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Sample records for dm related transcription

  1. The Drosophila melanogaster DmCK2beta transcription unit encodes for functionally non-redundant protein isoforms.

    Science.gov (United States)

    Jauch, Eike; Wecklein, Heike; Stark, Felix; Jauch, Mandy; Raabe, Thomas

    2006-06-07

    Genes encoding for the two evolutionary highly conserved subunits of a heterotetrameric protein kinase CK2 holoenzyme are present in all examined eukaryotic genomes. Depending on the organism, multiple transcription units encoding for a catalytically active CK2alpha subunit and/or a regulatory CK2beta subunit may exist. The phosphotransferase activity of members of the protein kinase CK2alpha family is thought to be independent of second messengers but is modulated by interaction with CK2beta-like proteins. In the genome of Drosophila melanogaster, one gene encoding for a CK2alpha subunit and three genes encoding for CK2beta-like proteins are present. The X-linked DmCK2beta transcription unit encodes for several CK2beta protein isoforms due to alternative splicing of its primary transcript. We addressed the question whether CK2beta-like proteins are redundant in function. Our in vivo experiments show that variations of the very C-terminal tail of CK2beta isoforms encoded by the X-linked DmCK2beta transcription unit influence their functional properties. In addition, we find that CK2beta-like proteins encoded by the autosomal D. melanogaster genes CK2betates and CK2beta' cannot fully substitute for a loss of CK2beta isoforms encoded by DmCK2beta.

  2. Hypertension and related risk factors in type 2 diabetes mellitus (DM ...

    African Journals Online (AJOL)

    Results: During the study it was found out that 61.2%of DM patients had hypertension, 56.4% obesity, 33.5% hypercholesterolemia and 38.9% hypertriglyceredemia. In the study, hypertension was associated with age, sex, type of DM, body mass index (BMI) and hypertriglyceredemia. Conclusion: The study found out that ...

  3. Substituted piperazines as nootropic agents: 2- or 3-phenyl derivatives structurally related to the cognition-enhancer DM235.

    Science.gov (United States)

    Guandalini, Luca; Martino, Maria Vittoria; Di Cesare Mannelli, Lorenzo; Bartolucci, Gianluca; Melani, Fabrizio; Malik, Ruchi; Dei, Silvia; Floriddia, Elisa; Manetti, Dina; Orlandi, Francesca; Teodori, Elisabetta; Ghelardini, Carla; Romanelli, Maria Novella

    2015-04-15

    A series of 2-phenyl- or 3-phenyl piperazines, structurally related to DM235 and DM232, two potent nootropic agents, have been prepared and tested in the mouse passive-avoidance test, to assess their ability to revert scopolamine-induced amnesia. Although the newly synthesized molecules were less potent than the parent compounds, some useful information has been obtained from structure-activity relationships. A small but significant enantioselectivity has been found for the most potent compound 5a. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Resistance-related gene transcription and antioxidant enzyme ...

    African Journals Online (AJOL)

    The two tobacco relatives of Nicotiana alata and Nicotiana longiflora display a high level of resistance against Colletotrichum nicotianae and the two genes NTF6 and NtPAL related to pathogen defense transcription were higher in N. alata and N. longiflora than the commercial cv. K326. Inoculation with C. nicotianae ...

  5. Five-Year Effectiveness of the Multidisciplinary Risk Assessment and Management Programme-Diabetes Mellitus (RAMP-DM) on Diabetes-Related Complications and Health Service Uses-A Population-Based and Propensity-Matched Cohort Study.

    Science.gov (United States)

    Wan, Eric Yuk Fai; Fung, Colman Siu Cheung; Jiao, Fang Fang; Yu, Esther Yee Tak; Chin, Weng Yee; Fong, Daniel Yee Tak; Wong, Carlos King Ho; Chan, Anca Ka Chun; Chan, Karina Hiu Yen; Kwok, Ruby Lai Ping; Lam, Cindy Lo Kuen

    2018-01-01

    To evaluate the 5-year effectiveness of a multidisciplinary Risk Assessment and Management Programme-Diabetes Mellitus (RAMP-DM) in primary care patients with type 2 diabetes. A 5-year prospective cohort study was conducted with 121,584 Chinese primary care patients with type 2 DM who were recruited between August 2009 and June 2011. Missing data were dealt with multiple imputations. After excluding patients with prior diabetes mellitus (DM)-related complications and one-to-one propensity score matching on all patient characteristics, 26,718 RAMP-DM participants and 26,718 matched usual care patients were followed up for a median time of 4.5 years. The effect of RAMP-DM on nine DM-related complications and all-cause mortality were evaluated using Cox regressions. The first incidence for each event was used for all models. Health service use was analyzed using negative binomial regressions. Subgroup analyses on different patient characteristics were performed. The cumulative incidence of all events (DM-related complications and all-cause mortality) was 23.2% in the RAMP-DM group and 43.6% in the usual care group. RAMP-DM led to significantly greater reductions in cardiovascular disease (CVD) risk by 56.6% (95% CI 54.5, 58.6), microvascular complications by 11.9% (95% CI 7.0, 16.6), mortality by 66.1% (95% CI 64.3, 67.9), specialist attendance by 35.0% (95% CI 33.6, 36.4), emergency attendance by 41.2% (95% CI 39.8, 42.5), and hospitalizations by 58.5% (95% CI 57.2, 59.7). Patients with low baseline CVD risks benefitted the most from RAMP-DM, which decreased CVD and mortality risk by 60.4% (95% CI 51.8, 67.5) and 83.6% (95% CI 79.3, 87.0), respectively. This naturalistic study highlighted the importance of early optimal DM control and risk factor management by risk stratification and multidisciplinary, protocol-driven, chronic disease model care to delay disease progression and prevent complications. © 2017 by the American Diabetes Association.

  6. Transcriptional regulation of genes related to progesterone production.

    Science.gov (United States)

    Mizutani, Tetsuya; Ishikane, Shin; Kawabe, Shinya; Umezawa, Akihiro; Miyamoto, Kaoru

    2015-01-01

    Steroid hormones are synthesized from cholesterol in various tissues, mainly in the adrenal glands and gonads. Because these lipid-soluble steroid hormones immediately diffuse through the cells in which they are produced, their secretion directly reflects the activity of the genes related to their production. Progesterone is important not only for luteinization and maintenance of pregnancy, but also as a substrate for most other steroids. Steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3β-HSD) are well-known proteins essential for progesterone production. In addition to them, glutathione S-transferase A1-1 and A3-3 are shown to exert Δ(5)-Δ(4) isomerization activity to produce progesterone in a cooperative fashion with 3β-HSD. 5-Aminolevulinic acid synthase 1, ferredoxin 1, and ferredoxin reductase also play a role in steroidogenesis as accessory factors. Members of the nuclear receptor 5A (NR5A) family (steroidogenic factor 1 and liver receptor homolog 1) play a crucial role in the transcriptional regulation of these genes. The NR5A family activates these genes by binding to NR5A responsive elements present within their promoter regions, as well as to the elements far from their promoters. In addition, various NR5A-interacting proteins including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear receptor subfamily 0, group B, member 1 (DAX-1), and CCAAT/enhancer-binding proteins (C/EBP) are involved in the transcription of NR5A target genes and regulate the transcription either positively or negatively under both basal and tropic hormone-stimulated conditions. In this review, we describe the transcriptional regulation of genes related to progesterone production.

  7. Vascular endothelial growth factor (VEGF-related single nucleotide polymorphisms rs10738760 and rs6921438 are not associated with diabetic retinopathy (DR in Slovenian patients with type 2 diabetes mellitus (T2DM

    Directory of Open Access Journals (Sweden)

    Rifet Terzić

    2017-11-01

    Full Text Available Diabetic retinopathy (DR is a complication of diabetes characterized by vascular permeability, increased tissue ischemia, and angiogenesis. One of the most important proteins involved in angiogenesis is vascular endothelial growth factor (VEGF, also known as VEGFA. A previous study demonstrated that two single nucleotide polymorphisms (SNPs, rs6921438 and rs10738760, account for nearly half the variation in circulating VEGF levels. The aim of our study was to assess the association between rs6921438 and rs10738760 and DR in Slovenian patients with type 2 diabetes mellitus (T2DM. This case-control study enrolled 1037 unrelated Slovenian individuals (Caucasians with T2DM. DR group included 415 T2DM patients with DR, while control group included 622 T2DM patients with no clinical signs of DR. The clinical and laboratory data were obtained from the medical records of the patients. The genotyping of rs6921438 and rs10738760 SNPs was carried out with real-time PCR assays. Significant differences were observed between patients with DR and controls in the duration of diabetes (p < 0.001, insulin therapy (p < 0.001, glycated hemoglobin (p = 0.001, body mass index (p = 0.002, total cholesterol (p = 0.002, and low-density lipoprotein cholesterol (p < 0.001. However, we did not observe significant differences in the genotype and allele distribution of the two SNPs, between DR and control group (p < 0.05. Logistic regression analysis showed that rs6921438 and rs10738760 were not independent genetic risk factors for DR in the co-dominant model adjusted for the above-mentioned clinical and laboratory data. In conclusion, VEGF-related SNPs rs10738760 and rs6921438 are not associated with DR in our group of Slovenian patients (Caucasians with T2DM.

  8. The ArDM experiment

    CERN Document Server

    Haranczyk, M; Badertscher, A; Boccone, V; Bourgeois, N; Bueno, A; Carmona-Benitez, M C; Chorowski, M; Creus, W; Curioni, A; Daw, E; Degunda, U; Dell'Antone, A; Droge, M; Epprecht, L; Haller, C; Horikawa, S; Kaufmann, L; Kisiel, J; Knecht, L; Laffranchi, M; Lagoda, J; Lazzaro, C; Lightfoot, P; Lozano, J; Lussi, D; Maire, G; Mania, S; Marchionni, A; Mavrokoridis, K; Melgarejo, A; Mijakowski, P; Natterer, G; Navas-Concha, S; Otiougova, P; Piotrowska, A; Polinski, J; de Prado, M; Przewlocki, P; Ravat, S; Regenfus, C; Resnati, F; Robinson, M; Rochet, J; Romero, L; Rondio, E; Rubbia, A; Scotto-Lavina, L; Spooner, N; Viant, T; Trawinski, A; Ulbricht, J; Zalewska, A

    2010-01-01

    The aim of the ArDM project is the development and operation of a one ton double-phase liquid argon detector for direct Dark Matter searches. The detector measures both the scintillation light and the ionization charge from ionizing radiation using two independent readout systems. This paper briefly describes the detector concept and presents preliminary results from the ArDM R&D program, including a 3 l prototype developed to test the charge readout system.

  9. DM Considerations for Deep Drilling

    OpenAIRE

    Dubois-Felsmann, Gregory

    2016-01-01

    An outline of the current situation regarding the DM plans for the Deep Drilling surveys and an invitation to the community to provide feedback on what they would like to see included in the data processing and visualization of these surveys.

  10. 12 billion DM for Germany

    International Nuclear Information System (INIS)

    Anon.

    1975-01-01

    The German atomic industry has achieved the break-through to the world market: Brazil orders eight nuclear electricity generating plants from Siemens-AEG daughter Kraftwerk-Union. US concerns attacked the twelve billion DM deal, the biggest export order in the history of German industry. Without avail - the contract is to be signed in Bonn this week. (orig./LH) [de

  11. Asymmetric WIMP Dark Matter in the presence of DM/anti-DM oscillations

    International Nuclear Information System (INIS)

    Zaharijas, G.

    2014-01-01

    The general class of 'Asymmetric Dark Matter (DM)' scenarios assumes the existence of a primordial particle/anti-particle asymmetry in the dark matter sector related to the asymmetry in the baryonic one, as a way to achieve the observed similarity between the baryonic and dark matter energy densities today. Focusing on this framework we study the effect of oscillations between dark matter and its anti-particle on the re-equilibration of the initial asymmetry. We calculate the evolution of the dark matter relic abundance and show how oscillations re-open the parameter space of asymmetric dark matter models, in particular in the direction of allowing large (WIMP-scale) DM masses. We found in particular that a typical WIMP with a mass at the EW scale (about 1 TeV) having a primordial asymmetry of the same order as the baryon asymmetry, naturally gets the correct relic abundance if the δm mass term is in the ∼ meV range. This turns out to be a natural value for fermionic DM arising from the higher dimensional operator H 2 DM 2 /Λ where H is the Higgs field and Λ ∼ M Pl . Finally, we constrain the parameter space in this framework by applying up-to-date bounds from indirect detection signals on annihilating DM

  12. Expanded [CCTG]n repetitions are not associated with abnormal methylation at the CNBP locus in myotonic dystrophy type 2 (DM2) patients.

    Science.gov (United States)

    Santoro, Massimo; Fontana, Luana; Maiorca, Francesca; Centofanti, Federica; Massa, Roberto; Silvestri, Gabriella; Novelli, Giuseppe; Botta, Annalisa

    2018-03-01

    Myotonic Dystrophy type 2 (DM2) is a multisystemic disorder associated with an expanded [CCTG]n repeat in intron 1 of the CNBP gene. Epigenetic modifications have been reported in many repeat expansion disorders, including myotonic dystrophy type 1 (DM1), either as a mechanism to explain somatic repeat instability or transcriptional alterations in disease genes. The purpose of our work was to determine the effect of DM2 mutation on the methylation status of CpG islands localized in the 5' promoter region and in the 3' end of the [CCTG]n expansion of the CNBP gene. By bisulfite pyrosequencing, we characterized the methylation profile of two different CpG islands within these regions, either in whole blood and skeletal muscle tissues of DM2 patients (n=72 and n=7, respectively) and controls (n=50 and n=7, respectively). Moreover, we compared the relative mRNA transcript levels of CNBP gene in leukocytes and in skeletal muscle tissues from controls and DM2 patients. We found that CpG sites located in the promoter region showed hypomethylation, whereas CpG sites at 3' end of the CCTG array are hypermethylated. Statistical analyses did not demonstrate any significant differences in the methylation profile between DM2 patients and controls in both tissues analyzed. According to the methylation analysis, CNBP gene expression levels are not significantly altered in DM2 patients. These results show that [CCTG]n repeat expansion, differently from the DM1 mutation, does not influence the methylation status of the CNBP gene and suggest that other molecular mechanisms are involved in the pathogenesis of DM2. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Expression of mink cell focus-forming murine leukemia virus-related transcripts in AKR mice

    International Nuclear Information System (INIS)

    Khan, A.S.; Laigret, F.; Rodi, C.P.

    1987-01-01

    The authors used a synthetic 16-base-pair mink cell focus-forming (MCF) env-specific oligomer as radiolabeled probe to study MCF murine leukemia virus (MuLV)-related transcripts in brain, kidney, liver, spleen, and thymus tissues of AKR mice ranging from 5 weeks to 6 months (mo) of age. Tissue-specific expression of poly(A) + RNAs was seen. In addition, all the tissues tested contained 3.0-kb messages. The transcription of these MCF-related mRNAs was independent of the presence of ecotropic and xenotropic MuLVs. In general, expression of the MCF env-related transcripts appeared to peak at 2 mo of age; these messages were barely detectable in brain, kidney, liver, and spleen tissues after 2 mo and in thymus tissue after 4 mo of age. All of the subgenomic MCF env-related mRNAs appeared to contain the 190-base-pair cellular DNA insert, characteristic of the long terminal repeats associated with endogenous MCF env-related proviruses. No genomic-size (8.4-kb) transcripts corresponding to endogenous MCF-related proviruses were detected. An 8.4-kb MCF env-related mRNA was first seen at 3 mo of age, exclusively in thymus tissue. This species most likely represents the first appearance of a recombinant MCF-related MuLV genome. The transcripts which were detected in thymus tissue might be involved in the generation of leukemogenic MCF viruses

  14. Factors associated with diabetes-related distress over time among patients with T2DM in a tertiary hospital in Singapore.

    Science.gov (United States)

    Tan, Maudrene L; Tan, Chuen S; Griva, Konstadina; Lee, Yung S; Lee, Jeannette; Tai, E S; Khoo, Eric Y; Wee, Hwee-Lin

    2017-06-23

    Persistent diabetes-related distress (DRD) is experienced by patients with Type 2 Diabetes Mellitus. Knowing factors associated with persistent DRD will aid clinicians in prioritising interventions efforts. A total of 216 patients were recruited from a tertiary hospital in Singapore, an Asian city state, and followed for 1.5 years (2011-2014). Data was collected by self-completed questionnaires assessing DRD (measured by the Problem Areas in Diabetes score) and other psychosocial aspects such as social support, presenteeism, depression, health-related quality of life (HRQoL) and excessive daytime sleepiness (EDS) at three time points. Clinical data (body-mass-index and glycated haemoglobin) was obtained from medical records. Change score was calculated for each clinical and psychosocial variable to capture changes in these variables from baseline. Generalized Linear Model with Generalized Estimating Equation method was used to assess whether baseline and change scores in clinical and psychosocial are associated with DRD over time. Complete data was available for 73 patients, with mean age 44 (SD 12.5) years and 67% males. Persistent DRD was experienced by 21% of the patients. In the final model, baseline HRQoL (OR = 0.56, p < 0.05) and change score of EDS (OR = 1.22, p < 0.05) was significantly associated with DRD over time. EDS might be a surrogate marker for persistent DRD and should be explored in larger samples of population to confirm the findings from this study.

  15. Myocardin-related transcription factors are required for cardiac development and function

    OpenAIRE

    Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

    2015-01-01

    Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the d...

  16. Relations Between Atherogenic Index of Plasma, Ratio of Small Dense Low Density Lipoprotein/Lecithin Cholesterol Acyl Transferase and Ratio of Small Dense Low Density Lipoprotein/Cholesteryl Ester Transfer Protein of Controlled and Uncontrolled Type 2 DM

    Directory of Open Access Journals (Sweden)

    Ellis Susanti

    2009-08-01

    Full Text Available BACKGROUND: Patients with Diabetes Melitus are proven to be prone to atherosclerosis and coronary heart disease, especially type 2 Diabetes Melitus (T2DM patient who have higher risk and mortality for cardiovascular risk factor. The Dyslipidemia condition is very common in T2DM as one of the risk factors. Diabetic dyslipidemia is marked by the increased triglyceride (TG, low HDL cholesterol (HDL-C, and increased small dense LDL and apolipoprotein B. Therefore the aim of this study is to assess the differential and correlation between Atherogenic Index of Plasma (AIP, ratio of small dense low density lipoprotein (sdLDL/lecithin cholesterol acyl transferase (LCAT and ratio of sdLDL/cholesteryl ester transfer protein (CETP of controlled and uncontrolled T2DM. METHODS: This study was observational with cross sectional design. In total of 72 patients with T2DM consist of 36 controlled and 36 uncontrolled, participated in this study. The serum TG, HDL-C, sdLDL, LCAT and CETP were examined in their relationship with to T2DM risk. RESULTS: The results of the study indicate that the AIP (p<0.001 increase controlled and uncontrolled T2DM and the ratio of sdLDL/CETP (p=0.004, odds ratio of AIP was 4 (95% CI: 1.501-10.658 and odds ratio of sdLDL/CETP ratio was 4 (95% CI: 1.501-10.658 in uncontrolled T2DM. CONCLUSIONS: This study showed that the AIP and ratio of small dense LDL/CETP had a significant correlation with the uncontrolled T2DM. The AIP and ratio of small dense LDL/CETP increase was found at the uncontrolled T2DM to be 4 times greater than the controlled T2DM. KEYWORDS: T2DM, atherosclerosis, atherogenic index of plasma, small dense LDL, LCAT, CETP, ratio of sdLDL/LCAT, ratio of sdLDL/CETP.

  17. Hippocampal CA1 transcriptional profile of sleep deprivation: relation to aging and stress.

    Directory of Open Access Journals (Sweden)

    Nada M Porter

    Full Text Available Many aging changes seem similar to those elicited by sleep-deprivation and psychosocial stress. Further, sleep architecture changes with age suggest an age-related loss of sleep. Here, we hypothesized that sleep deprivation in young subjects would elicit both stress and aging-like transcriptional responses.F344 rats were divided into control and sleep deprivation groups. Body weight, adrenal weight, corticosterone level and hippocampal CA1 transcriptional profiles were measured. A second group of animals was exposed to novel environment stress (NES, and their hippocampal transcriptional profiles measured. A third cohort exposed to control or SD was used to validate transcriptional results with Western blots. Microarray results were statistically contrasted with prior transcriptional studies. Microarray results pointed to sleep pressure signaling and macromolecular synthesis disruptions in the hippocampal CA1 region. Animals exposed to NES recapitulated nearly one third of the SD transcriptional profile. However, the SD-aging relationship was more complex. Compared to aging, SD profiles influenced a significant subset of genes. mRNA associated with neurogenesis and energy pathways showed agreement between aging and SD, while immune, glial, and macromolecular synthesis pathways showed SD profiles that opposed those seen in aging.We conclude that although NES and SD exert similar transcriptional changes, selective presynaptic release machinery and Homer1 expression changes are seen in SD. Among other changes, the marked decrease in Homer1 expression with age may represent an important divergence between young and aged brain response to SD. Based on this, it seems reasonable to conclude that therapeutic strategies designed to promote sleep in young subjects may have off-target effects in the aged. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel therapeutic targets to counter

  18. The roles of Dmrt (Double sex/Male-abnormal-3 Related Transcription factor) genes in sex determination and differentiation mechanisms: Ubiquity and diversity across the animal kingdom.

    Science.gov (United States)

    Picard, Marion Anne-Lise; Cosseau, Céline; Mouahid, Gabriel; Duval, David; Grunau, Christoph; Toulza, Ève; Allienne, Jean-François; Boissier, Jérôme

    2015-07-01

    The Dmrt (Double sex/Male-abnormal-3 Related Transcription factor) genes have been intensively studied because they represent major transcription factors in the pathways governing sex determination and differentiation. These genes have been identified in animal groups ranging from cnidarians to mammals, and some of the genes functionally studied. Here, we propose to analyze (i) the presence/absence of various Dmrt gene groups in the different taxa across the animal kingdom; (ii) the relative expression levels of the Dmrt genes in each sex; (iii) the specific spatial (by organ) and temporal (by developmental stage) variations in gene expression. This review considers non-mammalian animals at all levels of study (i.e. no particular importance is given to animal models), and using all types of sexual strategy (hermaphroditic or gonochoric) and means of sex determination (i.e. genetic or environmental). To conclude this global comparison, we offer an analysis of the DM domains conserved among the different DMRT proteins, and propose a general sex-specific pattern for each member of the Dmrt gene family. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  19. Identification of transcripts related to high egg production in the chicken hypothalamus and pituitary gland.

    Science.gov (United States)

    Shiue, Yow-Ling; Chen, Lih-Ren; Chen, Chih-Feng; Chen, Yi-Ling; Ju, Jhy-Phen; Chao, Ching-Hsien; Lin, Yuan-Ping; Kuo, Yu-Ming; Tang, Pin-Chi; Lee, Yen-Pai

    2006-09-15

    To identify transcripts related to high egg production expressed specifically in the hypothalamus and pituitary gland of the chicken, two subtracted cDNA libraries were constructed. Two divergently selected strains of Taiwan Country Chickens (TCCs), B (sire line) and L2 (dam line) were used; they had originated from a single population and were further subjected (since 1982) to selection for egg production to 40 wk of age and body weight/comb size, respectively. A total of 324 and 370 clones were identified from the L2-B (L2-subtract-B) and the B-L2 subtracted cDNA libraries, respectively. After sequencing and annotation, 175 and 136 transcripts that represented 53 known and 65 unknown non-redundant sequences were characterized in the L2-B subtracted cDNA library. Quantitative reverse-transcription (RT)-PCR was used to screen the mRNA expression levels of 32 randomly selected transcripts in another 78 laying hens from five different strains. These strains included the two original strains (B and L2) used to construct the subtracted cDNA libraries and an additional three commercial strains, i.e., Black- and Red-feather TCCs and Single-Comb White Leghorn (WL) layer. The mRNA expression levels of 16 transcripts were significantly higher in the L2 than in the B strain, whereas the mRNA expression levels of nine transcripts, BDH, NCAM1, PCDHA@, PGDS, PLAG1, PRL, SAR1A, SCG2 and STMN2, were significantly higher in two high egg production strains, L2 and Single-Comb WL; this indicated their usefulness as molecular markers of high egg production.

  20. Coupled DM Heating in SCDEW Cosmologies

    Directory of Open Access Journals (Sweden)

    Silvio Bonometto

    2017-08-01

    Full Text Available Strongly-Coupled Dark Energy plus Warm dark matter (SCDEW cosmologies admit the stationary presence of ∼1% of coupled-DM and DE, since inflationary reheating. Coupled-DM fluctuations therefore grow up to non-linearity even in the early radiative expansion. Such early non-linear stages are modelized here through the evolution of a top-hat density enhancement, reaching an early virial balance when the coupled-DM density contrast is just 25–26, and the DM density enhancement is ∼10 % of the total density. During the time needed to settle in virial equilibrium, the virial balance conditions, however, continue to modify, so that “virialized” lumps undergo a complete evaporation. Here, we outline that DM particles processed by overdensities preserve a fraction of their virial momentum. Although fully non-relativistic, the resulting velocities (moderately affect the fluctuation dynamics over greater scales, entering the horizon later on.

