System (INIS)

    Tolkendorf, E.

    1979-01-01

    Asynchronously grown cultures of Chinese hamster cells V79-4 were irradiated in suspension with 180 kV X-rays and fast neutrons (average energy of 6.2 MeV). The damage was assessed by measuring cell survival and frequencies of chromosome aberrations in the first post-irradiation metaphases. The experimental data for survival and chromosome aberrations were fitted by computer programmes. From the fitted curves the relative biological effectiveness (RBE) of fast neutrons was calculated. The RBE shows a similar dose dependence for killed and aberrant cells. The RBE decreases with increasing dose and amounts to approximately 5 for both effects for small neutron doses. The highest RBE is found for asymmetrical chromosomal exchanges and is dependent on the neutron dose, too. However, for isochromatid deletions the RBE is dose independent with a value of 3.6. (author)

  18. Aberration correction during real time in vivo imaging of bone marrow with sensorless adaptive optics confocal microscope.

    Science.gov (United States)

    Wang, Zhibin; Wei, Dan; Wei, Ling; He, Yi; Shi, Guohua; Wei, Xunbin; Zhang, Yudong

    2014-08-01

    We have demonstrated adaptive correction of specimen-induced aberration during in vivo imaging of mouse bone marrow vasculature with confocal fluorescence microscopy. Adaptive optics system was completed with wavefront sensorless correction scheme based on stochastic parallel gradient descent algorithm. Using image sharpness as the optimization metric, aberration correction was performed based upon Zernike polynomial modes. The experimental results revealed the improved signal and resolution leading to a substantially enhanced image contrast with aberration correction. The image quality of vessels at 38- and 75-μm depth increased three times and two times, respectively. The corrections allowed us to detect clearer bone marrow vasculature structures at greater contrast and improve the signal-to-noise ratio.

  19. Role of base damage in aberration formation: interaction of aphidicolin and x-rays

    International Nuclear Information System (INIS)

    Bender, M.A.; Preston, R.J.

    1981-01-01

    The base analog cytosine arabinoside (CA) is an inhibitor of DNA synthesis that is able to induce chromosomal aberrations not only in the DNA synthetic (S) phase of the cell cycle but in cells in the pre- (G 0 or G 1 ) and in the post-DNA-synthetic (G 2 ) phases of the cell cycle as well. Incubation of human peripheral lymphocytes in CA following either G 0 or G 2 x irradiation causes a synergistic increase in chromosomal aberration frequency. CA is believed to preferentially inhibit DNA polymerase α. It is suggested that it is inhibition of the repair of x-ray-induced base damage that is responsible for the synergistic effect on chromosomal aberration production observed with x-ray and CA treatment of human peripheral lymphocytes. It has also been observed that CA induces sister chromatid exchanges (SCE) in mammalian cells when present during normal DNA replication and that it also interacts synergistically with uv in the induction of SCE. A number of other inhibitors of DNA synthesis were also tested, one, aphidicolin (APC), did produce effects similar to CA at the same concentration. Aphidicolin is a tetracyclic diterpinoid that inhibits the growth of eukaryotic cells by inhibition of DNA synthesis. This action has been shown to result from specific inhibition of DNA polymerase α, but not of polymerases β or γ. Unlike CA, it seems likely that APC inhibits by binding to and inactivating the DNA-α polymerase complex. Because both CA and APC are α polymerase inhibitors and because both interact synergistically with uv in the production of SCE, studies were conducted to determine whether APC also shares other cytogenetic properties of CA. Results to date have shown that, like CA, APC is clastogenic in both G 0 and G 2 , and it also interacts synergistically with x rays to increase chromosomal aberration production in both G 0 and G 2

  20. Revisiting Cross-Channel Information Transfer for Chromatic Aberration Correction

    KAUST Repository

    Sun, Tiancheng

    2017-12-25

    Image aberrations can cause severe degradation in image quality for consumer-level cameras, especially under the current tendency to reduce the complexity of lens designs in order to shrink the overall size of modules. In simplified optical designs, chromatic aberration can be one of the most significant causes for degraded image quality, and it can be quite difficult to remove in post-processing, since it results in strong blurs in at least some of the color channels. In this work, we revisit the pixel-wise similarity between different color channels of the image and accordingly propose a novel algorithm for correcting chromatic aberration based on this cross-channel correlation. In contrast to recent weak prior-based models, ours uses strong pixel-wise fitting and transfer, which lead to significant quality improvements for large chromatic aberrations. Experimental results on both synthetic and real world images captured by different optical systems demonstrate that the chromatic aberration can be significantly reduced using our approach.

  1. Induction of chromosomal aberrations in human primary fibroblasts and immortalized cancer cells exposed to extremely-low-frequency electromagnetic fields

    International Nuclear Information System (INIS)

    Seyyedi, S. S.; Mozdarani, H.; Rezaei Tavirani, M.; Heydari, S.

    2010-01-01

    Rapidly increasing possibilities of exposure to environmental extremely low-frequency electromagnetic fields have become a topic of worldwide investigation. Epidemiological and laboratory studies suggest that exposure to extremely low-frequency electromagnetic fields may increase cancer risk therefore assessment of chromosomal damage in various cell lines might be of predictive value for future risk estimation. Materials and Methods: Primary cultures of fibroblasts from human skin biopsy were exposed to continuous extremely low-frequency electromagnetic fields (3, 50 and 60 Hz, sinusoidal, 3h, and 4 m T). Also immortalized cell lines, SW480, MCF-7 and 1321N1 were exposed to continuous extremely low-frequency electromagnetic fields (50 Hz, sinusoidal, 3 h, 4 m T). Metaphase plates Were prepared according to standard methods and stained in 5% Giemsa solution. Chromosomal aberrations of both chromosome and chromatid types were scored to evaluate the effects of extremely low-frequency electromagnetic fields on primary or established cell lines. Results: Results indicate that by increasing the frequency of extremely low-frequency electromagnetic fields, chromosomal aberrations were increased up to 7-fold above background levels in primary human fibroblast cells. In addition, continuous exposure to a 50 Hz electromagnetic field led to a significant increase in chromosomal aberrations in SW480, MCF-7 and 1321N1 cell lines compared to sham control. Conclusion: Results obtained indicate that extremely low-frequency electromagnetic fields has the potential for induction of chromosomal aberrations in all cell types.

  2. Spherical aberration and other higher-order aberrations in the human eye : from summary wave-front analysis data to optical variables relevant to visual perception

    NARCIS (Netherlands)

    Jansonius, Nomdo M.

    Wave-front analysis data from the human eye are commonly presented using the aberration coefficient c(4)(0) (primary spherical aberration) together with an overall measure of all higher-order aberrations. If groups of subjects are compared, however, the relevance of an observed difference cannot

  3. The aberrant asynchronous replication — characterizing lymphocytes of cancer patients — is erased following stem cell transplantation

    International Nuclear Information System (INIS)

    Nagler, Arnon; Cytron, Samuel; Mashevich, Maya; Korenstein-Ilan, Avital; Avivi, Lydia

    2010-01-01

    Aberrations of allelic replication timing are epigenetic markers observed in peripheral blood cells of cancer patients. The aberrant markers are non-cancer-type-specific and are accompanied by increased levels of sporadic aneuploidy. The study aimed at following the epigenetic markers and aneuploidy levels in cells of patients with haematological malignancies from diagnosis to full remission, as achieved by allogeneic stem cell transplantation (alloSCT). TP53 (a tumor suppressor gene assigned to chromosome 17), AML1 (a gene assigned to chromosome 21 and involved in the leukaemia-abundant 8;21 translocation) and the pericentomeric satellite sequence of chromosome 17 (CEN17) were used for replication timing assessments. Aneuploidy was monitored by enumerating the copy numbers of chromosomes 17 and 21. Replication timing and aneuploidy were detected cytogenetically using fluorescence in situ hybridization (FISH) technology applied to phytohemagglutinin (PHA)-stimulated lymphocytes. We show that aberrant epigenetic markers are detected in patients with hematological malignancies from the time of diagnosis through to when they are scheduled to undergo alloSCT. These aberrations are unaffected by the clinical status of the disease and are displayed both during accelerated stages as well as in remission. Yet, these markers are eradicated completely following stem cell transplantation. In contrast, the increased levels of aneuploidy (irreversible genetic alterations) displayed in blood lymphocytes at various stages of disease are not eliminated following transplantation. However, they do not elevate and remain unchanged (stable state). A demethylating anti-cancer drug, 5-azacytidine, applied in vitro to lymphocytes of patients prior to transplantation mimics the effect of transplantation: the epigenetic aberrations disappear while aneuploidy stays unchanged. The reversible nature of the replication aberrations may serve as potential epigenetic blood markers for evaluating

  4. [Effect of manual acupuncture stimulation of "Baihui" (GV 20) and "Dazhui" (GV 14) on contents of 5-HT, dopamine and ACh and expression of 5-HT mRNA, DA mRNA and AChE mRNA in the hippocampus in methamphetamine addiction rats].

    Science.gov (United States)

    Yu, Shuang; Chen, Ling; Cai, Xing-hui; Song, Xiao-ge; Zhang, Yue; Zhang, Yang; Song, Rui; Li, Yi-fang

    2014-10-01

    To observe the effect of manual acupuncture stimulation on changes of hippocampal monoamine neurotransmitter levels and expression of 5-hydorxytryptamine (5-HT) mRNA, dopamine (DA) mRNA and acetylcholine esterase (AChE) mRNA in methamphetamine addiction rats, so as to explore its mechanism underlying improvement of drug addiction. SD rats were randomly divided into normal control, model and manual acupuncture groups (n=10 in each group). Drug addiction model was established by i.p. of methamphetamine (5 mg/kg), once a day for 15 days. Manual acupuncture stimu- lation was applied to "Baihui" (GV 20) and "Dazhui" (GV 14) once daily for 10 days. The contents of hippocampal 5-HT, DA, acetylcholine (ACh), AChE were measured by ELISA. The expressive Ilieels of hippocampal 5-HT mRNA, DA mRNA and AChE mRNA were determined by fluorescence quantitative RT-POR. In comparison with the normal control group, the con- tents of 5-HT, DA, ACh and AChE and the expression levels of 5-HT mRNA, DA mRNA and AChE mRNA were significantly increased in the model group (PAChE genes.

  5. Regulation of mRNA Translation Is a Novel Mechanism for Phthalate Toxicity.

    Science.gov (United States)

    Ling, Jun; Lopez-Dee, Zenaida P; Cottell, Colby; Wolfe, Laura; Nye, Derek

    2016-01-01

    Phthalates are a group of plasticizers that are widely used in many consumer products and medical devices, thus generating a huge burden to human health. Phthalates have been known to cause a number of developmental and reproductive disorders functioning as endocrine modulators. They are also involved in carcinogenesis with mechanisms less understood. To further understand the molecular mechanisms of phthalate toxicity, in this study we reported a new effect of phthalates on mRNA translation/protein synthesis, a key regulatory step of gene expression. Butyl benzyl phthalate (BBP) was found to directly inhibit mRNA translation in vitro but showed a complicated pattern of affecting mRNA translation in cells. In human kidney embryonic cell (HEK-293T), BBP increased cap-dependent mRNA translation at lower concentrations but showed inhibitory effect at higher concentrations. Cap-independent translation was not affected. On the other hand, mono (2-ethylhexyl) phthalate (MEHP) as a major metabolite of another important phthalate di (2-ethylhexyl) phthalate (DEHP) inhibited both can-dependent and -independent mRNA translation in vivo. In contrast, BBP and MEHP exhibited an overall promoting effect on mRNA translation in cancer cells. Mechanistic studies identified that the level and phosphorylation of eIF4E-BP (eIF4E binding protein) and the amount of eIF4GI in eIF4F complex were altered in accordance with the effect of BBP on translation. BBP was also identified to directly bind to eIF4E, providing a further mechanism underlying the regulation of mRNA by phthalate. At the cellular level BBP inhibited normal cell growth but slightly promoted cancer cells (HT29) growth. Overall, this study provides the first evidence that phthalates can directly regulate mRNA translation as a novel mechanism to mediate their biological toxicities.

  6. Regulation of mRNA Translation Is a Novel Mechanism for Phthalate Toxicity.

    Directory of Open Access Journals (Sweden)

    Jun Ling

    Full Text Available Phthalates are a group of plasticizers that are widely used in many consumer products and medical devices, thus generating a huge burden to human health. Phthalates have been known to cause a number of developmental and reproductive disorders functioning as endocrine modulators. They are also involved in carcinogenesis with mechanisms less understood. To further understand the molecular mechanisms of phthalate toxicity, in this study we reported a new effect of phthalates on mRNA translation/protein synthesis, a key regulatory step of gene expression. Butyl benzyl phthalate (BBP was found to directly inhibit mRNA translation in vitro but showed a complicated pattern of affecting mRNA translation in cells. In human kidney embryonic cell (HEK-293T, BBP increased cap-dependent mRNA translation at lower concentrations but showed inhibitory effect at higher concentrations. Cap-independent translation was not affected. On the other hand, mono (2-ethylhexyl phthalate (MEHP as a major metabolite of another important phthalate di (2-ethylhexyl phthalate (DEHP inhibited both can-dependent and -independent mRNA translation in vivo. In contrast, BBP and MEHP exhibited an overall promoting effect on mRNA translation in cancer cells. Mechanistic studies identified that the level and phosphorylation of eIF4E-BP (eIF4E binding protein and the amount of eIF4GI in eIF4F complex were altered in accordance with the effect of BBP on translation. BBP was also identified to directly bind to eIF4E, providing a further mechanism underlying the regulation of mRNA by phthalate. At the cellular level BBP inhibited normal cell growth but slightly promoted cancer cells (HT29 growth. Overall, this study provides the first evidence that phthalates can directly regulate mRNA translation as a novel mechanism to mediate their biological toxicities.

  7. Perinuclear Mlp proteins downregulate gene expression in response to a defect in mRNA export.

    Science.gov (United States)

    Vinciguerra, Patrizia; Iglesias, Nahid; Camblong, Jurgi; Zenklusen, Daniel; Stutz, Françoise

    2005-02-23

    The mRNA export adaptor Yra1p/REF contributes to nascent mRNP assembly and recruitment of the export receptor Mex67p. yra1 mutants exhibit mRNA export defects and a decrease in LacZ reporter and certain endogenous transcripts. The loss of Mlp1p/Mlp2p, two TPR-like proteins attached to nuclear pores, rescues LacZ mRNA levels and increases their appearance in the cytoplasm, without restoring bulk poly(A)+ RNA export. Chromatin immunoprecipitation, FISH and pulse-chase experiments indicate that Mlps downregulate LacZ mRNA synthesis in a yra1 mutant strain. Microarray analyses reveal that Mlp2p also reduces a subset of cellular transcripts in the yra1 mutant. Finally, we show that Yra1p genetically interacts with the shuttling mRNA-binding protein Nab2p and that loss of Mlps rescues the growth defect of yra1 and nab2 but not other mRNA export mutants. We propose that Nab2p and Yra1p are required for proper mRNP docking to the Mlp platform. Defects in Yra1p prevent mRNPs from crossing the Mlp gate and this block negatively feeds back on the transcription of a subset of genes, suggesting that Mlps link mRNA transcription and export.

  8. An influence of occupational exposure on level of chromosome aberrations in nuclear power plant workers

    International Nuclear Information System (INIS)

    Birute Griciene; Grazina Slapsyte

    2007-01-01

    analyzed for chromosome aberrations. Results. Chromosome aberration analyses revealed significant increase in the total chromosome aberration frequency for the radiation workers with internal exposure (2.42±0.40 CA/100 cells, P=0.01) and for those with additional neutron exposure (2.63±0.40 CA/100 cells, P=0.01). However, no significant differences between the workers with external gamma radiation exposure and the controls (1.62±0.25 vs. 1.65±0.15 CA/100 cells, P=0.83) was observed. There was no correlation between the chromosome aberration frequency and the cumulative dose, mean annual doses averaged over the last 3-years or the last year before the blood sampling. The confounding effects of internal and neutron exposure on the frequency of chromosome aberrations was determined. The impact of other factors (smoking habits, age, duration of employment, cumulative dose) was found to be not significant. Conclusion. Though no increase in chromosome aberration frequency was determined in workers exposed to external gamma radiation only, the demonstration of the elevated levels of chromosome aberrations in the workers with incorporated radionuclides and neutron exposure indicates their more hazardous work activities with consequential risk to health.

  9. Circumflex coronary artery with aberrant origin and atherosclerosis

    International Nuclear Information System (INIS)

    Ozcan, E.; Bozlar, U.; Celik, T.; Tasar, M.

    2012-01-01

    Full text: Introduction: Circumflex (Cx) coronary artery congenital anomaly is reported to be less than 1% incidence. Coronary arteries with aberrant origin are more likely to have atherosclerosis according to some published literatures. Objectives and tasks: In this study we aim to present computed tomography (CT) angiography findings of a patient, who has Cx artery with aberrant origin and atherosclerotic. Materials and methods: 57-year-old woman without any symptoms who has risk factors to atherosclerosis was referred to our clinic for coronary CT angiography. Results: In CT angiography; we detected Cx coronary artery with aberrant origin (right sinus of valsalva) and retroaortic course. Also we saw intimal irregularities and calcified plaque causing severe narrowing in the proximal segment of artery. Right coronary and left anterior descendant arteries had mild atherosclerosis. Conclusion: Coroner CT angiography, which allows multiplanar imaging with high resolution, is an effective diagnostic tool for coronary artery disease, like not only congenital anomalies but also acquired atherosclerotic disease

  10. Correcting the Chromatic Aberration in Barrel Distortion of Endoscopic Images

    Directory of Open Access Journals (Sweden)

    Y. M. Harry Ng

    2003-04-01

    Full Text Available Modern endoscopes offer physicians a wide-angle field of view (FOV for minimally invasive therapies. However, the high level of barrel distortion may prevent accurate perception of image. Fortunately, this kind of distortion may be corrected by digital image processing. In this paper we investigate the chromatic aberrations in the barrel distortion of endoscopic images. In the past, chromatic aberration in endoscopes is corrected by achromatic lenses or active lens control. In contrast, we take a computational approach by modifying the concept of image warping and the existing barrel distortion correction algorithm to tackle the chromatic aberration problem. In addition, an error function for the determination of the level of centroid coincidence is proposed. Simulation and experimental results confirm the effectiveness of our method.

  11. Biological dosimetry: chromosomal aberration analysis for dose assessment

    International Nuclear Information System (INIS)

    1986-01-01

    In view of the growing importance of chromosomal aberration analysis as a biological dosimeter, the present report provides a concise summary of the scientific background of the subject and a comprehensive source of information at the technical level. After a review of the basic principles of radiation dosimetry and radiation biology basic information on the biology of lymphocytes, the structure of chromosomes and the classification of chromosomal aberrations are presented. This is followed by a presentation of techniques for collecting blood, storing, transporting, culturing, making chromosomal preparations and scaring of aberrations. The physical and statistical parameters involved in dose assessment are discussed and examples of actual dose assessments taken from the scientific literature are given

  12. Screening for aberrant behavior in the nuclear industry

    International Nuclear Information System (INIS)

    Borofsky, G.L.

    1987-01-01

    This paper attempts to promote a fuller understanding of how psychological assessment procedures can be used to reduce the threat from aberrant behavior in the nuclear industry. It begins with a discussion of the scientifically based methods that are used by psychologists in constructing, scoring, and interpreting these procedures. This discussion includes an emphasis on the concepts of validity and reliability and their central importance when one is choosing specific psychological screening tools. Criteria for selecting and using psychological assessment procedures when screening for aberrant behavior are also provided. Some commonly used assessment procedures that satisfy these criteria are discussed. A number a psychological assessment procedures specifically recommended for use in screening for aberrant behavior in the nuclear industry are described

  13. Menopause versus aging: The predictor of obesity and metabolic aberrations among menopausal women of Karnataka, South India

    Directory of Open Access Journals (Sweden)

    Shruti Dasgupta

    2012-01-01

    Conclusions: Menopausal transition brings about anomalies in total body composition characterized by an increased body fat mass and central adiposity. This creates a compatible atmosphere for abnormal metabolism and aggravated cardio metabolic risk factors. Thus, menopausal status and associated obesity is the major predictor of metabolic aberrations over age in menopausal women.

  14. Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health

    DEFF Research Database (Denmark)

    Bonassi, S; Hagmar, L; Strömberg, U

    2000-01-01

    An increased risk of cancer in healthy individuals with high levels of chromosomal aberrations (CAs) in peripheral blood lymphocytes has been described in recent epidemiological studies. This association did not appear to be modified by sex, age, country, or time since CA test, whereas the role p...

  15. Reducing starbursts in highly aberrated eyes with pupil miosis.

    Science.gov (United States)

    Xu, Renfeng; Kollbaum, Pete; Thibos, Larry; Lopez-Gil, Norberto; Bradley, Arthur

    2018-01-01

    To test the hypothesis that marginal ray deviations determine perceived starburst sizes, and to explore different strategies for decreasing starburst size in highly aberrated eyes. Perceived size of starburst images and visual acuities were measured psychophysically for eyes with varying levels of spherical aberration, pupil sizes, and defocus. Computationally, we use a polychromatic eye model including the typical levels of higher order aberrations (HOAs) for keratoconic and post-LASIK eyes to quantify the image quality (the visually weighted Strehl ratio derived from the optical transfer function, VSOTF) with different pupil sizes at both photopic and mesopic light levels. For distance corrected post-LASIK and keratoconic eyes with a night-time pupil (e.g., 7 mm), the starburst diameter is about 1.5 degrees (1 degree for normal presbyopic eyes), which can be reduced to ≤0.25 degrees with pupil sizes ≤3 mm. Starburst size is predicted from the magnitude of the longitudinal spherical aberration. Refracting the eye to focus the pupil margin also removed starbursts, but, unlike small pupils, significantly degraded visual acuity. Reducing pupil diameter to 3 mm improved image quality for these highly aberrated eyes by about 2.7 ×  to 1.7 ×  relative to the natural pupils when light levels were varied from 0.1 to 1000 cd m -2 , respectively. Subjects with highly aberrated eyes observed larger starbursts around bright lights at night predictable by the deviated marginal rays. These were effectively attenuated by reducing pupil diameters to ≤3 mm, which did not cause a drop in visual acuity or modelled image quality even at mesopic light levels. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

  16. [Genetic Aberration and Pathological Diagnosis in Bone and Soft-Tissue Tumors].

    Science.gov (United States)

    Iura, Kunio; Oda, Yoshinao

    2016-03-01

    Bone and soft-tissue sarcomas comprise a rare, complex, and heterogeneous group of tumors for which it is difficult for even experienced pathologists to provide a conclusive diagnosis. The number of diagnoses made using genetic analysis has increased since the detection of fusion genes in several soft-tissue tumors in the 1990s. Moreover, other specific genetic aberrations have been reported in various bone and soft-tissue tumors. In addition, molecular therapeutic targets have been sought in advanced cases of soft-tissue and bone tumors similar to other organ malignancies. To enable the pathological diagnosis of bone and soft-tissue tumors, it is necessary to combine histological diagnosis with immunohistochemistry and gene analysis findings including fusion gene or other genetic aberrations. In this review, we describe the fusion genes recently reported in bone and soft-tissue tumors such as solitary fibrous tumor, aneurysmal bone cyst, nodular fasciitis, CIC-DUX4 fusion gene-positive small round cell tumors, or BCOR-CCNB3-positive sarcoma as well as other genetic aberrations in dedifferentiated liposarcoma, malignant rhabdoid tumor, cartilaginous tumor, Langerhans cell histiocytosis chondroblastoma, or giant cell tumor of the bone. We also demonstrate their association with pathological diagnosis.

  17. Antioxidant action of bixin against cisplatin-induced chromosome aberrations and lipid peroxidation in rats.

    Science.gov (United States)

    Silva, C R; Antunes, L M; Bianchi, M L

    2001-06-01

    Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but has serious side effects, inducing nephrotoxicity and chromosome aberrations. In this study we evaluated the role of the carotenoid bixin on cisplatin-induced oxidative stress in Wistar rats through three markers of oxidative damage: chromosome aberrations, glutathione depletion and lipid peroxidation. The animals were divided into six treatment groups with six rats in each (n= 6). The dose of cisplatin (5.0 mg kg(-1)body wt.) was injected i.p. and bixin (2.5 or 5.0 mg kg(-1)body wt.) was given by gavage at 48, 24 h and 10 min before the cisplatin injection. The treatment with the highest dose of bixin resulted in a statistically significant reduction, by about 33%, in cisplatin-induced abnormal metaphases (P< 0.05). A single dose of cisplatin enhanced the formation of lipid peroxides in 29% and resulted in a 29% depletion in renal glutathione 24 h after cisplatin administration (P< 0.05). The pretreatment with bixin reduced the total number of chromosome aberrations, inhibited the increase in lipid peroxidation, and inhibited renal glutathione depletion induced by cisplatin. Since the pretreatment with bixin alone was safe, under the present experimental conditions, the results suggest that bixin may have future clinical application after further studies. Copyright 2001 Academic Press.

  18. Induction of aberrations in human lymphocytes by γ-rays and fast heavy ions

    International Nuclear Information System (INIS)

    Govorun, R.D.; Repin, M.V.; Krasavin, E.A.; Lukasova, E.; Kozubek, S.; Kroha, V.

    1998-01-01

    Frequencies of aberrations induced by different doses of γ-rays and 14 N ions (LET ∼ 77 keV/μm) in the chromosomes 1 and 2 of human lymphocytes as detected by FISH were compared with those detected by conventional staining in the whole genome. The results have shown that the induction of aberrations in the chromosomes 1 and 2 is more frequent than that in the rest of genome. The frequencies of dicentrics detected by FISH in the chromosomes 1 and 2 recalculated for the whole genome are in good agreement with those detected by conventional staining at different doses of 14 N, but they are about 2 times lower at low doses of γ-rays. Translocation frequencies calculated in the same manner from the frequencies induced in the chromosome 1 by γ-rays correspond to the frequencies of dicentrics detected by conventional staining, however, they are about 2 times higher than those detected by convectional staining at doses lower than 2 Gy of 14 N. The differences between the frequencies of these aberration types increase at higher doses of both radiation types

  19. Multiphoton imaging microscopy at deeper layers with adaptive optics control of spherical aberration.

    Science.gov (United States)

    Bueno, Juan M; Skorsetz, Martin; Palacios, Raquel; Gualda, Emilio J; Artal, Pablo

    2014-01-01

    Despite the inherent confocality and optical sectioning capabilities of multiphoton microscopy, three-dimensional (3-D) imaging of thick samples is limited by the specimen-induced aberrations. The combination of immersion objectives and sensorless adaptive optics (AO) techniques has been suggested to overcome this difficulty. However, a complex plane-by-plane correction of aberrations is required, and its performance depends on a set of image-based merit functions. We propose here an alternative approach to increase penetration depth in 3-D multiphoton microscopy imaging. It is based on the manipulation of the spherical aberration (SA) of the incident beam with an AO device while performing fast tomographic multiphoton imaging. When inducing SA, the image quality at best focus is reduced; however, better quality images are obtained from deeper planes within the sample. This is a compromise that enables registration of improved 3-D multiphoton images using nonimmersion objectives. Examples on ocular tissues and nonbiological samples providing different types of nonlinear signal are presented. The implementation of this technique in a future clinical instrument might provide a better visualization of corneal structures in living eyes.

  20. Cancer Grafted in Aberrant Breast Tissue Cáncer injertado en tejido mamario aberrante

    Directory of Open Access Journals (Sweden)

    Lidia Torres Ajá

    2012-03-01

    Full Text Available Among the anomalies during embryonic development of the breasts we may find supernumerary breasts and aberrant ectopic tissue. In both of them, malignant tumors of the breast can proliferate, mostly in aberrant tissue. We present the case of a female patient aged 73, who refers to have always had a "little mammary gland in the left submammary that never caused discomfort to the last two months when its volume increased and the skin retracted". Excisional biopsy allowed diagnosing an infiltrating ductal carcinoma, the first case of carcinoma grafted in aberrant breast tissue diagnosed in the province.

    Entre las anomalías del desarrollo embrionario de las mamas se encuentran las mamas supernumerarias y el tejido ectópico aberrante. Ambas pueden ser asiento de tumores malignos de la mama, en mayor número  el tejido aberrante. Se presenta el caso de una paciente femenina de 73 años, que refiere tiene desde siempre una “mamita pequeña en el surco submamario izquierdo la cual nunca le ocasiono molestias hasta hace 2 meses en que aumentó de volumen y se le retrajo la piel". Mediante biopsia escisional se le diagnostica un carcinoma ductal infiltrante, siendo así  el primer caso de carcinoma injertado en tejido mamario aberrante diagnosticado en nuestra provincia.