  1. Regulation of an H-ras-related transcript by parathyroid hormone in rat osteosarcoma cells

    Science.gov (United States)

    Scott, D. K.; Weaver, W. R.; Clohisy, J. C.; Brakenhoff, K. D.; Kahn, A. J.; Partridge, N. C.

    1992-01-01

    The rat osteosarcoma cell line UMR 106-01 is a commonly used model system for the study of osteoblast function. However, it also expresses a phenotype characteristic of transformed cells. To test whether the latter could be accounted for by aberrant oncogene expression, we probed Northern blots of UMR and other osteoblastic cells with a panel of oncogene probes. These blots, when probed with a cDNA specific for v-H-ras, revealed a 7.0-kilobase (kb) H-ras-related transcript (designated HRRT) in UMR 106-01 cells that was not expressed in other osteoblastic cells. Osteoblast-enriched calvarial cells expressed the typical 1.1-kb H-ras mRNA, which was absent in UMR cells. Additionally, Western blots of lysates of UMR cells documented the presence of three proteins immunologically related to H-rasp21. To determine whether HRRT represented a recombinant retrovirus product, Northern blots were probed with a cDNA specific for the highly conserved gag-pol region of Moloney murine leukemia virus. These blots showed parallel cross-reactivity with an apparently identical transcript of 7.0 kb. The 7.0-kb transcripts detected by both v-H-ras and gag-pol probes declined to the same extent after treatment with concentrations of PTH known to inhibit proliferation of these cells. PTH regulated the abundance of HRRT in a time- and dose-dependent manner, with greatest repression of the transcript after 8 h of treatment with 10(-8) M PTH. The decrease in HRRT could not be completely accounted for by changes in transcriptional activity, as determined by nuclear run-on assays.(ABSTRACT TRUNCATED AT 250 WORDS).

  2. Transcriptional effects of glucocorticoid receptors in the dentate gyrus increase anxiety-related behaviors.

    Directory of Open Access Journals (Sweden)

    Nadège Sarrazin

    Full Text Available The Glucocorticoid Receptor (GR is a transcription factor ubiquitously expressed in the brain. Activation of brain GRs by high levels of glucocorticoid (GC hormones modifies a large variety of physiological and pathological-related behaviors. Unfortunately the specific cellular targets of GR-mediated behavioral effects of GC are still largely unknown. To address this issue, we generated a mutated form of the GR called DeltaGR. DeltaGR is a constitutively transcriptionally active form of the GR that is localized in the nuclei and activates transcription without binding to glucocorticoids. Using the tetracycline-regulated system (Tet-OFF, we developed an inducible transgenic approach that allows the expression of the DeltaGR in specific brain areas. We focused our study on a mouse line that expressed DeltaGR almost selectively in the glutamatergic neurons of the dentate gyrus (DG of the hippocampus. This restricted expression of the DeltaGR increased anxiety-related behaviors without affecting other behaviors that could indirectly influence performance in anxiety-related tests. This behavioral phenotype was also associated with an up-regulation of the MAPK signaling pathway and Egr-1 protein in the DG. These findings identify glutamatergic neurons in the DG as one of the cellular substrate of stress-related pathologies.

  3. Relative expression of the products of glyoxylate bypass operon: contributions of transcription and translation.

    OpenAIRE

    Chung, T; Resnik, E; Stueland, C; LaPorte, D C

    1993-01-01

    Although the genes of the aceBAK operon are expressed from the same promoter, the relative cellular levels of their products are approximately 0.3:1:0.003. Gene and operon fusions with lacZ were constructed to characterize this differential expression. The upshift in expression between aceB and aceA resulted from differences in translational efficiency. In contrast, inefficient translation and premature transcriptional termination contributed to the downshift in expression between aceA and ac...

  4. Differences in relative amounts of two novel mutant HEXA transcripts in a juvenile TSD Druze patient

    Energy Technology Data Exchange (ETDEWEB)

    Drucker, L.; Navon, R. [Tel Aviv Univ. (Israel)]|[Sapir Medical Center, Kfar Sava (Israel)

    1994-09-01

    An Israeli-Druze patient with juvenile Tay-Sachs disease, born to first cousins, was found to be a compound heterozygote for two novel mutant HEXA alleles. SSCP analysis of the parents` genomic DNA revealed alterations in both exons 5 and 8. Direct sequencing showed a novel missense mutation T{sup 835}{r_arrow}C (Ser{sup 279}{r_arrow}Pro) in exon 8, of maternal origin. The mutant allele of paternal origin carried a novel double mutation in exon 5, (i) a C{sup 496} deletion, resulting in a frameshift and eventually a stop codon, (ii) a C{sup 496}{r_arrow}G transition which is a silent mutation. Both these latter mutations occur in the same codon. New restriction sites for ScrFI were introduced into the two mutant alleles, enabling rapid screening for their presence. In order to detect differences of the relative levels of the transcripts originating from the two mutant alleles, we applied allele-specific transcripts polymerase chain reaction (AST-PCR) to the RNA extractions prepared from the heterozygous parents (each carry a normal and mutant allele). In order to distinguish between the transcripts originating from the normal allele and those originating from each of the mutant alleles, the transcripts were digested by ScrFI. A severe depletion of the mRNA coded by the allele carrying the mutation in exon 5 was found. The phenomena corresponds with citations in the literature in cases of stop mutations. The allele carrying the transversion in exon 8, contrary to our expectations, also had a distinctly lower level of transcripts. The AST-PCR approach offers a molecular tool to study allele-specific gene expression in heterozygous individuals.

  5. Transcriptional profiling of immune-related genes in Pacific white shrimp (Litopenaeus vannamei) during ontogenesis.

    Science.gov (United States)

    Quispe, Ruth L; Justino, Emily B; Vieira, Felipe N; Jaramillo, Michael L; Rosa, Rafael D; Perazzolo, Luciane M

    2016-11-01

    We have performed here a gene expression analysis to determine the developmental stage at the main genes involved in crustacean immune response begin to be expressed and their changes in mRNA abundance during shrimp development. By using a quantitative PCR-based approach, we have measured the mRNA abundance of 24 immune-related genes from different functional categories in twelve developmental stages ranging from fertilized eggs to larval and postlarval stages and also in juveniles. We showed for the first time that the main genes from the RNAi-based post-transcriptional pathway involved in shrimp antiviral immunity are transcribed in all developmental stages, but exhibit a diverse pattern of gene expression during shrimp ontogenesis. On the other hand, hemocyte-expressed genes mainly involved in antimicrobial defenses appeared to be transcribed in larval stages, indicating that hematopoiesis initiates early in development. Moreover, transcript levels of some genes were early detected in fertilized eggs at 0-4 h post-spawning, suggesting a maternal contribution of immune-related transcripts to shrimp progeny. Altogether, our results provide important clues regarding the ontogenesis of hemocytes as well the establishment of antiviral and antimicrobial defenses in shrimp. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. RESPON DAN KOPING PASIEN DM POST AMPUTASI

    Directory of Open Access Journals (Sweden)

    Candra Kusuma Negara

    2017-09-01

    Full Text Available Penyakit DM merupakan masalah kesehatan yang sangat penting karena berkaitan dengan tingginya kejadian komplikasi dan mortalitas yang tinggi. Bagi kebanyakan orang penyakit DM adalah suatu penyakit yang sangat mengkhawatirkan dan masyarakat sadar akan besarnya potensi bahaya yang ditimbulkannya. Bagi individu yang menderita DM dengan pasca amputasi, kehidupan selanjutnya merupakan babak baru yang penuh tantangan dan perubahan serta akan melalui proses koping terhadap proses perubahan tersebut. Secara umum penelitian ini bertujuan untuk mengeksplorasi berbagai pengalaman pasien DM pasca amputasi tentang respon dan koping yang dialaminya. Penelitian ini menggunakan studi fenomenologi. Pengambilan data menggunakan indepth interview pada empat orang partisipan yang dirawat jalan di Poli kaki diabetic RSUD Ulin Banjarmasin yang dilengkapi dengan pedoman wawancara dan informed consent. Metode analisis yang terstruktur dari Creswell menjadi 6 langkah. Terdapat 2 Tema yang ditemukan dalam penelitian ini yaitu berbagai respon post amputasi dan Berbagai koping pasien DM post amputasi. Berbagai respon post amputasi terdiri dari tiga Sub-Tema yaitu: (1 Mengalami hambatan fisik, (2 Mengalami perubahan peran, (3 Mengalami proses berduka, dan Terdapat empat Sub-Tema yang menggambarkan berbagai koping pasien DM post amputasi yaitu: (1 Lebih banyak beribadah, (2 Menerima keadaan, (3 Motivasi yang kuat, (4 Mencari dukungan sosial.

  7. Transcriptional profiles of hybrid Eucalyptus genotypes with contrasting lignin content reveal that monolignol biosynthesis-related genes regulate wood composition

    Directory of Open Access Journals (Sweden)

    Tomotaka eShinya

    2016-04-01

    Full Text Available Eucalyptus species constitutes the most widely planted hardwood trees in temperate and subtropical regions. In this study, we compared the transcript levels of genes involved in lignocellulose formation such as cellulose, hemicellulose and lignin biosynthesis in two selected three-year old hybrid Eucalyptus (Eucalyptus urophylla x E. grandis genotypes (AM063 and AM380 that have different lignin content. AM063 and AM380 had 20.2 and 35.5% of Klason lignin content and 59.0% and 48.2%, -cellulose contents, respectively. We investigated the correlation between wood properties and transcript levels of wood formation-related genes using RNA-seq with total RNAs extracted from developing xylem tissues at a breast height. Transcript levels of cell wall construction genes such as cellulose synthase (CesA and sucrose synthase (SUSY were almost the same in both genotypes. However, AM063 exhibited higher transcript levels of UDP-glucose pyrophosphorylase (UGP and xyloglucan endotransglucoxylase (XTH than those in AM380. Most monolignol biosynthesis- related isozyme genes showed higher transcript levels in AM380. These results indicate monolignol biosynthesis-related genes may regulate wood composition in Eucalyptus. Flavonoids contents were also observed at much higher levels in AM380 as a result of the elevated transcript levels of common phenylpropanoid pathway genes, phenylalanine ammonium lyase (PAL, cinnamate-4-hydroxylase (C4H and 4-coumarate-CoA ligase (4CL. Secondary plant cell wall formation is regulated by many transcription factors. We analyzed genes encoding NAC, WRKY, AP2/ERF and KNOX transcription factors and found higher transcript levels of these genes in AM380. We also observed increased transcription of some MYB and LIM domain transcription factors in AM380 compared to AM063. All these results show that genes related to monolignol biosynthesis may regulate the wood composition and help maintain the ratio of cellulose and lignin contents

  8. Identification of transcription factors potential related to brown planthopper resistance in rice via microarray expression profiling

    Directory of Open Access Journals (Sweden)

    Wang Yubing

    2012-12-01

    Full Text Available Abstract Background Brown planthopper (BPH, Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties. Results We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT. We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1. We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC of more than 2.0 (P10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT. Conclusions We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants protect themselves by reducing their metabolic level to inhibit feeding by BPH and prevent damage from water and nutrient loss. We have selected 21 TF genes related to BPH resistance for further analyses to understand the molecular responses to BPH feeding in rice.

  9. Consequences of DM/antiDM oscillations for asymmetric WIMP darkmatter

    DEFF Research Database (Denmark)

    Cirelli, M.; Panci, P.; Servant, G.

    2012-01-01

    Assuming the existence of a primordial asymmetry in the dark sector, a scenario usually dubbed Asymmetric Dark Matter (aDM), we study the effect of oscillations between dark matter and its antiparticle on the re-equilibration of the initial asymmetry before freeze-out, which enable efficient...... a primordial asymmetry of the same order as the baryon asymmetry naturally gets the correct relic abundance if the DM-number-violating Delta(DM) = 2 mass term is in the similar to meV range. The re-establishment of annihilations implies that constraints from the accumulation of aDM in astrophysical bodies...

  10. Conserved regional patterns of GABA-related transcript expression in the neocortex of subjects with schizophrenia.

    Science.gov (United States)

    Hashimoto, Takanori; Bazmi, H Holly; Mirnics, Karoly; Wu, Qiang; Sampson, Allan R; Lewis, David A

    2008-04-01

    Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia. Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects. Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the alpha 1 and delta subunits of GABA(A) receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas. Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.

  11. Identification of transcription factors potential related to brown planthopper resistance in rice via microarray expression profiling.

    Science.gov (United States)

    Wang, Yubing; Guo, Huimin; Li, Haichao; Zhang, Hao; Miao, Xuexia

    2012-12-10

    Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most destructive insect pests of rice. The molecular responses of plants to sucking insects resemble responses to pathogen infection. However, the molecular mechanism of BPH-resistance in rice remains unclear. Transcription factors (TF) are up-stream regulators of various genes that bind to specific DNA sequences, thereby controlling the transcription from DNA to mRNA. They are key regulators for transcriptional expression in biological processes, and are probably involved in the BPH-induced pathways in resistant rice varieties. We conducted a microarray experiment to analyze TF genes related to BPH resistance in a Sri Lankan rice cultivar, Rathu Heenati (RHT). We compared the expression profiles of TF genes in RHT with those of the susceptible rice cultivar Taichun Native 1 (TN1). We detected 2038 TF genes showing differential expression signals between the two rice varieties. Of these, 442 TF genes were probably related to BPH-induced resistance in RHT and TN1, and 229 may be related to constitutive resistance only in RHT. These genes showed a fold change (FC) of more than 2.0 (Pgenes related to BPH-induced resistance, most of them were readily induced in TN1 than in RHT by BPH feeding, for instance, 154 TF genes were up-regulated in TN1, but only 31 TF genes were up-regulated in RHT at 24 hours after BPH infestation; 2-4 times more TF genes were induced in TN1 than in RHT by BPH. At an FC threshold of >10, there were 37 induced TF genes and 26 constitutive resistance TF genes. Of these, 13 were probably involved in BPH-induced resistance, and 8 in constitutive resistance to BPH in RHT. We explored the molecular mechanism of resistance to BPH in rice by comparing expressions of TF genes between RHT and TN1. We speculate that the level of gene repression, especially for early TF genes, plays an important role in the defense response. The fundamental point of the resistance strategy is that plants

  12. Consequences of DM/antiDM Oscillations for Asymmetric WIMP Dark Matter

    CERN Document Server

    Cirelli, Marco; Servant, Geraldine; Zaharijas, Gabrijela

    2012-01-01

    Assuming the existence of a primordial asymmetry in the dark sector, a scenario usually dubbed Asymmetric Dark Matter (aDM), we study the effect of oscillations between dark matter and its antiparticle on the re-equilibration of the initial asymmetry before freeze-out, which enable efficient annihilations to recouple. We calculate the evolution of the DM relic abundance and show how oscillations re-open the parameter space of aDM models, in particular in the direction of allowing large (WIMP-scale) DM masses. A typical wimp with a mass at the EW scale (\\sim 100 GeV - 1 TeV) presenting a primordial asymmetry of the same order as the baryon asymmetry naturally gets the correct relic abundance if the DM-number-violating Delta(DM) = 2 mass term is in the \\sim meV range. The re-establishment of annihilations implies that constraints from the accumulation of aDM in astrophysical bodies are evaded. On the other hand, the ordinary bounds from BBN, CMB and indirect detection signals on annihilating DM have to be consi...

  13. Myocardin-related transcription factors are required for cardiac development and function

    Science.gov (United States)

    Mokalled, Mayssa H.; Carroll, Kelli J.; Cenik, Bercin K.; Chen, Beibei; Liu, Ning; Olson, Eric N.; Bassel-Duby, Rhonda

    2016-01-01

    Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. PMID:26386146

  14. Expression of Root-Related Transcription Factors Associated with Flooding Tolerance of Soybean (Glycine max

    Directory of Open Access Journals (Sweden)

    Babu Valliyodan

    2014-09-01

    Full Text Available Much research has been conducted on the changes in gene expression of the model plant Arabidopsis to low-oxygen stress. Flooding results in a low oxygen environment in the root zone. However, there is ample evidence that tolerance to soil flooding is more than tolerance to low oxygen alone. In this study, we investigated the physiological response and differential expression of root-related transcription factors (TFs associated with the tolerance of soybean plants to soil flooding. Differential responses of PI408105A and S99-2281 plants to ten days of soil flooding were evaluated at physiological, morphological and anatomical levels. Gene expression underlying the tolerance response was investigated using qRT-PCR of root-related TFs, known anaerobic genes, and housekeeping genes. Biomass of flood-sensitive S99-2281 roots remained unchanged during the entire 10 days of flooding. Flood-tolerant PI408105A plants exhibited recovery of root growth after 3 days of flooding. Flooding induced the development of aerenchyma and adventitious roots more rapidly in the flood-tolerant than the flood-sensitive genotype. Roots of tolerant plants also contained more ATP than roots of sensitive plants at the 7th and 10th days of flooding. Quantitative transcript analysis identified 132 genes differentially expressed between the two genotypes at one or more time points of flooding. Expression of genes related to the ethylene biosynthesis pathway and formation of adventitious roots was induced earlier and to higher levels in roots of the flood-tolerant genotype. Three potential flood-tolerance TFs which were differentially expressed between the two genotypes during the entire 10-day flooding duration were identified. This study confirmed the expression of anaerobic genes in response to soil flooding. Additionally, the differential expression of TFs associated with soil flooding tolerance was not qualitative but quantitative and temporal. Functional analyses of

  15. Expression of root-related transcription factors associated with flooding tolerance of soybean (Glycine max).

    Science.gov (United States)

    Valliyodan, Babu; Van Toai, Tara T; Alves, Jose Donizeti; de Fátima P Goulart, Patricia; Lee, Jeong Dong; Fritschi, Felix B; Rahman, Mohammed Atiqur; Islam, Rafiq; Shannon, J Grover; Nguyen, Henry T

    2014-09-29

    Much research has been conducted on the changes in gene expression of the model plant Arabidopsis to low-oxygen stress. Flooding results in a low oxygen environment in the root zone. However, there is ample evidence that tolerance to soil flooding is more than tolerance to low oxygen alone. In this study, we investigated the physiological response and differential expression of root-related transcription factors (TFs) associated with the tolerance of soybean plants to soil flooding. Differential responses of PI408105A and S99-2281 plants to ten days of soil flooding were evaluated at physiological, morphological and anatomical levels. Gene expression underlying the tolerance response was investigated using qRT-PCR of root-related TFs, known anaerobic genes, and housekeeping genes. Biomass of flood-sensitive S99-2281 roots remained unchanged during the entire 10 days of flooding. Flood-tolerant PI408105A plants exhibited recovery of root growth after 3 days of flooding. Flooding induced the development of aerenchyma and adventitious roots more rapidly in the flood-tolerant than the flood-sensitive genotype. Roots of tolerant plants also contained more ATP than roots of sensitive plants at the 7th and 10th days of flooding. Quantitative transcript analysis identified 132 genes differentially expressed between the two genotypes at one or more time points of flooding. Expression of genes related to the ethylene biosynthesis pathway and formation of adventitious roots was induced earlier and to higher levels in roots of the flood-tolerant genotype. Three potential flood-tolerance TFs which were differentially expressed between the two genotypes during the entire 10-day flooding duration were identified. This study confirmed the expression of anaerobic genes in response to soil flooding. Additionally, the differential expression of TFs associated with soil flooding tolerance was not qualitative but quantitative and temporal. Functional analyses of these genes will be

  16. Application of anti-listerial bacteriocins: monitoring enterocin expression by multiplex relative reverse transcription-PCR.

    Science.gov (United States)

    Williams, D Ross; Chanos, Panagiotis

    2012-12-01

    Listeriosis is a deadly food-borne disease, and its incidence may be limited through the biotechnological exploitation of a number of anti-listerial biocontrol agents. The most widely used of these agents are bacteriocins and the Class II enterocins are characterized by their activity against Listeria. Enterocins are primarily produced by enterococci, particularly Enterococcus faecium and many strains have been described, often encoding multiple bacteriocins. The use of these strains in food will require that they are free of virulence functions and that they exhibit a high level expression of anti-listerial enterocins in fermentation conditions. Multiplex relative RT (reverse transcription)-PCR is a technique that is useful in the discovery of advantageous expression characteristics among enterocin-producing strains. It allows the levels of individual enterocin gene expression to be monitored and determination of how expression is altered under different growth conditions.

  17. Gene transcription profiles, global DNA methylation and potential transgenerational epigenetic effects related to Zn exposure history in Daphnia magna

    International Nuclear Information System (INIS)

    Vandegehuchte, Michiel B.; De Coninck, Dieter; Vandenbrouck, Tine; De Coen, Wim M.; Janssen, Colin R.

    2010-01-01

    A reduced level of DNA methylation has recently been described in both Zn-exposed and non-exposed offspring of Daphnia magna exposed to Zn. The hypothesis examined in this study is that DNA hypomethylation has an effect on gene transcription. A second hypothesis is that accumulative epigenetic effects can affect gene transcription in non-exposed offspring from parents with an exposure history of more than one generation. Transcriptional gene regulation was studied with a cDNA microarray. In the exposed and non-exposed hypomethylated daphnids, a large proportion of common genes were similarly up- or down-regulated, indicating a possible effect of the DNA hypomethylation. Two of these genes can be mechanistically involved in DNA methylation reduction. The similar transcriptional regulation of two and three genes in the F 0 and F 1 exposed daphnids on one hand and their non-exposed offspring on the other hand, could be the result of a one-generation temporary transgenerational epigenetic effect, which was not accumulative. - Zn-induced DNA hypomethylation is related to gene transcription in Daphnia magna and Zn exposure potentially induced limited temporary transgenerational effects on gene transcription.

  18. Hyperuricaemia and the metabolic syndrome in type 2 DM

    Directory of Open Access Journals (Sweden)

    Ogbera Anthonia O

    2010-04-01

    Full Text Available Abstract Background Elevated serum uric acid levels (SUA have been associated with an increased risk of cardiovascular diseases and the metabolic syndrome (MetS and are often reported to be higher in females than in males. The aim of this report is to determine the prevalence and clinical correlates of hyperuricaemia and also to evaluate associations with the MetS in people with type 2 diabetes mellitus (DM. Methods This was a cross-sectional study conducted in people with type 2 DM in Lagos, Nigeria. Hyperuricaemia was defined by cut-off values of > 7 mg/dl for men and > 6 mg/dl for women. The diagnosis of MetS was made using the new definition by the American Heart Association and other related bodies. Clinical and biochemical parameters were compared between subjects with hyperuricaemia and normouricaemia. Statistical analysis included usage of Student's t test, Pearson correlation coefficients, multivariate regression analysis and chi square. Results 601 patients with type 2 DM aged between 34-91 years were recruited for the study. The prevalence rates of hyperuricaemia and the MetS were 25% and 60% respectively. The frequency of occurrence of hyperuricaemia was comparable in both genders (59% vs 41%, p = 0.3. Although, the prevalence of the MetS in subjects with hyperuricaemia and normouricaemia was comparable (61 vs 56%, p = 0.1, a higher proportion of hyperuricaemic subjects had 3 or more components of the Mets compared with normouricaemic subjects. Possible predictors of hyperuricaemia include central obesity, smoking and elevated serum triglycerides (TG. SUA levels were found to be positively and significantly associated with serum TG (r = 0.2, p = 0.0001 and total cholesterol (r = 13, p = 0.001. Conclusion The prevalence of hyperuricaemia in subjects with type 2 DM is comparable in both genders and possible predictors of hyperuricaemia are potentially modifiable. SUA is positively and significantly associated with serum TG and total

  19. Cis-Natural Antisense Transcripts Are Mainly Co-expressed with Their Sense Transcripts and Primarily Related to Energy Metabolic Pathways during Muscle Development.

    Science.gov (United States)

    Zhao, Yunxia; Hou, Ye; Zhao, Changzhi; Liu, Fei; Luan, Yu; Jing, Lu; Li, Xinyun; Zhu, Mengjin; Zhao, Shuhong

    2016-01-01

    Cis-natural antisense transcripts (cis-NATs) are a new class of RNAs identified in various species. However, the biological functions of cis-NATs are largely unknown. In this study, we investigated the transcriptional characteristics and functions of cis-NATs in the muscle tissue of lean Landrace and indigenous fatty Lantang pigs. In total, 3,306 cis-NATs of 2,469 annotated genes were identified in the muscle tissue of pigs. More than 1,300 cis-NATs correlated with their sense genes at the transcriptional level, and approximately 80% of them were co-expressed in the two breeds. Furthermore, over 1,200 differentially expressed cis-NATs were identified during muscle development. Function annotation showed that the cis-NATs participated in muscle development mainly by co-expressing with genes involved in energy metabolic pathways, including citrate cycle (TCA cycle), glycolysis or gluconeogenesis, mitochondrial activation and so on. Moreover, these cis-NATs and their sense genes abruptly increased at the transition from the late fetal stages to the early postnatal stages and then decreased along with muscle development. In conclusion, the cis-NATs in the muscle tissue of pigs were identified and determined to be mainly co-expressed with their sense genes. The co-expressed cis-NATs and their sense gene were primarily related to energy metabolic pathways during muscle development in pigs. Our results offered novel evidence on the roles of cis-NATs during the muscle development of pigs.