  1. Induction of chromosome aberrations and mitotic arrest by cytomegalovirus in human cells

    International Nuclear Information System (INIS)

    AbuBakar, S.; Au, W.W.; Legator, M.S.; Albrecht, T.

    1988-01-01

    Human cytomegalovirus (CMV) is potentially an effective but often overlooked genotoxic agent in humans. We report here evidence that indicates that infection by CMV can induce chromosome alterations and mitotic inhibition. The frequency of chromosome aberrations induced was dependent on the input multiplicity of infection (m.o.i.) for human lung fibroblasts (LU), but not for human peripheral blood lymphocytes (PBLs) when both cell types were infected at the GO phase of the cell cycle. The aberrations induced by CMV were mostly chromatid breaks and chromosome pulverizations that resembled prematurely condensed S-phase chromatin. Pulverized chromosomes were not observed in LU cells infected with virus stocks that had been rendered nonlytic by UV-irradiation at 24,000 ergs/mm2 or from infection of human lymphocytes. In LU cells infected with UV-irradiated CMV, the frequency of aberrations induced was inversely dependent on the extent of the exposure of the CMV stock to the UV-light. In permissive CMV infection of proliferating LU cells at 24 hr after subculture, a high percentage (greater than 40%) of the metaphase cells were arrested at their first metaphase and displayed severely condensed chromosomes when harvested 48 hr later. A significant increase (p less than 0.05) in the chromosome aberration frequency was also observed. Our study shows that CMV infection is genotoxic to host cells. The types and extent of damage are dependent on the viral genome expression and on the cell cycle stage of the cells at the time of infection. The possible mechanisms for induction of chromosome damage by CMV are discussed

  2. Generalized Doppler and aberration kernel for frequency-dependent cosmological observables

    Science.gov (United States)

    Yasini, Siavash; Pierpaoli, Elena

    2017-11-01

    We introduce a frequency-dependent Doppler and aberration transformation kernel for the harmonic multipoles of a general cosmological observable with spin weight s , Doppler weight d and arbitrary frequency spectrum. In the context of cosmic microwave background (CMB) studies, the frequency-dependent formalism allows to correct for the motion-induced aberration and Doppler effects on individual frequency maps with different masks. It also permits to deboost background radiations with non-blackbody frequency spectra, like extragalactic foregrounds and CMB spectra with primordial spectral distortions. The formalism can also be used to correct individual E and B polarization modes and account for motion-induced E/B mixing of polarized observables with d ≠1 at different frequencies. We apply the generalized aberration kernel on polarized and unpolarized specific intensity at 100 and 217 GHz and show that the motion-induced effects typically increase with the frequency of observation. In all-sky CMB experiments, the frequency-dependence of the motion-induced effects for a blackbody spectrum are overall negligible. However in a cut-sky analysis, ignoring the frequency dependence can lead to percent level error in the polarized and unpolarized power spectra over all angular scales. In the specific cut-sky used in our analysis (b >4 5 ° ,fsky≃14 % ), and for the dipole-inferred velocity β =0.00123 typically attributed to our peculiar motion, the Doppler and aberration effects can change polarized and unpolarized power spectra of specific intensity in the CMB rest frame by 1 - 2 % , but we find the polarization cross-leakage between E and B modes to be negligible.

  3. Potential Osteoinductive Effects of Calcitriol on the m-RNA of Mesenchymal Stem Cells Derived from Human Alveolar Periosteum

    Directory of Open Access Journals (Sweden)

    Hsiang-Hsi Hong

    2016-01-01

    Full Text Available This study characterized alveolar periosteum-derived mesenchymal stem cells (P-MSCs and examined the hypothesis that 1,25-(OH2D3 (calcitriol exerts osteoinductive effects on P-MSCs. The mRNA expressions of alkaline phosphatase (ALP, bone sialoprotein (BSP, core-binding factor alpha-1 (CBFA1, collagen-1 (Col-1, osteocalcin (OCN, and vitamin D3 receptor (VDR were assessed after incubation with calcitriol for 2 weeks. Vitamin C as positive control (Vit. C-p increased ALP and CBFA1 mRNA expression at both 1 and 2 weeks and increased BSP and Col-1 mRNA expression only at the first week. A concentration of 10−8 M calcitriol enhanced ALP, CBFA1, Col-1, and OCN mRNA expression at both weeks and BSP mRNA expression at the first week. Furthermore, 10−7 M calcitriol increased the mRNA expressions of all compounds at both weeks, except that of CBFA1 at the first week. 10−8 M calcitriol and Vit. C-p enhanced ALP activity at the second and third weeks. The results revealed that 10−9, 10−8, and 10−7 M calcitriol induced osteoinduction in alveolar P-MSCs by increasing ALP, CBFA1, Col-1, and OCN mRNA expression. A 10−7 M calcitriol yielded a higher mRNA expression than Vit. Cp on VDR and OCN mRNA expression at both weeks and on Col-1 mRNA at the second week.

  4. Outline of an aberration correct optical channel without space charge

    International Nuclear Information System (INIS)

    Bruck, H.

    1978-01-01

    A beam transport line is described which guides a particle bunch from a storage ring to the target, located at the center of the ring, for heavy ion fusion. The device was conceived to prevent spectral analysis and coma aberration, owing to the deflecting sector, and also chromatic and spherical aberrations. Space charge is not considered here. The device includes the following elements: (1) extraction from the storage ring, (2) adaptation to (3) the deflecting magnet sector, (4) collimator lens, and (5) 10m drift space to the target plane

  5. Measurement of eye aberrations in a speckle field

    International Nuclear Information System (INIS)

    Larichev, A V; Ivanov, P V; Iroshnikov, N G; Shmalgauzen, V I

    2001-01-01

    The influence of speckles on the performance of a Shark-Hartmann wavefront sensor is investigated in the eye aberration studies. The dependence of the phase distortion measurement error on the characteristic speckle size is determined experimentally. Scanning of the reference source was used to suppress the speckle structure of the laser beam scattered by the retina. The technique developed by us made it possible to study the time dependence of the human eye aberrations with a resolution of 30 ms. (laser applications and other topics in quantum electronics)

  6. Investigation of spherical aberration effects on coherent lidar performance

    DEFF Research Database (Denmark)

    Hu, Qi; Rodrigo, Peter John; Iversen, Theis Faber Quist

    2013-01-01

    In this paper we demonstrate experimentally the performance of a monostatic coherent lidar system under the influence of phase aberrations, especially the typically predominant spherical aberration (SA). The performance is evaluated by probing the spatial weighting function of the lidar system...... with different telescope configurations using a hard target. It is experimentally and numerically proven that the SA has a significant impact on lidar antenna efficiency and optimal beam truncation ratio. Furthermore, we demonstrate that both effective probing range and spatial resolution of the system...

  7. [Prenatal diagnostics of chromosomal aberrations Czech Republic: 1994-2007].

    Science.gov (United States)

    Gregor, V; Sípek, A; Sípek, A; Horácek, J '; Langhammer, P; Petrzílková, L; Calda, P

    2009-02-01

    An analysis of prenatal diagnostics efficiency of selected types of chromosomal aberrations in the Czech Republic in 2007. Update of 1994-2007 data according to particular selected diagnoses. Retrospective epidemiological analysis of pre- and postnatal chromosomal aberrations diagnostics and its efficiency. Data on pre- and postnatally diagnosed birth defects in the Czech Republic during 1994-2007 were used. Data on prenatally diagnosed birth defects (and for terminated pregnancies) were collected from particular departments of prenatal diagnostics, medical genetics and ultrasound diagnostics in the Czech Republic, data on birth defects in births from the National Birth Defects Register (Institute for Health Information and Statistics). Total numbers over the period under the study, mean incidences of selected types of chromosomal aberrations and mean prenatal diagnostics efficiencies were analyzed. Following chromosomal aberrations were studied: Down, Edwards, Patau, Turner and Klinefelter syndromes and syndromes 47,XXX and 47,XYY. A relative proportion of Down, Edwards and Patau syndromes as well as other autosomal and gonosomal aberration is presented in figures. Recently, trisomies 13, 18 and 21 present around 70% of all chromosomal aberrations in selectively aborted fetuses, in other pregnancies, "other chromosomal aberrations" category (mostly balanced reciprocal translocations and inversions) present more than 2/3 of all diagnoses. During the period under the study, following total numbers, mean relative incidences (per 10,000 live births, in brackets) and mean prenatal diagnostics efficiency (in %) were found in following chromosomal syndromes: Down syndrome 2,244 (16.58) and 63.37%, Edwards syndrome 521 (3.85) and 79.93%, Patau syndrome 201 (1.49) and 68.87%, Turner syndrome 380 (2.81) and 79.89%, 47,XXX syndrome 61 (0.45) and 59.74%, Klinefelter syndrome 163 (1.20) and 73.65% and 47,XYY syndrome 22 (0.16) and 54.76%. The study gives updated results of

  8. The decapping activator Edc3 and the Q/N-rich domain of Lsm4 function together to enhance mRNA stability and alter mRNA decay pathway dependence in Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Susanne Huch

    2016-10-01

    Full Text Available The rate and regulation of mRNA decay are major elements in the proper control of gene expression. Edc3 and Lsm4 are two decapping activator proteins that have previously been shown to function in the assembly of RNA granules termed P bodies. Here, we show that deletion of edc3, when combined with a removal of the glutamine/asparagine rich region of Lsm4 (edc3Δ lsm4ΔC reduces mRNA stability and alters pathways of mRNA degradation. Multiple tested mRNAs exhibited reduced stability in the edc3Δ lsm4ΔC mutant. The destabilization was linked to an increased dependence on Ccr4-mediated deadenylation and mRNA decapping. Unlike characterized mutations in decapping factors that either are neutral or are able to stabilize mRNA, the combined edc3Δ lsm4ΔC mutant reduced mRNA stability. We characterized the growth and activity of the major mRNA decay systems and translation in double mutant and wild-type yeast. In the edc3Δ lsm4ΔC mutant, we observed alterations in the levels of specific mRNA decay factors as well as nuclear accumulation of the catalytic subunit of the decapping enzyme Dcp2. Hence, we suggest that the effects on mRNA stability in the edc3Δ lsm4ΔC mutant may originate from mRNA decay protein abundance or changes in mRNPs, or alternatively may imply a role for P bodies in mRNA stabilization.

  9. The Ccr4-Pop2-NOT mRNA Deadenylase Contributes to Septin Organization in Saccharomyces cerevisiae

    Science.gov (United States)

    Traven, Ana; Beilharz, Traude H.; Lo, Tricia L.; Lueder, Franziska; Preiss, Thomas; Heierhorst, Jörg

    2009-01-01

    In yeast, assembly of the septins at the cell cortex is required for a series of key cell cycle events: bud-site selection, the morphogenesis and mitotic exit checkpoints, and cytokinesis. Here we establish that the Ccr4-Pop2-NOT mRNA deadenylase contributes to septin organization. mRNAs encoding regulators of septin assembly (Ccd42, Cdc24, Rga1, Rga2, Bem3, Gin4, Cla4, and Elm1) presented with short poly(A) tails at steady state in wild-type (wt) cells, suggesting their translation could be restricted by deadenylation. Deadenylation of septin regulators was dependent on the major cellular mRNA deadenylase Ccr4-Pop2-NOT, whereas the alternative deadenylase Pan2 played a minor role. Consistent with deadenylation of septin regulators being important for function, deletion of deadenylase subunits CCR4 or POP2, but not PAN2, resulted in septin morphology defects (e.g., ectopic bud-localized septin rings), particularly upon activation of the Cdc28-inhibitory kinase Swe1. Aberrant septin staining was also observed in the deadenylase-dead ccr4-1 mutant, demonstrating the deadenylase activity of Ccr4-Pop2 is required. Moreover, ccr4Δ, pop2Δ, and ccr4-1 mutants showed aberrant cell morphology previously observed in septin assembly mutants and exhibited genetic interactions with mutations that compromise septin assembly (shs1Δ, cla4Δ, elm1Δ, and gin4Δ). Mutations in the Not subunits of Ccr4-Pop2-NOT, which are thought to predominantly function in transcriptional control, also resulted in septin organization defects. Therefore, both mRNA deadenylase and transcriptional functions of Ccr4-Pop2-NOT contribute to septin organization in yeast. PMID:19487562

  10. Effect of taurine on mRNA expression of thioredoxin interacting protein in Caco-2 cells.

    Science.gov (United States)

    Gondo, Yusuke; Satsu, Hideo; Ishimoto, Yoko; Iwamoto, Taku; Shimizu, Makoto

    2012-09-28

    Taurine (2-aminoethanesulfonic acid), a sulfur-containing β-amino acid, plays an important role in several essential biological processes; although, the underlying mechanisms for these regulatory functions remain to be elucidated, especially at the genetic level. We investigated the effects of taurine on the gene expression profile in Caco-2 cells using DNA microarray. Taurine increased the mRNA expression of thioredoxin interacting protein (TXNIP), which is involved in various metabolisms and diseases. β-Alanine or γ-aminobutyric acid (GABA), which are structurally or functionally related to taurine, did not increase TXNIP mRNA expression. These suggest the expression of TXNIP mRNA is induced specifically by taurine. β-Alanine is also known to be a substrate of taurine transporter (TAUT) and competitively inhibits taurine uptake. Inhibition of taurine uptake by β-alanine eliminated the up-regulation of TXNIP, which suggests TAUT is involved in inducing TXNIP mRNA expression. The up-regulation of TXNIP mRNA expression by taurine was also observed at the protein level. Furthermore, taurine significantly increased TXNIP promoter activity. Our present study demonstrated the taurine-specific phenomenon of TXNIP up-regulation, which sheds light on the physiological function of taurine. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Novel plumage aberrations in Paraguayan non-Passerine Birds, and the definition of a new plumage aberration unique to Psittacidae

    Directory of Open Access Journals (Sweden)

    Paul Smith

    2017-07-01

    Full Text Available Anomalous plumage colourations are reported for three species of non-passerine birds from Paraguay, Limpkin (Aramaus guarauna; Aramidae, Nanday Parakeet (Nandayus nenday; Psittacidae, and the Little Woodpecker (Veniliornis passerinus; Picidae. A leucistic Limpkin is the first published report of a colour anomaly for the family Aramidae. The colour aberration in N. nenday is hypothesised to be a result of an excess of red psittacofulvin pigments, which are unique to the Psittacidae. Although the mechanisms causing this colour aberration remain unknown, we suggest the term psittacofulvism for the phenotypic effect observed.

  12. Differential algebraic method for arbitrary order curvilinear-axis combined geometric-chromatic aberration analysis

    CERN Document Server

    Cheng Min; Lu Yi Long; Yao Zhen Hua

    2003-01-01

    The principle of differential algebra is applied to analyse and calculate arbitrary order curvilinear-axis combined geometric-chromatic aberrations of electron optical systems. Expressions of differential algebraic form of high order combined aberrations are obtained and arbitrary order combined aberrations can be calculated numerically. As an example, a typical wide electron beam focusing system with curved optical axes named magnetic immersion lens has been studied. All the second-order and third-order combined geometric-chromatic aberrations of the lens have been calculated, and the patterns of the corresponding geometric aberrations and combined aberrations have been given as well.

  13. Aberration of a negative ion beam caused by space charge effect.

    Science.gov (United States)

    Miyamoto, K; Wada, S; Hatayama, A

    2010-02-01

    Aberrations are inevitable when the charged particle beams are extracted, accelerated, transmitted, and focused with electrostatic and magnetic fields. In this study, we investigate the aberration of a negative ion accelerator for a neutral beam injector theoretically, especially the spherical aberration caused by the negative ion beam expansion due to the space charge effect. The negative ion current density profiles with the spherical aberration are compared with those without the spherical aberration. It is found that the negative ion current density profiles in a log scale are tailed due to the spherical aberration.

  14. Regulation of growth hormone (GH) receptor (GHR1 and GHR2) mRNA level by GH and metabolic hormones in primary cultured tilapia hepatocytes.

    Science.gov (United States)

    Pierce, A L; Breves, J P; Moriyama, S; Uchida, K; Grau, E G

    2012-10-01

    Growth hormone (GH) regulates essential physiological functions in teleost fishes, including growth, metabolism, and osmoregulation. Recent studies have identified two clades of putative receptors for GH (GHR1 clade and GHR2 clade) in fishes, both of which are highly expressed in the liver. Moreover, the liver is an important target for the anabolic effects of GH via endocrine IGFs, and liver sensitivity to GH is modulated by metabolic hormones. We investigated the effects of GH, insulin, glucagon, cortisol and triiodothyronine on GHR1 and GHR2 mRNA levels in primary cultured tilapia hepatocytes. Physiological concentrations of GH strongly stimulated GHR2 mRNA level (0.5-50×10(-9) M), but did not affect GHR1 mRNA level. Insulin suppressed stimulation of GHR2 mRNA level by GH (10(-8)-10(-6) M). Insulin increased basal GHR1 mRNA level (10(-8)-10(-6) M). Cortisol increased basal GHR2 mRNA level (10(-7)-10(-6) M), but did not consistently affect GH-stimulated GHR2 mRNA level. Cortisol increased basal GHR1 mRNA level (10(-9)-10(-6) M). Glucagon suppressed GH-stimulated GHR2 mRNA level and increased basal GHR1 mRNA level at a supraphysiological concentration (10(-6) M). A single injection of GH (5 μg/g) increased liver GHR2 mRNA level, and insulin injection (5 μg/g) decreased both basal and GH-stimulated GHR2 mRNA levels after 6 h. In contrast, insulin and GH injection had little effect on liver GHR1 mRNA level. This study shows that GHR1 and GHR2 gene expression are differentially regulated by physiological levels of GH and insulin in tilapia primary hepatocytes. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Comparative study of visual function and ocular aberrations of two different one-piece designed hydrophilic acrylic intraocular lens.

    Science.gov (United States)

    Zhao, Yuxin; Wang, Zhaoxia; Tian, Xia; Wang, Xuehong; Gao, Xining

    2017-05-30

    To determine whether the aspherical IOL, Tecnis ZCB00, can improve the visual quality by measuring visual acuity, wavefront aberrations, and contrast sensitivity. It was a retrospective case series. Patients who underwent phacoemulsification cataract surgery were divided into two groups. One group (Group TC) was implanted with one-piece aspherical acrylic IOL (Tecnis ZCB00, AMO); the other (Group SA) was implanted with one-piece spherical acrylic IOL (Sensar AAB00, AMO). Eighty-eight eyes were selected into this study, among them 43 eyes in 26 male cases and 45 eyes in 29 female cases. Thirty-six eyes in 23 cases were in Group TC, and 52 eyes in 32 cases were in Group SA. Three months postoperatively, aberrations were analyzed with i-Trace visual function analyzer (Tracy Technologies, USA). Contrast sensitivities were measured with Takaci-CGT-1000 contrast glare tester (Seiko, Japan). All the 88 eyes underwent phacoemulsification with intraocular lens implantation, without complications during or after surgery. Three months postoperatively, the uncorrected vision acuity in Group TC was significantly better than in Group SA (P = 0.007). At the pupil size of 5.0 mm, higher-order aberrations in Group TC were significantly higher than in Group SA (P = 0.02), especially the spherical aberration (Z 4 0 ) (P < 0.001); at the pupil size of 4.0 mm, Z 4 0 in Group SA was statistically higher than in Group TC (P < 0.001); at the pupil size of 3.0 mm, higher-order aberrations such as coma (Z 3 -1,1 ) and trefoil aberration (Z 3 -3,3 ) in Group SA were obviously higher than in Group TC (P = 0.01). In the low spatial frequency, the contrast sensitivity and the glare sensitivity in Group TC were significantly higher than in Group SA (P < 0.05). By the short-term follow-up (3 months), the aspherical acrylic IOL can reduce the higher-order aberrations (especially the spherical aberration) and increase the contrast sensitivity to improve the visual performance.

  16. Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse.

    Science.gov (United States)

    Wu, Wenda; He, Kaiyu; Zhou, Hui-Ren; Berthiller, Franz; Adam, Gerhard; Sugita-Konishi, Yoshiko; Watanabe, Maiko; Krantis, Anthony; Durst, Tony; Zhang, Haibin; Pestka, James J

    2014-07-15

    The foodborne mycotoxin deoxynivalenol (DON) induces a ribotoxic stress response in mononuclear phagocytes that mediate aberrant multi-organ upregulation of TNF-α, interleukins and chemokines in experimental animals. While other DON congeners also exist as food contaminants or pharmacologically-active derivatives, it is not known how these compounds affect expression of these cytokine genes in vivo. To address this gap, we compared in mice the acute effects of oral DON exposure to that of seven relevant congeners on splenic expression of representative cytokine mRNAs after 2 and 6h. Congeners included the 8-ketotrichothecenes 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), nivalenol (NIV), the plant metabolite DON-3-glucoside (D3G) and two synthetic DON derivatives with novel satiety-inducing properties (EN139528 and EN139544). DON markedly induced transient upregulation of TNF-α IL-1β, IL-6, CXCL-2, CCL-2 and CCL-7 mRNA expressions. The two ADONs also evoked mRNA expression of these genes but to a relatively lesser extent. FX induced more persistent responses than the other DON congeners and, compared to DON, was: 1) more potent in inducing IL-1β mRNA, 2) approximately equipotent in the induction of TNF-α and CCL-2 mRNAs, and 3) less potent at upregulating IL-6, CXCL-2, and CCL-2 mRNAs. EN139528's effects were similar to NIV, the least potent 8-ketotrichothecene, while D3G and EN139544 were largely incapable of eliciting cytokine or chemokine mRNA responses. Taken together, the results presented herein provide important new insights into the potential of naturally-occurring and synthetic DON congeners to elicit aberrant mRNA upregulation of cytokines associated with acute and chronic trichothecene toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Chromosomal aberrations in tire plant workers and interaction with

    Czech Academy of Sciences Publication Activity Database

    Musak, L.; Souček, P.; Vodičková, Ludmila; Naccarati, Alessio; Halasová, E.; Poláková, Veronika; Slyšková, Jana; Susová, S.; Buchancová, J.; Šmerhovský, Z.; Sediková, J.; Klimentová, G.; Osina, O.; Hemminki, K.; Vodička, Pavel

    2008-01-01

    Roč. 641, 1-2 (2008), s. 36-42 ISSN 0027-5107 R&D Projects: GA MZd NR8563 Institutional research plan: CEZ:AV0Z50390512 Keywords : Chromosomal aberrations * Genetic polymorphisms * DNA repair genes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.198, year: 2008

  18. Aberrant Right Subclavian Artery: A Life‑threatening Anomaly that ...

    African Journals Online (AJOL)

    ARCA, who suffered concurrently from esophageal cancer. CASE REPORT. The patient was a 56-year-old ... concurrent aberrant subclavian artery and esophageal cancer. The transhiatal esophagectomy was ... Department of Surgery, Imam Khomeini Training Hospital,. Urmia University of Medical Sciences, Ershad ...

  19. Detecting and explaining aberrant responding on the Outcome Questionnaire-45

    NARCIS (Netherlands)

    Conijn, J.M.; Emons, W.H.M.; de Jong, K.; Sijtsma, K.

    2015-01-01

    We applied item response theory based person-fit analysis (PFA) to data of the Outcome Questionnaire-45 (OQ-45) to investigate the prevalence and causes of aberrant responding in a sample of Dutch clinical outpatients. The Formula person-fit statistic was used to detect misfitting item-score

  20. New trends and techniques in chromosome aberration analysis

    International Nuclear Information System (INIS)

    Bender, M.A.

    1978-01-01

    The following topics are discussed: automation of chromosome analysis; storage of fixed cells from cultures of lymphocytes obtained routinely during periodic employee medical examinations; analysis of banded chromosomes; identification of first division metaphases; sister chromatid exchange; and patterns of aberration induction

  1. Aberrant Pattern of Scanning in Prosopagnosia Reflects Impaired Face Processing

    Science.gov (United States)

    Stephan, Blossom Christa Maree; Caine, Diana

    2009-01-01

    Visual scanpath recording was used to investigate the information processing strategies used by a prosopagnosic patient, SC, when viewing faces. Compared to controls, SC showed an aberrant pattern of scanning, directing attention away from the internal configuration of facial features (eyes, nose) towards peripheral regions (hair, forehead) of the…

  2. Frequency and distribution studies of asymmetrical versus symmetrical chromosome aberrations

    International Nuclear Information System (INIS)

    Savage, J.R.K.; Papworth, D.G.

    1982-01-01

    Two aspects of the relationship between Asymmetrical (A) and Symmetrical (S) radiation-induced chromosomal aberrations are considered in this paper. (1) Are A and S truly alternative modes of lesion interaction. Relative frequencies for chromatid-type and chromosome-type are examined, and new lymphocyte data using banding is used to look at this, and also for parallelism in chromosome participation of the two forms for various aberration categories. All the tests applied suggest that A and S are alternative interaction modes. (2) The long-term survival characteristics of A and S are discussed, and the differences in expected frequencies of derived S per surviving cell from chromosome-type and chromatid-types are stressed. Since many in vivo tissues have varying mixtures of potential chromatid and chromosome aberration-bearing target cells, ultimate cell survival and derived S frequencies may differ between tissues for the same absorbed dose. An Appendix gives Relative Corrected Lengths (RCL) for chromosomes of the human karyotype which should be used when testing the various exchange aberration categories for random chromosome participation. (orig.)

  3. Testicular artery arising from an aberrant right renal artery | Suluba ...

    African Journals Online (AJOL)

    This case report we discovered the rare variation of the origin of the right testicular artery arising from the right aberrant renal artery with double renal artery irrigating both left and right kidneys. These variations in the testicular arteries and renal arteries have implication to surgical procedures such as orchidopexy repair for ...

  4. Iatrogenic injury of an aberrant right posterior sectoral bile duct

    African Journals Online (AJOL)

    (Figs 1 and 2). A week later, an endoscopic retrograde cholangiopancreatography. (ERCP) examination was performed. This showed no filling of the right posterior sectoral ducts but normal opacification of the other ducts. (Figs 3a and b). These findings led to the diagnosis of an aberrant right posterior sectoral bile duct that ...

  5. Expressions for third-order aberration theory for holographic images

    Indian Academy of Sciences (India)

    Expressions for third-order aberration theory for holographic images. S K TRIPATHY and S ANANDA RAO. Department of Physics, Jagannath Institute for Technology and Management,. Parlakhemundi 761 200, India. Email: sukantatripathy@sify.com. MS received 14 September 2001; revised 5 August 2002. Abstract.

  6. Chromosomal aberrations and SCEs as biomarkers of cancer risk

    Czech Academy of Sciences Publication Activity Database

    Norppa, H.; Bonassi, S.; Hansteen, I. L.; Hagmar, L.; Strömberg, U.; Rössner st., Pavel; Boffetta, P.; Lindholm, C.; Gundy, S.; Lazutka, J.; Cebulska-Wasilewska, A.; Fabiánová, E.; Šrám, Radim; Knudsen, L. E.; Barale, R.; Fucic, A.

    2006-01-01

    Roč. 600, - (2006), s. 37-45 ISSN 0027-5107 Institutional research plan: CEZ:AV0Z50390512 Keywords : biomarkers * chromosomal aberration * sister chromatid exchange Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 4.111, year: 2006

  7. Aberrant behavior of preschool children: Evaluation of questionnaire

    Directory of Open Access Journals (Sweden)

    Fajgelj Stanislav

    2007-01-01

    Full Text Available In the study metric characteristics of children aberrant behavior questionnaire were analyzed. The analysis was performed on the sample of 1.165 children, aged 4-7, in preschool institutions in several towns of Vojvodina. The questionnaire contained 36 items of the Likert-type scale and was filled in by one parent of each child. The authors examined main metric characteristics of the complete questionnaire, as well as individual items under the Rasche’s measurement model. Generally, parents seldom notice aberrant behavior in their children. Most frequently they notice stubbornness, while very rarely torturing of animals. The item discrimination, on the whole, was found satisfying. The reliability of the questionnaire is 0.84., and all indicators of misfit are within satisfactory ranges. According to differential functioning of the items, the authors found gender and age specificities of parents’ evaluation of aberrant behavior of their children. Parents often notice stubbornness and moldiness in girls, and aggression in boys. According to the parent’s observations, younger children are characterized by nail nibbling, ticklishness, and fearfulness, whereas older children show a tendency to force their way by crying, waywardness and bed-wetting. By means of factor analysis of the items, three principal facets of aberrant behavior were determined: overindulgence, shyness and quarrelsomeness. Cross validation (hold out showed that these three facets were robust in relation to the selection of the sample.

  8. Consequences of Aberrant Hedgehog Signaling During Zebrafish Development

    NARCIS (Netherlands)

    Koudijs, M.J.

    2007-01-01

    The Hedgehog signaling pathway is controlling proliferation, patterning and differentiation during development of vertebrates and invertebrates. Aberrant Hedgehog activity has been shown to be one of the underlying causes of a number of congenital disorders and multiple types of cancer. We

  9. Aberrant Right Subclavian Artery: A Life‑threatening Anomaly that ...

    African Journals Online (AJOL)

    Aberrant right subclavian artery (ARSA) is a rare anomaly, in which the right subclavian artery arises directly from the aortic arch instead of originating from the brachiocephalic artery. This anomaly should be taken into consideration during surgical procedures around esophagus, such as esophagectomy. Any unintentional ...

  10. Thermally induced lensing determination from the coefficient of defocus aberration

    CSIR Research Space (South Africa)

    Bell, Teboho

    2014-07-01

    Full Text Available The effects of a temperature gradient in a laser crystal in an end-pumped configuration in a solid-state laser resonator results in thermally induced aberrations. Of particular interest we measure the thermally induced lens from the coefficient...

  11. Splicing aberrations caused by constitutional RB1 gene mutations in ...

    Indian Academy of Sciences (India)

    . [Parsam VL, Ali MJ, Honavar SG, Vemuganti GK and Kannabiran C 2011 Splicing aberrations caused by constitutional RB1 gene mutations in retinoblastoma. J. Biosci. 36 281–287] DOI 10.1007/s12038-011-9062-9. 1. Introduction.

  12. Telomere Length in Circulating Lymphocytes: Association with Chromosomal Aberrations

    Czech Academy of Sciences Publication Activity Database

    Hemminki, K.; Rachakonda, S.; Musak, L.; Vymetálková, Veronika; Halasová, E.; Forsti,, A.; Vodičková, Ludmila; Buchancová, J.; Vodička, Pavel; Kumar, R.

    2015-01-01

    Roč. 54, č. 3 (2015), s. 194-196 ISSN 1045-2257 Institutional support: RVO:68378041 Keywords : structural chromosome aberrations * healthy subjects * relative telomere length * genotoxicity * telomere biology Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.960, year: 2015

  13. The Aberrant Salience Inventory: A New Measure of Psychosis Proneness

    Science.gov (United States)

    Cicero, David C.; Kerns, John G.; McCarthy, Denis M.

    2010-01-01

    Aberrant salience is the unusual or incorrect assignment of salience, significance, or importance to otherwise innocuous stimuli and has been hypothesized to be important for psychosis and psychotic disorders such as schizophrenia. Despite the importance of this concept in psychosis research, no questionnaire measures are available to assess…

  14. Frequency of primary amenorrhea due to chromosomal aberration

    International Nuclear Information System (INIS)

    Jabbar, S.

    2004-01-01

    Objective: To find out the frequency of primary amenorrhea due to chromosomal aberration and the different options available for management. Subjects and Methods: All patients with primary amenorrhea due to chromosomal aberrations were included in study. Patient's detailed history, general physical examination, presence or absence of secondary sexual characteristics, abdominal and pelvic examination finding were noted. Targeted investigations, including ultrasound, hormonal assay, buccal smear and karyotyping results were recorded. The management options were individually tailored with focus n psychological management. Results: Eighteen patients out of 30,000 patients were diagnosed as having primary amenorrhea. Six had primary amenorrhea due to chromosomal aberrations with the frequency of 0.02%. The age at presentation was 20 years and above in 50%. The most common cause was Turner's syndrome seen in 4 out of 6. The presenting symptoms were delay in onset of menstruation in 05 patients and primary infertility in 01 patient. Conclusion: Primary amenorrhea due to chromosomal aberration is an uncommon condition requiring an early and accurate diagnosis. Turner's syndrome is a relatively common cause of this condition. Management should be multi-disciplinary and individualized according to the patient's age and symptom at presentation. Psychological management is very important and counselling throughout treatment is recommended. (author)

  15. The double monochromator geometric theory and compensation of aberrations

    NARCIS (Netherlands)

    Sokolova, E.; Mogo, S.

    2001-01-01

    The light path function for the double monochromator is constructed, and the formulas of account of the members of its expanding in ascending power series adequate for the defocusing and the first order astigmatism aberrations are found. On the basis of results of the minimisation of obtained

  16. Oxidative stress and chromosomal aberrations in an environmentally exposed population

    Czech Academy of Sciences Publication Activity Database

    Rössner ml., Pavel; Rössnerová, Andrea; Šrám, Radim

    2011-01-01

    Roč. 707, 1-2 (2011), s. 34-41 ISSN 0027-5107 R&D Projects: GA MŽP(CZ) SP/1B3/8/08 Institutional research plan: CEZ:AV0Z50390512 Keywords : air pollution * oxidative stress * chromosomal aberrations Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.850, year: 2011

  17. TOP1 gene copy numbers are increased in cancers of the bile duct and pancreas

    DEFF Research Database (Denmark)

    Grunnet, Mie; Calatayud, Dan; Schultz, Nicolai Aa.

    2015-01-01

    ) poison. Top1 protein, TOP1 gene copy number and mRNA expression, respectively, have been proposed as predictive biomarkers of response to irinotecan in other cancers. Here we investigate the occurrence of TOP1 gene aberrations in cancers of the bile ducts and pancreas. Material and methods. TOP1...

  18. Reactivation of latently infected HIV-1 viral reservoirs and correction of aberrant alternative splicing in the LMNA gene via AMPK activation: Common mechanism of action linking HIV-1 latency and Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Finley, Jahahreeh

    2015-09-01

    Although the use of antiretroviral therapy (ART) has proven highly effective in controlling and suppressing HIV-1 replication, the persistence of latent but replication-competent proviruses in a small subset of CD4(+) memory T cells presents significant challenges to viral eradication from infected individuals. Attempts to eliminate latent reservoirs are epitomized by the 'shock and kill' approach, a strategy involving the combinatorial usage of compounds that influence epigenetic modulation and initiation of proviral transcription. However, efficient regulation of viral pre-mRNA splicing through manipulation of host cell splicing machinery is also indispensible for HIV-1 replication. Interestingly, aberrant alternative splicing of the LMNA gene via the usage of a cryptic splice site has been shown to be the cause of most cases of Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic condition characterized by an accelerated aging phenotype due to the accumulation of a truncated form of lamin A known as progerin. Recent evidence has shown that inhibition of the splicing factors ASF/SF2 (or SRSF1) and SRp55 (or SRSF6) leads to a reduction or an increase in progerin at both the mRNA and protein levels, respectively, thus altering the LMNA pre-mRNA splicing ratio. It is also well-established that during the latter stages of HIV-1 infection, an increase in the production and nuclear export of unspliced viral mRNA is indispensible for efficient HIV-1 replication and that the presence of ASF/SF2 leads to excessive viral pre-mRNA splicing and a reduction of unspliced mRNA, while the presence of SRp55 inhibits viral pre-mRNA splicing and aids in the generation and translation of unspliced HIV-1 mRNAs. The splicing-factor associated protein and putative mitochondrial chaperone p32 has also been shown to inhibit ASF/SF2, increase unspliced HIV-1 viral mRNA, and enhance mitochondrial DNA replication and oxidative phosphorylation. It is our hypothesis that activation of

  19. Effect of Single Administration of Coffee on Pupil Size and Ocular Wavefront Aberration Measurements in Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Handan Bardak

    2016-01-01

    Full Text Available No study has so far evaluated the impact of coffee drinking on ocular wavefront aberration (OWA measurements. This study presents novel findings regarding the OWA of the eye following coffee intake. We aimed to evaluate the acute changes in pupil size and OWA of the eye after single administration of coffee. A total of 30 otherwise healthy participants were included in this prospective study. All subjects drank a cup of coffee containing 57 mg caffeine. Measurements of pupil size, total coma (TC, total trefoil (TF, total spherical aberration (TSA, and total higher order aberration (HOA were performed before and at 5 minutes, at 30 minutes, and at 4 hours after coffee drinking using a wavefront aberrometer device (Irx3, Imagine Eyes, Orsay, France. The mean age of the study population was 20.30 ± 2.74 years. Pupil size did not show a significant change during the measurements (p>0.05. A significant increase was observed in TF and HOA measurements following coffee intake (p=0.029 and p=0.009, resp.. Single administration of coffee results in significant increase in TF and total HOAs in healthy subjects without any effect on pupil diameter. Ultrastructural changes in the cornea following coffee intake might be of relevance to the alterations in ocular aberrations in healthy subjects.

  20. Effect of Single Administration of Coffee on Pupil Size and Ocular Wavefront Aberration Measurements in Healthy Subjects.

    Science.gov (United States)

    Bardak, Handan; Gunay, Murat; Mumcu, Ugur; Bardak, Yavuz

    2016-01-01

    No study has so far evaluated the impact of coffee drinking on ocular wavefront aberration (OWA) measurements. This study presents novel findings regarding the OWA of the eye following coffee intake. We aimed to evaluate the acute changes in pupil size and OWA of the eye after single administration of coffee. A total of 30 otherwise healthy participants were included in this prospective study. All subjects drank a cup of coffee containing 57 mg caffeine. Measurements of pupil size, total coma (TC), total trefoil (TF), total spherical aberration (TSA), and total higher order aberration (HOA) were performed before and at 5 minutes, at 30 minutes, and at 4 hours after coffee drinking using a wavefront aberrometer device (Irx3, Imagine Eyes, Orsay, France). The mean age of the study population was 20.30 ± 2.74 years. Pupil size did not show a significant change during the measurements (p > 0.05). A significant increase was observed in TF and HOA measurements following coffee intake (p = 0.029 and p = 0.009, resp.). Single administration of coffee results in significant increase in TF and total HOAs in healthy subjects without any effect on pupil diameter. Ultrastructural changes in the cornea following coffee intake might be of relevance to the alterations in ocular aberrations in healthy subjects.

  1. Temporal thrombospondin-1 mRNA response in skeletal muscle exposed to acute and chronic exercise.

    Science.gov (United States)

    Olfert, I Mark; Breen, Ellen C; Gavin, Timothy P; Wagner, Peter D

    2006-12-01

    Thrombospondin-l (TSP-1) is believed to be an endogenous angiogenic inhibitor. In this study, we report that a single 1 h bout of treadmill running increases TSP-1 mRNA 3-4-fold (p response of TSP-1 mRNA to exercise was ablated after 3 days. Following long-term training (8 weeks, 1 h/day, 5 d/wk), in either normoxia or chronic hypoxia, the TSP-1 mRNA response to an acute bout of exercise was restored and increased 3-4-fold (p response to a single acute exercise bout, its temporal response to repetitive exercise bouts, and the putative role of TSP-1 in the angiogenic process, we speculate that TSP-1 may play a role in regulating the onset of skeletal muscle angiogenesis in response to exercise.

  2. Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise

    DEFF Research Database (Denmark)

    Frydelund-Larsen, Lone; Åkerström, Thorbjörn; Nielsen, Søren

    2006-01-01

    in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of Vo(2 max) or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4......Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression.......5, and 6 h in response to exercise (n = 8) compared with preexercise samples and compared with the resting control group (n = 7, P = 0.001). Visfatin mRNA expression in skeletal muscle was not influenced by exercise. The exercise-induced increase in adipose tissue visfatin was, however, not accompanied...

  3. Aberrant orbitofrontal connectivity in marijuana smoking adolescents

    Directory of Open Access Journals (Sweden)

    Melissa Patricia Lopez-Larson

    2015-12-01

    Discussion: Findings indicate atypical OFC functional connectivity patterns in attentional/executive, motor and reward networks in adolescents with heavy MJ use. These anomalies may be related to suboptimal decision making capacities and increased impulsivity. Results also suggest different OFC connectivity patterns may be present in adolescents with early onset of MJ use and high lifetime exposure to MJ.

  4. A comprehensive characterization of genome-wide copy number aberrations in colorectal cancer reveals novel oncogenes and patterns of alterations.

    Directory of Open Access Journals (Sweden)

    Tao Xie

    Full Text Available To develop a comprehensive overview of copy number aberrations (CNAs in stage-II/III colorectal cancer (CRC, we characterized 302 tumors from the PETACC-3 clinical trial. Microsatellite-stable (MSS samples (n = 269 had 66 minimal common CNA regions, with frequent gains on 20 q (72.5%, 7 (41.8%, 8 q (33.1% and 13 q (51.0% and losses on 18 (58.6%, 4 q (26% and 21 q (21.6%. MSS tumors have significantly more CNAs than microsatellite-instable (MSI tumors: within the MSI tumors a novel deletion of the tumor suppressor WWOX at 16 q23.1 was identified (p<0.01. Focal aberrations identified by the GISTIC method confirmed amplifications of oncogenes including EGFR, ERBB2, CCND1, MET, and MYC, and deletions of tumor suppressors including TP53, APC, and SMAD4, and gene expression was highly concordant with copy number aberration for these genes. Novel amplicons included putative oncogenes such as WNK1 and HNF4A, which also showed high concordance between copy number and expression. Survival analysis associated a specific patient segment featured by chromosome 20 q gains to an improved overall survival, which might be due to higher expression of genes such as EEF1B2 and PTK6. The CNA clustering also grouped tumors characterized by a poor prognosis BRAF-mutant-like signature derived from mRNA data from this cohort. We further revealed non-random correlation between CNAs among unlinked loci, including positive correlation between 20 q gain and 8 q gain, and 20 q gain and chromosome 18 loss, consistent with co-selection of these CNAs. These results reinforce the non-random nature of somatic CNAs in stage-II/III CRC and highlight loci and genes that may play an important role in driving the development and outcome of this disease.

  5. Network modeling of the transcriptional effects of copy number aberrations in glioblastoma

    Science.gov (United States)

    Jörnsten, Rebecka; Abenius, Tobias; Kling, Teresia; Schmidt, Linnéa; Johansson, Erik; Nordling, Torbjörn E M; Nordlander, Bodil; Sander, Chris; Gennemark, Peter; Funa, Keiko; Nilsson, Björn; Lindahl, Linda; Nelander, Sven

    2011-01-01

    DNA copy number aberrations (CNAs) are a hallmark of cancer genomes. However, little is known about how such changes affect global gene expression. We develop a modeling framework, EPoC (Endogenous Perturbation analysis of Cancer), to (1) detect disease-driving CNAs and their effect on target mRNA expression, and to (2) stratify cancer patients into long- and short-term survivors. Our method constructs causal network models of gene expression by combining genome-wide DNA- and RNA-level data. Prognostic scores are obtained from a singular value decomposition of the networks. By applying EPoC to glioblastoma data from The Cancer Genome Atlas consortium, we demonstrate that the resulting network models contain known disease-relevant hub genes, reveal interesting candidate hubs, and uncover predictors of patient survival. Targeted validations in four glioblastoma cell lines support selected predictions, and implicate the p53-interacting protein Necdin in suppressing glioblastoma cell growth. We conclude that large-scale network modeling of the effects of CNAs on gene expression may provide insights into the biology of human cancer. Free software in MATLAB and R is provided. PMID:21525872

  6. Frequent induction of chromosomal aberrations in in vivo skin fibroblasts after allogeneic stem cell transplantation: hints to chromosomal instability after irradiation

    International Nuclear Information System (INIS)

    Massenkeil, G.; Zschieschang, P.; Thiel, G.; Hemmati, P. G.; Budach, V.; Dörken, B.; Pross, J.; Arnold, R.

    2015-01-01

    Total body irradiation (TBI) has been part of standard conditioning regimens before allogeneic stem cell transplantation for many years. Its effect on normal tissue in these patients has not been studied extensively. We studied the in vivo cytogenetic effects of TBI and high-dose chemotherapy on skin fibroblasts from 35 allogeneic stem cell transplantation (SCT) patients. Biopsies were obtained prospectively (n = 18 patients) before, 3 and 12 months after allogeneic SCT and retrospectively (n = 17 patients) 23–65 months after SCT for G-banded chromosome analysis. Chromosomal aberrations were detected in 2/18 patients (11 %) before allogeneic SCT, in 12/13 patients (92 %) after 3 months, in all patients after 12 months and in all patients in the retrospective group after allogeneic SCT. The percentage of aberrant cells was significantly higher at all times after allogeneic SCT compared to baseline analysis. Reciprocal translocations were the most common aberrations, but all other types of stable, structural chromosomal aberrations were also observed. Clonal aberrations were observed, but only in three cases they were detected in independently cultured flasks. A tendency to non-random clustering throughout the genome was observed. The percentage of aberrant cells was not different between patients with and without secondary malignancies in this study group. High-dose chemotherapy and TBI leads to severe chromosomal damage in skin fibroblasts of patients after SCT. Our long-term data suggest that this damage increases with time, possibly due to in vivo radiation-induced chromosomal instability

  7. Effects of Silicone Hydrogel Contact Lens Application on Corneal High-order Aberration and Visual Guality in Patients with Corneal Opacities

    Directory of Open Access Journals (Sweden)

    Sevda Aydın Kurna

    2012-03-01

    Full Text Available Pur po se: Evaluation of the corneal high-order aberrations and visual quality changes after application of silicone hydrogel contact lenses in patients with corneal opacities due to various etiologies. Ma te ri al and Met hod: Fifteen eyes of 13 patients with corneal opacities were included in the study. During the ophthalmologic examination before and after contact lens application, visual acuity was measured with Snellen acuity chart and contrast sensitivity - with Bailey-Lowie Charts in letters. Aberrations were measured with corneal aberrometer (NIDEK Magellan Mapper under a naturally dilated pupil. Spherical aberration, coma, trefoil, irregular astigmatism and total high-order root mean square (RMS values were recorded. Measurements were repeated with balafilcon A lenses (PureVision 2 HD, B&L on all patients. Re sults: Patient age varied between 23 and 50 years. Two eyes had subepithelial infiltrates due to adenoviral keratitis, 1 had nebulae due to previous infections or trauma, and 2 had Salzmann’s nodular degeneration. We observed a mean increase of 1 line in visual acuity and 5 letters in contrast sensitivity with contact lenses versus glasses in the patients. Mean RMS values of spherical aberration, irregular astigmatism and total high-order aberrations decreased significantly with contact lenses. Dis cus si on: Silicone hydrogel soft contact lenses may improve visual quality by decreasing the corneal aberrations in patients with corneal opacities. (Turk J Ophthalmol 2012; 42: 97-102

  8. Subjective face recognition difficulties, aberrant sensibility, sleeping disturbances and aberrant eating habits in families with Asperger syndrome

    Directory of Open Access Journals (Sweden)

    Källman Tiia

    2005-04-01

    Full Text Available Abstract Background The present study was undertaken in order to determine whether a set of clinical features, which are not included in the DSM-IV or ICD-10 for Asperger Syndrome (AS, are associated with AS in particular or whether they are merely a familial trait that is not related to the diagnosis. Methods Ten large families, a total of 138 persons, of whom 58 individuals fulfilled the diagnostic criteria for AS and another 56 did not to fulfill these criteria, were studied using a structured interview focusing on the possible presence of face recognition difficulties, aberrant sensibility and eating habits and sleeping disturbances. Results The prevalence for face recognition difficulties was 46.6% in individuals with AS compared with 10.7% in the control group. The corresponding figures for subjectively reported presence of aberrant sensibilities were 91.4% and 46.6%, for sleeping disturbances 48.3% and 23.2% and for aberrant eating habits 60.3% and 14.3%, respectively. Conclusion An aberrant processing of sensory information appears to be a common feature in AS. The impact of these and other clinical features that are not incorporated in the ICD-10 and DSM-IV on our understanding of AS may hitherto have been underestimated. These associated clinical traits may well be reflected by the behavioural characteristics of these individuals.

  9. Subjective face recognition difficulties, aberrant sensibility, sleeping disturbances and aberrant eating habits in families with Asperger syndrome

    Science.gov (United States)

    Nieminen-von Wendt, Taina; Paavonen, Juulia E; Ylisaukko-Oja, Tero; Sarenius, Susan; Källman, Tiia; Järvelä, Irma; von Wendt, Lennart

    2005-01-01

    Background The present study was undertaken in order to determine whether a set of clinical features, which are not included in the DSM-IV or ICD-10 for Asperger Syndrome (AS), are associated with AS in particular or whether they are merely a familial trait that is not related to the diagnosis. Methods Ten large families, a total of 138 persons, of whom 58 individuals fulfilled the diagnostic criteria for AS and another 56 did not to fulfill these criteria, were studied using a structured interview focusing on the possible presence of face recognition difficulties, aberrant sensibility and eating habits and sleeping disturbances. Results The prevalence for face recognition difficulties was 46.6% in individuals with AS compared with 10.7% in the control group. The corresponding figures for subjectively reported presence of aberrant sensibilities were 91.4% and 46.6%, for sleeping disturbances 48.3% and 23.2% and for aberrant eating habits 60.3% and 14.3%, respectively. Conclusion An aberrant processing of sensory information appears to be a common feature in AS. The impact of these and other clinical features that are not incorporated in the ICD-10 and DSM-IV on our understanding of AS may hitherto have been underestimated. These associated clinical traits may well be reflected by the behavioural characteristics of these individuals. PMID:15826308

  10. Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA).

    Science.gov (United States)

    Nakamura, Yasuhiro; Hattangady, Namita G; Ye, Ping; Satoh, Fumitoshi; Morimoto, Ryo; Ito-Saito, Takako; Sugawara, Akira; Ohba, Koji; Takahashi, Kazuhiro; Rainey, William E; Sasano, Hironobu

    2014-03-25

    Aberrant expression of gonadotropin-releasing hormone receptor (GnRHR) has been reported in human adrenal tissues including aldosterone-producing adenoma (APA). However, the details of its expression and functional role in adrenals are still not clear. In this study, quantitative RT-PCR analysis revealed the mean level of GnRHR mRNA was significantly higher in APAs than in human normal adrenal (NA) (P=0.004). GnRHR protein expression was detected in human NA and neoplastic adrenal tissues. In H295R cells transfected with GnRHR, treatment with GnRH resulted in a concentration-dependent increase in CYP11B2 reporter activity. Chronic activation of GnRHR with GnRH (100nM), in a cell line with doxycycline-inducible GnRHR (H295R-TR/GnRHR), increased CYP11B2 expression and aldosterone production. These agonistic effects were inhibited by blockers for the calcium signaling pathway, KN93 and calmidazolium. These results suggest GnRH, through heterotopic expression of its receptor, may be a potential regulator of CYP11B2 expression levels in some cases of APA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Aberrant expression of the sFRP and WIF1 genes in invasive non-functioning pituitary adenomas.

    Science.gov (United States)

    Song, Wang; Qian, Liu; Jing, Guo; Jie, Feng; Xiaosong, Shan; Chunhui, Liu; Yangfang, Li; Guilin, Li; Gao, Hua; Yazhuo, Zhang

    2018-03-16

    Non-functioning pituitary adenomas (NFPAs) are the most common pituitary tumors and mainly invade the sphenoid, cavernous sinus or dura mate. Aberrant regulation of the Wnt signaling pathway plays an important role in tumorigenesis. This study was designed to investigate the relationships between secreted frizzled-related proteins (sFRPs), WIF1 genes and the invasion of NFPAs by tissue microassays (TMAs) of samples from 163 patients. Significantly weaker staining of WIF1 and sFRP4 were detected in the invasive group compared with the non-invasive group by TMAs (p = 0.002, p < 0.001). Univariate analysis showed a significant correlation between tumor invasion and low expression of WIF1 and sFRP4 (p = 0.002, p < 0.001). A similar trend was observed when analyzing the mRNA and protein levels through RT-PCR and western blot experiments. Methylation of the WIF1 promoter was significantly increased in invasive NFPAs compared with the noninvasive group (p = 0.004). The average progression free survival time in the high WIF1 group was longer than that in the low WIF1 group (p = 0.025). Furthermore, RT-PCR measured the levels of 11 miRNAs targeting WIF1 according to the Targetscan database and PubMed. The levels of miRNA-137, miRNA-374a-5p and miRNA-374b-5p in the invasive group were 0.037-fold, 0.577-fold and 0.44-fold that of the noninvasive group (p = 0.003, p = 0.049 and p = 0.047). Overexpression of miRNA-137 could inhibit the proliferation and invasion of GH3 cells through cell viability and Transwell experiments (p < 0.05). Furthermore, the WIF1 level was upregulated after overexpression of miRNA-137 compared with miRNA-137-NC (control miRNA) in GH3 cells. Our data suggest that WIF1 may be potential biomarker for the aggressiveness of NFPAs. miRNA-137 plays an important role in the Wnt signaling pathway by affecting promoter methylation of WIF1. Copyright © 2018. Published by Elsevier B.V.

  12. Corneal aberration changes after rigid gas permeable contact lens wear in keratokonic patients

    Directory of Open Access Journals (Sweden)

    Fereshteh Shokrollahzadeh

    2016-12-01

    Conclusion: In this study, corneal aberrations remained unchanged 3 months after wearing RGP contact lens. Further studies with sufficient samples in different groups of keratoconus severity or baseline aberrations are needed to obtain more accurate results.

  13. Image transfer with spatial coherence for aberration corrected transmission electron microscopes.

    Science.gov (United States)

    Hosokawa, Fumio; Sawada, Hidetaka; Shinkawa, Takao; Sannomiya, Takumi

    2016-08-01

    The formula of spatial coherence involving an aberration up to six-fold astigmatism is derived for aberration-corrected transmission electron microscopy. Transfer functions for linear imaging are calculated using the newly derived formula with several residual aberrations. Depending on the symmetry and origin of an aberration, the calculated transfer function shows characteristic symmetries. The aberrations that originate from the field's components, having uniformity along the z direction, namely, the n-fold astigmatism, show rotational symmetric damping of the coherence. The aberrations that originate from the field's derivatives with respect to z, such as coma, star, and three lobe, show non-rotational symmetric damping. It is confirmed that the odd-symmetric wave aberrations have influences on the attenuation of an image via spatial coherence. Examples of image simulations of haemoglobin and Si [211] are shown by using the spatial coherence for an aberration-corrected electron microscope. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana

    NARCIS (Netherlands)

    Ji, X.

    2014-01-01

    Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. I studied numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. The large genomic changes are important for

  15. Modulated protonation of side chain aminoethylene repeats in N-substituted polyaspartamides promotes mRNA transfection.

    Science.gov (United States)

    Uchida, Hirokuni; Itaka, Keiji; Nomoto, Takahiro; Ishii, Takehiko; Suma, Tomoya; Ikegami, Masaru; Miyata, Kanjiro; Oba, Makoto; Nishiyama, Nobuhiro; Kataoka, Kazunori

    2014-09-03

    Fine-tuning of chemical structures of polycation-based carriers (polyplexes) is an attractive strategy for safe and efficient mRNA transfaction. Here, mRNA polyplexes comprising N-substituted polyaspartamides with varied numbers of side chain aminoethylene repeats were constructed, and their transfection ability against human hepatoma cells was examined. Transfection efficacy clearly correlated with the number of aminoethylene repeats: polyplexes with odd number repeats (PA-Os) produced sustained increases in mRNA expression compared with those with even number repeats (PA-Es). This predominant efficacy of PA-Os over PA-Es was contradictory to our previous findings for pDNA polyplexes prepared from the same N-substituted polyaspartamides, that is, PA-Es revealed superior transfection efficacy of pDNA than PA-Os. Intracellular FRET analysis using flow cytometry and polyplex tracking under confocal laser scanning microscopy revealed that overall transfection efficacy was determined through the balance between endosomal escaping capability and stability of translocated mRNA in cytoplasm. PA-Es efficiently transported mRNA into the cytoplasm. However, their poor cytoplasmic stability led to facile degradation of mRNA, resulting in a less durable pattern of transfection. Alternatively, PA-Os with limited capability of endosomal escape eventually protect mRNA in the cytoplasm to induce sustainable mRNA expression. Higher cytoplasmic stability of pDNA compared to mRNA may shift the limiting step in transfection from cytoplasmic stability to endosomal escape capacity, thereby giving an opposite odd-even effect in transfection efficacy. Endosomal escaping capability and nuclease stability of polyplexes are correlated with the modulated protonation behavior in aminoethylene repeats responding to pH, appealing the substantial importance of chemistry to design polycation structures for promoted mRNA transfection.

  16. No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblasts after alpha particle irradiation

    Science.gov (United States)

    Hu, Burong; Zhu, Jiayun; Zhou, Hongning; Hei, Tom K.