  20. Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis

    Directory of Open Access Journals (Sweden)

    Nakamura Shinichiro

    2011-01-01

    Full Text Available Abstract Background Runt-related transcription factor 3 (RUNX3 is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC. Methods RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. Results RUNX3 protein expression was frequently inactivated in the HCC cell lines (91% and tissues (90%. RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. Conclusion RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.

  1. Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton

    DEFF Research Database (Denmark)

    Ly, Donald L.; Waheed, Faiza; Lodyga, Monika

    2013-01-01

    Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin-regulated coactiv......Hyperosmotic stress initiates several adaptive responses, including the remodeling of the cytoskeleton. Besides maintaining structural integrity, the cytoskeleton has emerged as an important regulator of gene transcription. Myocardin-related transcription factor (MRTF), an actin......-regulated coactivator of serum response factor, is a major link between the actin skeleton and transcriptional control. We therefore investigated whether MRTF is regulated by hyperosmotic stress. Here we show that hypertonicity induces robust, rapid, and transient translocation of MRTF from the cytosol to the nucleus...... in kidney tubular cells. We found that the hyperosmolarity-triggered MRTF translocation is mediated by the RhoA/Rho kinase (ROK) pathway. Moreover, the Rho guanine nucleotide exchange factor GEF-H1 is activated by hyperosmotic stress, and it is a key contributor to the ensuing RhoA activation and MRTF...

  2. Arabidopsis transcriptional responses differentiating closely related chemicals (herbicides) and cross-species extrapolation to Brassica

    Science.gov (United States)

    Using whole genome Affymetrix ATH1 GeneChips we characterized the transcriptional response of Arabidopsis thaliana Columbia 24 hours after treatment with five different herbicides. Four of them (chloransulam, imazapyr, primisulfuron, sulfometuron) inhibit acetolactate synthase (A...

  3. Transcriptional interference networks coordinate the expression of functionally related genes clustered in the same genomic loci.

    Science.gov (United States)

    Boldogköi, Zsolt

    2012-01-01

    The regulation of gene expression is essential for normal functioning of biological systems in every form of life. Gene expression is primarily controlled at the level of transcription, especially at the phase of initiation. Non-coding RNAs are one of the major players at every level of genetic regulation, including the control of chromatin organization, transcription, various post-transcriptional processes, and translation. In this study, the Transcriptional Interference Network (TIN) hypothesis was put forward in an attempt to explain the global expression of antisense RNAs and the overall occurrence of tandem gene clusters in the genomes of various biological systems ranging from viruses to mammalian cells. The TIN hypothesis suggests the existence of a novel layer of genetic regulation, based on the interactions between the transcriptional machineries of neighboring genes at their overlapping regions, which are assumed to play a fundamental role in coordinating gene expression within a cluster of functionally linked genes. It is claimed that the transcriptional overlaps between adjacent genes are much more widespread in genomes than is thought today. The Waterfall model of the TIN hypothesis postulates a unidirectional effect of upstream genes on the transcription of downstream genes within a cluster of tandemly arrayed genes, while the Seesaw model proposes a mutual interdependence of gene expression between the oppositely oriented genes. The TIN represents an auto-regulatory system with an exquisitely timed and highly synchronized cascade of gene expression in functionally linked genes located in close physical proximity to each other. In this study, we focused on herpesviruses. The reason for this lies in the compressed nature of viral genes, which allows a tight regulation and an easier investigation of the transcriptional interactions between genes. However, I believe that the same or similar principles can be applied to cellular organisms too.

  4. The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

    Science.gov (United States)

    Hurst, H C; Masson, N; Jones, N C; Lee, K A

    1990-12-01

    Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We demonstrated that CREB and ATF-47 are identical and that CREB and ATF-43 form protein-protein complexes. We also found that the cis requirements for stable DNA binding by ATF-43 and CREB are different. Using antibodies to ATF-43 we have identified a group of polypeptides (ATF-43) in the size range from 40 to 43 kDa. ATF-43 polypeptides are related by their reactivity with anti-ATF-43, DNA-binding specificity, complex formation with CREB, heat stability, and phosphorylation by protein kinase A. Certain cell types vary in their ATF-43 complement, suggesting that CREB activity is modulated in a cell-type-specific manner through interaction with ATF-43. ATF-43 polypeptides do not appear simply to correspond to the gene products of the ATF multigene family, suggesting that the size of the ATF family at the protein level is even larger than predicted from cDNA-cloning studies.

  5. Transcription Factor EB Expression in Early Breast Cancer Relates to Lysosomal/Autophagosomal Markers and Prognosis.

    Science.gov (United States)

    Giatromanolaki, Alexandra; Sivridis, Efthimios; Kalamida, Dimitra; Koukourakis, Michael I

    2017-06-01

    Disrupting the autophagic balance to trigger autophagic death may open new strategies for cancer therapy. Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and may play a role in cancer biology and clinical behavior. The expression of TFEB and the lysosomal cancer cell content (expression of lysosomal associated membrane protein 2a [LAMP2a] and cathepsin D) was studied in a series of 100 T1-stage breast carcinomas. Expression patterns were correlated with autophagy/hypoxia-related proteins, angiogenesis, and clinical outcome. The effect of hypoxic/acidic conditions on TFEB kinetics was studied in the MCF-7 cancer cell line. Overexpression of TFEB in cancer cell cytoplasm and the perinuclear/nuclear area was noted in 23 (23%) of 100 cases. High LAMP2a and cathepsin D expression was noted in 30 (30%) of 100 and 28 (28%) of 100 cases, respectively. TFEB expression was directly linked with LAMP2a (P factor 2-alpha (HIF-2α) (P = .01, r = 0.25) expression and inversely with progesterone receptor (P = .01, r = 0.22). High vascular density was directly linked with LAMP2a (P = .05, r = 0.18) and cathepsin D (P = .005, r = 0.28). In Kaplan-Meier survival analysis, TFEB and cathepsin D expression were related to an ominous prognosis (P = .001 and P = .03, respectively). In multivariate analysis, TFEB expression sustained its independent prognostic significance (P = .05, hazard ratio 2.1). In in vitro experiments, acidity triggered overexpression of TFEB and nuclear translocation. Intense TFEB expression and lysosomal biogenesis, evident in one fourth of early breast carcinomas, define poor prognosis. Tumor acidity is among the microenvironmental conditions that trigger TFEB overactivity. TFEB is a sound target for the development of lysosomal targeting therapies. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The Mediator Complex MED15 Subunit Mediates Activation of Downstream Lipid-Related Genes by the WRINKLED1 Transcription Factor.

    Science.gov (United States)

    Kim, Mi Jung; Jang, In-Cheol; Chua, Nam-Hai

    2016-07-01

    The Mediator complex is known to be a master coordinator of transcription by RNA polymerase II, and this complex is recruited by transcription factors (TFs) to target promoters for gene activation or repression. The plant-specific TF WRINKLED1 (WRI1) activates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. However, no Mediator subunit has yet been identified that mediates WRI1 transcriptional activity. Promoter-β-glucuronidase fusion experiments showed that MEDIATOR15 (MED15) is expressed in the same cells in the embryo as WRI1. We found that the Arabidopsis (Arabidopsis thaliana) MED15 subunit of the Mediator complex interacts directly with WRI1 in the nucleus. Overexpression of MED15 or WRI1 increased transcript levels of WRI1 target genes involved in glycolysis and fatty acid biosynthesis; these genes were down-regulated in wild-type or WRI1-overexpressing plants by silencing of MED15 However, overexpression of MED15 in the wri1 mutant also increased transcript levels of WRI1 target genes, suggesting that MED15 also may act with other TFs to activate downstream lipid-related genes. Chromatin immunoprecipitation assays confirmed the association of MED15 with six WRI1 target gene promoters. Additionally, silencing of MED15 resulted in reduced fatty acid content in seedlings and mature seeds, whereas MED15 overexpression increased fatty acid content in both developmental stages. Similar results were found in wri1 mutant and WRI1 overexpression lines. Together, our results indicate that the WRI1/MED15 complex transcriptionally regulates glycolysis-related and fatty acid biosynthetic genes during embryogenesis. © 2016 American Society of Plant Biologists. All Rights Reserved.

  7. Modulation of Caenorhabditis elegans transcription factor activity by HIM-8 and the related Zinc-Finger ZIM proteins.

    Science.gov (United States)

    Sun, Hongliu; Nelms, Brian L; Sleiman, Sama F; Chamberlin, Helen M; Hanna-Rose, Wendy

    2007-10-01

    The previously reported negative regulatory activity of HIM-8 on the Sox protein EGL-13 is shared by the HIM-8-related ZIM proteins. Furthermore, mutation of HIM-8 can modulate the effects of substitution mutations in the DNA-binding domains of at least four other transcription factors, suggesting broad regulatory activity by HIM-8.

  8. Novel estrogen receptor-related Transcripts in Marisa cornuarietis; a freshwater snail with reported sensitivity to estrogenic chemicals.

    Science.gov (United States)

    Bannister, Richard; Beresford, Nicola; May, Denise; Routledge, Edwin J; Jobling, Susan; Rand-Weaver, Mariann

    2007-04-01

    We have isolated novel molluskan steroid receptor transcripts orthologous to vertebrate estrogen receptors (ERs) and estrogen receptor-related receptors (ERRs) from the freshwater snail Marisa cornuarietis. Radiolabeled ligand binding analyses showed that neither recombinant receptor protein specifically bound 17beta-estradiol over the range applied (0.3-9.6 nM). These novel receptor transcripts have thus been designated mcER-like and mcERR respectively. Quantitative PCR revealed mcER-like to be expressed ubiquitously throughout a range of male and female structures studied, including neural and reproductive tissues. Highest absolute levels were seen in the male penis-sheath complex. The mcERR mRNA was also expressed ubiquitously throughout all male and female tissues analyzed here, with very low absolute transcript numbers in female accessory sex structures compared to other tissues.

  9. Transcript Abundance of Photorhabdus Insect-Related (Pir Toxin in Manduca sexta and Galleria mellonella Infections

    Directory of Open Access Journals (Sweden)

    Anaïs Castagnola

    2016-09-01

    Full Text Available In this study, we assessed pirAB toxin transcription in Photorhabdus luminescens laumondii (strain TT01 (Enterobacteriaceae by comparing mRNA abundance under in vivo and in vitro conditions. In vivo assays considered both natural and forced infections with two lepidopteran hosts: Galleria mellonella and Manduca sexta. Three portals of entry were utilized for the forced infection assays: (a integument; (b the digestive route (via mouth and anus; and (c the tracheal route (via spiracles. We also assessed plu4093-2 transcription during the course of a natural infection; this is when the bacteria are delivered by Heterorhabditis bacteriophora nematodes. Transcript abundance in G. mellonella was higher than in M. sexta at two of the observed time points: 15 and 18 h. Expression of pirAB plu4093-2 reached above endogenous control levels at 22 h in G. mellonella but not in M. sexta. Overall, pirAB plu4093-2 transcripts were not as highly expressed in M. sexta as in G. mellonella, from 15 to 22 h. This is the first study to directly compare pirAB plu4093-2 toxin transcript production considering different portals of entry.

  10. Effects of Replication and Transcription on DNA Structure-Related Genetic Instability.

    Science.gov (United States)

    Wang, Guliang; Vasquez, Karen M

    2017-01-05

    Many repetitive sequences in the human genome can adopt conformations that differ from the canonical B-DNA double helix (i.e., non-B DNA), and can impact important biological processes such as DNA replication, transcription, recombination, telomere maintenance, viral integration, transposome activation, DNA damage and repair. Thus, non-B DNA-forming sequences have been implicated in genetic instability and disease development. In this article, we discuss the interactions of non-B DNA with the replication and/or transcription machinery, particularly in disease states (e.g., tumors) that can lead to an abnormal cellular environment, and how such interactions may alter DNA replication and transcription, leading to potential conflicts at non-B DNA regions, and eventually result in genetic stability and human disease.

  11. Cytokines, Type 2 DM and the Metabolic Syndrome | Ogbera ...

    African Journals Online (AJOL)

    comparable in the DM subjects with and without the Mets and also comparable in obese DM and non obese DM subjects. Of the Mets defining criteria, waist circumference (WC) and Triglyceride (TG) were found to be significantly associated with only two of the studied cytokines. The correlation coefficient and p values of ...

  12. Reorganization of the actin cytoskeleton via transcriptional regulation of cytoskeletal/focal adhesion genes by myocardin-related transcription factors (MRTFs/MAL/MKLs)

    International Nuclear Information System (INIS)

    Morita, Tsuyoshi; Mayanagi, Taira; Sobue, Kenji

    2007-01-01

    RhoA is a crucial regulator of stress fiber and focal adhesion formation through the activation of actin nucleation and polymerization. It also regulates the nuclear translocation of myocardin-related transcription factor-A and -B (MRTF-A/B, MAL or MKL 1/2), which are co-activators of serum response factor (SRF). In dominant-negative MRTF-A (DN-MRTF-A)-expressing NIH 3T3 cell lines, the expressions of several cytoskeletal/focal adhesion genes were down-regulated, and the formation of stress fiber and focal adhesion was severely diminished. MRTF-A/B-knockdown cells also exhibited such cytoskeletal defects. In reporter assays, both RhoA and MRTF-A enhanced promoter activities of these genes in a CArG-box-dependent manner, and DN-MRTF-A inhibited the RhoA-mediated activation of these promoters. In dominant-negative RhoA (RhoA-N19)-expressing NIH 3T3 cell lines, the nuclear translocation of MRTF-A/B was predominantly prevented, resulting in the reduced expression of cytoskeletal/focal adhesion proteins. Further, constitutive-active MRTF-A/B increased the expression of endogenous cytoskeletal/focal adhesion proteins, and thereby rescued the defective phenotype of stress fibers and focal adhesions in RhoA-N19 expressing cells. These results indicate that MRTF-A/B act as pivotal mediators of stress fiber and focal adhesion formation via the transcriptional regulation of a subset of cytoskeletal/focal adhesion genes

  13. Survival of Listeria monocytogenes in simulated gastrointestinal system and transcriptional profiling of stress- and adhesion-related genes

    DEFF Research Database (Denmark)

    Jiang, Lingli; Olesen, Inger; Andersen, Thomas

    2010-01-01

    -related genes after exposure to the conditions similar to those encountered in the mouth, stomach, and small intestine. None of the L. monocytogenes strains investigated could survive in the gastric juice at pH 2.5 or 3.0. Their survival increased at higher pH (3.5 and 4.0) in the gastric stress. Relative...... afterpassing through the simulated gastrointestinal tract, whereas that of the adhesion-related gene ami was downregulated. Taken together, this study revealed that L. monocytogenes strains enhanced the expression of stressrelated genes and decreased the transcription of adhesion-related gene in order...

  14. The Role of Estrogen Related Receptor in Modulating Estrogen Receptor Mediated Transcription in Breast Cancer Cells

    Science.gov (United States)

    2005-04-01

    tumors correlates with an unfavorable prognosis (Ariazi 2002; Lu 2001; Suzuki 2004; Vanacker 1999). The transcriptional activity of ERRa is not inhibited...SA. 101:6570-5. Needham, M ., S. Raines, J. McPheat, C. Stacey, J. Ellston, S. Hoare, and M . Parker. 2000. Differential interaction of steroid hormone...R. Graves, M . Wright, and B.M. Spiegelman. 1998. A cold- inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 92:829- 39

  15. Transcription factor Fos-Related Antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis

    OpenAIRE

    Maurer, B; Busch, N; Jüngel, A; Pileckyte, M; Gay, R E; Michel, B A; Schett, G; Gay, S; Distler, J; Distler, O

    2009-01-01

    BACKGROUND: -Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Methods and Results-Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endo...

  16. Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD

    International Nuclear Information System (INIS)

    Prokopec, Stephenie D.; Watson, John D.; Lee, Jamie; Pohjanvirta, Raimo; Boutros, Paul C.

    2015-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male and female C57BL/6 mice to 500 μg/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6 h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144 h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear. - Highlights: • Differences exist between the toxicity phenotypes to TCDD in male and female mice. • TCDD-mediated transcriptomic differences were identified between the sexes. • Resistant female mice displayed a large, early-onset, transcriptomic response.

  17. Survival-related profile, pathways, and transcription factors in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Anne P G Crijns

    2009-02-01

    Full Text Available BACKGROUND: Ovarian cancer has a poor prognosis due to advanced stage at presentation and either intrinsic or acquired resistance to classic cytotoxic drugs such as platinum and taxoids. Recent large clinical trials with different combinations and sequences of classic cytotoxic drugs indicate that further significant improvement in prognosis by this type of drugs is not to be expected. Currently a large number of drugs, targeting dysregulated molecular pathways in cancer cells have been developed and are introduced in the clinic. A major challenge is to identify those patients who will benefit from drugs targeting these specific dysregulated pathways.The aims of our study were (1 to develop a gene expression profile associated with overall survival in advanced stage serous ovarian cancer, (2 to assess the association of pathways and transcription factors with overall survival, and (3 to validate our identified profile and pathways/transcription factors in an independent set of ovarian cancers. METHODS AND FINDINGS: According to a randomized design, profiling of 157 advanced stage serous ovarian cancers was performed in duplicate using approximately 35,000 70-mer oligonucleotide microarrays. A continuous predictor of overall survival was built taking into account well-known issues in microarray analysis, such as multiple testing and overfitting. A functional class scoring analysis was utilized to assess pathways/transcription factors for their association with overall survival. The prognostic value of genes that constitute our overall survival profile was validated on a fully independent, publicly available dataset of 118 well-defined primary serous ovarian cancers. Furthermore, functional class scoring analysis was also performed on this independent dataset to assess the similarities with results from our own dataset. An 86-gene overall survival profile discriminated between patients with unfavorable and favorable prognosis (median survival, 19

  18. Sex-related differences in murine hepatic transcriptional and proteomic responses to TCDD

    Energy Technology Data Exchange (ETDEWEB)

    Prokopec, Stephenie D.; Watson, John D. [Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto (Canada); Lee, Jamie [Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto (Canada); Department of Pharmacology & Toxicology, University of Toronto, Toronto (Canada); Pohjanvirta, Raimo [Laboratory of Toxicology, National Institute for Health and Welfare, Kuopio Finland (Finland); Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki (Finland); Boutros, Paul C., E-mail: Paul.Boutros@oicr.on.ca [Informatics and Bio-computing Program, Ontario Institute for Cancer Research, Toronto (Canada); Department of Pharmacology & Toxicology, University of Toronto, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

    2015-04-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces myriad toxicities in most mammals. In rodents alone, there is a huge divergence in the toxicological response across species, as well as among different strains within a species. But there are also significant differences between males and females animals of a single strain. These differences are inconsistent across model systems: the severity of toxicity is greater in female rats than males, while male mice and guinea pigs are more sensitive than females. Because the specific events that underlie this difference remain unclear, we characterized the hepatic transcriptional response of adult male and female C57BL/6 mice to 500 μg/kg TCDD at multiple time-points. The transcriptional profile diverged significantly between the sexes. Female mice demonstrated a large number of altered transcripts as early as 6 h following treatment, suggesting a large primary response. Conversely, male animals showed the greatest TCDD-mediated response 144 h following exposure, potentially implicating significant secondary responses. Nr1i3 was statistically significantly induced at all time-points in the sensitive male animals. This mRNA encodes the constitutive androstane receptor (CAR), a transcription factor involved in the regulation of xenobiotic metabolism, lipid metabolism, cell cycle and apoptosis. Surprisingly though, changes at the protein level (aside from the positive control, CYP1A1) were modest, with only FMO3 showing clear induction, and no genes with sex-differences. Thus, while male and female mice show transcriptional differences in their response to TCDD, their association with TCDD-induced toxicities remains unclear. - Highlights: • Differences exist between the toxicity phenotypes to TCDD in male and female mice. • TCDD-mediated transcriptomic differences were identified between the sexes. • Resistant female mice displayed a large, early-onset, transcriptomic response.

  19. The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

    OpenAIRE

    Hurst, H C; Masson, N; Jones, N C; Lee, K A

    1990-01-01

    Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We...

  20. [The role of Smads and related transcription factors in the signal transduction of bone morphogenetic protein inducing bone formation].

    Science.gov (United States)

    Xu, Xiao-liang; Dai, Ke-rong; Tang, Ting-ting

    2003-09-01

    To clarify the mechanisms of the signal transduction of bone morphogenetic proteins (BMPs) inducing bone formation and to provide theoretical basis for basic and applying research of BMPs. We looked up the literature of the role of Smads and related transcription factors in the signal transduction of BMPs inducing bone formation. The signal transduction processes of BMPs included: 1. BMPs combined with type II and type I receptors; 2. the type I receptor phosphorylated Smads; and 3. Smads entered the cell nucleus, interacted with transcription factors and influenced the transcription of related proteins. Smads could be divided into receptor-regulated Smads (R-Smads: Smad1, Smad2, Smad3, Smad5, Smad8 and Smad9), common-mediator Smad (co-Smad: Smad4), and inhibitory Smads (I-Smads: Smad6 and Smad7). Smad1, Smad5, Smad8, and probable Smad9 were involved in the signal transduction of BMPs. Multiple kinases, such as focal adhesion kinase (FAK), Ras-extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and Akt serine/threonine kinase were related to Smads signal transduction. Smad1 and Smad5 related with transcription factors included core binding factor A1 (CBFA1), smad-interacting protein 1 (SIP1), ornithine decarboxylase antizyme (OAZ), activating protein-1 (AP-1), xenopus ventralizing homeobox protein-2 (Xvent-2), sandostatin (Ski), antiproliferative proteins (Tob), and homeodomain-containing transcriptian factor-8 (Hoxc-8), et al. CBFA1 could interact with Smad1, Smad2, Smad3, and Smad5, so it was involved in TGF-beta and BMP-2 signal transduction, and played an important role in the bone formation. Cleidocranial dysplasia (CCD) was thought to be caused by heterozygous mutations in CBFA1. The CBFA1 knockout mice showed no osteogenesis and had maturational disturbance of chondrocytes. Smads and related transcription factors, especially Smad1, Smad5, Smad8 and CBFA1, play an important role in the signal transduction of BMPs inducing bone

  1. Two MYB-related transcription factors play opposite roles in sugar signaling in Arabidopsis.

    Science.gov (United States)

    Chen, Yi-Shih; Chao, Yi-Chi; Tseng, Tzu-Wei; Huang, Chun-Kai; Lo, Pei-Ching; Lu, Chung-An

    2017-02-01

    Sugar regulation of gene expression has profound effects at all stages of the plant life cycle. Although regulation at the transcriptional level is one of the most prominent mechanisms by which gene expression is regulated, only a few transcription factors have been identified and demonstrated to be involved in the regulation of sugar-regulated gene expression. OsMYBS1, an R1/2-type MYB transcription factor, has been demonstrated to be involved in sugar- and hormone-regulated α-amylase gene expression in rice. Arabidopsis contains two OsMYBS1 homologs. In the present study, we investigate MYBS1 and MYBS2 in sugar signaling in Arabidopsis. Our results indicate that MYBS1 and MYBS2 play opposite roles in regulating glucose and ABA signaling in Arabidopsis during seed germination and early seedling development. MYB proteins have been classified into four subfamilies: R2R3-MYB, R1/2-MYB, 3R-MYB, and 4R-MYB. An R1/2-type MYB transcription factor, OsMYBS1, has been demonstrated to be involved in sugar- and hormone-regulated α-amylase genes expression in rice. In this study, two genes homologous to OsMYBS1, MYBS1 and MYBS2, were investigated in Arabidopsis. Subcellular localization analysis showed that MYBS1 and MYBS2 were localized in the nucleus. Rice embryo transient expression assays indicated that both MYBS1 and MYBS2 could recognize the sugar response element, TA-box, in the promoter and induced promoter activity. mybs1 mutant exhibited hypersensitivity to glucose, whereas mybs2 seedlings were hyposensitive to it. MYBS1 and MYBS2 are involved in the control of glucose-responsive gene expression, as the mybs1 mutant displayed increased expression of a hexokinase gene (HXK1), chlorophyll a/b-binding protein gene (CAB1), ADP-glucose pyrophosphorylase gene (APL3), and chalcone synthase gene (CHS), whereas the mybs2 mutant exhibited decreased expression of these genes. mybs1 also showed an enhanced response to abscisic acid (ABA) in the seed germination and seedling

  2. Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta.