    2013-02-01

    A major concern for bystander effects is the probability that normal healthy cells adjacent to the irradiated cells become genomically unstable and undergo further carcinogenesis after therapeutic irradiation or space mission where astronauts are exposed to low dose of heavy ions. Genomic instability is a hallmark of cancer cells. In the present study, two irradiation protocols were performed in order to ensure pure populations of bystander cells and the genomic instability in their progeny were investigated. After irradiation, chromosomal aberrations of cells were analyzed at designated time points using G2 phase premature chromosome condensation (G2-PCC) coupled with Giemsa staining and with multiplex fluorescent in situ hybridization (mFISH). Our Giemsa staining assay demonstrated that elevated yields of chromatid breaks were induced in the progeny of pure bystander primary fibroblasts up to 20 days after irradiation. mFISH assay showed no significant level of inheritable interchromosomal aberrations were induced in the progeny of the bystander cell groups, while the fractions of gross aberrations (chromatid breaks or chromosomal breaks) significantly increased in some bystander cell groups. These results suggest that genomic instability occurred in the progeny of the irradiation associated bystander normal fibroblasts exclude the inheritable interchromosomal aberration.

  17. Aberrant retropharyngeal internal carotid artery associated with retropharyngeal abscess: determination of a safe drainage zone with computed tomography

    International Nuclear Information System (INIS)

    Akay, S.; Battal, B.; Karaman, B.; Tasar, M.

    2012-01-01

    Full text: Introduction: During surgery, interventional procedures and anesthesia-related actions, awareness of the aberrant course of the internal carotid artery (ICA) may prevent vascular damage and massive hemorrhage. Objectives and tasks: To emphasize the importance of guiding of the imaging performed before the interventional procedures, in the light of the computed tomography (CT) findings of a case with aberrant retropharingeal ICA associated with retropharyngeal abscess. Materials and methods: A 60-year-old woman visited the Ear Nose and Throat (ENT) department of our hospital complaining of sore throat that persisted since 2 weeks. She was prescribed oral antibiotherapy, during which she experienced dysphagia and increasing fever. After endoscopic study, a retropharyngeal abscess was detected and was thought to be due to the bulging of the right posterior pharyngeal wall that has smooth and intact mucosa. Results: On CT, we observed an abscess formation, and enlargement of the right retropharyngeal space. CT images also displayed an aberrant course of the right ICA that was very close to the right posteromedial wall of the pharynx. After obtaining detailed anatomical information from the CT, abscess drainage from the right superolateral wall of the nasopharynx was performed at the ENT department. No hemorrhagic or other complications were encountered. On control CT examination performed 20 days after drainage, no abscess formation was seen. Conclusion: Imaging studies can show and confirm the aberrant course of the ICA, thereby reducing the risk of hemorrhagic complications

  18. The actin binding cytoskeletal protein Moesin is involved in nuclear mRNA export.

    Science.gov (United States)

    Kristó, Ildikó; Bajusz, Csaba; Borsos, Barbara N; Pankotai, Tibor; Dopie, Joseph; Jankovics, Ferenc; Vartiainen, Maria K; Erdélyi, Miklós; Vilmos, Péter

    2017-10-01

    Current models imply that the evolutionarily conserved, actin-binding Ezrin-Radixin-Moesin (ERM) proteins perform their activities at the plasma membrane by anchoring membrane proteins to the cortical actin network. Here we show that beside its cytoplasmic functions, the single ERM protein of Drosophila, Moesin, has a novel role in the nucleus. The activation of transcription by heat shock or hormonal treatment increases the amount of nuclear Moesin, indicating biological function for the protein in the nucleus. The distribution of Moesin in the nucleus suggests a function in transcription and the depletion of mRNA export factors Nup98 or its interacting partner, Rae1, leads to the nuclear accumulation of Moesin, suggesting that the nuclear function of the protein is linked to mRNA export. Moesin localizes to mRNP particles through the interaction with the mRNA export factor PCID2 and knock down of Moesin leads to the accumulation of mRNA in the nucleus. Based on our results we propose that, beyond its well-known, manifold functions in the cytoplasm, the ERM protein of Drosophila is a new, functional component of the nucleus where it participates in mRNA export. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The effect of aberrated recording beams on reflecting Bragg gratings

    Science.gov (United States)

    SeGall, Marc; Ott, Daniel; Divliansky, Ivan; Glebov, Leonid B.

    2013-03-01

    The effect of aberrations present in the recording beams of a holographic setup is discussed regarding the period and spectral response of a reflecting volume Bragg grating. Imperfect recording beams result in spatially varying resonant wavelengths and the side lobes of the spectrum are washed out. Asymmetrical spectra, spectral broadening, and a reduction in peak diffraction efficiency may also be present, though these effects are less significant for gratings with wider spectral widths. Reflecting Bragg gratings (RBGs) are used as elements in a variety of applications including spectral beam combining1,2, mode locking3,4, longitudinal and transverse mode selection in lasers5,6, and sensing7,8. For applications requiring narrow spectral selectivity9, or large apertures10, these gratings must have a uniform period throughout the length of the recording medium, which may be on the order of millimeters. However, when using typical recording techniques such as two-beam interference for large aperture gratings and phase-mask recording of fiber gratings, aberrations from the optical elements in the system result in an imperfect grating structure11-13. In this paper we consider the effects of aberrations on large aperture gratings recorded in thick media using the two-beam interference technique. Previous works in analyzing the effects of aberrations have considered the effects of aberrations in a single recording plane where the beams perfectly overlap. Such an approach is valid for thin media (on the order of tens of microns), but for thick recording media (on the order of several millimeters) there will be a significant shift in the positions of the beams relative to each other as they traverse the recording medium. Therefore, the fringe pattern produced will not be constant throughout the grating if one or both beams have a non-uniform wavefront. Such non-uniform gratings may have a wider spectral width, a shifted resonant wavelength, or other problems. It is

  20. Analysis of chromosomal aberrations, micronuclei and hematological disorders among workers of wireless communication instruments and cell phone (Mobile) users

    International Nuclear Information System (INIS)

    Eldawy, H.A.; Khattab, F.I.; Hassan, N.H.A.; Amin, Y.M.; Mahmoud, M.M.A.

    2003-01-01

    This study was carried out to investigate the hazardous effect of electromagnetic radiation (EMR) such as chromosomal aberration, disturbed micronucleus formation and hematological disorders that may detected among workers of wireless communication instruments and mobile phone users. Seven individuals ( 3 males and 4 females) of a central workers in the microwave unit of the wireless station and 7 users of Mobil phone (4 males and 3 females ) were volunteered to give blood samples. Chromosomes and micronucleus were prepared for cytogenetic analysis as well as blood film for differential count. The results obtained in the microwave group indicated that, the total summation of all types of aberrations (chromosomes and chromatid aberrations) had a frequency of 6. 14% for the exposed group, whereas, the frequency in the control group amounted to 1.57%. In Mobil phone users, the total summation of all types of aberrations(chromosome and chromatid aberrations) had a frequency of 4.43% for the exposed group and 1.71% for the control group. The incidence of the total number of micronuclei in the exposed microwave group was increased 4.3 folds as compared with those of the control group The incidence of the total number of micronuclei in the exposed mobile phone group was increased 2 fold as compared with those in the control group. On the other hand, normal ranges of total white blood cells counts were determined for mobile phone users but abnormalities in the differential counts of the different types of the white blood cells such as neutropenia, eosinophilia and lymphocytosis were observed in the individuals number 1,2,3,7 in microwave group

  1. pEVL: A Linear Plasmid for Generating mRNA IVT Templates With Extended Encoded Poly(A Sequences

    Directory of Open Access Journals (Sweden)

    Alexandra E Grier

    2016-01-01

    Full Text Available Increasing demand for large-scale synthesis of in vitro transcribed (IVT mRNA is being driven by the increasing use of mRNA for transient gene expression in cell engineering and therapeutic applications. An important determinant of IVT mRNA potency is the 3′ polyadenosine (poly(A tail, the length of which correlates with translational efficiency. However, present methods for generation of IVT mRNA rely on templates derived from circular plasmids or PCR products, in which homopolymeric tracts are unstable, thus limiting encoded poly(A tail lengths to ≃120 base pairs (bp. Here, we have developed a novel method for generation of extended poly(A tracts using a previously described linear plasmid system, pJazz. We find that linear plasmids can successfully propagate poly(A tracts up to ≃500 bp in length for IVT mRNA production. We then modified pJazz by removing extraneous restriction sites, adding a T7 promoter sequence upstream from an extended multiple cloning site, and adding a unique type-IIS restriction site downstream from the encoded poly(A tract to facilitate generation of IVT mRNA with precisely defined encoded poly(A tracts and 3′ termini. The resulting plasmid, designated pEVL, can be used to generate IVT mRNA with consistent defined lengths and terminal residue(s.

  2. Aberrant innate immune activation following tissue injury impairs pancreatic regeneration.

    Directory of Open Access Journals (Sweden)

    Alexandra E Folias

    Full Text Available Normal tissue architecture is disrupted following injury, as resident tissue cells become damaged and immune cells are recruited to the site of injury. While injury and inflammation are critical to tissue remodeling, the inability to resolve this response can lead to the destructive complications of chronic inflammation. In the pancreas, acinar cells of the exocrine compartment respond to injury by transiently adopting characteristics of progenitor cells present during embryonic development. This process of de-differentiation creates a window where a mature and stable cell gains flexibility and is potentially permissive to changes in cellular fate. How de-differentiation can turn an acinar cell into another cell type (such as a pancreatic β-cell, or a cell with cancerous potential (as in cases of deregulated Kras activity is of interest to both the regenerative medicine and cancer communities. While it is known that inflammation and acinar de-differentiation increase following pancreatic injury, it remains unclear which immune cells are involved in this process. We used a combination of genetically modified mice, immunological blockade and cellular characterization to identify the immune cells that impact pancreatic regeneration in an in vivo model of pancreatitis. We identified the innate inflammatory response of macrophages and neutrophils as regulators of pancreatic regeneration. Under normal conditions, mild innate inflammation prompts a transient de-differentiation of acinar cells that readily dissipates to allow normal regeneration. However, non-resolving inflammation developed when elevated pancreatic levels of neutrophils producing interferon-γ increased iNOS levels and the pro-inflammatory response of macrophages. Pancreatic injury improved following in vivo macrophage depletion, iNOS inhibition as well as suppression of iNOS levels in macrophages via interferon-γ blockade, supporting the impairment in regeneration and the

  3. Aberration-corrected multipole Wien filter for energy-filtered x-ray photoemission electron microscopy

    OpenAIRE

    Niimi, Hironobu; Chun, Wang-Jae; Suzuki, Shushi; Asakura, Kiyotaka; Kato, Makoto

    2007-01-01

    The aberration of a multipole Wien filter for energy-filtered x-ray photoemission electron microscopy was analyzed and the optimized Fourier components of the electric and magnetic fields for the third-order aperture aberration corrections were obtained. It was found that the third-order aperture aberration correction requires 12 electrodes and magnetic poles. ©2007 American Institute of Physics

  4. Aberration-corrected multipole Wien filter for energy-filtered x-ray photoemission electron microscopy

    Science.gov (United States)

    Niimi, Hironobu; Chun, Wang-Jae; Suzuki, Shushi; Asakura, Kiyotaka; Kato, Makoto

    2007-06-01

    The aberration of a multipole Wien filter for energy-filtered x-ray photoemission electron microscopy was analyzed and the optimized Fourier components of the electric and magnetic fields for the third-order aperture aberration corrections were obtained. It was found that the third-order aperture aberration correction requires 12 electrodes and magnetic poles.

  5. Nodular Hyperplasia Arising from the Lateral Aberrant Thyroid Tissue: A Case Report

    International Nuclear Information System (INIS)

    Jeong, Min Hye; Park, Jeong Seon; Lee, Young Jun

    2012-01-01

    The presence of aberrant thyroid tissue in the lateral neck is very rare. In addition, nodular hyperplasia in ectopic thyroid has rarely been reported. Due to the unusual location, the presence of lateral aberrant thyroid tissue could be misdiagnosed as a lymphadenopathy, neurogenic tumor, etc. We report on a case of nodular hyperplasia arising from the right lateral aberrant thyroid tissue.

  6. Image transfer with spatial coherence for aberration corrected transmission electron microscopes

    Energy Technology Data Exchange (ETDEWEB)

    Hosokawa, Fumio, E-mail: hosokawa@bio-net.co.jp [BioNet Ltd., 2-3-28 Nishikityo, Tachikwa, Tokyo (Japan); Tokyo Institute of Technology, 4259 Nagatsuta, Midoriku, Yokohama 226-8503 (Japan); Sawada, Hidetaka [JEOL (UK) Ltd., JEOL House, Silver Court, Watchmead, Welwyn Garden City, Herts AL7 1LT (United Kingdom); Shinkawa, Takao [BioNet Ltd., 2-3-28 Nishikityo, Tachikwa, Tokyo (Japan); Sannomiya, Takumi [Tokyo Institute of Technology, 4259 Nagatsuta, Midoriku, Yokohama 226-8503 (Japan)

    2016-08-15

    The formula of spatial coherence involving an aberration up to six-fold astigmatism is derived for aberration-corrected transmission electron microscopy. Transfer functions for linear imaging are calculated using the newly derived formula with several residual aberrations. Depending on the symmetry and origin of an aberration, the calculated transfer function shows characteristic symmetries. The aberrations that originate from the field’s components, having uniformity along the z direction, namely, the n-fold astigmatism, show rotational symmetric damping of the coherence. The aberrations that originate from the field’s derivatives with respect to z, such as coma, star, and three lobe, show non-rotational symmetric damping. It is confirmed that the odd-symmetric wave aberrations have influences on the attenuation of an image via spatial coherence. Examples of image simulations of haemoglobin and Si [211] are shown by using the spatial coherence for an aberration-corrected electron microscope. - Highlights: • The formula of partial coherence for aberration corrected TEM is derived. • Transfer functions are calculated with several residual aberrations. • The calculated transfer function shows the characteristic damping. • The odd-symmetric wave aberrations can cause the attenuation of image via coherence. • The examples of aberration corrected TEM image simulations are shown.

  7. Aberrations Involving Chromosome 1 as a Possible Predictor of Odds Ratio for Colon Cancer--Results from the Krakow Case-Control Study.

    Directory of Open Access Journals (Sweden)

    Aleksander Galas

    Full Text Available There is still an open question how to predict colorectal cancer risk before any morphological changes appear in the colon.The purpose was to investigate aberrations in chromosomes 1, 2 and 4 in peripheral blood lymphocytes analyzed by fluorescence in situ hybridization technique as a tool to assess the likelihood of colorectal cancer.A hospital-based case-control study included 20 colon cancer patients and 18 hospital-based controls. Information about potential covariates was collected by interview. The frequency of stable and unstable chromosome aberrations in chromosome 1, 2 and 4 was assessed by fluorescence in situ hybridization technique.Colorectal cancer patients, as compared to controls, had a relatively higher frequency of chromosome 1 translocations (median: 3.5 versus 1.0 /1000 cells, p = 0.006, stable aberrations (3.8 versus 1.0 /1000 cells, p = 0.007 and total aberrations (p = 0.009. There were no differences observed for chromosomes 2 and 4. Our results showed an increase in the odds of having colon cancer by about 50-80% associated with an increase by 1/1000 cells in the number of chromosome 1 aberrations.The results revealed that the frequency of chromosomal aberrations, especially translocations in chromosome 1, seems to be a promising method to show a colon cancer risk. Additionally, our study suggests the reasonableness of use of biomarkers such as chromosome 1 aberrations in peripheral blood lymphocytes in screening prevention programs for individuals at higher colon cancer risk to identify those who are at increased risk and require more frequent investigations, e.g. by sigmoidoscopy.

  8. Overexpression of protease nexin-1 mRNA and protein in oral squamous cell carcinomas

    DEFF Research Database (Denmark)

    Gao, Shan; Krogdahl, Annelise; Sørensen, Jens Ahm

    2007-01-01

    Protease nexin-1 (PN-1) belongs to the serpin family of serine protease inhibitors. It is the phylogenetically closest relative of plasminogen activator inhibitor-1 (PAI-1). Whilst there are numerous studies of the occurrence and functions of PAI-1 in cancer, a possible tumour biological role of PN......-1 has been almost totally neglected. We have now compared the level of PN-1 mRNA in 20 cases of oral squamous cell carcinomas and in matched samples of the corresponding normal oral tissues. We found that the average PN-1 mRNA level in tumours and normal tissues was significantly different, being...... increased up to 13 fold in tumour samples compared with the average level in normal tissues. The PN-1 mRNA level was significantly higher in tumours from patients with lymph node metastasis than in tumours from patients without. We could conclude that PN-1 is frequently overexpressed in oral squamous cell...

  9. Quantitative PCR--new diagnostic tool for quantifying specific mRNA and DNA molecules

    DEFF Research Database (Denmark)

    Schlemmer, B O; Sorensen, B S; Overgaard, J

    2004-01-01

    , and the treatment is considered to be justified if the tumor displays an increased amount of HER2. For this reason there is a need for techniques suitable for HER2 measurements. A LightCycler real-time PCR method used for HER2/neu DNA quantification was evaluated and the results compared with those obtained...... significant (p DNA quantification kit" produces results with a high level of reproducibility and its ease of use allows rapid screening for amplification of HER2. In this paper useful information is given on how real-time PCR compares with FISH and IHC. The data show...... of mRNA or DNA in biological samples. In this study quantitative PCR was used to investigate the role of the EGF (epidermal growth factor) system in cancer both for measurements of mRNA concentrations and for measurements of the number of copies of specific genes. It is shown that the mRNA expression...

  10. Cloning of prepro-adrenomedullin and mRNA expression in cats.

    Science.gov (United States)

    Kanno, Nobuyuki; Asano, Kazushi; Teshima, Kenji; Seki, Mamiko; Edamura, Kazuya; Tanaka, Shigeo

    2010-10-01

    The objective of this paper was to evaluate the sequence of feline prepro-adrenomedullin (AM) and its tissue distribution and to investigate whether expression of feline AM mRNA increases in association with spontaneous cardiomyopathy. The feline prepro-AM cDNA sequence and deduced amino acids were 564 base pairs and 188 residues, respectively. The cDNA sequences of feline prepro-AM including AM and proadrenomedullin N-terminal 20 peptide showed high homology with those of other mammalian species. The mRNA expression of AM was detectable in various normal tissues. The mRNA levels of AM were elevated in hearts with cardiomyopathy compared with normal hearts. This study suggests that AM has an important role as a neurohumoral factor in cats with spontaneous heart diseases.

  11. mRNA quality control pathways in Saccharomyces cerevisiae

    Indian Academy of Sciences (India)

    To prevent this possibility, mRNA quality control systems have evolved both in the nucleus and cytoplasm in eukaryotes to scrutinize various stages of mRNP biogenesis and translation. In this review, we will focus on the physiological role of some of these mRNA quality control systems in the simplest model eukaryote ...

  12. Aberrant leukocyte telomere length in Birdshot Uveitis.

    Directory of Open Access Journals (Sweden)

    Nadia Vazirpanah

    Full Text Available Birdshot Uveitis (BU is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.To study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls.Although LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL = 4.87 (= 74131 base pair compared to 4.31 (= 20417 base pair in unaffected controls (P<0.0001. The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1.These findings suggest that BU is accompanied by significantly longer LTL.

  13. Mutagenic effect of the decay of 32P incorporated in mRNA

    International Nuclear Information System (INIS)

    Zakharov, I.A.; Korolev, V.G.; Gracheva, L.M.

    1978-01-01

    32 P decay in mRNA transcribed using the Escherichia coli lactose operone leads to an authentic increase of Lac - mutants frequency as compared to the check. The principle possibility of the realization of directed mutagenesis using molecules labeled with radioactive isotopes connected with certain RNA units is shown

  14. Expression of IL-1{beta} mRNA in mice after whole body X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nemoto, Kumie; Ishihara, Hiroshi; Tanaka, Izumi; Suzuki, Gen; Tsuneoka, Kazuko; Yoshida, Kazuko; Ohtsu, Hiroshi [National Inst. of Radiological Sciences, Chiba (Japan)

    1995-06-01

    IL-1{beta} is a stimulator of hematopoietic and inflammatory systems, and also acts as a radioprotector. After whole-body exposure to sublethal doses of ionizing radiation, the IL-1{beta} mRNA level in spleen cells increases for a short time prior to regeneration of the spleen. We analyzed spleen cells of C3H/He mice after whole-body irradiation with 3 Gy x-rays to determine the cause of this short-term increase in the transcription level. An increase in the level of the message in spleen cells, found by Northern blot hybridization, reached its peak 5 to 7 days after irradiation. There was a low correlation between the curves of the mRNA level and the ratio of monocyte/macrophage lineage cells; a typical source of the message. Spleen macrophages that produce a large amount of the message were found 7 days after irradiation in an in situ hybridization experiment in which heterogeneous spleen cell populations were used. In contrast, spleen cells had no detectable levels of macrophages rich in IL-1{beta} mRNA before and 17 days after irradiation. Additionally, the population of message-rich cells was 9.4% of the total number of monocytes/macrophages in the spleen. These results suggest that the short-term increase in IL-1{beta} mRNA is a result of the heterogeneous differentiation of a subpopulation of spleen macrophages before regeneration of the spleen. (author).

  15. Prostaglandins stimulate renin secretion and renin mRNA in mouse renal juxtaglomerular cells

    DEFF Research Database (Denmark)

    Jensen, B L; Schmid, C; Kurtz, A

    1996-01-01

    identified PGI2 and PGE2 as stimulators of renin secretion; the effects were dose and time dependent. PGE2 also increased renin mRNA accumulation time and dose dependent. PGE2 and PGI2 activated adenylate cyclase concentration dependent in granular cells. PGE2 stimulations of renin secretion and renin m...

  16. Measuring Hematocrit in Mice Injected with In Vitro-Transcribed Erythropoietin mRNA.

    Science.gov (United States)

    Mahiny, Azita Josefine; Karikó, Katalin

    2016-01-01

    In vitro-transcribed (IVT) mRNA encoding therapeutic protein has the potential to treat a variety of diseases by serving as template for translation in the patient. To optimize conditions for such therapy, reporter protein-encoding mRNAs are usually used. One preferred reporter is erythropoietin (EPO), which stimulates erythropoiesis and leads to an increase in hematocrit. Measurement of hematocrit is a fast and reliable method to determine the potency of the in vitro-transcribed EPO mRNA. However, frequent blood draw from mice can increase hematocrit due to blood loss. Therefore, instead of using conventional hematocrit capillary tubes, we adapted glass microcapillaries for hematocrit measurement. Daily monitoring of mice can be accomplished by drawing less than 20 μL of blood, thus avoiding blood loss-related hematocrit increase. Due to the small volume of the withdrawn blood the hematocrit remains the same for mice injected with control mRNA, whereas significant hematocrit increase is measured between day 4 and 20 postinjection for those injected with pseudouridine-modified EPO mRNA. Following hematocrit measurement the microcapillaries are snapped easily to recover plasma for further analyses, including EPO measurement by ELISA.

  17. Arsenic Induces Polyadenylation of Canonical Histone mRNA by Down-regulating Stem-Loop-binding Protein Gene Expression*

    Science.gov (United States)

    Brocato, Jason; Fang, Lei; Chervona, Yana; Chen, Danqi; Kiok, Kathrin; Sun, Hong; Tseng, Hsiang-Chi; Xu, Dazhong; Shamy, Magdy; Jin, Chunyuan; Costa, Max

    2014-01-01

    The replication-dependent histone genes are the only metazoan genes whose messenger RNA (mRNA) does not terminate with a poly(A) tail at the 3′-end. Instead, the histone mRNAs display a stem-loop structure at their 3′-end. Stem-loop-binding protein (SLBP) binds the stem-loop and regulates canonical histone mRNA metabolism. Here we report that exposure to arsenic, a carcinogenic metal, decreased cellular levels of SLBP by inducing its proteasomal degradation and inhibiting SLBP transcription via epigenetic mechanisms. Notably, arsenic exposure dramatically increased polyadenylation of canonical histone H3.1 mRNA possibly through down-regulation of SLBP expression. The polyadenylated H3.1 mRNA induced by arsenic was not susceptible to normal degradation that occurs at the end of S phase, resulting in continued presence into mitosis, increased total H3.1 mRNA, and increased H3 protein levels. Excess expression of canonical histones have been shown to increase sensitivity to DNA damage as well as increase the frequency of missing chromosomes and induce genomic instability. Thus, polyadenylation of canonical histone mRNA following arsenic exposure may contribute to arsenic-induced carcinogenesis. PMID:25266719

  18. An investigation of nutrient-dependent mRNA translation in Drosophila larvae

    Directory of Open Access Journals (Sweden)

    Sabarish Nagarajan

    2014-10-01

    Full Text Available The larval period of the Drosophila life cycle is characterized by immense growth. In nutrient rich conditions, larvae increase in mass approximately two hundred-fold in five days. However, upon nutrient deprivation, growth is arrested. The prevailing view is that dietary amino acids drive this larval growth by activating the conserved insulin/PI3 kinase and Target of rapamycin (TOR pathways and promoting anabolic metabolism. One key anabolic process is protein synthesis. However, few studies have attempted to measure mRNA translation during larval development or examine the signaling requirements for nutrient-dependent regulation. Our work addresses this issue. Using polysome analyses, we observed that starvation rapidly (within thirty minutes decreased larval mRNA translation, with a maximal decrease at 6–18 hours. By analyzing individual genes, we observed that nutrient-deprivation led to a general reduction in mRNA translation, regardless of any starvation-mediated changes (increase or decrease in total transcript levels. Although sugars and amino acids are key regulators of translation in animal cells and are the major macronutrients in the larval diet, we found that they alone were not sufficient to maintain mRNA translation in larvae. The insulin/PI3 kinase and TOR pathways are widely proposed as the main link between nutrients and mRNA translation in animal cells. However, we found that genetic activation of PI3K and TOR signaling, or regulation of two effectors – 4EBP and S6K – could not prevent the starvation-mediated translation inhibition. Similarly, we showed that the nutrient stress-activated eIF2α kinases, GCN2 and PERK, were not required for starvation-induced inhibition of translation in larvae. These findings indicate that nutrient control of mRNA translation in larvae is more complex than simply amino acid activation of insulin and TOR signaling.

  19. Research on reflective optical telescope system's wavefront aberration compensation method

    Science.gov (United States)

    Duan, Xueting

    Wavefront aberration measurement of the image quality of reflective telescope system which has a large aperture and long focal length is one of the frequently-used methods of high-precision test and alignment. It was widely used during the large aperture telescope manufacturing process. The influences of surface shape error of the reflective optical telescope system components were simulated and analyst by input the actual measuring data into the optical design software CODE V in this article. According to the test results compared to the alignment process, the accuracy of the simulation method was indicated. At the same time, the wavefront aberration optical compensation principle of the reflective optical telescope system was proved by the simulation of alignment. And in this article, the feasibility of the application of optical phase compensation alignment method was investigated.

  20. Complex Pupil Masks for Aberrated Imaging of Closely Spaced Objects

    Science.gov (United States)

    Reddy, A. N. K.; Sagar, D. K.; Khonina, S. N.

    2017-12-01

    Current approach demonstrates the suppression of optical side-lobes and the contraction of the main lobe in the composite image of two object points of the optical system under the influence of defocusing effect when an asymmetric phase edges are imposed over the apodized circular aperture. The resolution of two point sources having different intensity ratio is discussed in terms of the modified Sparrow criterion, functions of the degree of coherence of the illumination, the intensity difference and the degree of asymmetric phase masking. Here we have introduced and explored the effects of focus aberration (defect-of-focus) on the two-point resolution of the optical systems. Results on the aberrated composite image of closely spaced objects with amplitude mask and asymmetric phase masks forms a significant contribution in astronomical and microscopic observations.

  1. Membrane-based aberration-corrected tunable micro-lenses

    Science.gov (United States)

    Waibel, Philipp; Ermantraut, Eugen; Mader, Daniel; Zappe, Hans; Seifert, Andreas

    2010-05-01

    We present measurements and simulations of membrane-based micro-lens stacks, tunable in focal length in the range of 10mm to 50mm without chromatic aberration. The pressure-actuated, liquid-filled, membrane-based micro-lenses are fabricated by an all-silicone molding approach and consist of three chambers separated by two highly flexible silicone-membranes. Based on the idea of the classical achromatic Fraunhofer doublet, two different liquids with suitable optical properties are used. Pressure-dependent surface topologies are measured by profilometry for determining the correlation between refraction and applied pressure. The profiles are fit to polynomials; the coefficients of the polynomials are pressure-dependent and fit to empirically determined functions which are then used as an input for optical ray-tracing. Using this approach, the focal length is tunable while compensating for chromatic aberration by suitably applied pressures.