    Science.gov (United States)

    Vanacker, J M; Pettersson, K; Gustafsson, J A; Laudet, V

    1999-01-01

    The physiological activities of estrogens are thought to be mediated by specific nuclear receptors, ERalpha and ERbeta. However, certain tissues, such as the bone, that are highly responsive to estrogens only express a low level of these receptors. Starting from this apparent contradiction, we have evaluated the potentials of two related receptors ERRalpha and ERRbeta to intervene in estrogen signaling. ERalpha, ERRalpha and ERRbeta bind to and activate transcription through both the classical estrogen response element (ERE) and the SF-1 response element (SFRE). In contrast, ERbeta DNA-binding and transcriptional activity is restricted to the ERE. Accordingly, the osteopontin gene promoter is stimulated through SFRE sequences, by ERRalpha as well as by ERalpha, but not by ERbeta. Analysis of the cross-talk within the ER/ERR subgroup of nuclear receptors thus revealed common targets but also functional differences between the two ERs. PMID:10428965

  3. Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity.

    Directory of Open Access Journals (Sweden)

    Suzhen Dong

    Full Text Available BACKGROUND: Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. METHODOLOGY: We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. CONCLUSIONS: The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity.

  4. Curcumin Enhances Neurogenesis and Cognition in Aged Rats: Implications for Transcriptional Interactions Related to Growth and Synaptic Plasticity

    Science.gov (United States)

    Mitchell, E. Siobhan; Xiu, Jin; Tiwari, Jyoti K.; Hu, Yinghe; Cao, Xiaohua; Zhao, Zheng

    2012-01-01

    Background Curcumin has been demonstrated to have many neuroprotective properties, including improvement of cognition in humans and neurogenesis in animals, yet the mechanism of such effects remains unclear. Methodology We assessed behavioural performance and hippocampal cell proliferation in aged rats after 6- and 12-week curcumin-fortified diets. Curcumin enhanced non-spatial and spatial memory, as well as dentate gyrate cell proliferation as compared to control diet rats. We also investigated underlying mechanistic pathways that might link curcumin treatment to increased cognition and neurogenesis via exon array analysis of cortical and hippocampal mRNA transcription. The results revealed a transcriptional network interaction of genes involved in neurotransmission, neuronal development, signal transduction, and metabolism in response to the curcumin treatment. Conclusions The results suggest a neurogenesis- and cognition-enhancing potential of prolonged curcumin treatment in aged rats, which may be due to its diverse effects on genes related to growth and plasticity. PMID:22359574

  5. nalyot, a mutation of the Drosophila myb-related Adf1 transcription factor, disrupts synapse formation and olfactory memory.

    Science.gov (United States)

    DeZazzo, J; Sandstrom, D; de Belle, S; Velinzon, K; Smith, P; Grady, L; DelVecchio, M; Ramaswami, M; Tully, T

    2000-07-01

    nalyot (nal) is a novel olfactory memory mutant of Drosophila, encoding Adf1, a myb-related transcription factor. Following extended training sessions, Adf1 mutants show normal early memory but defective longterm memory. Adf1 shows widespread spatiotemporal expression, yet mutant alleles reveal no discernible disruptions in gross morphology of the nervous system. Studies at the larval neuromuscular junction, however, reveal a role for Adf1 in the modulation of synaptic growth-in contrast to the role established for dCREB2 in the control of synaptic function (Davis et al., 1996). These findings suggest that Adf1 and dCREB2 regulate distinct transcriptional cascades involved in terminal stages of synapse maturation. More generally, Adf1 provides a novel link between molecular mechanisms of developmental and behavioral plasticity.

  6. Combined effect of copper and cadmium on Chlorella vulgaris growth and photosynthesis-related gene transcription

    International Nuclear Information System (INIS)

    Qian Haifeng; Li Jingjing; Sun Liwei; Chen Wei; Sheng, G. Daniel; Liu Weiping; Fu Zhengwei

    2009-01-01

    Chlorella vulgaris was tested to assess their toxicities in freshwater contaminated by the metal compounds of copper (Cu) and cadmium (Cd), both singly and combined. Exposure to 0.5 and 1.5 μM Cu or 1.0 and 2.0 μM Cd alone significantly decreased algal growth and chlorophyll content and increased reactive oxygen species (ROS) content. Two-way ANOVA analysis shows that the combination of these two metal compounds decreased cell growth, chlorophyll content and increased ROS content synergistically. The highest algal cell inhibition was 78.55%, the lowest levels of chl a, chl b and total-chl were 10.59%, 33.33% and 17.94% of the control, respectively. The highest increase in ROS was 9.15-fold greater than that of the control when exposed to Cu(1.5) + Cd(2.0). Real-time PCR shows that Cu and Cd reduced the transcript abundance of psbA and rbcL, but without a synergistic interaction, whereas Cu and Cd increased the transcript abundance of psaB synergistically. These results demonstrate that Cu and Cd independently inhibit PSII activity and CO 2 assimilation, but synergistically increase ROS content to disrupt chlorophyll synthesis and inhibit cell growth.

  7. Combined effect of copper and cadmium on Chlorella vulgaris growth and photosynthesis-related gene transcription

    Energy Technology Data Exchange (ETDEWEB)

    Qian Haifeng; Li Jingjing; Sun Liwei; Chen Wei; Sheng, G. Daniel; Liu Weiping [College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China); Fu Zhengwei, E-mail: azwfu2003@yahoo.com.cn [College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032 (China)

    2009-08-13

    Chlorella vulgaris was tested to assess their toxicities in freshwater contaminated by the metal compounds of copper (Cu) and cadmium (Cd), both singly and combined. Exposure to 0.5 and 1.5 {mu}M Cu or 1.0 and 2.0 {mu}M Cd alone significantly decreased algal growth and chlorophyll content and increased reactive oxygen species (ROS) content. Two-way ANOVA analysis shows that the combination of these two metal compounds decreased cell growth, chlorophyll content and increased ROS content synergistically. The highest algal cell inhibition was 78.55%, the lowest levels of chl a, chl b and total-chl were 10.59%, 33.33% and 17.94% of the control, respectively. The highest increase in ROS was 9.15-fold greater than that of the control when exposed to Cu(1.5) + Cd(2.0). Real-time PCR shows that Cu and Cd reduced the transcript abundance of psbA and rbcL, but without a synergistic interaction, whereas Cu and Cd increased the transcript abundance of psaB synergistically. These results demonstrate that Cu and Cd independently inhibit PSII activity and CO{sub 2} assimilation, but synergistically increase ROS content to disrupt chlorophyll synthesis and inhibit cell growth.

  8. Transcriptional profiling of protein expression related genes of Pichia pastoris under simulated microgravity.

    Directory of Open Access Journals (Sweden)

    Feng Qi

    Full Text Available The physiological responses and transcription profiling of Pichia pastoris GS115 to simulated microgravity (SMG were substantially changed compared with normal gravity (NG control. We previously reported that the recombinant P. pastoris grew faster under SMG than NG during methanol induction phase and the efficiencies of recombinant enzyme production and secretion were enhanced under SMG, which was considered as the consequence of changed transcriptional levels of some key genes. In this work, transcriptiome profiling of P. pastoris cultured under SMG and NG conditions at exponential and stationary phases were determined using next-generation sequencing (NGS technologies. Four categories of 141 genes function as methanol utilization, protein chaperone, RNA polymerase and protein transportation or secretion classified according to Gene Ontology (GO were chosen to be analyzed on the basis of NGS results. And 80 significantly changed genes were weighted and estimated by Cluster 3.0. It was found that most genes of methanol metabolism (85% of 20 genes and protein transportation or secretion (82.2% of 45 genes were significantly up-regulated under SMG. Furthermore the quantity and fold change of up-regulated genes in exponential phase of each category were higher than those of stationary phase. The results indicate that the up-regulated genes of methanol metabolism and protein transportation or secretion mainly contribute to enhanced production and secretion of the recombinant protein under SMG.

  9. Genomic survey of bZIP transcription factor genes related to tanshinone biosynthesis in Salvia miltiorrhiza

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2018-03-01

    Full Text Available Tanshinones are a class of bioactive components in the traditional Chinese medicine Salvia miltiorrhiza, and their biosynthesis and regulation have been widely studied. Current studies show that basic leucine zipper (bZIP proteins regulate plant secondary metabolism, growth and developmental processes. However, the bZIP transcription factors involved in tanshinone biosynthesis are unknown. Here, we conducted the first genome-wide survey of the bZIP gene family and analyzed the phylogeny, gene structure, additional conserved motifs and alternative splicing events in S. miltiorrhiza. A total of 70 SmbZIP transcription factors were identified and categorized into 11 subgroups based on their phylogenetic relationships with those in Arabidopsis. Moreover, seventeen SmbZIP genes underwent alternative splicing events. According to the transcriptomic data, the SmbZIP genes that were highly expressed in the Danshen root and periderm were selected. Based on the prediction of bZIP binding sites in the promoters and the co-expression analysis and co-induction patterns in response to Ag+ treatment via quantitative real-time polymerase chain reaction (qRT-PCR, we concluded that SmbZIP7 and SmbZIP20 potentially participate in the regulation of tanshinone biosynthesis. These results provide a foundation for further functional characterization of the candidate SmbZIP genes, which have the potential to increase tanshinone production. KEY WORDS: bZIP genes, Salvia miltiorrhiza, Phylogenetic analysis, Expression pattern analysis, Tanshinone biosynthesis

  10. Validation of aspirin response-related transcripts in patients with coronary artery disease and preliminary investigation on CMTM5 function.

    Science.gov (United States)

    Zhang, J W; Liu, T F; Chen, X H; Liang, W Y; Feng, X R; Wang, L; Fu, Sidney W; McCaffrey, Timothy A; Liu, M L

    2017-08-15

    Aspirin is widely used in the prevention of cardiovascular diseases, but the antiplatelet responses vary from one patient to another. To validate aspirin response related transcripts and illustrate their roles in predicting cardiovascular events, we have quantified the relative expression of 14 transcripts previously identified as related to high on-aspirin platelet reactivity (HAPR) in 223 patients with coronary artery disease (CAD) on regular aspirin treatment. All patients were followed up regularly for cardiovascular events (CVE). The mean age of our enrolled population was 75.80±8.57years. HAPR patients showed no significant differences in terms of co-morbidities and combined drugs. Besides, the relative expression of HLA-DQA1 was significantly lower in low on-aspirin platelet reactivity (LAPR) patients, when compared with HAPR and high normal (HN) group (p=0.028). What's more, the number of arteries involved, HAPR status and the relative expression of CLU, CMTM5 and SPARC were independent risk factors for CVE during follow up (p<0.05). In addition, overexpression of CMTM5 attenuated endothelial cells (ECs) migration and proliferation, with significantly decreased phosphorylated-Akt levels, while its inhibition promoted these processes in vitro (p<0.05).Our study provides evidence that circulating transcripts might be potential biomarkers in predicting cardiovascular events. CMTM5 might exert anti-atherosclerotic effects via suppressing migration and proliferation in the vessel wall. Nevertheless, larger-scale and long-term studies are still needed. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. The transcriptional landscape

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2011-01-01

    The application of new and less biased methods to study the transcriptional output from genomes, such as tiling arrays and deep sequencing, has revealed that most of the genome is transcribed and that there is substantial overlap of transcripts derived from the two strands of DNA. In protein coding...... regions, the map of transcripts is very complex due to small transcripts from the flanking ends of the transcription unit, the use of multiple start and stop sites for the main transcript, production of multiple functional RNA molecules from the same primary transcript, and RNA molecules made...... by independent transcription from within the unit. In genomic regions separating those that encode proteins or highly abundant RNA molecules with known function, transcripts are generally of low abundance and short-lived. In most of these cases, it is unclear to what extent a function is related to transcription...

  12. Identification of the G13 (cAMP-response-element-binding protein-related protein) gene product related to activating transcription factor 6 as a transcriptional activator of the mammalian unfolded protein response.

    Science.gov (United States)

    Haze, K; Okada, T; Yoshida, H; Yanagi, H; Yura, T; Negishi, M; Mori, K

    2001-04-01

    Eukaryotic cells control the levels of molecular chaperones and folding enzymes in the endoplasmic reticulum (ER) by a transcriptional induction process termed the unfolded protein response (UPR). The mammalian UPR is mediated by the cis-acting ER stress response element consisting of 19 nt (CCAATN(9)CCACG), the CCACG part of which is considered to provide specificity. We recently identified the basic leucine zipper (bZIP) protein ATF6 as a mammalian UPR-specific transcription factor; ATF6 is activated by ER stress-induced proteolysis and binds directly to CCACG. Here we report that eukaryotic cells express another bZIP protein closely related to ATF6 in both structure and function. This protein encoded by the G13 (cAMP response element binding protein-related protein) gene is constitutively synthesized as a type II transmembrane glycoprotein anchored in the ER membrane and processed into a soluble form upon ER stress as occurs with ATF6. The proteolytic processing of ATF6 and the G13 gene product is accompanied by their relocation from the ER to the nucleus; their basic regions seem to function as a nuclear localization signal. Overexpression of the soluble form of the G13 product constitutively activates the UPR, whereas overexpression of a mutant lacking the activation domain exhibits a strong dominant-negative effect. Furthermore, the soluble forms of ATF6 and the G13 gene product are unable to bind to several point mutants of the cis-acting ER stress response element in vitro that hardly respond to ER stress in vivo. We thus concluded that the two related bZIP proteins are crucial transcriptional regulators of the mammalian UPR, and propose calling the ATF6 gene product ATF6alpha and the G13 gene product ATF6beta.

  13. AGO6 functions in RNA-mediated transcriptional gene silencing in shoot and root meristems in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Changho Eun

    Full Text Available RNA-directed DNA methylation (RdDM is a small interfering RNA (siRNA-mediated epigenetic modification that contributes to transposon silencing in plants. RdDM requires a complex transcriptional machinery that includes specialized RNA polymerases, named Pol IV and Pol V, as well as chromatin remodelling proteins, transcription factors, RNA binding proteins, and other plant-specific proteins whose functions are not yet clarified. In Arabidopsis thaliana, DICER-LIKE3 and members of the ARGONAUTE4 group of ARGONAUTE (AGO proteins are involved, respectively, in generating and using 24-nt siRNAs that trigger methylation and transcriptional gene silencing of homologous promoter sequences. AGO4 is the main AGO protein implicated in the RdDM pathway. Here we report the identification of the related AGO6 in a forward genetic screen for mutants defective in RdDM and transcriptional gene silencing in shoot and root apical meristems in Arabidopsis thaliana. The identification of AGO6, and not AGO4, in our screen is consistent with the primary expression of AGO6 in shoot and root growing points.

  14. Search for Higgs portal DM at the ILC

    Energy Technology Data Exchange (ETDEWEB)

    Ko, P. [School of Physics, KIAS,Seoul 02455 (Korea, Republic of); Quantum Universe Center, KIAS,Seoul 02455 (Korea, Republic of); Yokoya, Hiroshi [Quantum Universe Center, KIAS,Seoul 02455 (Korea, Republic of)

    2016-08-18

    Higgs portal dark matter (DM) models are simple interesting and viable DM models. There are three types of the models depending on the DM spin: scalar, fermion and vector DM models. In this paper, we consider renormalizable, unitary and gauge invariant Higgs portal DM models, and study how large parameter regions can be surveyed at the International Linear Collider (ILC) experiment at √s=500 GeV. For the Higgs portal singlet fermion and vector DM cases, the force mediator involves two scalar propagators, the SM-like Higgs boson and the dark Higgs boson. We show that their interference generates interesting and important patterns in the mono-Z plus missing E{sub T} signatures at the ILC, and the results are completely different from those obtained from the Higgs portal DM models within the effective field theories. In addition, we show that it would be possible to distinguish the spin of DM in the Higgs portal scenarios, if the shape of the recoil-mass distribution is observed. We emphasize that the interplay between these collider observations and those in the direct detection experiments has to be performed in the model with renomalizability and unitarity to combine the model analyses in different scales.

  15. Primary effect of chemotherapy on the transcription profile of AIDS-related Kaposi's sarcoma

    International Nuclear Information System (INIS)

    Kuyl, Antoinette C van der; Burg, Remco van den; Zorgdrager, Fokla; Dekker, John T; Maas, Jolanda; Noesel, Carel JM van; Goudsmit, Jaap; Cornelissen, Marion

    2002-01-01

    Drugs & used in anticancer chemotherapy have severe effects upon the cellular transcription and replication machinery. From in vitro studies it has become clear that these drugs can affect specific genes, as well as have an effect upon the total transcriptome. Total mRNA from two skin lesions from a single AIDS-KS patient was analyzed with the SAGE (Serial Analysis of Gene Expression) technique to assess changes in the transcriptome induced by chemotherapy. SAGE libraries were constructed from material obtained 24 (KS-24) and 48 (KS-48) hrs after combination therapy with bleomycin, doxorubicin and vincristine. KS-24 and KS-48 were compared to SAGE libraries of untreated AIDS-KS, and to libraries generated from normal skin and from isolated CD4+ T-cells, using the programs USAGE and HTM. SAGE libraries were also compared with the SAGEmap database. In order to assess the primary response of AIDS-related Kaposi's sarcoma (AIDS-KS) to chemotherapy in vivo, we analyzed the transcriptome of AIDS-KS skin lesions from a HIV-1 seropositive patient at two time points after therapy. The mRNA profile was found to have changed dramatically within 24 hours after drug treatment. There was an almost complete absence of transcripts highly expressed in AIDS-KS, probably due to a transcription block. Analysis of KS-24 suggested that mRNA pool used in its construction originated from poly(A) binding protein (PABP) mRNP complexes, which are probably located in nuclear structures known as interchromatin granule clusters (IGCs). IGCs are known to fuse after transcription inhibition, probably affecting poly(A)+RNA distribution. Forty-eight hours after chemotherapy, mRNA isolated from the lesion was largely derived from infiltrating lymphocytes, confirming the transcriptional block in the AIDS-KS tissue. These in vivo findings indicate that the effect of anti-cancer drugs is likely to be more global than up- or downregulation of specific genes, at least in this single patient with

  16. Inhibition of transcription of abscisic acid in relation to the binding with DNA

    International Nuclear Information System (INIS)

    Basak, Sukla; Basu, P.S.; Biswas, B.B.

    1976-01-01

    Abscisic acid (ABA), a plant substance inhibits RNA synthesis in vivo and vitro. In vitro inhibition by ABA has been demonstrated in isolated RNA polymerase system from coconut endosperm chromatin. This inhibition can be partly reversible with indole acetic acid-receptor protein complex if added in the system. To find the mechanism of inhibition of transcription by ABA, it has been found that ABA (10 -4 -10 -5 M) can bind with DNA and can prevent strand separation. This binding increases the Tm value. ABA binds with DNA but not with RNA. Moreover, ABA can equally bind and prevent denaturation of calfthymus DNA and E. coli DNA. pH optimum for this binding is 8.0. The bound complex is resistant to alkali and alcohol but susceptible to acid below pH 5.0. It has further been demonstrated that free aBA at this pH is changed to another component which has tentatively been identified as lactone form of ABA. (author)

  17. Konfirmasi spesifitas GAD65 terhadap anti-GAD65 pada tikus DM dan pasien DM tipe 1

    Directory of Open Access Journals (Sweden)

    Aulanni’a Aulanni’a

    2012-02-01

    Full Text Available The use of glutamic acid decarboxylase (GAD65 from bovine brain has been studied to obtain basic knowledge and diagnosis and prediction of Type 1 Diabetes Mellitus (DM patients. The importance of GAD65 in DM diagnosis based on its patogenesis. One of the autoimmune marker that can be used to detect beta-pancreas destruction in Diabetes Type I is the antibody to glutamic acid decarboxylase (GAD65. Most of the pre-diabetic patients indicate the reactive autoantibody to GAD65. For early detection of anti-GAD65 in the serum of the patient, human recombinat GAD65 has been succeed to be used. However this is not economical, therefore, it is necessary to find the alternative source of cheaper GAD65. The aim of this research is to develop an early detection kit of Type 1 DM based on antibody- GAD65, since the longest patient suffering from DM has higher probability to be complicated, especially for uncured patients. The anti- GAD65 antibodies induced by anti-GAD65 synthetized and labelled by alkaline phosphatase can be used as reagent detection early DM patients. The ten patients of DM as samples (positive of anti-GAD65 and five rats of DM were positive with western blott technique using reagents as result of this research. It can be concluded, GAD65 enzyme isolated from bovine brain induced anti-GAD65 production and have possibilities to be packaged in a diagnostic kit for patient pre DM.

  18. Pou1f1, the key transcription factor related to somatic growth in tilapia (Orechromis niloticus), is regulated by two independent post-transcriptional regulation mechanisms.

    Science.gov (United States)

    Wang, Dongfang; Qin, Jingkai; Jia, Jirong; Yan, Peipei; Li, Wensheng

    2017-01-29

    This study aims to determine the post-transcriptional regulation mechanism of the transcription factor pou1f1 (pou class 1 homeobox 1), which is the key gene for pituitary development, somatic growth in vertebrates, and transcription of several hormone genes in teleost fish. MicroRNA miR-223-3p was identified as a bona fide target of pou1f; overexpression of miR-223-3p in primary pituitary cells led to the down-regulation of pou1f1 and downstream genes, and inhibition of miR-223-3p led to the up-regulation of pou1f1 in Nile tilapia dispersed primary pituitary cells. An adenylate-uridylate-rich element (AU-Rich element) was found in the 3'UTR of pou1f1 mRNA, and deletion of the AU-Rich element led to slower mRNA decay and therefore more protein output. A potential mutual relationship between miR-223-3p and the AU-rich element was also investigated, and the results demonstrated that with or without the AU-Rich element, miR-223-3p induced the up-regulation of a reporter system under serum starvation conditions, indicating that miR-223-3p and the AU-Rich element function independent of each other. This study is the first to investigate the post-transcriptional mechanism of pou1f1, which revealed that miR-223-3p down-regulated pou1f1 and downstream gene expressions, and the AU-Rich element led to rapid decay of pou1f1 mRNA. MicroRNA miR-223-3p and the AU-Rich element co-regulated the post-transcriptional expression of pou1f1 independently in Nile tilapia, demonstrating that pou1f1 is under the control of a dual post-transcription regulation mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Whole-genome transcriptional analysis of Escherichia coli during heat inactivation processes related to industrial cooking.

    Science.gov (United States)

    Guernec, A; Robichaud-Rincon, P; Saucier, L

    2013-08-01

    Escherichia coli K-12 was grown to the stationary phase, for maximum physiological resistance, in brain heart infusion (BHI) broth at 37°C. Cells were then heated at 58°C or 60°C to reach a process lethality value \\[\\mathbf{\\left(}{{\\mathit{F}}^{\\mathit{o}}}_{\\mathbf{70}}^{\\mathbf{10}}\\mathbf{\\right)} \\] of 2 or 3 or to a core temperature of 71°C (control industrial cooking temperature). Growth recovery and cell membrane integrity were evaluated immediately after heating, and a global transcription analysis was performed using gene expression microarrays. Only cells heated at 58°C with F(o) = 2 were still able to grow on liquid or solid BHI broth after heat treatment. However, their transcriptome did not differ from that of bacteria heated at 58°C with F(o) = 3 (P value for the false discovery rate [P-FDR] > 0.01), where no growth recovery was observed posttreatment. Genome-wide transcriptomic data obtained at 71°C were distinct from those of the other treatments without growth recovery. Quantification of heat shock gene expression by real-time PCR revealed that dnaK and groEL mRNA levels decreased significantly above 60°C to reach levels similar to those of control cells at 37°C (P citE, glyS, oppB, and asd, whose expression was upregulated at 71°C, may be worth investigating as good biomarkers for accurately determining the efficiency of heat treatments, especially when cells are too injured to be enumerated using growth media.

  20. Quantitative Proteomic Analysis of Hepatic Tissue of T2DM Rhesus Macaque

    Directory of Open Access Journals (Sweden)

    Tingfu Du

    2017-01-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a metabolic disorder that severely affects human health, but the pathogenesis of the disease remains unknown. The high-fat/high-sucrose diets combined with streptozotocin- (STZ- induced nonhuman primate animal model of diabetes are a valuable research source of T2DM. Here, we present a study of a STZ rhesus macaque model of T2DM that utilizes quantitative iTRAQ-based proteomic method. We compared the protein profiles in the liver of STZ-treated macaques as well as age-matched healthy controls. We identified 171 proteins differentially expressed in the STZ-treated groups, about 70 of which were documented as diabetes-related gene in previous studies. Pathway analyses indicated that the biological functions of differentially expressed proteins were related to glycolysis/gluconeogenesis, fatty acid metabolism, complements, and coagulation cascades. Expression change in tryptophan metabolism pathway was also found in this study which may be associations with diabetes. This study is the first to explore genome-wide protein expression in hepatic tissue of diabetes macaque model using HPLC-Q-TOF/MS technology. In addition to providing potential T2DM biomarkers, this quantitative proteomic study may also shed insights regarding the molecular pathogenesis of T2DM.

  1. Two novel transcriptional regulators are essential for infection-related morphogenesis and pathogenicity of the rice blast fungus Magnaporthe oryzae.

    Directory of Open Access Journals (Sweden)

    Xia Yan

    2011-12-01

    Full Text Available The cyclic AMP-dependent protein kinase A signaling pathway plays a major role in regulating plant infection by the rice blast fungus Magnaporthe oryzae. Here, we report the identification of two novel genes, MoSOM1 and MoCDTF1, which were discovered in an insertional mutagenesis screen for non-pathogenic mutants of M. oryzae. MoSOM1 or MoCDTF1 are both necessary for development of spores and appressoria by M. oryzae and play roles in cell wall differentiation, regulating melanin pigmentation and cell surface hydrophobicity during spore formation. MoSom1 strongly interacts with MoStu1 (Mstu1, an APSES transcription factor protein, and with MoCdtf1, while also interacting more weakly with the catalytic subunit of protein kinase A (CpkA in yeast two hybrid assays. Furthermore, the expression levels of MoSOM1 and MoCDTF1 were significantly reduced in both Δmac1 and ΔcpkA mutants, consistent with regulation by the cAMP/PKA signaling pathway. MoSom1-GFP and MoCdtf1-GFP fusion proteins localized to the nucleus of fungal cells. Site-directed mutagenesis confirmed that nuclear localization signal sequences in MoSom1 and MoCdtf1 are essential for their sub-cellular localization and biological functions. Transcriptional profiling revealed major changes in gene expression associated with loss of MoSOM1 during infection-related development. We conclude that MoSom1 and MoCdtf1 functions downstream of the cAMP/PKA signaling pathway and are novel transcriptional regulators associated with cellular differentiation during plant infection by the rice blast fungus.

  2. PEA3/ETV4-related transcription factors coupled with active ERK signalling are associated with poor prognosis in gastric adenocarcinoma

    LENUS (Irish Health Repository)

    Keld, R

    2011-06-28

    Background: Transcription factors often play important roles in tumourigenesis. Members of the PEA3 subfamily of ETS-domain transcription factors fulfil such a role and have been associated with tumour metastasis in several different cancers. Moreover, the activity of the PEA3 subfamily transcription factors is potentiated by Ras-ERK pathway signalling, which is itself often deregulated in tumour cells.\\r\

  3. Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

    Energy Technology Data Exchange (ETDEWEB)

    Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com [Genentech, Inc., South San Francisco, CA (United States); Flagella, Kelly; Beyer, Joseph [Genentech, Inc., South San Francisco, CA (United States); Tibbitts, Jay [UCB, Brussels (Belgium); Kaur, Surinder; Saad, Ola; Yi, Joo-Hee; Girish, Sandhya; Dybdal, Noel; Reynolds, Theresa [Genentech, Inc., South San Francisco, CA (United States)

    2013-12-01

    Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeys and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and pharmacologic

  4. De Novo Transcriptome Assembly (NGS) of Curcuma longa L. Rhizome Reveals Novel Transcripts Related to Anticancer and Antimalarial Terpenoids

    Science.gov (United States)

    Jayakumar, Vasanthan; Damodaran, Anand C.; Rao, Sudha Narayana; Katta, Mohan A. V. S. K.; Gopinathan, Sreeja; Sarma, Santosh Prasad; Senthilkumar, Vanitha; Niranjan, Vidya; Gopinath, Ashok; Mugasimangalam, Raja C.

    2013-01-01

    Herbal remedies are increasingly being recognised in recent years as alternative medicine for a number of diseases including cancer. Curcuma longa L., commonly known as turmeric is used as a culinary spice in India and in many Asian countries has been attributed to lower incidences of gastrointestinal cancers. Curcumin, a secondary metabolite isolated from the rhizomes of this plant has been shown to have significant anticancer properties, in addition to antimalarial and antioxidant effects. We sequenced the transcriptome of the rhizome of the 3 varieties of Curcuma longa L. using Illumina reversible dye terminator sequencing followed by de novo transcriptome assembly. Multiple databases were used to obtain a comprehensive annotation and the transcripts were functionally classified using GO, KOG and PlantCyc. Special emphasis was given for annotating the secondary metabolite pathways and terpenoid biosynthesis pathways. We report for the first time, the presence of transcripts related to biosynthetic pathways of several anti-cancer compounds like taxol, curcumin, and vinblastine in addition to anti-malarial compounds like artemisinin and acridone alkaloids, emphasizing turmeric's importance as a highly potent phytochemical. Our data not only provides molecular signatures for several terpenoids but also a comprehensive molecular resource for facilitating deeper insights into the transcriptome of C. longa. PMID:23468859

  5. Global identification of the full-length transcripts and alternative splicing related to phenolic acid biosynthetic genes in Salvia miltiorrhiza

    Directory of Open Access Journals (Sweden)

    Zhichao eXu

    2016-02-01

    Full Text Available Salvianolic acids are among the main bioactive components in Salvia miltiorrhiza, and their biosynthesis has attracted widespread interest. However, previous studies on the biosynthesis of phenolic acids using next-generation sequencing platforms are limited with regard to the assembly of full-length transcripts. Based on hybrid-seq (next-generation and single molecular real-time sequencing of the S. miltiorrhiza root transcriptome, we experimentally identified 15 full-length transcripts and 4 alternative splicing events of enzyme-coding genes involved in the biosynthesis of rosmarinic acid. Moreover, we herein demonstrate that lithospermic acid B accumulates in the phloem and xylem of roots, in agreement with the expression patterns of the identified key genes related to rosmarinic acid biosynthesis. According to co-expression patterns, we predicted that 6 candidate cytochrome P450s and 5 candidate laccases participate in the salvianolic acid pathway. Our results provide a valuable resource for further investigation into the synthetic biology of phenolic acids in S. miltiorrhiza.

  6. The Related Transcriptional Enhancer Factor-1 Isoform, TEAD4216, Can Repress Vascular Endothelial Growth Factor Expression in Mammalian Cells

    Science.gov (United States)

    Appukuttan, Binoy; McFarland, Trevor J.; Stempel, Andrew; Kassem, Jean B.; Hartzell, Matthew; Zhang, Yi; Bond, Derek; West, Kelsey; Wilson, Reid; Stout, Andrew; Pan, Yuzhen; Ilias, Hoda; Robertson, Kathryn; Klein, Michael L.; Wilson, David; Smith, Justine R.; Stout, J. Timothy

    2012-01-01

    Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4216, which represses VEGF promoter activity. The TEAD4216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4216 isoform can competitively repress the stimulatory activity of the TEAD4434 and TEAD4148 enhancers. Synthesis of the native VEGF165 protein and cellular proliferation is suppressed by the TEAD4216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases. PMID:22761647

  7. De Novo transcriptome assembly (NGS of Curcuma longa L. rhizome reveals novel transcripts related to anticancer and antimalarial terpenoids.

    Directory of Open Access Journals (Sweden)

    Ramasamy S Annadurai

    Full Text Available Herbal remedies are increasingly being recognised in recent years as alternative medicine for a number of diseases including cancer. Curcuma longa L., commonly known as turmeric is used as a culinary spice in India and in many Asian countries has been attributed to lower incidences of gastrointestinal cancers. Curcumin, a secondary metabolite isolated from the rhizomes of this plant has been shown to have significant anticancer properties, in addition to antimalarial and antioxidant effects. We sequenced the transcriptome of the rhizome of the 3 varieties of Curcuma longa L. using Illumina reversible dye terminator sequencing followed by de novo transcriptome assembly. Multiple databases were used to obtain a comprehensive annotation and the transcripts were functionally classified using GO, KOG and PlantCyc. Special emphasis was given for annotating the secondary metabolite pathways and terpenoid biosynthesis pathways. We report for the first time, the presence of transcripts related to biosynthetic pathways of several anti-cancer compounds like taxol, curcumin, and vinblastine in addition to anti-malarial compounds like artemisinin and acridone alkaloids, emphasizing turmeric's importance as a highly potent phytochemical. Our data not only provides molecular signatures for several terpenoids but also a comprehensive molecular resource for facilitating deeper insights into the transcriptome of C. longa.

  8. De Novo transcriptome assembly (NGS) of Curcuma longa L. rhizome reveals novel transcripts related to anticancer and antimalarial terpenoids.

    Science.gov (United States)

    Annadurai, Ramasamy S; Neethiraj, Ramprasad; Jayakumar, Vasanthan; Damodaran, Anand C; Rao, Sudha Narayana; Katta, Mohan A V S K; Gopinathan, Sreeja; Sarma, Santosh Prasad; Senthilkumar, Vanitha; Niranjan, Vidya; Gopinath, Ashok; Mugasimangalam, Raja C

    2013-01-01

    Herbal remedies are increasingly being recognised in recent years as alternative medicine for a number of diseases including cancer. Curcuma longa L., commonly known as turmeric is used as a culinary spice in India and in many Asian countries has been attributed to lower incidences of gastrointestinal cancers. Curcumin, a secondary metabolite isolated from the rhizomes of this plant has been shown to have significant anticancer properties, in addition to antimalarial and antioxidant effects. We sequenced the transcriptome of the rhizome of the 3 varieties of Curcuma longa L. using Illumina reversible dye terminator sequencing followed by de novo transcriptome assembly. Multiple databases were used to obtain a comprehensive annotation and the transcripts were functionally classified using GO, KOG and PlantCyc. Special emphasis was given for annotating the secondary metabolite pathways and terpenoid biosynthesis pathways. We report for the first time, the presence of transcripts related to biosynthetic pathways of several anti-cancer compounds like taxol, curcumin, and vinblastine in addition to anti-malarial compounds like artemisinin and acridone alkaloids, emphasizing turmeric's importance as a highly potent phytochemical. Our data not only provides molecular signatures for several terpenoids but also a comprehensive molecular resource for facilitating deeper insights into the transcriptome of C. longa.

  9. Transcriptional profiling of primary endometrial epithelial cells following acute HIV-1 exposure reveals gene signatures related to innate immunity.

    Science.gov (United States)

    Zahoor, Muhammad Atif; Woods, Matthew William; Dizzell, Sara; Nazli, Aisha; Mueller, Kristen M; Nguyen, Philip V; Verschoor, Chris P; Kaushic, Charu

    2018-04-01

    Genital epithelial cells (GECs) line the mucosal surface of the female genital tract (FGT) and are the first cells that interface with both commensal microbiota and sexually transmitted pathogens. Despite the protective barrier formed by GECs, the FGT is a major site of HIV-1 infection. This highlights the importance of studying the interaction of HIV-1 and GECs. Using microarray analysis, we characterized the transcriptional profile of primary endometrial GECs grown in the presence or absence of physiological levels of E2 (10 -9  mol/L) or P4 (10 -7  mol/L) following acute exposure to HIV-1 for 6 hours. Acute exposure of primary endometrial GECs to HIV-1 resulted in the expression of genes related to inflammation, plasminogen activation, adhesion and diapedesis and interferon response. Interestingly, exposure to HIV-1 in the presence of E2 and P4 resulted in differential transcriptional profiles, suggesting that the response of primary endometrial GECs to HIV-1 exposure is modulated by female sex hormones. The gene expression signature of endometrial GECs indicates that the response of these cells may be key to determining host susceptibility to HIV-1 and that sex hormones modulate these interactions. This study allows us to explore possible mechanisms that explain the hormone-mediated fluctuation of HIV-1 susceptibility in women. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Cloning and expression analysis of transcription factor RrTTG1 related to prickle development in rose (Rosa Rugosa

    Directory of Open Access Journals (Sweden)

    Feng Li-Guo

    2015-01-01

    Full Text Available A prickle is an acuminate protuberance formed by the deformation of plant trichomes together with a few cortical cells. It is a type of multicellular eglandular trichome with special morphology, which originates from the phloem but is not connected to the xylem. Rosa rugosa is an important ornamental/commercial plant and an important raw material in the food and perfume industries. However, the firm prickles on its stems are inconvenient to field management, the harvesting of flowers and garden management. The TTG1 transcription factor related to the development of prickle was isolated from R. rugosa in the present study. Its expression patterns in different tissues and varieties were analyzed. Results showed the expression level of the RrTTG1 gene was highest in the leaves, followed by the stems, but was lower in the pericarps and petals. Moreover, the higher expression level of the RrTTG1 gene in all tissues of the ‘Ciguo rose’, as compared with that of the ‘Weihai wild rose’, follows the results of field morphological observation. Therefore, the RrTTG1 transcription factor is likely to regulate the development of rose prickles. This study allows for further discussion on the molecular mechanisms of prickle formation and development in R. rugosa and provides a molecular basis for the cultivation of roses with fewer or no prickles via genetic engineering.

  11. 1015 PTT Segment MEMS DM Development, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Microelectromechanical systems (MEMS) technology has the potential to create deformable mirrors (DM) with more than 10^4 actuators with size, weight, and power...

  12. Picometer-Resolution MEMS Segmented DM, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — Microelectromechanical systems (MEMS) technology has the potential to create deformable mirrors (DM) with 10^4 actuators that have size, weight, and power...

  13. Picometer-Resolution MEMS Segmented DM, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Microelectromechanical systems (MEMS) technology has the potential to create deformable mirrors (DM) with 10^4 actuators that have size, weight, and power...

  14. A functional polymorphism of the TNF-α gene that is associated with type 2 DM

    International Nuclear Information System (INIS)

    Susa, Shinji; Daimon, Makoto; Sakabe, Jun-Ichi; Sato, Hidenori; Oizumi, Toshihide; Karasawa, Shigeru; Wada, Kiriko; Jimbu, Yumi; Kameda, Wataru; Emi, Mitsuru; Muramatsu, Masaaki; Kato, Takeo

    2008-01-01

    To examine the association of the tumor necrosis factor-α (TNF-α) gene region with type 2 diabetes (DM), 11 single-nucleotide polymorphisms (SNPs) of the region were analyzed. The initial study using a sample set (148 cases vs. 227 controls) showed a significant association of the SNP IVS1G + 123A of the TNF-α gene with DM (p = 0.0056). Multiple logistic regression analysis using an enlarged sample set (225 vs. 716) revealed the significant association of the SNP with DM independently of any clinical traits examined (OR: 1.49, p = 0.014). The functional relevance of the SNP were examined by the electrophoretic mobility shift assays using nuclear extracts from the U937 and NIH3T3 cells and luciferase assays in these cells with Simian virus 40 promoter- and TNF-α promoter-reporter gene constructs. The functional analyses showed that YY1 transcription factor bound allele-specifically to the SNP region and, the IVS1 + 123A allele had an increase in luciferase expression compared with the G allele

  15. Effects of Pb(Ⅱ) exposure on Chlorella protothecoides and Chlorella vulgaris growth, malondialdehyde, and photosynthesis-related gene transcription.

    Science.gov (United States)

    Xiong, Bang; Zhang, Wei; Chen, Lin; Lin, Kuang-Fei; Guo, Mei-Jin; Wang, Wei-Liang; Cui, Xin-Hong; Bi, Hua-Song; Wang, Bin

    2014-11-01

    Greater exposure to Pb(Ⅱ) increases the likelihood of harmful effects in the environment. In this study, the aquatic unicellular alga Chlorella protothecoides (C. protothecoides) and Chlorella vulgaris (C. vulgaris) were chosen to assess the acute and chronic toxicity of Pb(Ⅱ) exposure. Results of the observations show dose-response relationships could be clearly observed between Pb(Ⅱ) concentration and percentage inhibition (PI). Exposure to Pb(Ⅱ) increased malondialdehyde (MDA) content by up to 4.22 times compared with the control, suggesting that there was some oxidative damage. ANOVA analysis shows that Pb(Ⅱ) decreased chlorophyll (chl) content, indicating marked concentration-dependent relationships, and the lowest levels of chl a, chl b, and total-chl were 14.53, 18.80, and 17.95% of the controls, respectively. A real-time PCR assay suggests the changes in transcript abundances of three photosynthetic-related genes. After 120 h exposure Pb(Ⅱ) reduced the transcript abundance of rbcL, psaB, and psbC, and the relative abundances of the three genes of C. protothecoides and C. vulgaris in response to Pb(Ⅱ) were 54.66-98.59, 51.68-95.59, 37.89-95.48, 36.04-94.94, 41.19-91.20, and 58.75-96.80% of those of the controls, respectively. As for 28 d treatments, the three genes displayed similar inhibitory trend. This research provides a basic understanding of Pb(Ⅱ) toxicity to aquatic organisms. Copyright © 2013 Wiley Periodicals, Inc.

  16. Transcription profiling and identification of infection-related genes in Phytophthora cactorum.

    Science.gov (United States)

    Chen, Xiao-Ren; Huang, Shen-Xin; Zhang, Ye; Sheng, Gui-Lin; Zhang, Bo-Yue; Li, Qi-Yuan; Zhu, Feng; Xu, Jing-You

    2018-04-01

    Phytophthora cactorum, an oomycete pathogen, infects more than 200 plant species within several plant families. To gain insight into the repertoire of the infection-related genes of P. cactorum, Illumina RNA-Seq was used to perform a global transcriptome analysis of three life cycle stages of the pathogen, mycelia (MY), zoospores (ZO) and germinating cysts with germ tubes (GC). From over 9.8 million Illumina reads for each library, 18,402, 18,569 and 19,443 distinct genes were identified for MY, ZO and GC libraries, respectively. Furthermore, the transcriptome difference among MY, ZO and GC stages was investigated. Gene ontology (GO) and KEGG pathway enrichment analyses revealed diverse biological functions and processes. Comparative analysis identified a large number of genes that are associated with specific stages and pathogenicity, including 166 effector genes. Of them, most of RXLR and NLP genes showed induction while the majority of CRN genes were down-regulated in GC, the important pre-infection stage, compared to either MY or ZO. And 14 genes encoding small cysteine-rich (SCR) secretory proteins showed differential expression during the developmental stages and in planta. Ectopic expression in the Solanaceae indicated that SCR113 and one elicitin PcINF1 can trigger cell death on Nicotiana benthamiana, tobacco (N. tabacum) and tomato (Solanum lycopersicum) leaves. Neither conserved domain nor homologues of SCR113 in other organisms can be identified. Collectively, our study provides a comprehensive examination of gene expression across three P. cactorum developmental stages and describes pathogenicity-related genes, all of which will help elucidate the pathogenicity mechanism of this destructive pathogen.

  17. [Functional activity of the modA, gene in Methylobacterium dichloromethanicum DM4].

    Science.gov (United States)

    Firsova, Y E; Trotsenko, Y A

    2014-01-01

    The putative METDI2644 (modA2) gene of Methylobacterium dichloromethanicum DM4, present in the 126-kbp chromosomal fragment associated with dichloromethane (DCM) degradation was investigated. While this gene is presumed to encode the periplasmic substrate-binding subunit of the molybdate ABC transporter, its conceptual translation also exhibits similarity to the proteins containing the ostA conservative domain and responsible for resistance of gram-negative bacteria to organic solvents. Reverse transcription polymerase chain reaction (RT-PCR) revealed the RNA transcripts of this gene in the cells grown on either DCM or methanol. The mobilizable suicide vector pK18mob was used to obtain a knockout mutant with the METDI2644 gene inactivated by insertion of the gentamycin cassette. The mutant pregrown on methanol exhibited lower growth rate on DCM than the wild-type strain DM4. The difference was not alleviated by addition of sodium molybdate. Our results suggest that the METDI2644 gene product plays a role in cell adaptation to DCM degradation.

  18. Changes in transcript related to osmosis and intracellular ion homeostasis in Paulownia tomentosa under salt stress

    Directory of Open Access Journals (Sweden)

    Guoqiang eFan

    2016-03-01

    Full Text Available Paulownia tomentosa is an important economic and greening tree species that is cultivated widely, including salt environment. Our previous studies indicated its autotetraploid induced by colchicine showed better stress tolerance, but the underlying molecular mechanism related to ploidy and salt stress is still unclear. To investigate this issue, physiological measurements and transcriptome profiling of diploid and autotetraploid plants untreated and treated with NaCl were performed. Through the comparisons among four accessions, for one thing, we found different physiological changes between diploid and autotetraploid P. tomentosa; for another, and we detected many differentially expressed unigenes involved in salt stress response. These differentially expressed unigenes were assigned to several metabolic pathways, including plant hormone signal transduction, RNA transporter, protein processing in endoplasmic reticulum and plant-pathogen interaction, which constructed the complex regulatory network to maintain osmotic and intracellular ion homeostasis. Quantitative real-time polymerase chain reaction was used to confirm the expression patterns of 20 unigenes. The results establish the foundation for the genetic basis of salt tolerance in P. tomentosa, which in turn accelerates Paulownia breeding and expands available arable land.

  19. Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer's Disease-Related Genes by In Silico Promoter Analysis and Microarrays

    Directory of Open Access Journals (Sweden)

    Regina Augustin

    2011-01-01

    Full Text Available The molecular mechanisms and genetic risk factors underlying Alzheimer's disease (AD pathogenesis are only partly understood. To identify new factors, which may contribute to AD, different approaches are taken including proteomics, genetics, and functional genomics. Here, we used a bioinformatics approach and found that distinct AD-related genes share modules of transcription factor binding sites, suggesting a transcriptional coregulation. To detect additional coregulated genes, which may potentially contribute to AD, we established a new bioinformatics workflow with known multivariate methods like support vector machines, biclustering, and predicted transcription factor binding site modules by using in silico analysis and over 400 expression arrays from human and mouse. Two significant modules are composed of three transcription factor families: CTCF, SP1F, and EGRF/ZBPF, which are conserved between human and mouse APP promoter sequences. The specific combination of in silico promoter and multivariate analysis can identify regulation mechanisms of genes involved in multifactorial diseases.

  20. Novel Variants in ZNF34 and Other Brain-Expressed Transcription Factors are Shared Among Early-Onset MDD Relatives

    Science.gov (United States)

    Subaran, Ryan L.; Odgerel, Zagaa; Swaminathan, Rajeswari; Glatt, Charles E.; Weissman, Myrna M.

    2018-01-01

    There are no known genetic variants with large effects on susceptibility to major depressive disorder (MDD). Although one proposed study approach is to increase sensitivity by increasing sample sizes, another is to focus on families with multiple affected individuals to identify genes with rare or novel variants with strong effects. Choosing the family-based approach, we performed whole-exome analysis on affected individuals (n = 12) across five MDD families, each with at least five affected individuals, early onset, and prepubertal diagnoses. We identified 67 genes where novel deleterious variants were shared among affected relatives. Gene ontology analysis shows that of these 67 genes, 18 encode transcriptional regulators, eight of which are expressed in the human brain, including four KRAB-A box-containing Zn2+ finger repressors. One of these, ZNF34, has been reported as being associated with bipolar disorder and as differentially expressed in bipolar disorder patients compared to healthy controls. We found a novel variant—encoding a non-conservative P17R substitution in the conserved repressor domain of ZNF34 protein—segregating completely with MDD in all available individuals in the family in which it was discovered. Further analysis showed a common ZNF34 coding indel segregating with MDD in a separate family, possibly indicating the presence of an unobserved, linked, rare variant in that particular family. Our results indicate that genes encoding transcription factors expressed in the brain might be an important group of MDD candidate genes and that rare variants in ZNF34 might contribute to susceptibility to MDD and perhaps other affective disorders. PMID:26823146

  1. Relating genes to function: identifying enriched transcription factors using the ENCODE ChIP-Seq significance tool.

    Science.gov (United States)

    Auerbach, Raymond K; Chen, Bin; Butte, Atul J

    2013-08-01

    Biological analysis has shifted from identifying genes and transcripts to mapping these genes and transcripts to biological functions. The ENCODE Project has generated hundreds of ChIP-Seq experiments spanning multiple transcription factors and cell lines for public use, but tools for a biomedical scientist to analyze these data are either non-existent or tailored to narrow biological questions. We present the ENCODE ChIP-Seq Significance Tool, a flexible web application leveraging public ENCODE data to identify enriched transcription factors in a gene or transcript list for comparative analyses. The ENCODE ChIP-Seq Significance Tool is written in JavaScript on the client side and has been tested on Google Chrome, Apple Safari and Mozilla Firefox browsers. Server-side scripts are written in PHP and leverage R and a MySQL database. The tool is available at http://encodeqt.stanford.edu. abutte@stanford.edu Supplementary material is available at Bioinformatics online.

  2. Gender-related aspects of transmasculine people's vocal situations: insights from a qualitative content analysis of interview transcripts.