  2. Aberrations and adaptive optics in super-resolution microscopy

    Science.gov (United States)

    Booth, Martin; Andrade, Débora; Burke, Daniel; Patton, Brian; Zurauskas, Mantas

    2015-01-01

    As one of the most powerful tools in the biological investigation of cellular structures and dynamic processes, fluorescence microscopy has undergone extraordinary developments in the past decades. The advent of super-resolution techniques has enabled fluorescence microscopy – or rather nanoscopy – to achieve nanoscale resolution in living specimens and unravelled the interior of cells with unprecedented detail. The methods employed in this expanding field of microscopy, however, are especially prone to the detrimental effects of optical aberrations. In this review, we discuss how super-resolution microscopy techniques based upon single-molecule switching, stimulated emission depletion and structured illumination each suffer from aberrations in different ways that are dependent upon intrinsic technical aspects. We discuss the use of adaptive optics as an effective means to overcome this problem. PMID:26124194

  3. Chromosomal Aberrations in Humans Induced by Urban Air Pollution

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, Hannu; Gamborg, Michael O.

    1999-01-01

    We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes......, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations....... as a biomarker of genotoxic damage and dimethylsulfate-induced unscheduled DNA synthesis in mononuclear WBCs, the glutathione S-transferase M1 (GSTM1) genotype, and the N-acetyltransferase 2 (NAT2) genotype as biomarkers of susceptibility. The bus drivers, who had previously been observed to have elevated levels...

  4. Chromosomal aberrations and micronuclei frequencies in Bulgarian control population

    International Nuclear Information System (INIS)

    Popova, I.; Hadjidekova, V.; Hristova, R.; Atanasova, P.

    2004-01-01

    The aim of this investigation is to represent the frequency of spontaneous chromosomal damages in peripheral blood lymphocytes of Bulgarian control population. Material and methods: The investigated group includes persons belonging to both sexes and different ages. Each of them is interviewed of their social and health status. Sixteen persons are examined using the chromosomal aberrations analysis and forty-five with micronucleus test. The frequency of chromosomal aberrations varied between 0 - 2.4 % and the mean value is 1.00 %. The frequency of cells with micronuclei varied between 4.5 - 24.5 % and the mean value 12,9 %. Further work on the investigation of spontaneous frequency of chromosomal damages is in progress. (authors)

  5. Chromosome Aberrations in Human Lymphocytes Irradiated with Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin Hong; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    The purpose of the present experiment was to provide data on the dose-dependent production of chromosome aberrations such as dicentrics, centric rings, and excess acentrics. Radiation is one of the more dangerous clastogens in the environment. Ionizing radiation causes chromosome breakages and various cytogenetic aberrations in exposed cells. In an investigation into radiation emergencies, it is important to estimate the dose to exposed persons for several reasons. Physical dosimeters (e. g., film badges) may misrepresent the actual radiation dose and may not be available in a radiological accident or terrorism incident. Biological dosimetry is suitable for estimating the radiation dose during such accidents. The dicentric chromosome assay is very sensitive and a reliable bio-indicator in cases of accidental overexposure.

  6. Aberrations and adaptive optics in super-resolution microscopy.

    Science.gov (United States)

    Booth, Martin; Andrade, Débora; Burke, Daniel; Patton, Brian; Zurauskas, Mantas

    2015-08-01

    As one of the most powerful tools in the biological investigation of cellular structures and dynamic processes, fluorescence microscopy has undergone extraordinary developments in the past decades. The advent of super-resolution techniques has enabled fluorescence microscopy - or rather nanoscopy - to achieve nanoscale resolution in living specimens and unravelled the interior of cells with unprecedented detail. The methods employed in this expanding field of microscopy, however, are especially prone to the detrimental effects of optical aberrations. In this review, we discuss how super-resolution microscopy techniques based upon single-molecule switching, stimulated emission depletion and structured illumination each suffer from aberrations in different ways that are dependent upon intrinsic technical aspects. We discuss the use of adaptive optics as an effective means to overcome this problem. © The Author 2015. Published by Oxford University Press on behalf of The Japanese Society of Microscopy.

  7. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    Science.gov (United States)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  8. Chromosomal Aberrations in DNA Repair Defective Cell Lines: Comparisons of Dose Rate and Radiation Quality

    Science.gov (United States)

    George, K. A.; Hada, M.; Patel, Z.; Huff, J.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Chromosome aberration yields were assessed in DNA double-strand break repair (DSB) deficient cells after acute doses of gamma-rays or high-LET iron nuclei, or low dose-rate (0.018 Gy/hr) gamma-rays. We studied several cell lines including fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase, DNA-PK activity. Chromosomes were analyzed using the fluorescence in-situ hybridization (FISH) chromosome painting method in cells at the first division post-irradiation and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma radiation induced higher yields of both simple and complex exchanges in the DSB repair defective cells than in the normal cells. The quadratic dose-response terms for both chromosome exchange types were significantly higher for the ATM and NBS defective lines than for normal fibroblasts. However, the linear dose-response term was significantly higher only for simple exchanges in the NBS cells. Large increases in the quadratic dose response terms indicate the important roles of ATM and NBS in chromatin modifications that facilitate correct DSB repair and minimize aberration formation. Differences in the response of AT and NBS deficient cells at lower doses suggests important questions about the applicability of observations of radiation sensitivity at high dose to low dose exposures. For all iron nuclei irradiated cells, regression models preferred purely linear and quadratic dose responses for simple and complex exchanges, respectively. All the DNA repair defective cell lines had lower Relative biological effectiveness (RBE) values than normal cells, the lowest being for the DNA-PK-deficient cells, which was near unity. To further

  9. Aberrant infestation of goat mandibles with Oestrus ovis larvae.

    Science.gov (United States)

    Godara, R; Sharma, R L; Sharma, C S

    2010-01-01

    Nasal oestrosis is primarily an infestation of sheep. However, a non descript goat, aged three years was presented in lateral recumbency with clinical history of sneezing fits, laboured breathing, eroded mandibular lesions and bilaterally housing nasal bots therein. The first ever occurrence of nasal bots in an aberrant location (mandibles) in a goat, its therapeutic management and public health significance have been documented and discussed.

  10. Induction of chromosome aberrations in vitro by phenolphthalein: mechanistic studies.

    Science.gov (United States)

    Armstrong, M J; Gara, J P; Gealy, R; Greenwood, S K; Hilliard, C A; Laws, G M; Galloway, S M

    2000-12-20

    Phenolphthalein induces tumors in rodents but because it is negative in assays for mutation in Salmonella and in mammalian cells, for DNA adducts and for DNA strand breaks, its primary mechanism does not seem to be DNA damage. Chromosome aberration (Ab) induction by phenolphthalein in vitro is associated with marked cytotoxicity. At very high doses, phenolphthalein induces weak increases in micronuclei (MN) in mouse bone marrow; a larger response is seen with chronic treatment. All this suggests genotoxicity is a secondary effect that may not occur at lower doses. In heterozygous TSG-p53((R)) mice, phenolphthalein induces lymphomas and also MN, many with kinetochores (K), implying chromosome loss. Induction of aneuploidy would be compatible with the loss of the normal p53 gene seen in the lymphomas. Here we address some of the postulated mechanisms of genotoxicity in vitro, including metabolic activation, inhibition of thymidylate synthetase, cytotoxicity, oxidative stress, DNA damage and aneuploidy. We show clearly that phenolphthalein does not require metabolic activation by S9 to induce Abs. Inhibition of thymidylate synthetase is an unlikely mechanism, since thymidine did not prevent Ab induction by phenolphthalein. Phenolphthalein dramatically inhibited DNA synthesis, in common with many non-DNA reactive chemicals that induce Abs at cytotoxic doses. Phenolphthalein strongly enhances levels of intracellular oxygen radicals (ROS). The radical scavenger DMSO suppresses phenolphthalein-induced toxicity and Abs whereas H(2)O(2) potentiates them, suggesting a role for peroxidative activation. Phenolphthalein did not produce DNA strand breaks in rat hepatocytes or DNA adducts in Chinese hamster ovary (CHO) cells. All the evidence points to an indirect mechanism for Abs that is unlikely to operate at low doses of phenolphthalein. We also found that phenolphthalein induces mitotic abnormalities and MN with kinetochores in vitro. These are also enhanced by H(2)O(2) and

  11. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  12. Chromosome aberrations in ataxia telangiectasia cells exposed to heavy ions

    Science.gov (United States)

    Kawata, T.; Cucinotta, F.; George, K.; Wu, H.; Shigematsu, N.; Furusawa, Y.; Uno, T.; Isobe, K.; Ito, H.

    Understanding of biological effects of heavy ions is important to assess healt h risk in space. One of the most important issues may be to take into account individual susceptibility. Ataxia telangiectasia (A-T) cells are known to exhibit abnormal responses to radiations but the mechanism of hyper radiosensitivity of A-T still remains unknown. We report chromosome aberrations in normal human fibroblasts and AT fibroblasts exposed to low- and high-LET radiations. A chemical-induced premature chromosome condensation (PCC) technique combined with chromosome- painting technique was applied to score chromosome aberrations in G2/M-phase cells. Following gamma irradiation, GM02052 cells were approximately 5 times more sensitive to g-rays than AG1522 cells. GM02052 cells had a much higher frequency of deletions and misrejoining than AG1522 cells. When the frequency of complex type aberrations was compared, GM02052 cells showed more than 10 times higher frequency than AG1522 cells. The results will be compared with those obtained from high-LET irradiations.

  13. Simple numerical chromosome aberrations in two pituitary adenomas

    DEFF Research Database (Denmark)

    Dietrich, C U; Pandis, N; Bjerre, P

    1993-01-01

    Cytogenetic analysis of short-term cultures of one non-secreting and one prolactin-producing pituitary adenoma revealed simple clonal numerical abnormalities in both tumors. The karyotype of the non-secreting adenoma was 48,XX, +4, +9[42]/49,XX, +4, +9, +20[2]/46,XX[6]. In the prolactin-secreting...... chromosomal anomaly.......-secreting adenoma, three aberrant clones were detected, giving the karyotype 45,X, -Y[20]/47,XY, +Y[6]/45,XY, -21[3]/46,XY[21]. One cell had the chromosome complement 46,X, -Y, +9; no other nonclonal aberrations were detected. The only hitherto published case of pituitary adenoma analyzed by banding techniques (Rey...... et al. [1986]: Cancer Genet Cytogenet 23:171-174) also had only numerical clonal changes that included extra copies of chromosome 9. We conclude that pituitary adenomas may be karyotypically characterized by numerical aberrations and that trisomy 9 seems to be the best candidate for a primary...

  14. Aberrant behavior and cognitive ability in preschool children

    Directory of Open Access Journals (Sweden)

    Bala Gustav

    2007-01-01

    Full Text Available The sample included 712 preschool boys and girls at the age of 4 to 7 years (mean 5.96 decimal years and standard deviation .96 from preschool institutions in Novi Sad, Sombor, Sremska Mitrovica and Bačka Palanka. Information concerning 36 indicators of aberrant behavior of the children were supplied by their parents, whereas their cognitive ability was tested by Raven’s progressive colored matrices. Based on factor analysis (promax method, four factors i.e. generators of aberrant behavior in children were singled out: aggression, anxiousness, dissociation, and hysteria, whose relations with cognitive functioning and age were also analyzed by factor analysis. Aberrant behavior and cognitive abilities show significant interrelatedness. Owing to orderly developed cognitive abilities, a child understands essence and reality of problems, realizes possibilities and manners of solving them, and succeeds in realizing successful psycho-social functioning. Developed cognitive abilities enable a child to recognize and understand her/his own reactions in different situations and develop manners of reacting, which leads to strengthening psycho-social safety and adapting behavior in accordance with her/his age and abilities.

  15. Origin of specific chromosome aberration in radiation-induced leukemia

    International Nuclear Information System (INIS)

    Ban, Nobuhiko; Kai, Michiaki; Masuno, Yoko

    2005-01-01

    The theme in the title is discussed from the four aspects of specific chromosome aberration (sAb) patterns in radiation-induced leukemia (RIL), possibility for radiation to induce the sAb in RIL, any evidence for participation of delayed aberration to form sAb and the proportion of such healthy humans as having the specifically rearranged genome. Data of sAb observed in leukemia of 25 A-bomb survivors and of 38 patients post radiotherapy of cancers give a rather common pattern. However, many inconsistent results are obtained for sAb in patients post radiotherapy, A-bomb survivors, residents living in radio-contaminated houses in Taipei, in vitro exposure, and Chernobyl residents. At present, any clear evidence is available neither for sAb derived from the delayed aberration nor for estimating the proportion with the specifically rearranged gene. As above, it is unlikely that radiation induces such a translocation abnormality as BCR-ABL specifically seen in leukemia, and this aspect will be important for studies on the genesis of RIL and its risk assessment. (S.I.)

  16. World petrochemical outlook: Is the current weakness a trend or an aberration?

    International Nuclear Information System (INIS)

    Baggett, P.E.

    1995-01-01

    While the focus of this conference is methanol, a review of the general petrochemical industry might be enlightening and valuable to understanding the methanol market. Methanol is certainly a commodity with similarities to hydrocarbons such as gasoline and similarities to base petrochemicals such as ethylene. Methanol stands with one foot in the fuels market via MTBE and the other in the chemicals business for acetic acid and formaldehyde, among many others. Is the world petrochemical market moving into a new trend of weak prices and profits or is the strong growth seen in 1994 and 1995 continuing and the current situation an aberration? In order to determine whether the current market is a trend or aberration, the author looks at issues that he believes caused the current situation and then considers where the world's economies and petrochemical markets are heading. The issues discussed are: unusually high price increase in a short period; inventory increase/decrease because of price changes; reduction in demand caused by high prices; increase in capacity caused by high prices; changes in growth of world economies; and political/economic issues in China

  17. Chromosome aberrations and rogue cells in lymphocytes of Chernobyl clean-up workers

    International Nuclear Information System (INIS)

    Lazutka, J.R.

    1996-01-01

    A cytogenetic analysis was performed on peripheral blood lymphocytes from 183 Chernobyl clean-up workers and 27 control individuals. Increased frequencies of chromosome aberrations were associated with exposure to radiation at Chernobyl, alcohol abuse and a history of recent influenza infection. However, only approximately 20% of Chernobyl clean-up workers had an increased frequency of dicentric and ring chromosomes. At the same time, an increased frequency of acentric fragments in lymphocytes of clean-up workers was characteristic. The use of multivitamins as dietary supplement significantly decreased the frequency of chromosome aberrations, especially of chromatid breaks. Rogue cells were found in lymphocytes of 28 clean-up workers and 3 control individuals. The appearance of rogue cells was associated with a recent history of acute respiratory disease (presumably caused by adenoviral infection) and, probably, alcohol abuse. Dicentric chromosomes in rogue cells were distributed according to a negative binomial distribution. Occurrence of rogue cells due to a perturbation of cell cycle control and abnormal apoptosis is suggested

  18. Spontaneous and induced chromosomal aberrations in bone marrow cells of mice of different strain and age

    Energy Technology Data Exchange (ETDEWEB)

    Lil' p, J.G.; Korogodina, Yu.V. (Akademiya Meditsinskikh Nauk SSSR, Moscow. Inst. Meditsinskoj Genetiki)

    1981-01-01

    The sensitivity of bone marrow cell chromosomes both to an alkylating agent thiophosphamide and ..gamma..-irradiation in 101/H, A/He, CBA, BALB/c and C57BL/6 aging mice has been studied. Changes in the sensitivity of bone marrow cell chromosomes with age are shown to depend both on mutagenic effect type and animal's genotype. The age dependent yield of chromosomal aberrations did not change in mice of all studied strains after ..gamma..-irradiation under conditions of our experiments. After the thiophosphamide effect, an increased sensitivity of bone marrow cell chromosomes was observed in the old 101/H, A/He and CBA mice as compared to the young ones. The level of induced chromosomal aberrations in C57BL/6 mice did not vary with age. Cells exhibiting multiple damages to chromosomes occurred in the bone marrow following the thiophosphamide effect. An increased sensitivity of old animals of certain strains resulted mainly from a sharp numerical growth of such cells. No increase in the number of cells in intact animals of all strains related to age dependent chromosomal structural damages was observed, whereas the accumulation of aneuploid cells probably depended on the genotype.

  19. Assessment of refractive astigmatism and simulated therapeutic refractive surgery strategies in coma-like-aberrations-dominant corneal optics.

    Science.gov (United States)

    Zhou, Wen; Stojanovic, Aleksandar; Utheim, Tor Paaske

    2016-01-01

    The aim of the study is to raise the awareness of the influence of coma-like higher-order aberrations (HOAs) on power and orientation of refractive astigmatism (RA) and to explore how to account for that influence in the planning of topography-guided refractive surgery in eyes with coma-like-aberrations-dominant corneal optics. Eleven eyes with coma-like-aberrations-dominant corneal optics and with low lenticular astigmatism (LA) were selected for astigmatism analysis and for treatment simulations with topography-guided custom ablation. Vector analysis was used to evaluate the contribution of coma-like corneal HOAs to RA. Two different strategies were used for simulated treatments aiming to regularize irregular corneal optics: With both strategies correction of anterior corneal surface irregularities (corneal HOAs) were intended. Correction of total corneal astigmatism (TCA) and RA was intended as well with strategies 1 and 2, respectively. Axis of discrepant astigmatism (RA minus TCA minus LA) correlated strongly with axis of coma. Vertical coma influenced RA by canceling the effect of the with-the-rule astigmatism and increasing the effect of the against-the-rule astigmatism. After simulated correction of anterior corneal HOAs along with TCA and RA (strategies 1 and 2), only a small amount of anterior corneal astigmatism (ACA) and no TCA remained after strategy 1, while considerable amount of ACA and TCA remained after strategy 2. Coma-like corneal aberrations seem to contribute a considerable astigmatic component to RA in eyes with coma-like-aberrations dominant corneal optics. If topography-guided ablation is programmed to correct the corneal HOAs and RA, the astigmatic component caused by the coma-like corneal HOAs will be treated twice and will result in induced astigmatism. Disregarding RA and treating TCA along with the corneal HOAs is recommended instead.

  20. Kinetin improves IKBKAP mRNA splicing in patients with familial dysautonomia

    Science.gov (United States)

    Axelrod, Felicia B.; Liebes, Leonard; Gold-von Simson, Gabrielle; Mendoza, Sandra; Mull, James; Leyne, Maire; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio; Slaugenhaupt, Susan A.

    2011-01-01

    Familial dysautonomia (FD) is caused by an intronic splice mutation in the IKBKAP gene that leads to partial skipping of exon 20 and tissue-specific reduction in I-κ-B kinase complex associated protein/ elongation protein 1 (IKAP/ELP-1) expression. Kinetin (6-furfurylaminopurine) has been shown to improve splicing and increase wild-type IKBKAP mRNA and IKAP protein expression in FD cell lines and carriers. To determine if oral kinetin treatment could alter mRNA splicing in FD subjects and was tolerable, we administered kinetin to eight FD individuals homozygous for the splice mutation. Subjects received 23.5 mg/Kg/day for 28 days. An increase in wild-type IKBKAP mRNA expression in leukocytes was noted after eight days in six of eight individuals; after 28 days the mean increase as compared to baseline was significant (p=0.002). We have demonstrated that kinetin is tolerable in this medically fragile population. Not only did kinetin produce the desired effect on splicing in FD patients, but also that effect appears to improve with time despite lack of dose change. This is the first report of a drug that produces in vivo mRNA splicing changes in individuals with FD and supports future long-term trials to determine if kinetin will prove therapeutic in FD patients. PMID:21775922

  1. Role of base damage in aberration formation: interaction of aphidicolin and x-rays

    Energy Technology Data Exchange (ETDEWEB)

    Bender, M.A.; Preston, R.J.

    1981-01-01

    The base analog cytosine arabinoside (CA) is an inhibitor of DNA synthesis that is able to induce chromosomal aberrations not only in the DNA synthetic (S) phase of the cell cycle but in cells in the pre- (G/sub 0/ or G/sub 1/) and in the post-DNA-synthetic (G/sub 2/) phases of the cell cycle as well. Incubation of human peripheral lymphocytes in CA following either G/sub 0/ or G/sub 2/ x irradiation causes a synergistic increase in chromosomal aberration frequency. CA is believed to preferentially inhibit DNA polymerase ..cap alpha... It is suggested that it is inhibition of the repair of x-ray-induced base damage that is responsible for the synergistic effect on chromosomal aberration production observed with x-ray and CA treatment of human peripheral lymphocytes. It has also been observed that CA induces sister chromatid exchanges (SCE) in mammalian cells when present during normal DNA replication and that it also interacts synergistically with uv in the induction of SCE. A number of other inhibitors of DNA synthesis were also tested, one, aphidicolin (APC), did produce effects similar to CA at the same concentration. Aphidicolin is a tetracyclic diterpinoid that inhibits the growth of eukaryotic cells by inhibition of DNA synthesis. This action has been shown to result from specific inhibition of DNA polymerase ..cap alpha.., but not of polymerases ..beta.. or ..gamma... Unlike CA, it seems likely that APC inhibits by binding to and inactivating the DNA-..cap alpha.. polymerase complex. Because both CA and APC are ..cap alpha.. polymerase inhibitors and because both interact synergistically with uv in the production of SCE, studies were conducted to determine whether APC also shares other cytogenetic properties of CA. Results to date have shown that, like CA, APC is clastogenic in both G/sub 0/ and G/sub 2/, and it also interacts synergistically with x rays to increase chromosomal aberration production in both G/sub 0/ and G/sub 2/. (ERB)

  2. Aberrant muscle syndrome: hypertrophy of the hand and arm due to aberrant muscles with or without hypertrophy of the muscles.

    Science.gov (United States)

    Ogino, Toshihiko; Satake, Hiroshi; Takahara, Masatoshi; Kikuchi, Noriaki; Watanabe, Tadayosi; Iba, Kousuke; Ishii, Seiichi

    2010-06-01

    Five patients were reported in our congenital anomaly registry who had six hands in total with muscular hyperplasia, aberrant muscles, ulnar drift of the fingers in the metacarpophalangeal (MP) joints, flexion contractures of the MP joints, and enlargement of the metacarpal spaces. Thirty patients with unilateral involvement of this condition have been reported previously. We reviewed these cases and found that the condition varied in severity and that it was reported using different names. However, this condition seems different from true macrodactyly and multiple camptodactyly, including windblown hand, and seems to be an isolated entity of congenital upper limb anomaly. The authors recommend 'aberrant muscle syndrome' or 'accessory muscle syndrome' as a diagnostic name, because this seems to be the most common pathological finding in this condition.

  3. Analysis of Chromosomal Aberrations after Low and High Dose Rate Gamma Irradiation in ATM or NBS Suppressed Human Fibroblast Cells

    Science.gov (United States)

    Hada, M.; Huff, J. L.; Patel, Z.; Pluth, J. M.; George, K. A.; Cucinotta, F. A.

    2009-01-01

    A detailed understanding of the biological effects of heavy nuclei is needed for space radiation protection and for cancer therapy. High-LET radiation produces more complex DNA lesions that may be non-repairable or that may require additional processing steps compared to endogenous DSBs, increasing the possibility of misrepair. Interplay between radiation sensitivity, dose, and radiation quality has not been studied extensively. Previously we studied chromosome aberrations induced by low- and high- LET radiation in several cell lines deficient in ATM (ataxia telangactasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. We found that the yields of both simple and complex chromosomal aberrations were significantly increased in the DSB repair defective cells compared to normal cells. The increased aberrations observed for the ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher in NBS cells only for simple exchanges. These results point to the importance of the functions of ATM and NBS in chromatin modifications that function to facilitate correct DSB repair and minimize aberration formation. To further understand the sensitivity differences that were observed in ATM and NBS deficient cells, in this study, chromosomal aberration analysis was performed in normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, or Mirin, an MRN complex inhibitor involved in activation of ATM. We are also testing siRNA knockdown of these proteins. Normal and ATM or NBS suppressed cells were irradiated with gamma-rays and chromosomes were collected with a premature chromosome

  4. Control of gene expression during T cell activation: alternate regulation of mRNA transcription and mRNA stability

    Directory of Open Access Journals (Sweden)

    Gorospe Myriam

    2005-05-01

    Full Text Available Abstract Background Microarray technology has become highly valuable for identifying complex global changes in gene expression patterns. The effective correlation of observed changes in gene expression with shared transcription regulatory elements remains difficult to demonstrate convincingly. One reason for this difficulty may result from the intricate convergence of both transcriptional and mRNA turnover events which, together, directly influence steady-state mRNA levels. Results In order to investigate the relative contribution of gene transcription and changes in mRNA stability regulation to standard analyses of gene expression, we used two distinct microarray methods which individually measure nuclear gene transcription and changes in polyA mRNA gene expression. Gene expression profiles were obtained from both polyA mRNA (whole-cell and nuclear run-on (newly transcribed RNA across a time course of one hour following the activation of human Jurkat T cells with PMA plus ionomycin. Comparative analysis revealed that regulation of mRNA stability may account for as much as 50% of all measurements of changes in polyA mRNA in this system, as inferred by the absence of any corresponding regulation of nuclear gene transcription activity for these groups of genes. Genes which displayed dramatic elevations in both mRNA and nuclear run-on RNA were shown to be inhibited by Actinomycin D (ActD pre-treatment of cells while large numbers of genes regulated only through altered mRNA turnover (both up and down were ActD-resistant. Consistent patterns across the time course were observed for both transcribed and stability-regulated genes. Conclusion We propose that regulation of mRNA stability contributes significantly to the observed changes in gene expression in response to external stimuli, as measured by high throughput systems.

  5. Brahmarasayana protects against Ethyl methanesulfonate or Methyl methanesulfonate induced chromosomal aberrations in mouse bone marrow cells

    Directory of Open Access Journals (Sweden)

    Guruprasad Kanive

    2012-08-01

    Full Text Available Abstract Background Ayurveda, the traditional Indian system of medicine has given great emphasis to the promotion of health. Rasayana is one of the eight branches of Ayurveda which refers to rejuvenant therapy. It has been reported that rasayanas have immuno-modulatory, antioxidant and antitumor functions, however, the genotoxic potential and modulation of DNA repair of many rasayanas have not been evaluated. Methods The present study assessed the role of Brahmarasayana (BR on Ethyl methanesulfonate (EMS-and Methyl methanesulfonate (MMS-induced genotoxicity and DNA repair in in vivo mouse test system. The mice were orally fed with BR (5 g or 8 mg / day for two months and 24 h later EMS or MMS was given intraperitoneally. The genotoxicity was analyzed by chromosomal aberrations, sperm count, and sperm abnormalities. Results The results have revealed that BR did not induce significant chromosomal aberrations when compared to that of the control animals (p >0.05. On the other hand, the frequencies of chromosomal aberrations induced by EMS (240 mg / kg body weight or MMS (125 mg / kg body weight were significantly higher (p Conclusion The effect of BR, as it relates to antioxidant activity was not evident in liver tissue however rasayana treatment was observed to increase constitutive DNA base excision repair and reduce clastogenicity. Whilst, the molecular mechanisms of such repair need further exploration, this is the first report to demonstrate these effects and provides further evidence for the role of brahmarasayana in the possible improvement of quality of life.

  6. Aberrant connectivity of areas for decoding degraded speech in patients with auditory verbal hallucinations.

    Science.gov (United States)

    Clos, Mareike; Diederen, Kelly M J; Meijering, Anne Lotte; Sommer, Iris E; Eickhoff, Simon B

    2014-03-01

    Auditory verbal hallucinations (AVH) are a hallmark of psychotic experience. Various mechanisms including misattribution of inner speech and imbalance between bottom-up and top-down factors in auditory perception potentially due to aberrant connectivity between frontal and temporo-parietal areas have been suggested to underlie AVH. Experimental evidence for disturbed connectivity of networks sustaining auditory-verbal processing is, however, sparse. We compared functional resting-state connectivity in 49 psychotic patients with frequent AVH and 49 matched controls. The analysis was seeded from the left middle temporal gyrus (MTG), thalamus, angular gyrus (AG) and inferior frontal gyrus (IFG) as these regions are implicated in extracting meaning from impoverished speech-like sounds. Aberrant connectivity was found for all seeds. Decreased connectivity was observed between the left MTG and its right homotope, between the left AG and the surrounding inferior parietal cortex (IPC) and the left inferior temporal gyrus, between the left thalamus and the right cerebellum, as well as between the left IFG and left IPC, and dorsolateral and ventrolateral prefrontal cortex (DLPFC/VLPFC). Increased connectivity was observed between the left IFG and the supplementary motor area (SMA) and the left insula and between the left thalamus and the left fusiform gyrus/hippocampus. The predisposition to experience AVH might result from decoupling between the speech production system (IFG, insula and SMA) and the self-monitoring system (DLPFC, VLPFC, IPC) leading to misattribution of inner speech. Furthermore, decreased connectivity between nodes involved in speech processing (AG, MTG) and other regions implicated in auditory processing might reflect aberrant top-down influences in AVH.