    Science.gov (United States)

    Azul, David

    2016-11-01

    Transmasculine people assigned female gender at birth but who do not identify with this classification have traditionally received little consideration in the voice literature. Existing analyses tend to be focused on evaluating speaker voice characteristics, whereas other factors that contribute to the production of vocal gender have remained underexplored. Most studies rely on researcher-centred perspectives, whereas very little is known about how transmasculine people themselves experience and make sense of their vocal situations. To explore how participants described their subjective gender positionings; which gender attributions they wished to receive from others; which gender they self-attributed to their voices; which gender attributions they had received from others; and how far participants were satisfied with the gender-related aspects of their vocal situations. Transcripts of semi-structured interviews with 14 German-speaking transmasculine people served as the original data corpus. Sections in which participants described the gender-related aspects of their vocal situations and that were relevant to the current research objectives were selected and explored using qualitative content analysis. The analysis revealed diverse accounts pertaining to the factors that contribute to the production of vocal gender for individual participants and variable levels of satisfaction with vocal gender presentation and attribution. Transmasculine people need to be regarded as a heterogeneous population and clinical practice needs to follow a client-centred, individualized approach. © 2016 Royal College of Speech and Language Therapists.

  3. Differential regulation of HIF-1α and HIF-2α in neuroblastoma: Estrogen-related receptor alpha (ERRα) regulates HIF2A transcription and correlates to poor outcome

    International Nuclear Information System (INIS)

    Hamidian, Arash; Stedingk, Kristoffer von; Munksgaard Thorén, Matilda; Mohlin, Sofie; Påhlman, Sven

    2015-01-01

    Hypoxia-inducible factors (HIFs) are differentially regulated in tumor cells. While the current paradigm supports post-translational regulation of the HIF-α subunits, we recently showed that hypoxic HIF-2α is also transcriptionally regulated via insulin-like growth factor (IGF)-II in the childhood tumor neuroblastoma. Here, we demonstrate that transcriptional regulation of HIF-2α seems to be restricted to neural cell-derived tumors, while HIF-1α is canonically regulated at the post-translational level uniformly across different tumor forms. Enhanced expression of HIF2A mRNA at hypoxia is due to de novo transcription rather than increased mRNA stability, and chemical stabilization of the HIF-α proteins at oxygen-rich conditions unexpectedly leads to increased HIF2A transcription. The enhanced HIF2A levels do not seem to be dependent on active HIF-1. Using a transcriptome array approach, we identified members of the Peroxisome proliferator-activated receptor gamma coactivator (PGC)/Estrogen-related receptor (ERR) complex families as potential regulators of HIF2A. Knockdown or inhibition of one of the members, ERRα, leads to decreased expression of HIF2A, and high expression of the ERRα gene ESRRA correlates with poor overall and progression-free survival in a clinical neuroblastoma material consisting of 88 tumors. Thus, targeting of ERRα and pathways regulating transcriptional HIF-2α are promising therapeutic avenues in neuroblastoma. - Highlights: • Transcriptional control of HIF-2α is restricted to neural cell-derived tumors. • Enhanced transcription of HIF2A is not due to increased mRNA stability. • Chemical stabilization of the HIF-α subunits leads to increased HIF2A transcription. • ERRα regulates HIF2A mRNA expression in neuroblastoma. • High expression of ESRRA correlates to poor outcome in neuroblastoma

  4. Differential regulation of HIF-1α and HIF-2α in neuroblastoma: Estrogen-related receptor alpha (ERRα) regulates HIF2A transcription and correlates to poor outcome

    Energy Technology Data Exchange (ETDEWEB)

    Hamidian, Arash; Stedingk, Kristoffer von; Munksgaard Thorén, Matilda; Mohlin, Sofie; Påhlman, Sven, E-mail: sven.pahlman@med.lu.se

    2015-06-05

    Hypoxia-inducible factors (HIFs) are differentially regulated in tumor cells. While the current paradigm supports post-translational regulation of the HIF-α subunits, we recently showed that hypoxic HIF-2α is also transcriptionally regulated via insulin-like growth factor (IGF)-II in the childhood tumor neuroblastoma. Here, we demonstrate that transcriptional regulation of HIF-2α seems to be restricted to neural cell-derived tumors, while HIF-1α is canonically regulated at the post-translational level uniformly across different tumor forms. Enhanced expression of HIF2A mRNA at hypoxia is due to de novo transcription rather than increased mRNA stability, and chemical stabilization of the HIF-α proteins at oxygen-rich conditions unexpectedly leads to increased HIF2A transcription. The enhanced HIF2A levels do not seem to be dependent on active HIF-1. Using a transcriptome array approach, we identified members of the Peroxisome proliferator-activated receptor gamma coactivator (PGC)/Estrogen-related receptor (ERR) complex families as potential regulators of HIF2A. Knockdown or inhibition of one of the members, ERRα, leads to decreased expression of HIF2A, and high expression of the ERRα gene ESRRA correlates with poor overall and progression-free survival in a clinical neuroblastoma material consisting of 88 tumors. Thus, targeting of ERRα and pathways regulating transcriptional HIF-2α are promising therapeutic avenues in neuroblastoma. - Highlights: • Transcriptional control of HIF-2α is restricted to neural cell-derived tumors. • Enhanced transcription of HIF2A is not due to increased mRNA stability. • Chemical stabilization of the HIF-α subunits leads to increased HIF2A transcription. • ERRα regulates HIF2A mRNA expression in neuroblastoma. • High expression of ESRRA correlates to poor outcome in neuroblastoma.

  5. Senam efektif Menurunkan Kadar Gula Darah Pasien DM Tipe 2

    Directory of Open Access Journals (Sweden)

    Jati Ekawati

    2018-01-01

    Full Text Available Background: Diabetes is one of the major threats to human health in the 21st century. Indonesia's own country with diabetes mellitus was ranked the world's fourth largest with 8.6% of the total prevalence of diabetes sufferers after India, China, and the United States. Factors that influence diabetes include; 1 age, 2 Obesity, 3 Family History, and 4 ethnic group. There are four pillars of prevention in Indonesia which is applied to the diabetes to control blood sugar levels, namely: 1 diet, 2 Physical Exercise, 3 medications, and 4 Health Education. Objective: To determine the effect of physical exercises Gymnastic DM administration and Gymnastic Senior to decrease blood sugar levels in patients with type 2 diabetes. Method: This study is a quantitative study with this type of study without a comparison group quasy experiments. The design of the study is a pretest-posttest one group design. Number of samples used were 41 respondents from the participants calisthenics DM in the psychiatric hospital. Prof. dr. Soerojo Magelang. Analysis of the data used is the analysis bivariabel univariabel and analysis using statistical models Paired sample t-tests with significance level α = 0.05. Result: There was a decrease in blood sugar levels after exercise DM for 3 times a week for 2 weeks, an average of 64.780 mg/dl. T count value obtained at 13.624 with a p-value 0.000 <0.05, means that there are significant differences in blood sugar levels before and after doing gymnastic DM and Gymnastic Senior. Conclusion: The provision of physical training exercises conducted by DM DM participants calisthenics in Prof. RSJ. Dr. Soerojo Magelang for 3 times a week for 2 weeks can lower blood sugar levels in patients with type 2 diabetes mellitus.

  6. NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland.

    Science.gov (United States)

    Ziros, Panos G; Habeos, Ioannis G; Chartoumpekis, Dionysios V; Ntalampyra, Eleni; Somm, Emmanuel; Renaud, Cédric O; Bongiovanni, Massimo; Trougakos, Ioannis P; Yamamoto, Masayuki; Kensler, Thomas W; Santisteban, Pilar; Carrasco, Nancy; Ris-Stalpers, Carrie; Amendola, Elena; Liao, Xiao-Hui; Rossich, Luciano; Thomasz, Lisa; Juvenal, Guillermo J; Refetoff, Samuel; Sykiotis, Gerasimos P

    2018-06-01

    The thyroid gland has a special relationship with oxidative stress. While generation of oxidative substances is part of normal iodide metabolism during thyroid hormone synthesis, the gland must also defend itself against excessive oxidation in order to maintain normal function. Antioxidant and detoxification enzymes aid thyroid cells to maintain homeostasis by ameliorating oxidative insults, including during exposure to excess iodide, but the factors that coordinate their expression with the cellular redox status are not known. The antioxidant response system comprising the ubiquitously expressed NFE2-related transcription factor 2 (Nrf2) and its redox-sensitive cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) defends tissues against oxidative stress, thereby protecting against pathologies that relate to DNA, protein, and/or lipid oxidative damage. Thus, it was hypothesized that Nrf2 should also have important roles in maintaining thyroid homeostasis. Ubiquitous and thyroid-specific male C57BL6J Nrf2 knockout (Nrf2-KO) mice were studied. Plasma and thyroids were harvested for evaluation of thyroid function tests by radioimmunoassays and of gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Nrf2-KO and Keap1-KO clones of the PCCL3 rat thyroid follicular cell line were generated using CRISPR/Cas9 technology and were used for gene and protein expression studies. Software-predicted Nrf2 binding sites on the thyroglobulin enhancer were validated by site-directed in vitro mutagenesis and chromatin immunoprecipitation. The study shows that Nrf2 mediates antioxidant transcriptional responses in thyroid cells and protects the thyroid from oxidation induced by iodide overload. Surprisingly, it was also found that Nrf2 has a dramatic impact on both the basal abundance and the thyrotropin-inducible intrathyroidal abundance of thyroglobulin (Tg), the precursor protein of thyroid hormones. This effect is mediated

  7. Assessment of complex water pollution with heavy metals and Pyrethroid pesticides on transcript levels of metallothionein and immune related genes.

    Science.gov (United States)

    Ghazy, Haneen A; Abdel-Razek, Mohamed A S; El Nahas, Abeer F; Mahmoud, Shawky

    2017-09-01

    Alteration of immunological function of an aquatic organism can be used as an indicator for evaluating the direct effect of exposure to pollutants. The aim of this work is to assess the impact of complex water pollution with special reference to Pyrethroid pesticides and heavy metals on mRNA transcript levels of Metallothionine and some immune related genes of Nile tilapia (Oreochromas Niloticus). Residues of six heavy metals and six Pyrethroid were assessed in water as well as fish tissues at three different sites of Lake Burullus, located at Northern Egypt. Variations of water physicochemical properties associated with different levels of heavy metals at the three different sections were recorded. Tissue residues of Fe, Mn and Zn, Cu, Ni exceed water levels in contrast to elevated water level of Pb. All assessed Pyrethroids are detected in fish tissue samples with higher concentration (3-42 folds) than that found in water samples especially Cypermethrin. Significant down-regulation of expression levels of metallothionein (MT) at the three sections of the lake was observed. The expression of immune related genes (IgM) and inflammatory cytokines (TNF, IL.8 and IL.1) were affected. IgM and TNF were significantly down-regulated at eastern and western section of the lake; meanwhile the expression of IL8 is down regulated at the three sections of the lack. IL1 was significantly up-regulated at eastern and middle sections. We conclude that, variable gene expression of MT and immune-related genes at the three sections of the lack impose different response to complex water pollution in relation to variable aquatic environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Molecular mechanisms in DM1 - a focus on foci

    DEFF Research Database (Denmark)

    Pettersson, Olof Joakim; Aagaard, Lars; Jensen, Thomas G.

    2015-01-01

    -expanded RNA remains in the nuclear compartment, while in dividing cells such as fibroblasts a considerable fraction of the mutant RNA reaches the cytoplasm, consistent with findings that both nuclear and cytoplasmic events are mis-regulated in DM1. Recent evidence suggests that the nuclear aggregates......, or ribonuclear foci, are more dynamic than previously anticipated and regulated by several proteins, including RNA helicases. In this review, we focus on the homeostasis of DMPK mRNA foci and discuss how their dynamic regulation may affect disease-causing mechanisms in DM1...

  9. Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis.

    Science.gov (United States)

    Maurer, Britta; Busch, Nicole; Jüngel, Astrid; Pileckyte, Margarita; Gay, Renate E; Michel, Beat A; Schett, Georg; Gay, Steffen; Distler, Jörg; Distler, Oliver

    2009-12-08

    Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endothelial and vascular smooth muscle cells. Fra-2 transgenic mice developed a severe loss of small blood vessels in the skin that was paralleled by progressive skin fibrosis at 12 weeks of age. The reduction in capillary density was preceded by a significant increase in apoptosis in endothelial cells at week 9 as detected by immunohistochemistry. Similarly, suppression of Fra-2 by small interfering RNA prevented human microvascular endothelial cells from staurosporine-induced apoptosis and improved both the number of tubes and the cumulative tube lengths in the tube formation assay. In addition, cell migration in the scratch assay and vascular endothelial growth factor-dependent chemotaxis in a modified Boyden chamber assay were increased after transfection of human microvascular endothelial cells with Fra-2 small interfering RNA, whereas proliferation was not affected. Fra-2 is present in human systemic sclerosis and may contribute to the development of microvasculopathy by inducing endothelial cell apoptosis and by reducing endothelial cell migration and chemotaxis. Fra-2 transgenic mice are a promising preclinical model to study the mechanisms and therapeutic approaches of the peripheral vasculopathy in systemic sclerosis.

  10. G-actin sequestering protein thymosin-β4 regulates the activity of myocardin-related transcription factor.

    Science.gov (United States)

    Morita, Tsuyoshi; Hayashi, Ken'ichiro

    2013-08-02

    Myocardin-related transcription factors (MRTFs) are robust coactivators of serum response factor (SRF). MRTFs contain three copies of the RPEL motif at their N-terminus, and they bind to monomeric globular actin (G-actin). Previous studies illustrate that G-actin binding inhibits MRTF activity by preventing the MRTFs nuclear accumulation. In the living cells, the majority of G-actin is sequestered by G-actin binding proteins that prevent spontaneous actin polymerization. Here, we demonstrate that the most abundant G-actin sequestering protein thymosin-β4 (Tβ4) was involved in the regulation of subcellular localization and activity of MRTF-A. Tβ4 competed with MRTF-A for G-actin binding; thus, interfering with G-actin-MRTF-A complex formation. Tβ4 overexpression induced the MRTF-A nuclear accumulation and activation of MRTF-SRF signaling. The activation rate of MRTF-A by the Tβ4 mutant L17A, whose affinity for G-actin is very low, was lower than that by wild-type Tβ4. In contrast, the β-actin mutant 3DA, which has a lower affinity for Tβ4, more effectively suppressed MRTF-A activity than wild-type β-actin. Furthermore, ectopic Tβ4 increased the endogenous expression of SRF-dependent actin cytoskeletal genes. Thus, Tβ4 is an important MRTF regulator that controls the G-actin-MRTFs interaction. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Copper oxide nanoparticles induce the transcriptional modulation of oxidative stress-related genes in Arbacia lixula embryos.

    Science.gov (United States)

    Giannetto, Alessia; Cappello, Tiziana; Oliva, Sabrina; Parrino, Vincenzo; De Marco, Giuseppe; Fasulo, Salvatore; Mauceri, Angela; Maisano, Maria

    2018-06-14

    Copper oxide nanoparticles (CuO NPs) are widely used in various industrial applications, i.e. semiconductor devices, batteries, solar energy converter, gas sensor, microelectronics, heat transfer fluids, and have been recently recognized as emerging pollutants of increasing concern for human and marine environmental health. Therefore, the toxicity of CuO NPs needs to be thoroughly understood. In this study, we evaluated the potential role of oxidative stress in CuO NP toxicity by exploring the molecular response of Arbacia lixula embryos to three CuO NP concentrations (0.7, 10, 20 ppb) by investigating the transcriptional patterns of oxidative stress-related genes (catalase and superoxide dismutase) and metallothionein, here cloned and characterized for the first time. Time- and concentration-dependent changes in gene expression were detected in A. lixula embryos exposed to CuO NPs, up to pluteus stage (72 h post-fertilization, hpf), indicating that oxidative stress is one of the toxicity mechanisms for CuO NPs. These findings provide new insights into the comprehension of the molecular mechanisms underlying copper nanoparticle toxicity in A. lixula sea urchin and give new tools for monitoring of aquatic areas, thus corroborating the suitability of this embryotoxicity assay for future evaluation of impacted sites. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training.

    Directory of Open Access Journals (Sweden)

    Sellamuthu S Gounder

    Full Text Available Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2 through antioxidant response cis-elements (AREs and are impaired in the aging heart. Whereas acute exercise stress (AES activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (~2 months, aging mouse (>23 months hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES, but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day for ~6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases.

  13. Transcriptional profiles of pilocytic astrocytoma are related to their three different locations, but not to radiological tumor features

    International Nuclear Information System (INIS)

    Zakrzewski, Krzysztof; Jarząb, Michał; Pfeifer, Aleksandra; Oczko-Wojciechowska, Małgorzata; Jarząb, Barbara; Liberski, Paweł P.; Zakrzewska, Magdalena

    2015-01-01

    Pilocytic astrocytoma is the most common type of brain tumor in the pediatric population, with a generally favorable prognosis, although recurrences or leptomeningeal dissemination are sometimes also observed. For tumors originating in the supra-or infratentorial location, a different molecular background was suggested, but plausible correlations between the transcriptional profile and radiological features and/or clinical course are still undefined. The purpose of this study was to identify gene expression profiles related to the most frequent locations of this tumor, subtypes based on various radiological features, and the clinical pattern of the disease. Eighty six children (55 males and 31 females) with histologically verified pilocytic astrocytoma were included in this study. Their age at the time of diagnosis ranged from fourteen months to seventeen years, with a mean age of seven years. There were 40 cerebellar, 23 optic tract/hypothalamic, 21 cerebral hemispheric, and two brainstem tumors. According to the radiological features presented on MRI, all cases were divided into four subtypes: cystic tumor with a non-enhancing cyst wall; cystic tumor with an enhancing cyst wall; solid tumor with central necrosis; and solid or mainly solid tumor. In 81 cases primary surgical resection was the only and curative treatment, and in five cases progression of the disease was observed. In 47 cases the analysis was done by using high density oligonucleotide microarrays (Affymetrix HG-U133 Plus 2.0) with subsequent bioinformatic analyses and confirmation of the results by independent RT-qPCR (on 39 samples). Bioinformatic analyses showed that the gene expression profile of pilocytic astrocytoma is highly dependent on the tumor location. The most prominent differences were noted for IRX2, PAX3, CXCL14, LHX2, SIX6, CNTN1 and SIX1 genes expression even within different compartments of the supratentorial region. Analysis of the genes potentially associated with radiological

  14. Biohydrogen production from desugared molasses (DM) using thermophilic mixed cultures immobilized on heat treated anaerobic sludge granules

    DEFF Research Database (Denmark)

    Kongjan, Prawit; O-Thong, Sompong; Angelidaki, Irini

    2011-01-01

    Hydrogen production from desugared molasses (DM) was investigated in both batch and continuous reactors using thermophilic mixed cultures enriched from digested manure by load shock (loading with DM concentration of 50.1 g-sugar/L) to suppress methanogens. H2 gas, free of methane, was produced......) and Thermoanaerobacterium thermosaccharolyticum with a relative abundance of 36%, 27%, and 10% of total microorganisms, respectively. This study shows that hydrogen production could be efficiently facilitated by using anaerobic granules as a carrier, where microbes from mixed culture enriched in the DM batch cultivation....... The enriched hydrogen producing mixed culture achieved from the 16.7 g-sugars/L DM batch cultivation was immobilized on heat treated anaerobic sludge granules in an up-flow anaerobic sludge blanket (UASB) reactor. The UASB reactor, operated at a hydraulic retention time (HRT) of 24 h fed with 16.7 g...

  15. Physiological changes and sHSPs genes relative transcription in relation to the acquisition of seed germination during maturation of hybrid rice seed.

    Science.gov (United States)

    Zhu, Li-Wei; Cao, Dong-Dong; Hu, Qi-Juan; Guan, Ya-Jing; Hu, Wei-Min; Nawaz, Aamir; Hu, Jin

    2016-03-30

    During the production of early hybrid rice seed, the seeds dehydrated slowly and retained high moisture levels when rainy weather lasted for a couple of days, and the rice seeds easily occurred pre-harvest sprouting (PHS) along with high temperature. Therefore it is necessary to harvest the seeds before the PHS occurred. The seeds of hybrid rice (Oryza sativa L. subsp. indica) cv. Qianyou No1 that harvests from 19 to 28 days after pollination (DAP) all had high seed vigour. The seed moisture content at 10 DAP was 36.1%, and declined to 28.6% at 19 DAP; the contents of soluble sugar and total starch increased significantly with the development of seeds. The soluble protein content, the level of abscisic acid (ABA) and gibberellin (GA3 ), and ascorbate peroxidase (APX) activity continued to decrease from 10 DAP to 19 DAP. The seeds at 19 DAP had the highest peroxidase (POD) activity and lowest catalase (CAT) activity while the superoxide dismutase (SOD) activity had no significant difference among the different developing periods. The relative expressions of genes 64S Hsp18.0 and Os03g0267200 transcripts increased significantly from 10 to 19 DAP, and then decreased. However, no significant change was recorded in soluble protein, sugar and GA3 after 16 DAP, and they all significantly correlated with seed viability and vigour during the process of seed maturity. The seeds of hybrid rice Qianyou No1 had a higher viability and vigour when harvested from 19 DAP to 28 DAP, the transcription levels of 64S Hsp18.0 and Os03g0267200 increased significantly from 10 DAP to 19 DAP and the highest value was recorded at 19 DAP. The seeds could be harvested as early as 19 DAP without negative influence on seed vigour and viability. © 2015 Society of Chemical Industry.

  16. Transcriptional interference networks coordinate the expression of functionally-related genes clustered in the same genomic loci

    Directory of Open Access Journals (Sweden)

    Zsolt eBoldogkoi

    2012-07-01

    Full Text Available The regulation of gene expression is essential for normal functioning of biological systems in every form of life. Gene expression is primarily controlled at the level of transcription, especially at the phase of initiation. Non-coding RNAs are one of the major players at every level of genetic regulation, including the control of chromatin organisation, transcription, various post-transcriptional processes and translation. In this study, the Transcriptional Interference Network (TIN hypothesis was put forward in an attempt to explain the global expression of antisense RNAs and the overall occurrence of tandem gene clusters in the genomes of various biological systems ranging from viruses to mammalian cells. The TIN hypothesis suggests the existence of a novel layer of genetic regulation, based on the interactions between the transcriptional machineries of neighbouring genes at their overlapping regions, which are assumed to play a fundamental role in coordinating gene expression within a cluster of functionally-linked genes. It is claimed that the transcriptional overlaps between adjacent genes are much more widespread in genomes than is thought today. The Waterfall model of the TIN hypothesis postulates a unidirectional effect of upstream genes on the transcription of downstream genes within a cluster of tandemly-arrayed genes, while the Seesaw model proposes a mutual interdependence of gene expression between the oppositely-oriented genes. The TIN represents an auto-regulatory system with an exquisitely timed and highly synchronised cascade of gene expression in functionally-linked genes located in close physical proximity to each other. In this study, we focused on herpesviruses. The reason for this lies in the compressed nature of viral genes, which allows a tight regulation and an easier investigation of the transcriptional interactions between genes. However, I believe that the same or similar principles can be applied to cellular

  17. How do stars affect ψDM halos?

    Science.gov (United States)

    Chan, James H. H.; Schive, Hsi-Yu; Woo, Tak-Pong; Chiueh, Tzihong

    2018-04-01

    Wave dark matter (ψDM) predicts a compact soliton core and a granular halo in every galaxy. This work presents the first simulation study of an elliptical galaxy by including both stars and ψDM, focusing on the systematic changes of the central soliton and halo granules. With the addition of stars in the inner halo, we find the soliton core consistently becomes more prominent by absorbing mass from the host halo than that without stars, and the halo granules become "non-isothermal", "hotter" in the inner halo and "cooler" in the outer halo, as opposed to the isothermal halo in pure ψDM cosmological simulations. Moreover, the composite (star+ψDM) mass density is found to follow a r-2 isothermal profile near the half-light radius in most cases. Most striking is the velocity dispersion of halo stars that increases rapidly toward the galactic center by a factor of at least 2 inside the half-light radius caused by the deepened soliton gravitational potential, a result that compares favorably with observations of elliptical galaxies and bulges in spiral galaxies. However in some rare situations we find a phase segregation turning a compact distribution of stars into two distinct populations with high and very low velocity dispersions; while the high-velocity component mostly resides in the halo, the very low-velocity component is bound to the interior of the soliton core, resembling stars in faint dwarf spheroidal galaxies.

  18. Semiautomatic estimation of breast density with DM-Scan software.

    Science.gov (United States)

    Martínez Gómez, I; Casals El Busto, M; Antón Guirao, J; Ruiz Perales, F; Llobet Azpitarte, R

    2014-01-01

    To evaluate the reproducibility of the calculation of breast density with DM-Scan software, which is based on the semiautomatic segmentation of fibroglandular tissue, and to compare it with the reproducibility of estimation by visual inspection. The study included 655 direct digital mammograms acquired using craniocaudal projections. Three experienced radiologists analyzed the density of the mammograms using DM-Scan, and the inter- and intra-observer agreement between pairs of radiologists for the Boyd and BI-RADS® scales were calculated using the intraclass correlation coefficient. The Kappa index was used to compare the inter- and intra-observer agreements with those obtained previously for visual inspection in the same set of images. For visual inspection, the mean interobserver agreement was 0,876 (95% CI: 0,873-0,879) on the Boyd scale and 0,823 (95% CI: 0,818-0,829) on the BI-RADS® scale. The mean intraobserver agreement was 0,813 (95% CI: 0,796-0,829) on the Boyd scale and 0,770 (95% CI: 0,742-0,797) on the BI-RADS® scale. For DM-Scan, the mean inter- and intra-observer agreement was 0,92, considerably higher than the agreement for visual inspection. The semiautomatic calculation of breast density using DM-Scan software is more reliable and reproducible than visual estimation and reduces the subjectivity and variability in determining breast density. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  19. SEPALLATA1/2-suppressed mature apples have low ethylene, high auxin and reduced transcription of ripening-related genes

    Science.gov (United States)

    Schaffer, Robert J.; Ireland, Hilary S.; Ross, John J.; Ling, Toby J.; David, Karine M.

    2012-01-01

    Background and aims Fruit ripening is an important developmental trait in fleshy fruits, making the fruit palatable for seed dispersers. In some fruit species, there is a strong association between auxin concentrations and fruit ripening. We investigated the relationship between auxin concentrations and the onset of ethylene-related ripening in Malus × domestica (apples) at both the hormone and transcriptome levels. Methodology Transgenic apples suppressed for the SEPALLATA1/2 (SEP1/2) class of gene (MADS8/9) that showed severely reduced ripening were compared with untransformed control apples. In each apple type, free indole-3-acetic acid (IAA) concentrations were measured during early ripening. The changes observed in auxin were assessed in light of global changes in gene expression. Principal results It was found that mature MADS8/9-suppressed apples had a higher concentration of free IAA. This was associated with increased expression of the auxin biosynthetic genes in the indole-3-acetamide pathway. Additionally, in the MADS8/9-suppressed apples, there was less expression of the GH3 auxin-conjugating enzymes. A number of genes involved in the auxin-regulated transcription (AUX/IAA and ARF classes of genes) were also observed to change in expression, suggesting a mechanism for signal transduction at the start of ripening. Conclusions The delay in ripening observed in MADS8/9-suppressed apples may be partly due to high auxin concentrations. We propose that, to achieve low auxin associated with fruit maturation, the auxin homeostasis is controlled in a two-pronged manner: (i) by the reduction in biosynthesis and (ii) by an increase in auxin conjugation. This is associated with the change in expression of auxin-signalling genes and the up-regulation of ripening-related genes. PMID:23346344

  20. Dwarf Tiller1, a Wuschel-related homeobox transcription factor, is required for tiller growth in rice.

    Directory of Open Access Journals (Sweden)

    Wenfei Wang

    2014-03-01

    Full Text Available Unlike many wild grasses, domesticated rice cultivars have uniform culm height and panicle size among tillers and the main shoot, which is an important trait for grain yield. However, the genetic basis of this trait remains unknown. Here, we report that Dwarf Tiller1 (DWT1 controls the developmental uniformity of the main shoot and tillers in rice (Oryza sativa. Most dwt1 mutant plants develop main shoots with normal height and larger panicles, but dwarf tillers bearing smaller panicles compared with those of the wild type. In addition, dwt1 tillers have shorter internodes with fewer and un-elongated cells compared with the wild type, indicating that DWT1 affects cell division and cell elongation. Map-based cloning revealed that DWT1 encodes a Wuschel-related homeobox (WOX transcription factor homologous to the Arabidopsis WOX8 and WOX9. The DWT1 gene is highly expressed in young panicles, but undetectable in the internodes, suggesting that DWT1 expression is spatially or temporally separated from its effect on the internode growth. Transcriptomic analysis revealed altered expression of genes involved in cell division and cell elongation, cytokinin/gibberellin homeostasis and signaling in dwt1 shorter internodes. Moreover, the non-elongating internodes of dwt1 are insensitive to exogenous gibberellin (GA treatment, and some of the slender rice1 (slr1 dwt1 double mutant exhibits defective internodes similar to the dwt1 single mutant, suggesting that the DWT1 activity in the internode elongation is directly or indirectly associated with GA signaling. This study reveals a genetic pathway synchronizing the development of tillers and the main shoot, and a new function of WOX genes in balancing branch growth in rice.

  1. DWARF TILLER1, a WUSCHEL-Related Homeobox Transcription Factor, Is Required for Tiller Growth in Rice

    Science.gov (United States)

    Wang, Wenfei; Li, Gang; Zhao, Jun; Chu, Huangwei; Lin, Wenhui; Zhang, Dabing; Wang, Zhiyong; Liang, Wanqi

    2014-01-01

    Unlike many wild grasses, domesticated rice cultivars have uniform culm height and panicle size among tillers and the main shoot, which is an important trait for grain yield. However, the genetic basis of this trait remains unknown. Here, we report that DWARF TILLER1 (DWT1) controls the developmental uniformity of the main shoot and tillers in rice (Oryza sativa). Most dwt1 mutant plants develop main shoots with normal height and larger panicles, but dwarf tillers bearing smaller panicles compared with those of the wild type. In addition, dwt1 tillers have shorter internodes with fewer and un-elongated cells compared with the wild type, indicating that DWT1 affects cell division and cell elongation. Map-based cloning revealed that DWT1 encodes a WUSCHEL-related homeobox (WOX) transcription factor homologous to the Arabidopsis WOX8 and WOX9. The DWT1 gene is highly expressed in young panicles, but undetectable in the internodes, suggesting that DWT1 expression is spatially or temporally separated from its effect on the internode growth. Transcriptomic analysis revealed altered expression of genes involved in cell division and cell elongation, cytokinin/gibberellin homeostasis and signaling in dwt1 shorter internodes. Moreover, the non-elongating internodes of dwt1 are insensitive to exogenous gibberellin (GA) treatment, and some of the slender rice1 (slr1) dwt1 double mutant exhibits defective internodes similar to the dwt1 single mutant, suggesting that the DWT1 activity in the internode elongation is directly or indirectly associated with GA signaling. This study reveals a genetic pathway synchronizing the development of tillers and the main shoot, and a new function of WOX genes in balancing branch growth in rice. PMID:24625559

  2. G-actin sequestering protein thymosin-β4 regulates the activity of myocardin-related transcription factor

    International Nuclear Information System (INIS)

    Morita, Tsuyoshi; Hayashi, Ken’ichiro

    2013-01-01

    Highlights: •Tβ4 competed with MRTF-A for G-actin binding. •Tβ4 activated the MRTF–SRF signaling pathway. •Tβ4 increased the endogenous expression of SRF-dependent genes. -- Abstract: Myocardin-related transcription factors (MRTFs) are robust coactivators of serum response factor (SRF). MRTFs contain three copies of the RPEL motif at their N-terminus, and they bind to monomeric globular actin (G-actin). Previous studies illustrate that G-actin binding inhibits MRTF activity by preventing the MRTFs nuclear accumulation. In the living cells, the majority of G-actin is sequestered by G-actin binding proteins that prevent spontaneous actin polymerization. Here, we demonstrate that the most abundant G-actin sequestering protein thymosin-β4 (Tβ4) was involved in the regulation of subcellular localization and activity of MRTF-A. Tβ4 competed with MRTF-A for G-actin binding; thus, interfering with G-actin–MRTF-A complex formation. Tβ4 overexpression induced the MRTF-A nuclear accumulation and activation of MRTF–SRF signaling. The activation rate of MRTF-A by the Tβ4 mutant L17A, whose affinity for G-actin is very low, was lower than that by wild-type Tβ4. In contrast, the β-actin mutant 3DA, which has a lower affinity for Tβ4, more effectively suppressed MRTF-A activity than wild-type β-actin. Furthermore, ectopic Tβ4 increased the endogenous expression of SRF-dependent actin cytoskeletal genes. Thus, Tβ4 is an important MRTF regulator that controls the G-actin–MRTFs interaction

  3. G-actin sequestering protein thymosin-β4 regulates the activity of myocardin-related transcription factor

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Tsuyoshi, E-mail: tsuyo@nbiochem.med.osaka-u.ac.jp; Hayashi, Ken’ichiro

    2013-08-02

    Highlights: •Tβ4 competed with MRTF-A for G-actin binding. •Tβ4 activated the MRTF–SRF signaling pathway. •Tβ4 increased the endogenous expression of SRF-dependent genes. -- Abstract: Myocardin-related transcription factors (MRTFs) are robust coactivators of serum response factor (SRF). MRTFs contain three copies of the RPEL motif at their N-terminus, and they bind to monomeric globular actin (G-actin). Previous studies illustrate that G-actin binding inhibits MRTF activity by preventing the MRTFs nuclear accumulation. In the living cells, the majority of G-actin is sequestered by G-actin binding proteins that prevent spontaneous actin polymerization. Here, we demonstrate that the most abundant G-actin sequestering protein thymosin-β4 (Tβ4) was involved in the regulation of subcellular localization and activity of MRTF-A. Tβ4 competed with MRTF-A for G-actin binding; thus, interfering with G-actin–MRTF-A complex formation. Tβ4 overexpression induced the MRTF-A nuclear accumulation and activation of MRTF–SRF signaling. The activation rate of MRTF-A by the Tβ4 mutant L17A, whose affinity for G-actin is very low, was lower than that by wild-type Tβ4. In contrast, the β-actin mutant 3DA, which has a lower affinity for Tβ4, more effectively suppressed MRTF-A activity than wild-type β-actin. Furthermore, ectopic Tβ4 increased the endogenous expression of SRF-dependent actin cytoskeletal genes. Thus, Tβ4 is an important MRTF regulator that controls the G-actin–MRTFs interaction.

  4. Identifying Bank Frauds Using CRISP-DM and Decision Trees

    OpenAIRE

    Bruno Carneiro da Rocha; Rafael Timóteo de Sousa Júnior

    2010-01-01

    This article aims to evaluate the use of techniques of decision trees, in conjunction with the managementmodel CRISP-DM, to help in the prevention of bank fraud. This article offers a study on decision trees, animportant concept in the field of artificial intelligence. The study is focused on discussing how these treesare able to assist in the decision making process of identifying frauds by the analysis of informationregarding bank transactions. This information is captured with the use of t...

  5. [Construction of Corynebacterium crenatum AS 1.542 δ argR and analysis of transcriptional levels of the related genes of arginine biosynthetic pathway].

    Science.gov (United States)

    Chen, Xuelan; Tang, Li; Jiao, Haitao; Xu, Feng; Xiong, Yonghua

    2013-01-04

    ArgR, coded by the argR gene from Corynebacterium crenatum AS 1.542, acts as a negative regulator in arginine biosynthetic pathway. However, the effect of argR on transcriptional levels of the related biosynthetic genes has not been reported. Here, we constructed a deletion mutant of argR gene: C. crenatum AS 1.542 Delta argR using marker-less knockout technology, and compared the changes of transcriptional levels of the arginine biosynthetic genes between the mutant strain and the wild-type strain. We used marker-less knockout technology to construct C. crenatum AS 1.542 Delta argR and analyzed the changes of the relate genes at the transcriptional level using real-time fluorescence quantitative PCR. C. crenatum AS 1.542 Delta argR was successfully obtained and the transcriptional level of arginine biosynthetic genes in this mutant increased significantly with an average of about 162.1 folds. The arginine biosynthetic genes in C. crenatum are clearly controlled by the negative regulator ArgR. However, the deletion of this regulator does not result in a clear change in arginine production in the bacteria.

  6. Focal plane based wavefront sensing with random DM probes

    Science.gov (United States)

    Pluzhnik, Eugene; Sirbu, Dan; Belikov, Ruslan; Bendek, Eduardo; Dudinov, Vladimir N.

    2017-09-01

    An internal coronagraph with an adaptive optical system for wavefront control is being considered for direct imaging of exoplanets with upcoming space missions and concepts, including WFIRST, HabEx, LUVOIR, EXCEDE and ACESat. The main technical challenge associated with direct imaging of exoplanets is to control of both diffracted and scattered light from the star so that even a dim planetary companion can be imaged. For a deformable mirror (DM) to create a dark hole with 10-10 contrast in the image plane, wavefront errors must be accurately measured on the science focal plane detector to ensure a common optical path. We present here a method that uses a set of random phase probes applied to the DM to obtain a high accuracy wavefront estimate even for a dynamically changing optical system. The presented numerical simulations and experimental results show low noise sensitivity, high reliability, and robustness of the proposed approach. The method does not use any additional optics or complex calibration procedures and can be used during the calibration stage of any direct imaging mission. It can also be used in any optical experiment that uses a DM as an active optical element in the layout.

  7. Molecular Characterization of a Leaf Senescence-Related Transcription Factor BrWRKY75 of Chinese Flowering Cabbage

    Directory of Open Access Journals (Sweden)

    Xiaoli Tan

    2016-09-01

    Full Text Available WRKY is a plant-specific transcription factor (TF involved in the regulation of many biological processes; however, its role in leaf senescence of leafy vegetables remains unknown. In the present work, a WRKY TF, termed BrWRKY75 was isolated from Chinese flowering cabbage [Brassica rapa L. ssp. chinensis (L. Mokino var. utilis Tsen et Lee]. Analysis of deduced amino acid sequence and the phylogenetic tree showed that BrWRKY75 has high homology with WRKY75 from Brassica oleracea and Arabidopsis thaliana, and belongs to the II c sub-group. Sub-cellular localization and transcriptional activity analysis revealed that BrWRKY75 is a nuclear protein with transcriptional repression activity, and was up-regulated during leaf senescence. Electrophoretic mobility shift assay confirmed that BrWRKY75 directly bound to the W-box (TTGAC cis-element. Collectively, these results provide a basis for further investigation of the transcriptional regulation of Chinese flowering cabbage leaf senescence.

  8. Caenorhabditis elegans DAF-16/FOXO Transcription Factor and Its Mammalian Homologs Associate with Age-Related Disease

    NARCIS (Netherlands)

    Hesp, K.; Smant, G.; Kammenga, J.E.

    2015-01-01

    The insulin/IGF-1 signaling pathway is evolutionarily conserved and its function is mediated largely by FOXO transcription factors. Reduced insulin/IGF-1 signaling leads to translocation of FOXO proteins from the cytoplasm to the nucleus where they activate a set of genes that mediate oxidative

  9. Impact of nitrogen concentration on validamycin A production and related gene transcription in fermentation of Streptomyces hygroscopicus 5008.

    Science.gov (United States)

    Wei, Zhen-Hua; Bai, Linquan; Deng, Zixin; Zhong, Jian-Jiang

    2012-09-01

    Validamycin A (VAL-A) is an important and widely used agricultural antibiotic. In this study, statistical screening designs were applied to identify significant medium variables for VAL-A production and to find their optimal levels. The optimized medium caused 70% enhancement of VAL-A production. The difference between optimized medium and original medium suggested that low nitrogen source level might attribute to the enhancement of VAL-A production. The addition of different nitrogen sources to the optimized medium inhibited VAL-A production, which confirmed the importance of nitrogen concentration for VAL-A production. Furthermore, differences in structural gene transcription and enzyme activity between the two media were assayed. The results showed that lower nitrogen level in the optimized medium could regulate VAL-A production in gene transcriptional level. Our previous study indicated that the transcription of VAL-A structural genes could be enhanced at elevated temperature. In this work, the increased fermentation temperature from 37 to 42 °C with the optimized medium enhanced VAL-A production by 39%, which testified to the importance of structural gene transcription in VAL-A production. The information is useful for further VAL-A production enhancement.

  10. Relative gene transcription and pathogenicity of enterohemorrhagic Escherichia coli after long-term adaptation to acid and salt stress

    DEFF Research Database (Denmark)

    Olesen, Inger; Jespersen, Lene

    2010-01-01

    Relative gene transcription and virulence potential, as measured by a Caco-2 adhesion assay, were investigated for three enterohemorrhagic Escherichia coli (EHEC) strains after long-term adaptation for 24 h to acid (BHI pH 5.5) and salt (BHI 4.5% (w/v) NaCl) stress. Five virulence genes (eae, lpf...... compared to EDL933 (O157:H7, raw hamburger). Long-term adaptation to salt stress significantly increased the adhesion of all three EHEC strains to Caco-2 compared to the non-stressed controls. The present study shows that long-term adaptation to food related stress factors such as acid and salt is capable...... of changing the relative transcription of important virulence and stress response genes and increasing the virulence potential as measured by adhesion to the human colonic epithelial cell line, Caco-2....

  11. Brassinosteroids-Induced Systemic Stress Tolerance was Associated with Increased Transcripts of Several Defence-Related Genes in the Phloem in Cucumis sativus.

    Directory of Open Access Journals (Sweden)

    Pingfang Li

    Full Text Available Brassinosteroids (BRs, a group of naturally occurring plant steroidal compounds, are essential for plant growth, development and stress tolerance. Recent studies showed that BRs could induce systemic tolerance to biotic and abiotic stresses; however, the molecular mechanisms by which BRs signals lead to responses in the whole plant are largely unknown. In this study, 24-epibrassinosteroid (EBR-induced systemic tolerance in Cucumis sativus L. cv. Jinyan No. 4 was analyzed through the assessment of symptoms of photooxidative stress by chlorophyll fluorescence imaging pulse amplitude modulation. Expression of defense/stress related genes were induced in both treated local leaves and untreated systemic leaves by local EBR application. With the suppressive subtractive hybridization (SSH library using cDNA from the phloem sap of EBR-treated plants as the tester and distilled water (DW-treated plants as the driver, 14 transcripts out of 260 clones were identified. Quantitative Real Time-Polymerase Chain Reaction (RT-qPCR validated the specific up-regulation of these transcripts. Of the differentially expressed transcripts with known functions, transcripts for the selected four cDNAs, which encode an auxin-responsive protein (IAA14, a putative ankyrin-repeat protein, an F-box protein (PP2, and a major latex, pathogenesis-related (MLP-like protein, were induced in local leaves, systemic leaves and roots after foliar application of EBR onto mature leaves. Our results demonstrated that EBR-induced systemic tolerance is accompanied with increased transcript of genes in the defense response in other organs. The potential role of phloem mRNAs as signaling components in mediating BR-regulated systemic resistance is discussed.

  12. PENGARUH PENDIDIKAN KESEHATAN TENTANG DIET DM TERHADAP PENINGKATAN PENGETAHUAN KELUARGA PENDERITA DM DI KELURAHAN BANYURADEN KECAMATAN GAMPING

    Directory of Open Access Journals (Sweden)

    Edi Nurrohmad

    2015-04-01

    Full Text Available Background:The number of people with diabetes mellitus in the world in 2030 is expected to114%.Families can be a very influential factor in determining treatment program diabetes mellitus. Knowledge ofdiabetes mellitus family owned very necessary to improve the health status of the family, asa family shouldgive good attention and care to the family members of people with diabetes mellitus.Objective:To determine the effectivity of health education about diabetes mellitus dietary to improving ofknowledge in family with DM disease in the banyuraden district.Method:This research Design is Pre Experimental with pretest-posttest control group design. The Sampleswas choosen by purposive sampling technique, family with diabetes mellitus disease in Banyuraden,Gamping District of Sleman as much as 36 respondent. The research instrument was used questionnaireand it was analyzed byIndependent Sample t-test.Results: level of knowledge family with diabetes mellitus disease about diabetes mellitus dietary onintervention and control group before given health education mayoritas is 55.6% less. After 7 days the levelof knowledge intervention group became 66.7%, and control group is enough 72.2%. The results ofindependent sample t-test test between intervention and control group design shown that p-value = 0.000.Conclusion:There is an effectivity of health education about DM dietary to improving of knowledge in familywith DM disease in the banyuraden district gamping.

  13. Transcription factor IID in the Archaea: sequences in the Thermococcus celer genome would encode a product closely related to the TATA-binding protein of eukaryotes

    Science.gov (United States)

    Marsh, T. L.; Reich, C. I.; Whitelock, R. B.; Olsen, G. J.; Woese, C. R. (Principal Investigator)

    1994-01-01

    The first step in transcription initiation in eukaryotes is mediated by the TATA-binding protein, a subunit of the transcription factor IID complex. We have cloned and sequenced the gene for a presumptive homolog of this eukaryotic protein from Thermococcus celer, a member of the Archaea (formerly archaebacteria). The protein encoded by the archaeal gene is a tandem repeat of a conserved domain, corresponding to the repeated domain in its eukaryotic counterparts. Molecular phylogenetic analyses of the two halves of the repeat are consistent with the duplication occurring before the divergence of the archael and eukaryotic domains. In conjunction with previous observations of similarity in RNA polymerase subunit composition and sequences and the finding of a transcription factor IIB-like sequence in Pyrococcus woesei (a relative of T. celer) it appears that major features of the eukaryotic transcription apparatus were well-established before the origin of eukaryotic cellular organization. The divergence between the two halves of the archael protein is less than that between the halves of the individual eukaryotic sequences, indicating that the average rate of sequence change in the archael protein has been less than in its eukaryotic counterparts. To the extent that this lower rate applies to the genome as a whole, a clearer picture of the early genes (and gene families) that gave rise to present-day genomes is more apt to emerge from the study of sequences from the Archaea than from the corresponding sequences from eukaryotes.

  14. Pioglitazone improves the ability of learning and memory via activating ERK1/2 signaling pathway in the hippocampus of T2DM rats.

    Science.gov (United States)

    Gao, F; Zang, L; Wu, D Y; Li, Y J; Zhang, Q; Wang, H B; Tian, G L; Mu, Y M

    2017-06-09

    To explore the correlation between effect of PIO (pioglitazone, PIO) on learning as well as memory and ERK1/2 (extracellular signal regulated kinase 1/2, ERK1/2) pathway in T2DM (type 2 diabetes mellitus, T2DM) rats, further to elucidate the potential mechanism of PIO in improvement of learning and memory. 12-week-old male SD rats (number of 10 per group) were randomly divided into control group (CON), T2DM group (DM) and T2DM +PIO group (DM+PG). Rats in DM and DM+PG groups were given high fat diet for 20 weeks, then treated with Streptozotocin (27mg/kg) by intraperitoneal injection at 21week. After 72h, the FBG (fasting blood glucose, FBG) was greater than 7.0mmol/L can considered T2DM rats. DM+PG group was treated with PIO (10 mg·kg -1 ·d -1 ) by gavage daily. After Hyperinsulinemic-Euglycemic Clamp Study and Morris water maze test at 30-week, all of animals were sacrificed. The expressions of RKIP (Raf-1 kinase inhibitor protein, RKIP) and ERK1/2 in hippocampus were detected using Western Blot and real-time PCR. The FBG level: DM group (7.68±0.54mmol/L) was higher than CON group (5.35±0.63mmol/L) and DM+PG group (6.07±0.84mmol/L), the differences were considered statistically significant (P 0.05); The relative content of p-ERK1/2 protein in CON group and DM+PG group rats dorsal were higher than those in group DM, the difference was considered statistically significant (P0.05). Activation of ERK1/2 signal transduction pathway via reducing RKIP in the hippocampus may be one of the mechanisms of PIO to improve the learning and memory of the T2DM rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Physico-Mechanical Properties of Coprocessed Excipient MicroceLac® 100 by DM(3) Approach.

    Science.gov (United States)

    Haware, Rahul V; Kancharla, Joseph P; Udupa, Aishwarya K; Staton, Scott; Gupta, Mali R; Al-Achi, Antoine; Stagner, William C

    2015-11-01

    To determine the effect of relative humidity (RH) and hydroxypropyl methylcellulose (HPMC) on the physico-mechanical properties of coprocessed MacroceLac(®) 100 using 'DM(3)' approach. Effects of RH and 5% w/w HPMC on MacroceLac(®) 100 Compressibility Index (CI) and tablet mechanical strength (TMS) were evaluated by 'DM(3)'. The 'DM(3)' approach evaluates material properties by combining 'design of experiments', material's 'macroscopic' properties, 'molecular' properties, and 'multivariate analysis' tools. A 4X4 full-factorial experimental design was used to study the relationship of MacroceLac(®) 100 molecular properties (moisture content, dehydration, crystallization, fusion enthalpy, and moisture uptake) and macroscopic particle size and shape on CI and TMS. A physical binary mixture (PBM) of similar composition to MacroceLac(®) 100 was also evaluated. Multivariate analysis of variance (MANOVA), principle component analysis, and partial least squares (PLS) were used to analyze the data. MANOVA CI ranking was: PBM-HPMC > PBM > MicroceLac(®)100 > MicroceLac(®)100-HPMC (p TMS values were lower than MicroceLac(®)100 and MicroceLac(®)100-HPMC (p TMS. Significant MicroceLac(®)100 changes occurred with % RH exposure affecting performance attributes. HPMC physical addition did not prevent molecular or macroscopic matrix changes.