  7. Study on ionizing radiation to the workers' lymphocyte micronucleus rate and chromosome aberrations

    International Nuclear Information System (INIS)

    Li Jianhua; Wang Linchao; He Wei

    2007-01-01

    Objective: To study lymphocyte genetic material of an iron and steel enterprise workers exposed to the ionizing radiation, find out measures to protect their health and reduce ionizing radiation occupation harm. Methods: 342 workers were choseh as the exposed group who worked in an iron and steel enterprise in the beam installment operation, to examine their circumference blood lymphocyte micronucleus rate and the chromosome aberrations, simultaneously select 280 chefs as the control group, The irradiation dosage was determined and statistical analysis was carded out wich the consideration of their length of work and differences in work post. Results: Exposed group: the micronucleus rate masculine gender (MNR), 4 people, the masculine gender pick out rate is 12.87%. The chromosome aberration factor masculine gender (CAF), 12 people, the masculine rate is 3.51%. Control group: MNR 3 people, the asculine gender pick out rate is 1.07%; CAF 2 people, masculine gender rate is 0.72%. Comparing the two groups, every item has the significant difference. Workers in is the exposed group workers have the average exposure dose of 6.73mSv/a, MNR,CAF are illuminated to the dosage have a positive line correlation. They become increased as the job lenght prolongs. The nucleon name, the material calculation and the medical X-radial are responsible for the highest ratio. Conclusion: In iron and steel enterprises, long-time ionizing radiation can cause the workers' circumference blood lymphocyte micronucleus rate and the chromosome aberrations obvious to rise. The beam protection measures strengthened so as to reduce the harms to workers. (authors)

  8. Novel RNA-binding activity of NQO1 promotes SERPINA1 mRNA translation.

    Science.gov (United States)

    Di Francesco, Andrea; Di Germanio, Clara; Panda, Amaresh C; Huynh, Phu; Peaden, Robert; Navas-Enamorado, Ignacio; Bastian, Paul; Lehrmann, Elin; Diaz-Ruiz, Alberto; Ross, David; Siegel, David; Martindale, Jennifer L; Bernier, Michel; Gorospe, Myriam; Abdelmohsen, Kotb; de Cabo, Rafael

    2016-10-01

    NAD(P)H: quinone oxidoreductase (NQO1) is essential for cell defense against reactive oxidative species, cancer, and metabolic stress. Recently, NQO1 was found in ribonucleoprotein (RNP) complexes, but NQO1-interacting mRNAs and the functional impact of such interactions are not known. Here, we used ribonucleoprotein immunoprecipitation (RIP) and microarray analysis to identify comprehensively the subset of NQO1 target mRNAs in human hepatoma HepG2 cells. One of its main targets, SERPINA1 mRNA, encodes the serine protease inhibitor α-1-antitrypsin, A1AT, which is associated with disorders including obesity-related metabolic inflammation, chronic obstructive pulmonary disease (COPD), liver cirrhosis and hepatocellular carcinoma. Biotin pulldown analysis indicated that NQO1 can bind the 3' untranslated region (UTR) and the coding region (CR) of SERPINA1 mRNA. NQO1 did not affect SERPINA1 mRNA levels; instead, it enhanced the translation of SERPINA1 mRNA, as NQO1 silencing decreased the size of polysomes forming on SERPINA1 mRNA and lowered the abundance of A1AT. Luciferase reporter analysis further indicated that NQO1 regulates SERPINA1 mRNA translation through the SERPINA1 3'UTR. Accordingly, NQO1-KO mice had reduced hepatic and serum levels of A1AT and increased activity of neutrophil elastase (NE), one of the main targets of A1AT. We propose that this novel mechanism of action of NQO1 as an RNA-binding protein may help to explain its pleiotropic biological effects. Published by Elsevier Inc.

  9. Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes

    Directory of Open Access Journals (Sweden)

    Liu Edison

    2007-06-01

    Full Text Available Abstract Background Melanoma is the major cause of skin cancer deaths and melanoma incidence doubles every 10 to 20 years. However, little is known about melanoma pathway aberrations. Here we applied the robust Gene Identification Signature Paired End diTag (GIS-PET approach to investigate the melanoma transcriptome and characterize the global pathway aberrations. Methods GIS-PET technology directly links 5' mRNA signatures with their corresponding 3' signatures to generate, and then concatenate, PETs for efficient sequencing. We annotated PETs to pathways of KEGG database and compared the murine B16F1 melanoma transcriptome with three non-melanoma murine transcriptomes (Melan-a2 melanocytes, E14 embryonic stem cells, and E17.5 embryo. Gene expression levels as represented by PET counts were compared across melanoma and melanocyte libraries to identify the most significantly altered pathways and investigate the expression levels of crucial cancer genes. Results Melanin biosynthesis genes were solely expressed in the cells of melanocytic origin, indicating the feasibility of using the PET approach for transcriptome comparison. The most significantly altered pathways were metabolic pathways, including upregulated pathways: purine metabolism, aminophosphonate metabolism, tyrosine metabolism, selenoamino acid metabolism, galactose utilization, nitrobenzene degradation, and bisphenol A degradation; and downregulated pathways: oxidative phosphorylation, ATPase synthesis, TCA cycle, pyruvate metabolism, and glutathione metabolism. The downregulated pathways concurrently indicated a slowdown of mitochondrial activities. Mitochondrial permeability was also significantly altered, as indicated by transcriptional activation of ATP/ADP, citrate/malate, Mg++, fatty acid and amino acid transporters, and transcriptional repression of zinc and metal ion transporters. Upregulation of cell cycle progression, MAPK, and PI3K/Akt pathways were more limited to certain

  10. On the Spatial Organization of mRNA, Plasmids, and Ribosomes in a Bacterial Host Overexpressing Membrane Proteins.

    Directory of Open Access Journals (Sweden)

    Lieke A van Gijtenbeek

    2016-12-01

    Full Text Available By using fluorescence imaging, we provide a time-resolved single-cell view on coupled defects in transcription, translation, and growth during expression of heterologous membrane proteins in Lactococcus lactis. Transcripts encoding poorly produced membrane proteins accumulate in mRNA-dense bodies at the cell poles, whereas transcripts of a well-expressed homologous membrane protein show membrane-proximal localization in a translation-dependent fashion. The presence of the aberrant polar mRNA foci correlates with cessation of cell division, which is restored once these bodies are cleared. In addition, activation of the heat-shock response and a loss of nucleoid-occluded ribosomes are observed. We show that the presence of a native-like N-terminal domain is key to SRP-dependent membrane localization and successful production of membrane proteins. The work presented gives new insights and detailed understanding of aberrant membrane protein biogenesis, which can be used for strategies to optimize membrane protein production.

  11. Chromosome aberrations induced in human lymphocytes by heavy charged particles in track segment mode

    International Nuclear Information System (INIS)

    Di Giorgio, M.; Edwards, A. A.; Moquet, J. E.; Finnon, P.; Hone, P. A.; Lloyd, D. C.; Kreiner, A. J.; Schuff, J. A.; Taja, M. R.; Vallerga, M. B.; Lopez, F. O.; Burlon, A.; Debray, M. E.; Valda, A.

    2004-01-01

    Human blood was irradiated with accelerated ions: 20 MeV 4 He, 425 MeV 12 C and 1480 MeV and 996 MeV 16 O. For each ion, the blood was exposed to a range of doses as thin specimens in the track segment mode, so that irradiations took place at nearly constant LETs of 31.4, 61, 52 and 69 keV μm -1 , respectively. Lymphocytes were cultured to the first in vitro metaphase, analysed for chromosomal damage and the dicentric aberration frequencies fitted to the linear quadratic model of dose-response. For these high LET radiations, the linear (α) yield coefficient predominated and increased with LET, at least up to 60 keV μm -1 . Apart from the 996 MeV oxygen ions, the data indicated the presence of a quadratic (β) coefficient, statistically consistent with values obtained with low LET radiations. However, the associated uncertainties on the measured β values were large, illustrating the general problem that β is more difficult to measure against a dominating and ever-increasing α term. The existence or otherwise of a β component of the dose-response at these radiation qualities has important consequences for modelling mechanisms of aberration induction by radiation. (authors)

  12. Inner Leaf Gel of Aloe striata Induces Adhesion-Reducing Morphological Hyphal Aberrations

    Directory of Open Access Journals (Sweden)

    Gloria Wada

    2018-02-01

    Full Text Available Fungi, particularly molds that are cosmopolitan in soils, are frequent etiologic agents of opportunistic mycoses. Members of the Fusarium solani and Fusarium oxysporum species complexes are the most commonly implicated etiologic agents of opportunistic fusarial infections in mammals, while Paecilomyces variotii is one of the most frequently encountered Paecilomyces species in human infections. Prevention and treatment of these mycoses are problematic because available antimycotics are limited and often have toxic side effects. Popular folk medicines, such as the inner leaf gel from Aloe spp., offer potential sources for novel antimycotic compounds. To screen for antifungal properties of Aloe striata, we treated conidia of three strains each of F. solani, F. oxysporum, and P. variotii with homogenized and filtered inner leaf gel. Exposure to gel homogenates caused minimal inhibition of conidial germination in tested strains. However, it significantly increased the frequency of hyphal aberrations characterized by increased hyphal diameters that resulted in intervals of non-parallel cell walls. Non-parallel cell walls ostensibly reduce total hyphal surface area available for adhesion. We found a significant decrease in the ability of aberrated P. variotii hyphae to remain adhered to microscope slides after repeated washing with reverse osmosis water. Our results suggest that treatment with A. striata contributes to a decrease in the adhesion frequency of tested P. variotii strains.

  13. Impact of fasting followed by short-term exposure to interleukin-6 on cytochrome P450 mRNA in mice.

    Science.gov (United States)

    Rasmussen, Martin Krøyer; Bertholdt, Lærke; Gudiksen, Anders; Pilegaard, Henriette; Knudsen, Jakob G

    2018-01-05

    The gene expression of the cytochrome P450 (CYP) enzyme family is regulated by numerous factors. Fasting has been shown to induce increased hepatic CYP mRNA in both humans and animals. However, the coordinated regulation of CYP, CYP-regulating transcription factors, and transcriptional co-factors in the liver linking energy metabolism to detoxification has never been investigated. Interleukin-6 (IL-6) has been suggested to be released during fasting and has been shown to regulate CYP expression. The present study investigated the hepatic mRNA content of selected CYP, AhR, CAR, PXR and PPARα in mice fasted for 18h and subsequently exposed to IL-6. Furthermore, the impact of fasting on PGC-1α, HNF-4α, SIRT1 and SIRT3 mRNA was examined. Fasting induced a marked increase in Cyp2b10, Cyp2e1 and Cyp4a10 mRNA, while CYP1a1, Cyp1a2, Cyp2a4 and Cyp3a11 mRNA levels remained unchanged. In accordance, the mRNA levels of CAR and PPARα were also increased with fasting. The PGC-1α, SIRT1 and SIRT3 mRNA levels were also increased after fasting, while the HNF-4α mRNA levels remained unchanged. In mice subjected to IL-6 injection, the fasting-induced PXR, PPARα and PGC-1α mRNA responses were lower than after saline injection. In conclusion, fasting was demonstrated to be a strong inducer of hepatic CYP mRNA as well as selected transcription factors controlling the expression of the investigated CYP. Moreover, the mRNA levels of transcriptional co-factors acting as energy sensors and co-factors for CYP regulation was also increased in the liver, suggesting crosstalk at the molecular level between regulation of energy metabolism and detoxification. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The peptidyl-prolyl isomerase Pin1 determines parathyroid hormone mRNA levels and stability in rat models of secondary hyperparathyroidism.

    Science.gov (United States)

    Nechama, Morris; Uchida, Takafumi; Mor Yosef-Levi, Irit; Silver, Justin; Naveh-Many, Tally

    2009-10-01

    Secondary hyperparathyroidism is a major complication of chronic kidney disease (CKD). In experimental models of secondary hyperparathyroidism induced by hypocalcemia or CKD, parathyroid hormone (PTH) mRNA levels increase due to increased PTH mRNA stability. K-homology splicing regulator protein (KSRP) decreases the stability of PTH mRNA upon binding a cis-acting element in the PTH mRNA 3' UTR region. As the peptidyl-prolyl isomerase (PPIase) Pin1 has recently been shown to regulate the turnover of multiple cytokine mRNAs, we investigated the role of Pin1 in regulating PTH mRNA stability in rat parathyroids and transfected cells. The data generated were consistent with Pin1 being a PTH mRNA destabilizing protein. Initial analysis indicated that Pin1 activity was decreased in parathyroid protein extracts from both hypocalcemic and CKD rats and that pharmacologic inhibition of Pin1 increased PTH mRNA levels posttranscriptionally in rat parathyroid and in transfected cells. Pin1 mediated its effects via interaction with KSRP, which led to KSRP dephosphorylation and activation. In the rat parathyroid, Pin1 inhibition decreased KSRP-PTH mRNA interactions, increasing PTH mRNA levels. Furthermore, Pin1-/- mice displayed increased serum PTH and PTH mRNA levels, suggesting that Pin1 determines basal PTH expression in vivo. These results demonstrate that Pin1 is a key mediator of PTH mRNA stability and indicate a role for Pin1 in the pathogenesis of secondary hyperparathyroidism in individuals with CKD.

  15. [Effect of the gardenia extracts-T9 on viral replication and IFN-gamma mRNA in Herpes simplex virus type-1 infected mice brains].

    Science.gov (United States)

    Shi, Yu-jing; Huang, Yang; Jiang, Jing; Guo, Shan-shan; Su, Dan; Zhao, Ye; Gao, Ying-jie; Cui, Xiao-lan

    2009-01-01

    RT-PCR was used to detect expression level of VP16 mRNA and IFN-gamma mRNA in Herpes simplex virus type-1 infected mice brains at 4th day, 7th day, 10th day, 14th day, 21st day post infection and investigate the effects of the Gardenia extracts-T9 on viral replication and host immunity. The results showed that expression of VP16 mRNA in Gardenia extracts-T9 high dose and low dose group were both lower than that in virus control group at same time point. Relative VP16 mRNA expression in low dose group decreased at 21st day and relative VP16 mRNA expression in high dose group decreased continuously. Relative expression of IFN-gamma mRNA in high dose and low dose groups were both higher than that in virus control group at all time point except the 4th day. IFN-gamma mRNA in low dose group increased from the 4th day till the 14th day, and after the 14th day, the expression decreased slightly. Relative IFN-gamma mRNA in high dose group maintained increasing from 4th day till 21st day. Base on these results, we conclude that Gardenia extracts-T9 might exert the inhibition effect of viral replication by upregulating expression of IFN-gamma mRNA.

  16. Differential regulation of renal cyclooxygenase mRNA by dietary salt intake

    DEFF Research Database (Denmark)

    Jensen, B L; Kurtz, A

    1997-01-01

    RNA correlated directly with salt intake. We conclude that dietary salt intake influences renal cyclooxygenase mRNAs zone-specifically with opposite responses between cortex and medulla. Cortical COX II-mediated prostaglandin formation is probably important in low salt states whereas medullary COX I......Experiments were done to investigate the influence of dietary salt intake on renal cyclooxygenase (COX) I and II mRNA levels. To this end rats were fed either a low NaCl diet (LS; 0.02% NaCl wt/wt) or a high NaCl diet (HS diet; 4% NaCl wt/wt) for 5, 10 and 20 days. After 10 days Na excretion...... differed 760-fold, plasma renin activity and renin mRNA were increased eight- and threefold in LS compared to HS animals. Total renal COX I mRNA decreased 50% following the LS diet and did not change after the HS diet. Conversely, COX II mRNA declined after HS intake and transiently increased after salt...

  17. Role of protein and mRNA oxidation in seed dormancy and germination

    Science.gov (United States)

    El-Maarouf-Bouteau, Hayat; Meimoun, Patrice; Job, Claudette; Job, Dominique; Bailly, Christophe

    2013-01-01

    Reactive oxygen species (ROS) are key players in the regulation of seed germination and dormancy. Although their regulated accumulation is a prerequisite for germination, the cellular basis of their action remains unknown, but very challenging to elucidate due to the lack of specificity of these compounds that can potentially react with all biomolecules. Among these, nucleic acids and proteins are very prone to oxidative damage. RNA is highly sensitive to oxidation because of its single-stranded structure and the absence of a repair system. Oxidation of mRNAs induces their decay through processing bodies or results in the synthesis of aberrant proteins through altered translation. Depending on the oxidized amino acid, ROS damage of proteins can be irreversible (i.e., carbonylation) thus triggering the degradation of the oxidized proteins by the cytosolic 20S proteasome or can be reversed through the action of thioredoxins, peroxiredoxins, or glutaredoxins (cysteine oxidation) or by methionine sulfoxide reductase (methionine oxidation). Seed dormancy alleviation in the dry state, referred to as after-ripening, requires both selective mRNA oxidation and protein carbonylation. Similarly, seed imbibition of non-dormant seeds is associated with targeted oxidation of a subset of proteins. Altogether, these specific features testify that such oxidative modifications play important role in commitment of the cellular functioning toward germination completion. PMID:23579315

  18. Aberrant topology of striatum's connectivity is associated with the number of episodes in depression.

    Science.gov (United States)

    Meng, Chun; Brandl, Felix; Tahmasian, Masoud; Shao, Junming; Manoliu, Andrei; Scherr, Martin; Schwerthöffer, Dirk; Bäuml, Josef; Förstl, Hans; Zimmer, Claus; Wohlschläger, Afra M; Riedl, Valentin; Sorg, Christian

    2014-02-01

    In major depressive disorder, depressive episodes reoccur in ∼60% of cases; however, neural mechanisms of depressive relapse are poorly understood. Depressive episodes are characterized by aberrant topology of the brain's intrinsic functional connectivity network, and the number of episodes is one of the most important predictors for depressive relapse. In this study we hypothesized that specific changes of the topology of intrinsic connectivity interact with the course of episodes in recurrent depressive disorder. To address this hypothesis, we investigated which changes of connectivity topology are associated with the number of episodes in patients, independently of current symptoms and disease duration. Fifty subjects were recruited including 25 depressive patients (two to 10 episodes) and 25 gender- and age-matched control subjects. Resting-state functional magnetic resonance imaging, Harvard-Oxford brain atlas, wavelet-transformation of atlas-shaped regional time-series, and their pairwise Pearson's correlation were used to define individual connectivity matrices. Matrices were analysed by graph-based methods, resulting in outcome measures that were used as surrogates of intrinsic network topology. Topological scores were subsequently compared across groups, and, for patients only, related with the number of depressive episodes and current symptoms by partial correlation analysis. Concerning the whole brain connectivity network of patients, small-world topology was preserved but global efficiency was reduced and global betweenness-centrality increased. Aberrant nodal efficiency and centrality of regional connectivity was found in the dorsal striatum, inferior frontal and orbitofrontal cortex as well as in the occipital and somatosensory cortex. Inferior frontal changes were associated with current symptoms, whereas aberrant right putamen network topology was associated with the number of episodes. Results were controlled for effects of total grey matter

  19. Chromosomal aberrations in lymphocytes of peripheral blood among mayak facility workers who inhaled insoluble forms of 239Pu

    International Nuclear Information System (INIS)

    Okladnikova, N. D.; Scott, B. R.; Tokarskaya, Z. B.; Zhuntova, G. V.; Khokhryakov, V. F.; Syrchikov, V. A.; Grigoryeva, E. S.

    2005-01-01

    A cytogenetic study was performed on 79 plutonium (Pu) workers chronically exposed to alpha radiation from inhaled, low-transportable (insoluble) compounds of airborne 239 Pu and to external gamma rays. Body burden estimates for 239 Pu ranged from 0 to 15.5 kBq. Chromosomal aberrations (CAs) (stable and unstable among peripheral blood lymphocytes and cumulative alpha radiation doses were evaluated ∼25 y after first contact with 239 Pu. For the cytogenetic analyses, a standard two-day peripheral blood lymphocyte culture technique was applied. While alpha radiation doses continually increase up to the time of cytogenetic measurements, significant gamma ray exposures essentially ceased long before the time of measurement, so that alpha and gamma doses were not correlated. For the exposed workers, the mean 239 Pu body burden (estimate), evaluated at the time of the cytogenetic measurement, was 1.23 ± 0.26 kBq and the corresponding mean absorbed external gamma ray dose (estimate) to the total body was 0.076 ± 0.009 Gy. Single and multivariate regression analyses were performed on the CA data. Stable, unstable and total aberrations increased as the 239 Pu body burden increased over the range 0-4.5 kBq. However, above this range little additional increase was observed. CAs were weakly correlated with time since the first intake of 239 Pu. No relationship between chromatid aberrations and 239 Pu incorporation was found. Unstable (but not stable) aberrations were correlated with gamma radiation dose. No significant relationship of CA and smoking was found. (authors)

  20. Full-length mRNA sequencing uncovers a widespread coupling between transcription initiation and mRNA processing.

    Science.gov (United States)

    Anvar, Seyed Yahya; Allard, Guy; Tseng, Elizabeth; Sheynkman, Gloria M; de Klerk, Eleonora; Vermaat, Martijn; Yin, Raymund H; Johansson, Hans E; Ariyurek, Yavuz; den Dunnen, Johan T; Turner, Stephen W; 't Hoen, Peter A C

    2018-03-29

    The multifaceted control of gene expression requires tight coordination of regulatory mechanisms at transcriptional and post-transcriptional level. Here, we studied the interdependence of transcription initiation, splicing and polyadenylation events on single mRNA molecules by full-length mRNA sequencing. In MCF-7 breast cancer cells, we find 2700 genes with interdependent alternative transcription initiation, splicing and polyadenylation events, both in proximal and distant parts of mRNA molecules, including examples of coupling between transcription start sites and polyadenylation sites. The analysis of three human primary tissues (brain, heart and liver) reveals similar patterns of interdependency between transcription initiation and mRNA processing events. We predict thousands of novel open reading frames from full-length mRNA sequences and obtained evidence for their translation by shotgun proteomics. The mapping database rescues 358 previously unassigned peptides and improves the assignment of others. By recognizing sample-specific amino-acid changes and novel splicing patterns, full-length mRNA sequencing improves proteogenomics analysis of MCF-7 cells. Our findings demonstrate that our understanding of transcriptome complexity is far from complete and provides a basis to reveal largely unresolved mechanisms that coordinate transcription initiation and mRNA processing.

  1. Splicing aberrations caused by constitutional RB1 gene mutations in ...

    Indian Academy of Sciences (India)

    Analysis of RB1 mRNA from blood leukocytes of patients with retinoblastoma identified the effects of mutations involving consensus splice site, exonic substitution and whole-exon deletions identified in genomic DNA of these patients. In addition, this study identified mutations in cases in which no mutations were detectable ...

  2. Splicing aberrations caused by constitutional RB1 gene mutations in ...

    Indian Academy of Sciences (India)

    Analysis of RB1 mRNA from blood leukocytes of patients with retinoblastoma identified the effects of mutations involving consensus splice site, .... bilateral Rb. Genomic DNA analysis from peripheral blood was as described by Parsam .... the patterns are not always the same in different studies (Klutz et al. 2002; Taylor et al.

  3. Quantification of Drug-Induced mRNA in Human Whole Blood

    Directory of Open Access Journals (Sweden)

    Masato Mitsuhashi

    2008-01-01

    Full Text Available Apoptosis was induced in heparinized human whole blood by 3 different ways (radiation, bleomycin, or etoposide, and various mRNA were quantified using the method we reported (Clin. Chem. 2006; 52:634-642. We found that cyclin-dependent kinase inhibitor 1A (p21 and p53 upregulated modulator of apoptosis (PUMA were the most sensitive and universal mRNA markers of apoptosis in leukocytes. In order to define positive and negative responses, a synthetic RNA was spiked into the lysis buffer and the fold increase was calculated. As a result, 837/880 (95.1% of data points stayed between 0.75 and 1.5 fold increase, and 874/880 (99.3% were within 0.5-2.0 fold increase. When blood samples from 40 healthy adults were stimulated with 22 different drugs, more than 75% of the samples responded to bleomycin (1 μM, idarubicin (2 μM, vincristine (1 μM, daunorubicin (2 μM, cytarabine (10 μM, to induce p21 and/or PUMA mRNA, and approximately 25% showed no induction. Significant correlation was found between p21 and PUMA mRNA responses, and between daunorubicin and cytarabine, idarubicin, and vincristine for both p21 and PUMA. The quantification of drug-induced mRNA in whole blood will be considered as ex vivo , and is a suitable platform for biomarker screening as well as a model system for drug sensitivity tests in future.

  4. Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations

    International Nuclear Information System (INIS)

    Becerikli, Mustafa; Jacobsen, Frank; Rittig, Andrea; Köhne, Wiebke; Nambiar, Sandeep; Mirmohammadsadegh, Alireza; Stricker, Ingo; Tannapfel, Andrea; Wieczorek, Stefan; Epplen, Joerg Thomas; Tilkorn, Daniel; Steinstraesser, Lars

    2013-01-01

    Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies “initial” and “final” passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations. -- Highlights: Increased proliferative potential of late passage STS cells was: • Not associated with epigenetic changes (methylation changes at LINE-1, PTEN). • Not associated with mutation status of KRAS, BRAF. • Dependent on presence/absence of chromosomal aberrations

  5. Growth rate of late passage sarcoma cells is independent of epigenetic events but dependent on the amount of chromosomal aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Becerikli, Mustafa; Jacobsen, Frank; Rittig, Andrea; Köhne, Wiebke [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany); Nambiar, Sandeep; Mirmohammadsadegh, Alireza; Stricker, Ingo; Tannapfel, Andrea [Institute of Pathology, Ruhr-University Bochum (Germany); Wieczorek, Stefan; Epplen, Joerg Thomas [Department of Human Genetics, Ruhr-University Bochum (Germany); Tilkorn, Daniel [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany); Steinstraesser, Lars, E-mail: lars.steinstraesser@rub.de [Department of Plastic Surgery, BG University Hospital Bergmannsheil, Ruhr-University Bochum (Germany)

    2013-07-15

    Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood. Therefore, we investigated the role of gene silencing (DNA promoter methylation of LINE-1, PTEN), genetic aberrations (karyotype, KRAS and BRAF mutations) as well as their contribution to the proliferation rate and migratory potential that underlies “initial” and “final” passage sarcoma cells. Three different cell lines were used, SW982 (synovial sarcoma), U2197 (malignant fibrous histiocytoma (MFH)) and HT1080 (fibrosarcoma). Increased proliferative potential of final passage STS cells was not associated with significant differences in methylation (LINE-1, PTEN) and mutation status (KRAS, BRAF), but it was dependent on the amount of chromosomal aberrations. Collectively, our data demonstrate that these fairly differentiated/advanced cancer cell lines have still the potential to gain an additional spontaneous growth benefit without external influences and that maintenance of increased proliferative potential towards longevity of STS cells (having crossed senescence barriers) may be independent of overt epigenetic alterations. -- Highlights: Increased proliferative potential of late passage STS cells was: • Not associated with epigenetic changes (methylation changes at LINE-1, PTEN). • Not associated with mutation status of KRAS, BRAF. • Dependent on presence/absence of chromosomal aberrations.

  6. Aberration-Coreected Electron Microscopy at Brookhaven National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Zhu,Y.; Wall, J.

    2008-04-01

    The last decade witnessed the rapid development and implementation of aberration correction in electron optics, realizing a more-than-70-year-old dream of aberration-free electron microscopy with a spatial resolution below one angstrom [1-9]. With sophisticated aberration correctors, modern electron microscopes now can reveal local structural information unavailable with neutrons and x-rays, such as the local arrangement of atoms, order/disorder, electronic inhomogeneity, bonding states, spin configuration, quantum confinement, and symmetry breaking [10-17]. Aberration correction through multipole-based correctors, as well as the associated improved stability in accelerating voltage, lens supplies, and goniometers in electron microscopes now enables medium-voltage (200-300kV) microscopes to achieve image resolution at or below 0.1nm. Aberration correction not only improves the instrument's spatial resolution but, equally importantly, allows larger objective lens pole-piece gaps to be employed thus realizing the potential of the instrument as a nanoscale property-measurement tool. That is, while retaining high spatial resolution, we can use various sample stages to observe the materials response under various temperature, electric- and magnetic- fields, and atmospheric environments. Such capabilities afford tremendous opportunities to tackle challenging science and technology issues in physics, chemistry, materials science, and biology. The research goal of the electron microscopy group at the Dept. of Condensed Matter Physics and Materials Science and the Center for Functional Nanomaterials, as well as the Institute for Advanced Electron Microscopy, Brookhaven National Laboratory (BNL), is to elucidate the microscopic origin of the physical- and chemical-behavior of materials, and the role of individual, or groups of atoms, especially in their native functional environments. We plan to accomplish this by developing and implementing various quantitative

  7. Theory of aberration fields for general optical systems with freeform surfaces.

    Science.gov (United States)

    Fuerschbach, Kyle; Rolland, Jannick P; Thompson, Kevin P

    2014-11-03

    This paper utilizes the framework of nodal aberration theory to describe the aberration field behavior that emerges in optical systems with freeform optical surfaces, particularly φ-polynomial surfaces, including Zernike polynomial surfaces, that lie anywhere in the optical system. If the freeform surface is located at the stop or pupil, the net aberration contribution of the freeform surface is field constant. As the freeform optical surface is displaced longitudinally away from the stop or pupil of the optical system, the net aberration contribution becomes field dependent. It is demonstrated that there are no new aberration types when describing the aberration fields that arise with the introduction of freeform optical surfaces. Significantly it is shown that the aberration fields that emerge with the inclusion of freeform surfaces in an optical system are exactly those that have been described by nodal aberration theory for tilted and decentered optical systems. The key contribution here lies in establishing the field dependence and nodal behavior of each freeform term that is essential knowledge for effective application to optical system design. With this development, the nodes that are distributed throughout the field of view for each aberration type can be anticipated and targeted during optimization for the correction or control of the aberrations in an optical system with freeform surfaces. This work does not place any symmetry constraints on the optical system, which could be packaged in a fully three dimensional geometry, without fold mirrors.

  8. Contraction-induced changes in skeletal muscle Na(+), K(+) pump mRNA expression - importance of exercise intensity and Ca(2+)-mediated signalling

    DEFF Research Database (Denmark)

    Nordsborg, Nikolai Baastrup; Kusuhara, K; Hellsten, Ylva

    2010-01-01

    Abstract Aim: To investigate if exercise intensity and Ca(2+) signalling regulate Na(+), K(+) pump mRNA expression in skeletal muscle. Methods: The importance of exercise intensity was evaluated by having trained and untrained humans perform intense intermittent and prolonged exercise...... skeletal muscles increased (PNa(+), K(+) pump alpha1 and beta1 mRNA expression in trained subjects are more...

  9. Reliable PCR quantitation of estrogen, progesterone and ERBB2 receptor mRNA from formalin-fixed, paraffin-embedded tissue is independent of prior macro-dissection

    DEFF Research Database (Denmark)

    Tramm, Trine; Hennig, Guido; Kyndi, Marianne

    2013-01-01

    Gene expression analysis on messenger RNA (mRNA) purified from formalin-fixed, paraffin-embedded tissue is increasingly used for research purposes. Tissue heterogeneity may question specificity and interpretation of results from mRNA isolated from a whole slide section, and thresholds for minimal...

  10. Genomic aberrations and survival in chronic lymphocytic leukemia.

    Science.gov (United States)

    Döhner, H; Stilgenbauer, S; Benner, A; Leupolt, E; Kröber, A; Bullinger, L; Döhner, K; Bentz, M; Lichter, P

    2000-12-28

    Fluorescence in situ hybridization has improved the detection of genomic aberrations in chronic lymphocytic leukemia. We used this method to identify chromosomal abnormalities in patients with chronic lymphocytic leukemia and assessed their prognostic implications. Mononuclear cells from the blood of 325 patients with chronic lymphocytic leukemia were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 6q21, 11q22-23, 13q14, and 17p13; trisomy of bands 3q26, 8q24, and 12q13; and translocations involving band 14q32. Molecular cytogenetic data were correlated with clinical findings. Chromosomal aberrations were detected in 268 of 325 cases (82 percent). The most frequent changes were a deletion in 13q (55 percent), a deletion in 11q (18 percent), trisomy of 12q (16 percent), a deletion in 17p (7 percent), and a deletion in 6q (7 percent). Five categories were defined with a statistical model: 17p deletion, 11q deletion, 12q trisomy, normal karyotype, and 13q deletion as the sole abnormality; the median survival times for patients in these groups were 32, 79, 114, 111, and 133 months, respectively. Patients in the 17p- and 11q-deletion groups had more advanced disease than those in the other three groups. Patients with 17p deletions had the shortest median treatment-free interval (9 months), and those with 13q deletions had the longest (92 months). In multivariate analysis, the presence or absence of a 17p deletion, the presence or absence of an 11q deletion, age, Binet stage, the serum lactate dehydrogenase level, and the white-cell count gave significant prognostic information. Genomic aberrations in chronic lymphocytic leukemia are important independent predictors of disease progression and survival. These findings have implications for the design of risk-adapted treatment strategies.

  11. A study of chromosomal aberrations in amniotic fluid cell cultures.

    Science.gov (United States)

    Wolstenholme, J; Crocker, M; Jonasson, J

    1988-06-01

    This paper represents the analysis of 1916 routine amniotic fluid specimens harvested by an in situ fixation technique in a prospective study with regard to cultural chromosome anomalies. Excluding constitutional abnormalities, 2.9 per cent of 19,432 cells analysed showed some form of chromosome anomaly, terminal deletions (57 per cent) and chromatid/chromosome breaks and gaps (18 per cent) being the most frequent, followed by interchange aberrations (13 per cent) and trisomy (5 per cent). No case was found of more than one colony from the same culture showing the same anomaly without it being present in other cultures from the same fluid. The wholly abnormal colonies had a surplus of trisomies and from the mathematical considerations presented one may infer that these are likely to reflect the presence of abnormal cells in the amniotic fluid. Partly abnormal colonies appeared at a frequency that would correspond to virtual absence of selection against chromosomally abnormal cells when cultured in vitro. The aberrations found were similar to those seen as single cell anomalies, except for chromatid breaks and exchanges. The data suggest a basic preferential induction of trisomy for chromosomes 2, 18, 21, and the Y-chromosome. Structural aberrations showed a marked clustering of breakpoints around the centromeres. The frequency of mutant cells was low (1.4 X 10(-3)) before culture was initiated. At harvest, the frequency of abnormal cells was much higher (3 X 10(-2)) corresponding to 3 X 10(-3) mutations per cell per generation accumulating over approximately ten generations in vitro.

  12. The Impact of Model-Based Clutter Suppression on Cluttered, Aberrated Wavefronts.

    Science.gov (United States)

    Dei, Kazuyuki; Byram, Brett

    2017-10-01

    Recent studies reveal that both phase aberration and reverberation play a major role in degrading ultrasound image quality. We previously developed an algorithm for suppressing clutter, but we have not yet tested it in the context of aberrated wavefronts. In this paper, we evaluate our previously reported algorithm, called aperture domain model image reconstruction (ADMIRE), in the presence of phase aberration and in the presence of multipath scattering and phase aberration. We use simulations to investigate phase aberration corruption and correction in the presence of reverberation. As part of this paper, we observed that ADMIRE leads to suppressed levels of aberration. In order to accurately characterize aberrated signals of interest, we introduced an adaptive component to ADMIRE to account for aberration, referred to as adaptive ADMIRE. We then use ADMIRE, adaptive ADMIRE, and conventional filtering methods to characterize aberration profiles on in vivo liver data. These in vivo results suggest that adaptive ADMIRE could be used to better characterize a wider range of aberrated wavefronts. The aberration profiles' full-width at half-maximum of ADMIRE, adaptive ADMIRE, and postfiltered data with 0.4- mm -1 spatial cutoff frequency are 4.0 ± 0.28 mm, 2.8 ± 1.3 mm, and 2.8 ± 0.57 mm, respectively, while the average root-mean square values in the same order are 16 ± 5.4 ns, 20 ± 6.3 ns, and 19 ± 3.9 ns, respectively. Finally, because ADMIRE suppresses aberration, we perform a limited evaluation of image quality using simulations and in vivo data to determine how ADMIRE and adaptive ADMIRE perform with and without aberration correction.

  13. Frequencies of chromosomal aberrations and sister chromatid exchanges in the benthic worm Neanthes arenaceodentata exposed to ionizing radiation

    International Nuclear Information System (INIS)

    Harrison, F.L.; Rice, D.W. Jr.; Moore, D.H.

    1984-07-01

    Traditional bioassays are unsuitable for assessing sublethal effects from ocean disposal of low-level radioactive waste because mortality and phenotypic responses are not anticipated. We compared the usefulness of chromosomal aberration and sister chromatid exchange (SCE) induction as measures of low-level radiation effects in a sediment-dwelling marine worm, Neanthes arenaceodentata. The SCEs, in contrast to chromosomal aberrations, do not alter the overall chromosome morphology and in mammalian cells appear to be a more sensitive indicator of DNA alterations caused by environmental mutagens. Newly hatched larvae were exposed to two radiation-exposure regimes of either x rays at a high dose rate of 0.7 Gy (70 rad)/min for as long as 5.5 min or to 60 Co gamma rays at a low dose rate of from 4.8 x 10 -5 to 1.2 x 10 -1 Gy (0.0048 to 12 rad)/h for 24 h. After irradiation, the larvae were exposed to 3 x 10 -5 M bromodeoxyuridine (BrdUrd) for 28 h (x-ray-irradiated larvae) or for 54 h ( 60 Co-irradiated larvae). Larval cells were examined for the proportion of cells in first, second, and third or greater division. Frequencies of chromosomal aberrations and SCEs were determined in first and second division cells, respectively. Results from x-ray irradiation indicated that dose-related increases occur in chromosome and chromatid deletions, but a dose of equal or greater 2 Gy (equal to or greater than 200 rad) was required to observe a significant increase. Worm larvae receiving 60 Co irradiation showed elevated SCE frequencies with a significant increase of 0.6 Gy (60 rad). We suggest that both SCEs and chromosomal aberrations may be useful for measuring effects on genetic material induced by radiation. 56 references, 7 figures, 9 tables

  14. Aberrant internal carotid artery presenting as a retrotympanic vascular mass

    International Nuclear Information System (INIS)

    Nicolay, Simon; De Foer, Bert; Bernaerts, Anja; Van Dinther, Joost; Parizel, Paul M

    2014-01-01

    We report a case of a young woman with an aberrant right internal carotid artery (ICA) presenting as a retrotympanic reddish mass. This variant of the ICA represents the collateral pathway that is formed as a result of an embryological agenesis of the cervical segment of the ICA. The embryonic inferior tympanic artery is recruited to bypass the absent carotid segment. This hypertrophied vessel may be seen otoscopically and wrongfully considered to be a vascular middle ear tumor. Informing the otorhinolaryngologist of this important vascular variant not only obviates biopsy but also helps in careful preoperative planning of eventual middle ear procedures

  15. Chromosomal aberrations and SCEs as biomarkers of cancer risk

    DEFF Research Database (Denmark)

    Norppa, H; Bonassi, S; Hansteen, I-L

    2006-01-01

    Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European...... of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic...

  16. Thymoma arising from aberrant cervical thymus: case reports

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hye Seong; Kim, Hak Hee [The Catholic Univ. Kangnam St. Mary' s Hospital, Seoul (Korea, Republic of)

    1998-12-01

    Thymoma is one of the most common neoplasms of the mediastinum, and the most frequent tumor of the anterosuperior compartment. Thymoma diveloping from arrested undescended thymic cells in the neck is, however, rare. The most common extrathoracic location is the vicinity of the thyroid. Two cases of aberrant cervical thymoma are presented. Both manifested as mass lesions at the thoracic inlet, with superior displacement of the thyroid. The masses had clinical features similar to those previously reported for cervical thymoma: preponderance in women, and the absence of myasthenic symptoms, but in one case there was malignant transformation.=20.

  17. Suppressing effect of antimutagenic flavorings on chromosome aberrations induced by UV-light or X-rays in cultured Chinese hamster cells

    International Nuclear Information System (INIS)

    Sasaki, Yu.F.; Imanishi, Hisako; Watanabe, Mie; Ohta, Toshihiro; Shirasu

    1990-01-01

    Chromosome aberrations induces by UV-light or X-rays were suppressed by the post-treatment with antimutagenic flavorings, such as anisaldehyde, cinnamaldehyde, coumarin, and vanillin. UV- or X-ray-irradiated surviving cells increased in the presence of each flavouring. X-ray-induced breakage-type and exchange-type chromosome aberrations were suppressed by the vanillin treatment in the G 1 phase of the cell cycle and a greater decrease in the number of X-ray-induced chromosome aberrations during G 1 holding was observed in the presence of vanillin. Furthermore, a greater decrease in the number of X-ray-induced DNA single-strand breaks was observed in the presence of vanillin. Treatment with vanillin in the G 2 phase suppressed UV-and X-ray-induced breakage-type but not exchange-type chromosome aberrations. The suppression of breakage-type aberrations was assumed to be due to a modification of the capability of the post-replicational repair of DNA double-strand breaks. (author). 28 refs.; 5 figs.; 6 tabs

  18. The impact of physical activity on the level of chromosome aberrations

    Directory of Open Access Journals (Sweden)

    Šošić Gordana M.

    2015-01-01

    Full Text Available During the lifetime, people are constantly exposed to the chemicals and agents of exogenic and endogenic sources, which through reaction with a molecule of DNA can cause the damage of genomes and their instability. The formation of micronuclei is a consequence of chromosomal aberrations caused by the influence of different genetic and environmental factors. Micronuclei are cytoplasmic chromatin masses that look like small nuclei and can originate from whole or parts of chromosomes. Micronucleus test ( MN test is used to detect genotoxic effects of various chemical , physical or biological mutagens, as well as the test for determination of chromosomal instability in a variety of cell types. Micronucleus frequency is directly proportional to the degree of chromosomal aberrations. It has been shown that genome damage may occur as a result of environmental exposure to genotoxins and medical procedures, due to deficiency of micronutrients and under the influence of various lifestyles and genetic factors. Unbalanced diet, lack of physical exercise, lack of sleep and overwork contribute significantly to increased frequency of micronuclei. It was also shown that strenuous exercise causes DNA damage, which results in the formation of micronuclei. As a professional athlete conduct highly Intensive physical training, these populations are at risk for the development of genomic instability and carcinogenesis. A healthy lifestyle, the optimal intake of antioxidants and regular moderate physical activity significantly reduced the frequency of micronuclei, and contribute to the stability of the genome.

  19. Radiation-induced chromosome aberrations in lymphocytes from man and crab-eating monkey

    International Nuclear Information System (INIS)

    Takahashi, E.; Hirai, M.; Tobari, I.; Utsugi, T.; Nakai, S.

    1982-01-01

    To obtain information on the relation between yield of chromosome aberrations and dose at low-dose levels, experiments were conducted with 5, 10, 20, 30 and 50 rad of 137 Cs γ-rays, on lymphocytes from man and crab-eating monkey (Macaca fascicularis). The dose-response relationship for dicentrics was obtained from the combined data of these low-dose experiments with those of our previous ones at high doses (100-400 rad). When the difference between observed yields and those expected from the linear-quadratic model were computed, the dose-response curve had a good fit for man, but not for the monkey. The linear regression lines between 0 and 30 rad were calculated, because the expected values of α/β for man and monkey would be about 100 and 60 rad. The human data gave a satisfactory fit to a linear model, i.e., a linear increase in aberration frequency with dose, whereas this was not so for those of the monkey. Furthermore, there was some suggestive evidence for the existence of a plateau in dicentric yields between 10 and 30 rad for the monkey and between 20 and 30 rad for human lymphocytes, but more data would be needed to verify this suggestion, particularly for human lymphocytes. (orig.)

  20. Aberrant Compartment Formation by HSPB2 Mislocalizes Lamin A and Compromises Nuclear Integrity and Function

    Directory of Open Access Journals (Sweden)

    Federica F. Morelli

    2017-08-01

    Full Text Available Small heat shock proteins (HSPBs contain intrinsically disordered regions (IDRs, but the functions of these IDRs are still unknown. Here, we report that, in mammalian cells, HSPB2 phase separates to form nuclear compartments with liquid-like properties. We show that phase separation requires the disordered C-terminal domain of HSPB2. We further demonstrate that, in differentiating myoblasts, nuclear HSPB2 compartments sequester lamin A. Increasing the nuclear concentration of HSPB2 causes the formation of aberrant nuclear compartments that mislocalize lamin A and chromatin, with detrimental consequences for nuclear function and integrity. Importantly, phase separation of HSPB2 is regulated by HSPB3, but this ability is lost in two identified HSPB3 mutants that are associated with myopathy. Our results suggest that HSPB2 phase separation is involved in reorganizing the nucleoplasm during myoblast differentiation. Furthermore, these findings support the idea that aberrant HSPB2 phase separation, due to HSPB3 loss-of-function mutations, contributes to myopathy.

  1. Phenolphthalein induces chromosome aberrations in human and Chinese hamster liver cells (CHEL) cultured in vitro.

    Science.gov (United States)

    Biondi, O; Andreozzi, L; Amoruso, S; Motta, S

    2000-01-01

    Phenolphthalein is a nonprescription laxative agent that has been widely used during this century. Recent studies in animal models have shown that phenolphthalein has carcinogenic activity. In order to assess cytogenetic effects on human cells in vitro, we tested phenolphthalein in a chromosome aberration assay in human embryo cells derived from amniotic fluid. Our results show that phenolphthalein induces a significant increase in the frequency of chromosome aberrations in human cells. The lowest dose level at which the clastogenic effect is evident is 23.2 microg/ml. Similar positive results were obtained in a Chinese hamster liver cell line, which is metabolically competent to activate different classes of promutagens and procarcinogens into biologically active metabolites. Instead, parallel experiments in Chinese hamster ovary cells did not show any clastogenic effect due to phenolphthalein. These latter data suggested that phenolphthalein acts as a promutagen and must be metabolically activated to exert its clastogenic effect. Teratogenesis Carcinog. Mutagen. 20:209-217, 2000. Copyright 2000 Wiley-Liss, Inc.

  2. Cyclic-AMP mediated regulation of ABCB mRNA expression in mussel haemocytes.

    Directory of Open Access Journals (Sweden)

    Silvia Franzellitti

    Full Text Available BACKGROUND: The multixenobiotic resistance system (MXR allows aquatic organisms to cope with their habitat despite high pollution levels by over-expressing membrane and intracellular transporters, including the P-glycoprotein (Pgp. In mammals transcription of the ABCB1 gene encoding Pgp is under cAMP/PKA-mediated regulation; whether this is true in mollusks is not fully clarified. METHODOLOGY/PRINCIPAL FINDINGS: cAMP/PKA regulation and ABCB mRNA expression were assessed in haemocytes from Mediterranean mussels (Mytilus galloprovincialis exposed in vivo for 1 week to 0.3 ng/L fluoxetine (FX alone or in combination with 0.3 ng/L propranolol (PROP. FX significantly decreased cAMP levels and PKA activity, and induced ABCB mRNA down-regulation. FX effects were abolished in the presence of PROP. In vitro experiments using haemocytes treated with physiological agonists (noradrenaline and serotonin and pharmacological modulators (PROP, forskolin, dbcAMP, and H89 of the cAMP/PKA system were performed to obtain clear evidence about the involvement of the signaling pathway in the transcriptional regulation of ABCB. Serotonin (5-HT decreased cAMP levels, PKA activity and ABCB mRNA expression but increased the mRNA levels for a putative 5-HT1 receptor. Interestingly, 5-HT1 was also over-expressed after in vivo exposures to FX. 5-HT effects were counteracted by PROP. Forskolin and dbcAMP increased PKA activity as well as ABCB mRNA expression; the latter effect was abolished in the presence of the PKA inhibitor H89. CONCLUSIONS: This study provides the first direct evidence for the cAMP/PKA-mediated regulation of ABCB transcription in mussels.

  3. Ammonium Chloride Ingestion Attenuates Exercise-Induced mRNA Levels in Human Muscle.

    Directory of Open Access Journals (Sweden)

    Johann Edge

    Full Text Available Minimizing the decrease in intracellular pH during high-intensity exercise training promotes greater improvements in mitochondrial respiration. This raises the intriguing hypothesis that pH may affect the exercise-induced transcription of genes that regulate mitochondrial biogenesis. Eight males performed 10x2-min cycle intervals at 80% VO2speak intensity on two occasions separated by ~2 weeks. Participants ingested either ammonium chloride (ACID or calcium carbonate (PLA the day before and on the day of the exercise trial in a randomized, counterbalanced order, using a crossover design. Biopsies were taken from the vastus lateralis muscle before and after exercise. The mRNA level of peroxisome proliferator-activated receptor co-activator 1α (PGC-1α, citrate synthase, cytochome c and FOXO1 was elevated at rest following ACID (P0.05; the difference in PGC-1α mRNA content 2 h post-exercise between ACID and PLA was not significant (P = 0.08. Thus, metabolic acidosis abolished the early post-exercise increase of PGC-1α mRNA and the mRNA of downstream mitochondrial and glucose-regulating proteins. These findings indicate that metabolic acidosis may affect mitochondrial biogenesis, with divergent responses in resting and post-exercise skeletal muscle.

  4. Demonstration that a mRNA Binding Protein is Responsible for GADD45 mRNA Destabilization

    National Research Council Canada - National Science Library

    Abcouwer, Steve

    2003-01-01

    ...) Using regions of the GADD45 mRNA 3'-untranslated region (UTR) in KNA gel shift assays, we have observed that glutamine causes distinct changes in RBP activities in cytoplasmic and nuclear protein extracts...

  5. Alterations in mRNA 3' UTR Isoform Abundance Accompany Gene Expression Changes in Human Huntington's Disease Brains.

    Science.gov (United States)

    Romo, Lindsay; Ashar-Patel, Ami; Pfister, Edith; Aronin, Neil

    2017-09-26

    The huntingtin gene has two mRNA isoforms that differ in their 3' UTR length. The relationship of these isoforms with Huntington's disease is not established. We provide evidence that the abundance of huntingtin 3' UTR isoforms differs between patient and control neural stem cells, fibroblasts, motor cortex, and cerebellum. Huntingtin 3' UTR isoforms, including a mid-3' UTR isoform, have different localizations, half-lives, polyA tail lengths, microRNA sites, and RNA-binding protein sites. Isoform shifts in Huntington's disease motor cortex are not limited to huntingtin; 11% of alternatively polyadenylated genes change the abundance of their 3' UTR isoforms. Altered expression of RNA-binding proteins may be associated with aberrant isoform abundance; knockdown of the RNA-binding protein CNOT6 in control fibroblasts leads to huntingtin isoform differences similar to those in disease fibroblasts. These findings demonstrate that mRNA 3' UTR isoform changes are a feature of molecular pathology in the Huntington's disease brain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation.

    Science.gov (United States)

    Geula, Shay; Moshitch-Moshkovitz, Sharon; Dominissini, Dan; Mansour, Abed AlFatah; Kol, Nitzan; Salmon-Divon, Mali; Hershkovitz, Vera; Peer, Eyal; Mor, Nofar; Manor, Yair S; Ben-Haim, Moshe Shay; Eyal, Eran; Yunger, Sharon; Pinto, Yishay; Jaitin, Diego Adhemar; Viukov, Sergey; Rais, Yoach; Krupalnik, Vladislav; Chomsky, Elad; Zerbib, Mirie; Maza, Itay; Rechavi, Yoav; Massarwa, Rada; Hanna, Suhair; Amit, Ido; Levanon, Erez Y; Amariglio, Ninette; Stern-Ginossar, Noam; Novershtern, Noa; Rechavi, Gideon; Hanna, Jacob H

    2015-02-27

    Naïve and primed pluripotent states retain distinct molecular properties, yet limited knowledge exists on how their state transitions are regulated. Here, we identify Mettl3, an N(6)-methyladenosine (m(6)A) transferase, as a regulator for terminating murine naïve pluripotency. Mettl3 knockout preimplantation epiblasts and naïve embryonic stem cells are depleted for m(6)A in mRNAs, yet are viable. However, they fail to adequately terminate their naïve state and, subsequently, undergo aberrant and restricted lineage priming at the postimplantation stage, which leads to early embryonic lethality. m(6)A predominantly and directly reduces mRNA stability, including that of key naïve pluripotency-promoting transcripts. This study highlights a critical role for an mRNA epigenetic modification in vivo and identifies regulatory modules that functionally influence naïve and primed pluripotency in an opposing manner. Copyright © 2015, American Association for the Advancement of Science.

  7. X-ray induced sister chromatid exchange and chromosomal aberrations in the lymphocytes from the patients with neurofibromatosis

    International Nuclear Information System (INIS)

    Hoshino, Hitoshi; Takeshita, Tatsuya; Iijima, Sumio; Asaka, Akio; Segawa, Masaya; Higurashi, Makoto.

    1990-01-01

    Neurofibromatosis (NF), an autosomal dominant disease, is diagnosed by the presence of more than 6 Cafe-au-lait spots and neurofibromas in late childhood or adolescence. We examined the frequencies of sister chromatid exchange (SCE) and chromosomal aberrations (dicentrics and rings) in cultured lymphocytes from patients with NF and normal controls after X-ray irradiation at doses of 2.5, 5.0 and 7.5 Gy. No differences in the baseline SCE frequencies were found between the NF patients and controls. The frequency of SCE increased with the irradiation dose in both patients and controls with no apparent differences between the two groups. In addition, the frequencies of spontaneous and X-ray induced chromosomal aberrations in the patients were not significantly different from those in the controls. The presence of genetic heterogeneity causing NF was suggested. (author)

  8. Relationship between ocular wavefront aberrations and refractive error in Chinese school children.

    Science.gov (United States)

    Li, Tao; Zhou, Xiaodong; Chen, Zhi; Zhou, Xingtao; Chu, Renyuan; Hoffman, Matthew R

    2012-07-01

    The relationship between ocular wavefront aberrations and refractive error in children's eyes remains controversial. The purpose of this study is to re-examine this relationship in Chinese school children under natural distance accommodation. Ocular wavefront aberrations were measured in 86 Chinese children with spherical equivalent refraction (SER) between +0.5 D and -6.0 D and astigmatism less than -1.00 D. Wavefront aberrations were calculated using an objective method based on the Hartmann-Shack principle. Refractive error was obtained using a phoropter after cycloplegia. Subjects were categorised into three groups based on the mean SER: emmetropia (SER from -0.50 D to +0.50 D), mild myopia (SER greater than -0.50 D to -3.00 D) and moderate myopia (SER greater than -3.00 D to -6.00 D). Of the 86 participants, 22 were emmetropic, 43 were mildly myopic and 21 were moderately myopic. The root mean square (RMS) values of higher-order aberrations, Zernike coefficients (third-, fourth- and fifth-order aberrations) and R(j) (the ratio of third-, fourth- or fifth-order aberrations to total higher-order aberrations) were compared across the three refractive groups. No significant correlations were found between the RMS values of total higher-order aberrations, third-order aberrations, fourth-order aberrations, fifth-order aberrations, spherical aberration or coma and SER. No significant differences in the RMS values of total higher-order aberrations or R(j) were observed among the groups. The difference in fifth-order aberrations was statistically significant among the groups (p = 0.022); no other differences in higher-order aberration were found. Aside from C (3,1), no other differences were observed for Zernike coefficients. Ocular wavefront aberrations are similar among Chinese school children with different refractive errors under natural accommodation for a distance target. There is no evidence that myopes have a different amount of ocular higher-order aberrations

  9. Induction of carbamoyl phosphate synthetase III and glutamine synthetase mRNA during confinement stress in gulf toadfish (Opsanus beta).

    Science.gov (United States)

    Kong, H; Kahatapitiya, N; Kingsley, K; Salo, W L; Anderson, P M; Wang, Y S; Walsh, P J

    2000-01-01

    Gulf toadfish (Opsanus &bgr;) rapidly switch to excretion of urea as their main nitrogenous waste product under several laboratory conditions, including confinement to small volumes of water. Prior evidence suggested that the activities of two key enzymes of urea synthesis exhibited potentially different modes of upregulation during this switch, with carbamoyl phosphate synthethase III (CPSase III) activated allosterically by N-acetylglutamate, and glutamine synthetase (GSase) activated by increases in the concentration of protein. The present study was undertaken to examine additional aspects of the regulation of these enzymes. The sequence for O. beta CPSase III cDNA was obtained, and it was found to be similar to that of other piscine CPSases. The sequence also allowed us to develop riboprobes for CPSase III mRNA analysis using ribonuclease protection assays (RPAs). CPSase III mRNA was expressed in liver, muscle, kidney and intestine, in agreement with prior enzymatic measurements. Levels of CPSase III mRNA increased five- to tenfold (relative to beta-actin mRNA) in liver (but not muscle) following 48 h of confinement stress. Measured by western analysis using an antibody to chicken GSase, confined O. beta GSase protein concentrations increased eightfold over control levels, in agreement with prior and present measurements of increases in GSase activity. Furthermore, RPAs of GSase mRNA levels demonstrated an increase of fivefold during confinement.

  10. Is 24-color FISH detection of in-vitro radiation-induced chromosomal aberrations suited to determine individual intrinsic radiosensitivity?

    International Nuclear Information System (INIS)

    Kuechler, A.; Wendt, T.G.; Neubauer, S.; Grabenbauer, G.G.; Sauer, R.; Claussen, U.; Liehr, T.

    2002-01-01

    Background: Reliable determination of intrinsic radiosensitivity in individual patients is a serious need in radiation oncology. Chromosomal aberrations are sensitive indicators of a previous exposure to ionizing irradiation. Former molecular cytogenetic studies showed that such aberrations as an equivalent of intrinsic radiosensitivity can be detected by fluorescence in-situ hybridization (FISH) techniques using whole chromosome painting (wcp) probes. However, only one up to three randomly chosen wcp probes have been applied for such approaches until now. As a random distribution of chromosomal rearrangements along the chromosomes is up to now still controversial, the power of the 24-color FISH approach should be elucidated in the present study. Methods and Material: Lymphocytes derived from lymphoblastoid cell lines of one patient with Nijmegen breakage syndrome (NBS homozygote) and of two NBS heterozygotes and peripheral blood lymphocytes of two controls were analyzed. Samples of each patient/control were irradiated in vitro with 0.0 Gy, 0.7 Gy or 2.0 Gy prior to cultivation. Chromosomal aberrations were analyzed in detail and quantified by means of 24-color FISH as an expression of the individual intrinsic radiosensitivity. Results: 24-color FISH analyses were done in a total of 1,674 metaphases. After in-vitro irradiation, 21% (0.7 Gy) or 57% (2.0 Gy) of the controls' cells, 15% (0.7 Gy) or 53% (2.0 Gy) of the heterozygotes' cells and 54% (0.7 Gy) or 79% (2.0 Gy) of the homozygote's cells contained aberrations. The highest average rates of breaks per mitosis [B/M] (0.7 Gy: 1.80 B/M, 2.0 Gy: 4.03 B/M) and complex chromosomal rearrangements [CCR] (0.7 Gy: 0.20 CCR/M, 2.0 Gy: 0.47 CCR/M) were observed in the NBS patient. Moreover, the proportion of different aberration types after irradiation showed a distinct increase in the rate of CCR combined with a decrease in dicentrics in the NBS homozygote. Conclusion: To come to a more complete picture of radiation

  11. Genetic Alterations in Pesticide Exposed Bolivian Farmers: An evaluation by analysis of chromosomal aberrations and the comet assay.

    Science.gov (United States)

    Jørs, Erik; Gonzáles, Ana Rosa; Ascarrunz, Maria Eugenia; Tirado, Noemi; Takahashi, Catharina; Lafuente, Erika; Dos Santos, Raquel A; Bailon, Natalia; Cervantes, Rafael; O, Huici; Bælum, Jesper; Lander, Flemming

    2007-11-12

    Pesticides are of concern in Bolivia because of increasing use. Frequent intoxications have been demonstrated due to use of very toxic pesticides, insufficient control of distribution and sale and little knowledge among farmers of protective measures and hygienic procedures. Questionnaires were applied and blood tests taken from 81 volunteers from La Paz County, of whom 48 were pesticide exposed farmers and 33 non-exposed controls. Sixty males and 21 females participated with a mean age of 37.3 years (range 17-76). Data of exposure and possible genetic damage were collected and evaluated by well known statistical methods, controlling for relevant confounders. To measure genetic damage chromosomal aberrations and the comet assay analysis were performed. Pesticide exposed farmers had a higher degree of genetic damage compared to the control group. The number of chromosomal aberrations increased with the intensity of pesticide exposure. Females had a lower number of chromosomal aberrations than males, and people living at altitudes above 2500 metres seemed to exhibit more DNA damage measured by the comet assay. Bolivian farmers showed signs of genotoxic damage, probably related to exposure to pesticides. Due to the potentially negative long term health effects of genetic damage on reproduction and the development of cancer, preventive measures are recommended. Effective control with imports and sales, banning of the most toxic pesticides, education and information are possible measures, which could help preventing the negative effects of pesticides on human health and the environment.

  12. Genetic Alterations in Pesticide Exposed Bolivian Farmers: An evaluation by analysis of chromosomal aberrations and the comet assay

    Directory of Open Access Journals (Sweden)

    Erik Jørs

    2007-01-01

    Full Text Available Background: Pesticides are of concern in Bolivia because of increasing use. Frequent intoxications have been demonstrated due to use of very toxic pesticides, insufficient control of distribution and sale and little knowledge among farmers of protective measures and hygienic procedures.Method: Questionnaires were applied and blood tests taken from 81 volunteers from La Paz County, of whom 48 were pesticide exposed farmers and 33 non-exposed controls. Sixty males and 21 females participated with a mean age of 37.3 years (range 17–76. Data of exposure and possible genetic damage were collected and evaluated by well known statistical methods, controlling for relevant confounders. To measure genetic damage chromosomal aberrations and the comet assay analysis were performed.Results: Pesticide exposed farmers had a higher degree of genetic damage compared to the control group. The number of chromosomal aberrations increased with the intensity of pesticide exposure. Females had a lower number of chromosomal aberrations than males, and people living at altitudes above 2500 metres seemed to exhibit more DNA damage measured by the comet assay.Conclusions: Bolivian farmers showed signs of genotoxic damage, probably related to exposure to pesticides. Due to the potentially negative long term health effects of genetic damage on reproduction and the development of cancer, preventive measures are recommended. Effective control with imports and sales, banning of the most toxic pesticides, education and information are possible measures, which could help preventing the negative effects of pesticides on human health and the environment.

  13. Dietary fat and risk of colon and rectal cancer with aberrant MLH1 expression, APC or KRAS genes.

    Science.gov (United States)

    Weijenberg, Matty P; Lüchtenborg, Margreet; de Goeij, Anton F P M; Brink, Mirian; van Muijen, Goos N P; de Bruïne, Adriaan P; Goldbohm, R Alexandra; van den Brandt, Piet A

    2007-10-01

    To investigate baseline fat intake and the risk of colon and rectal tumors lacking MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) repair gene expression and harboring mutations in the APC (adenomatous polyposis coli) tumor suppressor gene and in the KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) oncogene. After 7.3 years of follow-up of the Netherlands Cohort Study (n = 120,852), adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) were computed, based on 401 colon and 130 rectal cancer patients. Total, saturated and monounsaturated fat were not associated with the risk of colon or rectal cancer, or different molecular subgroups. There was also no association between polyunsaturated fat and the risk of overall or subgroups of rectal cancer. Linoleic acid, the most abundant polyunsaturated fatty acid in the diet, was associated with increased risk of colon tumors with only a KRAS mutation and no additional truncating APC mutation or lack of MLH1 expression (RR = 1.41, 95% CI 1.18-1.69 for one standard deviation (i.e., 7.5 g/day) increase in intake, p-trend over the quartiles of intake colon tumors without any of the gene defects, or with tumors harboring aberrations in either MLH1 or APC. Linoleic acid intake is associated with colon tumors with an aberrant KRAS gene, but an intact APC gene and MLH1 expression, suggesting a unique etiology of tumors with specific genetic aberrations.

  14. Cell-stage-specific enhancement by caffeine of the frequency of chromatid aberrations induced by X-rays in neutral ganglia of Drosophila melanogaster

    International Nuclear Information System (INIS)

    De Marco, A.; Polani, S.

    1981-01-01

    Caffeine (10 -2 M) induced a high level of chromatid aberrations in neural ganglia of third-instar larvae of Drosophila melanogaster only when it was added to cells in late G 2 and mitotic prophase. No aberrations were observed after treatment in late S-middle G 2 or C-mitosis. We observed that, in these stages, caffeine strongly increased X-ray-induced damage (500 R). This potentiation was quantitatively similar. But it involved all types of aberration after treatment in C-mitosis, and essentially isochromatid deletions and chromatid exhanges after treatment in S-G 2 . Some hypotheses are put forth to explain the possible mechanism of action of caffeine in the potentiation of X-ray-induced damage. (orig.)

  15. UV-induced chromatid aberrations in two cell linear of Chinese hamster with different repair activity

    International Nuclear Information System (INIS)

    Ikushima, Takaji

    1978-01-01

    To elucidate the mechanism of chromosomal aberration formation, the yield and type of chromosomal aberrations induced by ultraviolet light (UV) irradiation were compared in cultured Chinese hamster cells with different repair activity. After irradiation of low fluences of UV, chromatid aberrations were produced more frequently in one cell line with impaired repair activity, B14FAF than the other showing normal DNA repair replication, CHO. There were no difference in the spectrum of the aberration types between the two. The results imply that impaired excision repair of UV-induced pyrimidine dimers or other photoproducts results in higher yield of chromosomal aberrations, and suggest the involvement of DNA repair processes in chromosomal aberration formation. (author)

  16. Explanation of test and assessment of chromosomal aberrations on occupational health examinations for radiation workers

    International Nuclear Information System (INIS)

    Lu Yumin; Fu Baohua; Han Lin; Wang Xi'ai; Zhao Fengling

    2012-01-01

    Test and Assessment of Chromosomal Aberrations on Occupational Health Examinations for Radiation Workers was formulated for standardizing analysis and outcome assessment of chromosomal aberrations on occupational health examinations for radiation workers. In order to provide experimental and theoretical basis for implementation and extension of this standard, this paper interpreted the standard comprehensively, including some existed problems that methods on detection and outcome assessment of chromosomal aberrations is not unified in different laboratories in China, and related criteria,laws and regulations at home and abroad are not fit for the detection of chromosomal aberrations for radiation workers very well; some introduction on methods of chromosomal slide preparation, discriminant analysis and outcome assessment of chromosomal aberration; and some influencing factors in the quality of chromosomal aberration detection. (authors)

  17. Chromosomal aberrations as etiological factors of intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2008-01-01

    Full Text Available Background/Aim. Intrauterine growth retardation (IUGR is a pathological condition of pregnancy characterised by birth weight below the 10th centile. A number of fetal, placental and maternal causes can lead to IUGR; although, in most cases no specific causes can be identified. The aim of this study was to determine the part of chromosomal abnormalities in IUGR etiology. Methods. Fetal blood karyotype taken by cordocentesis from 168 fetuses with diagnosed IUGR was analyzed. Results. Chromosomal rearrangements both numerical and structural were detected in 14 cases (12.2%. Two cases were triploid. Patau syndrome, Edwards syndrome and Down syndrome were found in two cases each. There was one case of trisomy 7 (47, XY, +7 and one case of trisomy 16 (47, XX, +16; one translocation, 46, XY, t (2; 14(q23; q32 and a deletion 46, XYdel (12 (p12 as well as two cases of sex chromosomes abnormalities, 45, X (Turner syndrome and 47, XYY. Conclusion. These findings suggest that a consistent number of symmetrical IUGR cases (about 12% can be associated with chromosomal rearrangements. Chromosomal aberrations that cause IUGR are heterogeneous, aberration of autosomes, mostly autosomal trisomies, being the most common.

  18. Correction for polychromatic aberration in computed tomography images

    International Nuclear Information System (INIS)

    Naparstek, A.

    1979-01-01

    A method and apparatus for correcting a computed tomography image for polychromatic aberration caused by the non-linear interaction (i.e. the energy dependent attenuation characteristics) of different body constituents, such as bone and soft tissue, with a polychromatic X-ray beam are described in detail. An initial image is conventionally computed from path measurements made as source and detector assembly scan a body section. In the improvement, each image element of the initial computed image representing attenuation is recorded in a store and is compared with two thresholds, one representing bone and the other soft tissue. Depending on the element value relative to the thresholds, a proportion of the respective constituent is allocated to that element location and corresponding bone and soft tissue projections are determined and stored. An error projection generator calculates projections of polychromatic aberration errors in the raw image data from recalled bone and tissue projections using a multidimensional polynomial function which approximates the non-linear interaction involved. After filtering, these are supplied to an image reconstruction computer to compute image element correction values which are subtracted from raw image element values to provide a corrected reconstructed image for display. (author)

  19. Radioactivity and chromosome aberrations of residents of Misasa Spa

    International Nuclear Information System (INIS)

    Morinaga, Hiroshi; Mifune, Masaaki; Furuno, Katsushi

    1985-01-01

    Misasa Spa is one of the most highly radioactive hot springs in Japan, the waters of which contain mainly 222 Rn (437 ± 132 Bq/liter). Radon contents of indoor air of private houses and health resort hotels (built of wood) at Misasa Spa range from 18.5 to 55.5 mBq/liter and 22.2 to 129.5 mBq/liter, respectively. Radon contents in the air of facilities using spring waters at Misasa Branch Hospital of Okayama University were measured to be; bathroom 807 ± 78 mBq/liter; Hubbardtank bathroom 5306 ± 2568 mBq/liter; the drinking hall 1491 ± 178 mBq/liter. The environmental and dose rate inside private house's has been measured to be 14.0 ± 1.8 μR/h. Chromosome aberrations (dicentrics) in the peripheral blood lymphocytes of residents of Misasa Spa were investigated in 14 persons; the mean value of aberration frequencies were 0.21 %. (Kubozono, M.)

  20. Aberrantly methylated DNA as a biomarker in breast cancer

    DEFF Research Database (Denmark)

    Kristiansen, Søren; Jørgensen, Lars Mønster; Guldberg, Per

    2013-01-01

    Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA hypermethyla...... as a versatile biomarker tool for screening, diagnosis, prognosis and monitoring of breast cancer. Standardization of methods and biomarker panels will be required to fully exploit this clinical potential.......Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA...... hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients...

  1. Radiation induced chromosome aberrations and interphase DNA geometry

    International Nuclear Information System (INIS)

    Nasazzi, N.; Di Giorgio, M.; Otero, D.

    1995-01-01

    Ionizing radiation induces DNA double strand breaks (DSBs) and their interaction and illegitimate recombination produces chromosome aberrations. Stable chromosome aberrations comprise inter-chromosomal events (translocations) and intra-chromosomal events (inversions). Assuming DSBs induction and interaction is completely random and neglecting proximity effects, the expected ratio of translocations to inversions is F=86, based on chromosome arm lengths. We analyzed the number of translocations and inversions using G-banding, in 16 lymphocyte cultures from blood samples acutely irradiated with γ-rays (dose range: 0.5Gy-3Gy). Our results give F=13.5, significantly smaller than F=86. Literature data show similar small F values but strongly spread. The excess of inversions could be explained by a 'proximity effect', it means that more proximate DSBs have an extra probability of interaction. Therefore, it is possible to postulate a special chromosome arrangement during irradiation and the subsequent interval. We propose a model where individual chromosomes show spherical confinement with some degree of overlapping and DSBs induction proportional to cross section. We assume a DSBs interaction probability function with cut-off length = 1 μ. We propose that large spread in F data could be due to temporal variation in overlapping and spatial chromosome confinement. (author). 14 refs

  2. Doses in radiation accidents investigated by chromosome aberration analysis

    International Nuclear Information System (INIS)

    Lloyd, D.C.; Purrott, R.J.; Prosser, J.S.; Dolphin, G.W.; Tipper, P.A.; Reeder, E.J.; White, C.M.; Cooper, S.J.; Stephenson, B.D.

    1977-01-01

    Results from cytogenetic investigations into 66 cases of suspected over-exposure to radiation during 1976 are reviewed. This report is the sixth in an annual series which together contain data on 272 studies. Previous results were published in NRPB-R5, R10, R23, R35 and R41. Results from all investigations have been pooled for general analysis. Brief accounts are given in an appendix of the circumstances behind the past year's investigations and, where possible, physical estimates of dose have been included for comparison. A short review is given of the laboratory's recently published dose response data for several energies of neutron radiation. A description is also given of the group's collaboration in an international experiment in which comparisons were made between a variety of dosemeters exposed to a controlled criticality pulse. In a second appendix two experiments are described in which inter- and intra-donor effects on chromosome aberration yields were examined. It was found that differences in dicentric yields were small whereas acentric aberrations were more variable. (author)

  3. X-ray induction of mitotic and meiotic chromosome aberrations

    International Nuclear Information System (INIS)

    Yao, K.T.S.

    1980-01-01

    In 1964 six pairs of rat kangaroo (Potorous tridactylis) were obtained from Australia. The tissues of these animals were used to initiate cell lines. Since this species has a low chromosome number of six pairs, each pair with its own distinctive morphology, it is particularly favorable for cytogenetic research. In cell cultures derived from the corneal endothelial tissues of one animal there emerged a number of haploid cells. The number of haploid cells in the cultures reached as high as 20% of the total mitotic configurations. The in vitro diploid and haploid mixture cell cultures could be a resemblance or a coincidence to the mixture existence of the diploid primary spermatocytes and the haploid secondary spermatocytes (gametes) in the in vivo testicular tissues of the male animals. It would be interesting to compare reactions of the haploid and diploid cell mixture, either in the cultures or in the testes, to x-ray exposure. Two other studies involving x-ray effects on Chinese hamster oocyte maturation and meiotic chromosomes and the x-ray induction of Chinese hamster spermatocyte meiotic chromosome aberrations have been done in this laboratory. A review of these three studies involving diploid and haploid chromosomes may lead to further research in the x-ray induction of chromosome aberrations

  4. Mechanistic modeling of aberrant energy metabolism in human disease

    Directory of Open Access Journals (Sweden)

    Vineet eSangar

    2012-10-01

    Full Text Available Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.

  5. ABERRANT METHYLATION OF THE PROMOTER OF APC, CDH13 AND MGMT GENES IN COLORECTAL CANCER PATIENTS

    Directory of Open Access Journals (Sweden)

    O. I. Kit

    2016-01-01

    Full Text Available Aberrant methylation of gene promoter regions is the main epigenetic change characterizing colorectal cancer. Methylation levels of 42 CpG-sites of promoter regions of the MGMT, APC and CDH13 genes in colorectal cancer were studied in comparison with methylation levels of the adjacent normal tissue in 25 patients. Pyrosequencing showed an increase in methylation levels of promoter regions of the MGMT, APC and CDH13 genes in tumor samples by 3 to 5 times. These tumor samples were screened for activating SNP-mutations in the KRAS (40 %, NRAS (0 % and BRAF (0 % oncogenes. SNP-mutations in the KRAS gene were accompanied by hypermethylation of one or more promoters of the studied genes. Association of this epigenetic index with tumor metastasis was proved. The data on an increase in methylation of the promoter regions of oncosupressor genes can be used as sensitive prognostic markers of progression and metastasis of colorectal cancer.

  6. mRNA and DNA detection of human papillomaviruses in women of all ages attending two colposcopy clinics.

    Directory of Open Access Journals (Sweden)

    Aris Spathis

    Full Text Available OBJECTIVE: HPV infection is a common finding, especially in young women while the majority of infections are cleared within a short time interval. The aim of this study was to examine the efficacy of HPV DNA and mRNA testing in a population attending colposcopy units of two University hospitals. METHODS: 1173 liquid based cervical samples from two colposcopy clinics were tested for HPV DNA positivity using a commercial typing kit and HPV E6/E7 mRNA positivity with a flow cytometry based commercial kit. Statistic measures were calculated for both molecular tests and morphological cytology and colposcopy diagnosis according to histology results. RESULTS: HPV DNA, high-risk HPV DNA, HPV16 or 18 DNA and HPV mRNA was detected in 55.5%, 50.6%, 20.1% and 29.7% of the cervical smears respectively. Concordance between the DNA and the mRNA test was 71.6% with their differences being statistically significant. Both tests' positivity increased significantly as lesion grade progressed and both displayed higher positivity rates in samples from women under 30 years old. mRNA testing displayed similar NPV, slightly lower sensitivity but significantly higher specificity and PPV than DNA testing, except only when DNA positivity for either HPV16 or 18 was used. CONCLUSIONS: Overall mRNA testing displayed higher clinical efficacy than DNA testing, either when used as a reflex test or as an ancillary test combined with morphology. Due to enhanced specificity of mRNA testing and its comparable sensitivity in ages under 25 or 30 years old, induction of mRNA testing in young women could be feasible if a randomized trial verifies these results.

  7. Suppression of mRNA Nanoparticle Transfection in Human Fibroblasts by Selected Interferon Inhibiting Small Molecule Compounds.

    Science.gov (United States)

    Liu, Yang; Krishnan, Manoj N; Phua, Kyle K L

    2017-07-31

    In vitro transcribed (IVT) mRNA is increasingly applied in lieu of DNA to deliver reprogramming genes to fibroblasts for stem cell derivation. However, IVT mRNA induces interferon (IFN) responses from mammalian cells that reduces transfection efficiency. It has been previously suggested that small molecule inhibitors of IFN are a viable strategy to enhance mRNA transfection efficiency. Herein, we screen a list of commercially available small molecules, including published IFN inhibitors, for their potential to enhance mRNA transfection in BJ fibroblasts. Transfection enhancement is quantified by relative mean fluorescence intensity of translated green fluorescent protein (GFP) in treated cells compared to dimethyl sulfoxide treated controls. Within toxicological constrains, all tested small molecules did not enhance mRNA transfection in BJ fibroblasts while a third of the tested compounds unexpectedly inhibited GFP expression even though IFN-β production is inhibited. Based on the results of our study, we conclude that small molecule inhibitors, including IFN inhibitors, tested in this study do not enhance in vitro mRNA transfection efficiency in human fibroblasts.

  8. Aberrant splicing of androgen receptor mRNA results in synthesis of a nonfunctional receptor protein in a patient with androgen insensitivity

    NARCIS (Netherlands)

    Ris-Stalpers, C.; Kuiper, G. G.; Faber, P. W.; Schweikert, H. U.; van Rooij, H. C.; Zegers, N. D.; Hodgins, M. B.; Degenhart, H. J.; Trapman, J.; Brinkmann, A. O.

    1990-01-01

    Androgen insensitivity is a disorder in which the correct androgen response in an androgen target cell is impaired. The clinical symptoms of this X chromosome-linked syndrome are presumed to be caused by mutations in the androgen receptor gene. We report a G----T mutation in the splice donor site of

  9. Photon Sieve Bandwidth Broadening by Reduction of Chromatic Aberration Effects Using Second-Stage Diffractive Optics

    Science.gov (United States)

    2015-03-26

    thesis. 25 Still another manner in which to view chromatic aberration is in terms of Lateral Chromatic Aberration ( LCA ). Eq. 18 illustrates a...wavelength in addition to the in-focus location. This difference in height of images at two different colors is LCA (21:268). Aberration Correction... electrons incident on one detector pixel (Ne) during a set camera integration time (t), multiply Eq. 28 by this time as well as T and η (32:8), yielding

  10. Relationship of DNA lesions and their repair to chromosomal aberration production

    Energy Technology Data Exchange (ETDEWEB)

    Bender, M.A.

    1979-01-01

    Recent work on the roles of specific kinds of DNA lesions and their enzymatic repair systems in the production of chromosomal aberrations seems consistent with a simple molecular model of chromosomal aberrations formation. Evidence from experiments with the human repair-deficient genetic diseases xeroderma pigmentosom, ataxia telangiectasia, and Fanconi's anemia is reviewed in the light of the contributions to aberration production of single and double polynucleotide strand breaks, base damage, polynucleotide strand crosslinks, and pyrimidine cyclobutane dimers.

  11. Improved Methodology for Assessment of mRNA Levels in Blood of Patients with FMR1 Related Disorders

    Directory of Open Access Journals (Sweden)

    Godler David E

    2009-06-01

    Full Text Available Abstract Background Elevated levels of FMR1 mRNA in blood have been implicated in RNA toxicity associated with a number of clinical conditions. Due to the extensive inter-sample variation in the time lapse between the blood collection and RNA extraction in clinical practice, the resulting variation in mRNA quality significantly confounds mRNA analysis by real-time PCR. Methods Here, we developed an improved method to normalize for mRNA degradation in a sample set with large variation in rRNA quality, without sample omission. Initially, RNA samples were artificially degraded, and analyzed using capillary electrophoresis and real-time PCR standard curve method, with the aim of defining the best predictors of total RNA and mRNA degradation. Results We found that: (i the 28S:18S ratio and RNA quality indicator (RQI were good predictors of severe total RNA degradation, however, the greatest changes in the quantity of different mRNAs (FMR1, DNMT1, GUS, B2M and GAPDH occurred during the early to moderate stages of degradation; (ii chromatographic features for the 18S, 28S and the inter-peak region were the most reliable predictors of total RNA degradation, however their use for target gene normalization was inferior to internal control genes, of which GUS was the most appropriate. Using GUS for normalization, we examined in the whole blood the relationship between the FMR1 mRNA and CGG expansion in a non-coding portion of this gene, in a sample set (n = 30 with the large variation in rRNA quality. By combining FMR1 3' and 5' mRNA analyses the confounding impact of mRNA degradation on the correlation between FMR1 expression and CGG size was minimized, and the biological significance increased from p = 0.046 for the 5' FMR1 assay, to p = 0.018 for the combined FMR1 3' and 5' mRNA analysis. Conclusion Our observations demonstrate that, through the use of an appropriate internal control and the direct analysis of multiple sites of target mRNA, samples that

  12. Oxygen regulation of uricase and sucrose synthase synthesis in soybean callus tissue is exerted at the mRNA level

    DEFF Research Database (Denmark)

    Xue, Z T; Larsen, K; Jochimsen, B U

    1991-01-01

    The effect of lowering oxygen concentration on the expression of nodulin genes in soybean callus tissue devoid of the microsymbiont has been examined. Poly(A)+ RNA was isolated from tissue cultivated in 4% oxygen and in normal atmosphere. Quantitative mRNA hybridization experiments using nodule...... the callus tissue was incubated at reduced oxygen concentration. Concomitant with the increase in mRNA level a 6-fold increase in specific activity of sucrose synthase was observed. Two messengers representing poly-ubiquitin precursors also responded to lowering the oxygen concentration. The increase...

  13. BAY11 enhances OCT4 synthetic mRNA expression in adult human skin cells.

    Science.gov (United States)

    Awe, Jason P; Crespo, Agustin Vega; Li, You; Kiledjian, Megerditch; Byrne, James A

    2013-02-06

    The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11), at least partially through an NF-κB-inhibition based mechanism, could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. We tested various chemical and molecular small molecules on their ability to suppress the innate immune response seen upon synthetic mRNA transfection. Three molecules - B18R, BX795, and BAY11 - were used in immunocytochemical and proliferation-based assays. We also utilized global transcriptional meta-analysis coupled with quantitative PCR to identify relative gene expression downstream of OCT4. We found that human skin cells cultured in the presence of BAY11 resulted in reproducible increased expression of OCT4 that did not inhibit normal cell proliferation. The increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G, suggesting the expressed OCT4 was functional. We also discovered a novel OCT4 putative downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. For the first time we have shown that small molecule-based stabilization of synthetic mRNA expression can be achieved with use of BAY11. This small molecule-based inhibition of innate immune responses and subsequent robust expression of transfected synthetic mRNAs may have multiple applications for future cell-based research and therapeutics.

  14. Effect of carbamates on mRNA encoding lipid enzymes in hamster flank organs.

    Science.gov (United States)

    López-Lezama, Juan C; Cabeza, Marisa; Mayorga, Israel; Soriano, Juan; Sainz, Teresita; Bratoeff, Eugene

    2014-05-01

    Flank organs are an androgen-dependent pilosebaceous complex present in male and female hamsters. These organs have been used for the evaluation of antiandrogenic drugs, which could be used for the treatment of androgen-dependent afflictions. This study demonstrated the role of four different steroidal carbamates 7-10 in the expression of mRNAs coding for different enzymes involved in the lipid metabolism in flank organs. To determine the biological effects of compounds 7-10 on the expression of mRNA coding for lipid enzymes, steroids 7-10, testosterone (T), progesterone (P), and/or 7-10 were applied on the flank organs. Later, the mRNA expression for the enzymes was determined by polymerase chain reaction. The binding of 8 and 9 to the progesterone receptor (PR) as well as their effects on the activity of 5α-reductase were also evaluated. Treatments with T, P, and 7-10 increased the mRNA expression for glycerol 3-phosphate acyl transferase (GPAT), β-hydroxy-β-methylglutaryl-CoA synthase (HMG-CoA-S), β-hydroxy-β-methylglutaryl-CoA reductase (HMG-CoA-R), phosphatidylinositol synthase (PI-S), and squalene-synthase (SQ-S). However, the combined treatments