  16. Relative transcription of Listeria monocytogenes virulence genes in liver pâtés with varying NaCl content

    DEFF Research Database (Denmark)

    Olesen, Inger; Thorsen, Line; Jespersen, Lene

    2010-01-01

    three liver pâtés with reduced NaCl content of which one also has been supplied with organic acids (Ca-acetate and Ca-lactate). The three strains (EGD-e: reference strain; O57: more NaCl sensitive; 6896: more NaCl tolerant) were selected out of twelve strains based on their growth in BHI broth adjusted......B for both O57 and 6896 were significantly higher when the strains were grown in BHI compared to the standard liver pâté. Reducing the NaCl content of the standard liver pâté did not change relative transcription levels of prfA, inlA, sigB or clpC (except for prfA in O57 and sigB in 6896). However......, the presence of Ca-acetate and Ca-lactate induced relative transcription of the stress response gene, clpC, for all three strains. This study demonstrates that relative microbial gene transcription can be measured in complex food matrices and points to the need for designing experimental set-ups in real food...

  17. The ubiquitin ligase SEVEN IN ABSENTIA (SINA) ubiquitinates a defense-related NAC transcription factor and is involved in defense signaling.

    Science.gov (United States)

    Miao, Min; Niu, Xiangli; Kud, Joanna; Du, Xinran; Avila, Julian; Devarenne, Timothy P; Kuhl, Joseph C; Liu, Yongsheng; Xiao, Fangming

    2016-07-01

    We recently identified a defense-related tomato (Solanum lycopersicum) NAC (NAM, ATAF1,2, CUC2) transcription factor, NAC1, that is subjected to ubiquitin-proteasome system-dependent degradation in plant cells. In this study, we identified a tomato ubiquitin ligase (termed SEVEN IN ABSENTIA3; SINA3) that ubiquitinates NAC1, promoting its degradation. We conducted coimmunoprecipitation and bimolecular fluorescence complementation to determine that SINA3 specifically interacts with the NAC1 transcription factor in the nucleus. Moreover, we found that SINA3 ubiquitinates NAC1 in vitro and promotes NAC1 degradation via polyubiquitination in vivo, indicating that SINA3 is a ubiquitin ligase that ubiquitinates NAC1, promoting its degradation. Our real-time PCR analysis indicated that, in contrast to our previous finding that NAC1 mRNA abundance increases upon Pseudomonas infection, the SINA3 mRNA abundance decreases in response to Pseudomonas infection. Moreover, using Agrobacterium-mediated transient expression, we found that overexpression of SINA3 interferes with the hypersensitive response cell death triggered by multiple plant resistance proteins. These results suggest that SINA3 ubiquitinates a defense-related NAC transcription factor for degradation and plays a negative role in defense signaling. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  18. Decline in Proliferation and Immature Neuron Markers in the Human Subependymal Zone during Aging: Relationship to EGF- and FGF-related Transcripts

    Directory of Open Access Journals (Sweden)

    Christin Weissleder

    2016-11-01

    Full Text Available Neuroblasts exist within the human subependymal zone (SEZ; however, it is debated to what extent neurogenesis changes during normal aging. It is also unknown how precursor proliferation may correlate with the generation of neuronal and glial cells or how expression of growth factors and receptors may change throughout the adult lifespan. We provided evidence of dividing cells in the human SEZ in conjunction with a dramatic age-related decline (n=50; 21-103 years of mRNAs indicative of proliferating cells (Ki67 and immature neurons (doublecortin. Microglia mRNA (ionized calcium-binding adapter molecule 1 increased during aging, whereas transcript levels of stem/precursor cells (glial fibrillary acidic protein delta and achaete-scute homolog 1, astrocytes (vimentin and glial fibrillary acidic protein and oligodendrocytes (oligodendrocyte lineage transcription factor 2 remained stable. Epidermal growth factor receptor (EGFR and fibroblast growth factor 2 (FGF2 mRNAs increased throughout adulthood, while transforming growth factor alpha (TGFα, EGF, Erb-B2 receptor tyrosine kinase 4 (ErbB4 and FGF receptor 1 (FGFR1 mRNAs were unchanged across adulthood. Cell proliferation mRNA positively correlated with FGFR1 transcripts. Immature neuron and oligodendrocyte expression positively correlated with TGFα and ErbB4 mRNAs, whilst astrocyte transcripts positively correlated with EGF, FGF2 and FGFR1 mRNAs. Microglia mRNA positively correlated with EGF and FGF2 expression. Our findings indicate that neurogenesis in the human SEZ continues well into adulthood, although proliferation and neuronal differentiation may decline across adulthood. We suggest that mRNA expression of EGF- and FGF-related family members do not become limited during aging and may modulate neuronal and glial fate determination in the SEZ throughout human life.

  19. Relation of Transcriptional Factors to the Expression and Activity of Cytochrome P450 and UDP-Glucuronosyltransferases 1A in Human Liver: Co-Expression Network Analysis.

    Science.gov (United States)

    Zhong, Shilong; Han, Weichao; Hou, Chuqi; Liu, Junjin; Wu, Lili; Liu, Menghua; Liang, Zhi; Lin, Haoming; Zhou, Lili; Liu, Shuwen; Tang, Lan

    2017-01-01

    Cytochrome P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) play important roles in the metabolism of exogenous and endogenous compounds. The gene transcription of CYPs and UGTs can be enhanced or reduced by transcription factors (TFs). This study aims to explore novel TFs involved in the regulatory network of human hepatic UGTs/CYPs. Correlations between the transcription levels of 683 key TFs and CYPs/UGTs in three different human liver expression profiles (n = 640) were calculated first. Supervised weighted correlation network analysis (sWGCNA) was employed to define hub genes among the selected TFs. The relationship among 17 defined TFs, CYPs/UGTs expression, and activity were evaluated in 30 liver samples from Chinese patients. The positive controls (e.g., PPARA, NR1I2, NR1I3) and hub TFs (NFIA, NR3C2, and AR) in the Grey sWGCNA Module were significantly and positively associated with CYPs/UGTs expression. And the cancer- or inflammation-related TFs (TEAD4, NFKB2, and NFKB1) were negatively associated with mRNA expression of CYP2C9/CYP2E1/UGT1A9. Furthermore, the effect of NR1I2, NR1I3, AR, TEAD4, and NFKB2 on CYP450/UGT1A gene transcription translated into moderate influences on enzyme activities. To our knowledge, this is the first study to integrate Gene Expression Omnibus (GEO) datasets and supervised weighted correlation network analysis (sWGCNA) for defining TFs potentially related to CYPs/UGTs. We detected several novel TFs involved in the regulatory network of hepatic CYPs and UGTs in humans. Further validation and investigation may reveal their exact mechanism of CYPs/UGTs regulation.

  20. [Determination of fat, protein and DM in raw milk by portable short-wave near infrared spectrometer].

    Science.gov (United States)

    Li, Xiao-yun; Wang, Jia-hua; Huang, Ya-wei; Han, Dong-hai

    2011-03-01

    Near infrared diffuse reflectance spectroscopy calibrations of fat, protein and DM in raw milk were studied with partial least-squares (PLS) regression using portable short-wave near infrared spectrometer. The results indicated that good calibrations of fat and DM were found, the correlation coefficients were all 0.98, the RMSEC were 0.187 and 0.217, RMSEP were 0.187 and 0.296, the RPDs were 5.02 and 3.20 respectively; the calibration of protein needed to be improved but can be used for practice, the correlation coefficient was 0.95, RMSEC was 0.105, RMSEP was 0.120, and RPD was 2.60. Furthermore, the measuring accuracy was improved by analyzing the correction relation of fat and DM in raw milk This study will probably provide a new on-site method for nondestructive and rapid measurement of milk.

  1. Influence of ring size on the cognition-enhancing activity of DM235 and MN19, two potent nootropic drugs.

    Science.gov (United States)

    Guandalini, L; Martini, E; Di Cesare Mannelli, L; Dei, S; Manetti, D; Scapecchi, S; Teodori, E; Ghelardini, C; Romanelli, M N

    2012-03-01

    A series of analogs of DM235 and MN19, characterized by rings with different size, have been prepared and evaluated for their nootropic activity in the mouse passive-avoidance test. It was found that the optimal ring size for the analogs of DM235, showing endocyclic both amidic groups, is 6 or 7 atoms. For the compounds structurally related to MN19, carrying an exocyclic amide group, the piperidine ring is the moiety which gives the most interesting compounds. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Dataset on differential gene expression analysis for splenic transcriptome profiling and the transcripts related to six immune pathways in grass carp

    Directory of Open Access Journals (Sweden)

    Guoxi Li

    2017-02-01

    Full Text Available The data presented in this paper are related to the research article entitled “Transcriptome profiling of developing spleen tissue and discovery of immune-related genes in grass carp (Ctenopharyngodon idella” (Li et al. 2016 [1]. Please refer to this article for interpretation of the data. Data provided in this submission are comprised of the expression levels of unigenes, significantly differentially expressed genes(DEGs, significant enrichment GO term and KEGG pathway of DEGs, and information of the transcripts assigned to six immune pathways.

  3. The Eucalyptus grandis R2R3-MYB transcription factor family: evidence for woody growth-related evolution and function.

    Science.gov (United States)

    Soler, Marçal; Camargo, Eduardo Leal Oliveira; Carocha, Victor; Cassan-Wang, Hua; San Clemente, Hélène; Savelli, Bruno; Hefer, Charles A; Paiva, Jorge A Pinto; Myburg, Alexander A; Grima-Pettenati, Jacqueline

    2015-06-01

    The R2R3-MYB family, one of the largest transcription factor families in higher plants, controls a wide variety of plant-specific processes including, notably, phenylpropanoid metabolism and secondary cell wall formation. We performed a genome-wide analysis of this superfamily in Eucalyptus, one of the most planted hardwood trees world-wide. A total of 141 predicted R2R3-MYB sequences identified in the Eucalyptus grandis genome sequence were subjected to comparative phylogenetic analyses with Arabidopsis thaliana, Oryza sativa, Populus trichocarpa and Vitis vinifera. We analysed features such as gene structure, conserved motifs and genome location. Transcript abundance patterns were assessed by RNAseq and validated by high-throughput quantitative PCR. We found some R2R3-MYB subgroups with expanded membership in E. grandis, V. vinifera and P. trichocarpa, and others preferentially found in woody species, suggesting diversification of specific functions in woody plants. By contrast, subgroups containing key genes regulating lignin biosynthesis and secondary cell wall formation are more conserved across all of the species analysed. In Eucalyptus, R2R3-MYB tandem gene duplications seem to disproportionately affect woody-preferential and woody-expanded subgroups. Interestingly, some of the genes belonging to woody-preferential subgroups show higher expression in the cambial region, suggesting a putative role in the regulation of secondary growth. © 2014 The Authors New Phytologist © 2014 New Phytologist Trust.

  4. Effects of HIF-1 inhibition by chetomin on hypoxia-related transcription and radiosensitivity in HT 1080 human fibrosarcoma cells

    International Nuclear Information System (INIS)

    Staab, Adrian; Einsele, Hermann; Flentje, Michael; Vordermark, Dirk; Loeffler, Jürgen; Said, Harun M; Diehlmann, Désirée; Katzer, Astrid; Beyer, Melanie; Fleischer, Markus; Schwab, Franz; Baier, Kurt

    2007-01-01

    Hypoxia-inducible factor-1 (HIF-1) overexpression has been linked to tumor progression and poor prognosis. We investigated whether targeting of HIF-1 using chetomin, a disrupter of the interaction of HIF-1 with the transcriptional coactivator p300, influences the radiosensitivity of hypoxic HT 1080 human fibrosarcoma cells. Optimal dose of chetomin was determined by EGFP-HRE gene reporter assay in stably transfected HT 1080 cells. Cells were assayed for expression of the hypoxia-inducible genes carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) by RT-PCR and for clonogenic survival after irradiation with 2, 5 or 10 Gy, under normoxic or hypoxic (0.1% O 2 , 12 h) conditions in the presence or absence of chetomin (150 nM, 12 h, pre-treatment of 4 h). Chetomin treatment significantly reduced CA9 and VEGF mRNA expression in hypoxic cells to 44.4 ± 7.2% and 39.6 ± 16.0%, respectively, of untreated hypoxic controls. Chetomin clearly reduced the modified oxygen enhancement ratio (OER') compared to untreated cells, from 2.02 to 1.27, from 1.86 to 1.22 and from 1.49 to 1.06 at the 50%, 37% and 10% clonogenic survival levels, respectively. HIF-1 inhibition by chetomin effectively reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro

  5. Feast/famine regulatory proteins (FFRPs): Escherichia coli Lrp, AsnC and related archaeal transcription factors.

    Science.gov (United States)

    Yokoyama, Katsushi; Ishijima, Sanae A; Clowney, Lester; Koike, Hideaki; Aramaki, Hironori; Tanaka, Chikako; Makino, Kozo; Suzuki, Masashi

    2006-01-01

    Feast/famine regulatory proteins comprise a diverse family of transcription factors, which have been referred to in various individual identifications, including Escherichia coli leucine-responsive regulatory protein and asparagine synthase C gene product. A full length feast/famine regulatory protein consists of the N-terminal DNA-binding domain and the C-domain, which is involved in dimerization and further assembly, thereby producing, for example, a disc or a chromatin-like cylinder. Various ligands of the size of amino acids bind at the interface between feast/famine regulatory protein dimers, thereby altering their assembly forms. Also, the combination of feast/famine regulatory protein subunits forming the same assembly is altered. In this way, a small number of feast/famine regulatory proteins are able to regulate a large number of genes in response to various environmental changes. Because feast/famine regulatory proteins are shared by archaea and eubacteria, the genome-wide regulation by feast/famine regulatory proteins is traceable back to their common ancestor, being the prototype of highly differentiated transcription regulatory mechanisms found in organisms nowadays.

  6. Transcriptional regulation by competing transcription factor modules.

    Directory of Open Access Journals (Sweden)

    Rutger Hermsen

    2006-12-01

    Full Text Available Gene regulatory networks lie at the heart of cellular computation. In these networks, intracellular and extracellular signals are integrated by transcription factors, which control the expression of transcription units by binding to cis-regulatory regions on the DNA. The designs of both eukaryotic and prokaryotic cis-regulatory regions are usually highly complex. They frequently consist of both repetitive and overlapping transcription factor binding sites. To unravel the design principles of these promoter architectures, we have designed in silico prokaryotic transcriptional logic gates with predefined input-output relations using an evolutionary algorithm. The resulting cis-regulatory designs are often composed of modules that consist of tandem arrays of binding sites to which the transcription factors bind cooperatively. Moreover, these modules often overlap with each other, leading to competition between them. Our analysis thus identifies a new signal integration motif that is based upon the interplay between intramodular cooperativity and intermodular competition. We show that this signal integration mechanism drastically enhances the capacity of cis-regulatory domains to integrate signals. Our results provide a possible explanation for the complexity of promoter architectures and could be used for the rational design of synthetic gene circuits.

  7. Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver

    Energy Technology Data Exchange (ETDEWEB)

    Liu Yang [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100080 (China); Wang Jianshe; Wei Yanhong; Zhang Hongxia; Xu Muqi [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China); Dai Jiayin [Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Beijing 100101 (China)], E-mail: daijy@ioz.ac.cn

    2008-09-29

    The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80 {mu}g PFDoA/g body weight) and were then sacrificed 48 h, 96 h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48 h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48 h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48 h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48 h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48 h or 96 h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor {alpha} (PPAR{alpha}), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6

  8. Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver

    International Nuclear Information System (INIS)

    Liu Yang; Wang Jianshe; Wei Yanhong; Zhang Hongxia; Xu Muqi; Dai Jiayin

    2008-01-01

    The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80 μg PFDoA/g body weight) and were then sacrificed 48 h, 96 h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48 h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48 h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48 h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48 h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48 h or 96 h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor α (PPARα), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6 (ATPo6). These

  9. The NAD-Dependent Deacetylase Sirtuin-1 Regulates the Expression of Osteogenic Transcriptional Activator Runt-Related Transcription Factor 2 (Runx2 and Production of Matrix Metalloproteinase (MMP-13 in Chondrocytes in Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Koh Terauchi

    2016-06-01

    Full Text Available Aging is one of the major pathologic factors associated with osteoarthritis (OA. Recently, numerous reports have demonstrated the impact of sirtuin-1 (Sirt1, which is the NAD-dependent deacetylase, on human aging. It has been demonstrated that Sirt1 induces osteogenic and chondrogenic differentiation of mesenchymal stem cells. However, the role of Sirt1 in the OA chondrocytes still remains unknown. We postulated that Sirt1 regulates a hypertrophic chondrocyte lineage and degeneration of articular cartilage through the activation of osteogenic transcriptional activator Runx2 and matrix metalloproteinase (MMP-13 in OA chondrocytes. To verify whether sirtuin-1 (Sirt1 regulates chondrocyte activity in OA, we studied expressions of Sirt1, Runx2 and production of MMP-13, and their associations in human OA chondrocytes. The expression of Sirt1 was ubiquitously observed in osteoarthritic chondrocytes; in contrast, Runx2 expressed in the osteophyte region in patients with OA and OA model mice. OA relating catabolic factor IL-1βincreased the expression of Runx2 in OA chondrocytes. OA chondrocytes, which were pretreated with Sirt1 inhibitor, inhibited the IL-1β-induced expression of Runx2 compared to the control. Since the Runx2 is a promotor of MMP-13 expression, Sirt1 inactivation may inhibit the Runx2 expression and the resultant down-regulation of MMP-13 production in chondrocytes. Our findings suggest thatSirt1 may regulate the expression of Runx2, which is the osteogenic transcription factor, and the production of MMP-13 from chondrocytes in OA. Since Sirt1 activity is known to be affected by several stresses, including inflammation and oxidative stress, as well as aging, SIRT may be involved in the development of OA.

  10. Tumor protein D52 expression is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein via mRNA stability.

    Science.gov (United States)

    Motohashi, Hiromi; Mukudai, Yoshiki; Ito, Chihiro; Kato, Kosuke; Shimane, Toshikazu; Kondo, Seiji; Shirota, Tatsuo

    2017-05-04

    Although tumor protein D52 (TPD52) family proteins were first identified nearly 20 years ago, their molecular regulatory mechanisms remain unclear. Therefore, we investigated the post-transcriptional regulation of TPD52 family genes. An RNA immunoprecipitation (RIP) assay showed the potential binding ability of TPD52 family mRNAs to several RNA-binding proteins, and an RNA degradation assay revealed that TPD52 is subject to more prominent post-transcriptional regulation than are TPD53 and TPD54. We subsequently focused on the 3'-untranslated region (3'-UTR) of TPD52 as a cis -acting element in post-transcriptional gene regulation. Several deletion mutants of the 3'-UTR of TPD52 mRNA were constructed and ligated to the 3'-end of a reporter green fluorescence protein gene. An RNA degradation assay revealed that a minimal cis -acting region, located in the 78-280 region of the 5'-proximal region of the 3'-UTR, stabilized the reporter mRNA. Biotin pull-down and RIP assays revealed specific binding of the region to T-cell intracellular antigen 1 (TIA-1) and TIA-1-related protein (TIAR). Knockdown of TIA-1/TIAR decreased not only the expression, but also the stability of TPD52 mRNA; it also decreased the expression and stability of the reporter gene ligated to the 3'-end of the 78-280 fragment. Stimulation of transforming growth factor-β and epidermal growth factor decreased the binding ability of these factors, resulting in decreased mRNA stability. These results indicate that the 78-280 fragment and TIA-1/TIAR concordantly contribute to mRNA stability as a cis -acting element and trans -acting factor(s), respectively. Thus, we here report the specific interactions between these elements in the post-transcriptional regulation of the TPD52 gene. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  11. Method of Multiobject Detecting and Tracking Based on DM643

    Directory of Open Access Journals (Sweden)

    Yitao Liang

    2014-01-01

    Full Text Available The technology of moving objects detection has become an important research subject for its extensive application prospect. In this paper, it is presented that interframe difference algorithm and background difference algorithm are combined to update the background. The algorithm can deal with the flaw of background difference algorithm. The mathematical morphology method is employed to denoise the image, which may be helpful to improve the accuracy of the detection. The Pyramid algorithm is used to compress each frame data of video sequence. Then, the detecting and tracking of moving objects are tested on the hardware platform (DM643 and the software frame (RF5. The running speed is about 3 times faster than before. The result shows that the accuracy demanded by the detection is met. This method can provide a useful reference for similar application.

  12. Venom-related transcripts from Bothrops jararaca tissues provide novel molecular insights into the production and evolution of snake venom.

    Science.gov (United States)

    Junqueira-de-Azevedo, Inácio L M; Bastos, Carolina Mancini Val; Ho, Paulo Lee; Luna, Milene Schmidt; Yamanouye, Norma; Casewell, Nicholas R

    2015-03-01

    Attempts to reconstruct the evolutionary history of snake toxins in the context of their co-option to the venom gland rarely account for nonvenom snake genes that are paralogous to toxins, and which therefore represent important connectors to ancestral genes. In order to reevaluate this process, we conducted a comparative transcriptomic survey on body tissues from a venomous snake. A nonredundant set of 33,000 unigenes (assembled transcripts of reference genes) was independently assembled from six organs of the medically important viperid snake Bothrops jararaca, providing a reference list of 82 full-length toxins from the venom gland and specific products from other tissues, such as pancreatic digestive enzymes. Unigenes were then screened for nontoxin transcripts paralogous to toxins revealing 1) low level coexpression of approximately 20% of toxin genes (e.g., bradykinin-potentiating peptide, C-type lectin, snake venom metalloproteinase, snake venom nerve growth factor) in body tissues, 2) the identity of the closest paralogs to toxin genes in eight classes of toxins, 3) the location and level of paralog expression, indicating that, in general, co-expression occurs in a higher number of tissues and at lower levels than observed for toxin genes, and 4) strong evidence of a toxin gene reverting back to selective expression in a body tissue. In addition, our differential gene expression analyses identify specific cellular processes that make the venom gland a highly specialized secretory tissue. Our results demonstrate that the evolution and production of venom in snakes is a complex process that can only be understood in the context of comparative data from other snake tissues, including the identification of genes paralogous to venom toxins. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  13. Biochemical and molecular study on interleukin-1β gene expression and relation of single nucleotide polymorphism in promoter region with Type 2 diabetes mellitus.

    Science.gov (United States)

    Tayel, Safaa I; Fouda, Eman A M; Elshayeb, Elsayed I; Eldakamawy, Asmaa R A; El-Kousy, Salah M

    2018-01-11

    Interleukin-1β (IL-1β) assumes a centric role in the regulation of immune and inflammatory responses and thus has been recognized in immune mediated diseases like type 2 diabetes mellitus (T2DM). We aimed to investigate expressed level of IL-1β and its relation with IL-1β -511T>C polymorphism in T2DM patients. This study enrolled 80 subjects (50 patients with T2DM and 30 healthy control subjects). Laboratory investigations included fasting (FBG) and 2 h postprandial blood sugar (2 h PBG), HBA1c, lipid profile, and renal function tests. Genotyping of IL-1β -511T>C (rs16944) SNP assay by real-time PCR and relative quantitation of IL-1β gene expression transcript by real-time PCR. T2DM patients had significantly higher FBG and 2 h PBG, HBA1c, LDLc, TC, TG, systolic, and diastolic BP while lower HDLc compared with control group. IL 1- β -511 T>C, CC genotype and C allele were significantly associated with risk of T2DM with odds ratio (OR) 4.73, 95%CI (1.21-18.39) and OR 2.27, 95%CI (1.72-4.40), respectively. Moreover, diabetic patients had significantly higher IL 1- β gene transcript compared with control group (P  C had the highest significant level of IL 1- β gene transcript demonstrated compared with C/T and T/T genotypes (P C could be considered risk factor contributor to T2DM and excess level of IL-1 β transcript may disclose to some degree the inflammatory role of cytokines in T2DM. © 2018 Wiley Periodicals, Inc.

  14. Imaging HER2 in response to T-DM1 therapy in breast cancer xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana Vidal; Aweda, Tolulope; Marqueznostra, Bernadette; El Sayed, Reeta; Beacham, Rebecca; Lapi, Suzanne [University Of Alabama, Birmingham, AL (United States)

    2017-07-01

    Full text: Introduction: Monoclonal antibodies (mAbs) have become broadly used for the treatment of cancer because they can be engineered to bind specifically to the target and therefore typically have less toxicity compared to broad spectrum chemotherapies (Jauw YWS, Menke-van der Houven van Oordt CW, Hoekstra OS, et al. Front Pharmacol 2016, 7:1-15). Ado-trastuzumab emtansine (TDM1) is a newly approved HER2 targeted therapy which consists of a cytotoxic agent (DM1) linked to trastuzumab and has shown promising results in patients with HER2 positive metastatic breast cancer (Barok MT, Köninki M, Isola K et al. Breast Cancer Res 2011, 13:1465-5411). Although {sup 18}F-FDG is considered the gold standard in the diagnosis and staging of various types of cancer, it is a relatively non-specific marker (Janjigian YY, Viola-Villegas N, Holland JP, Divilov V, Carlin SD et al. J Nucl Med 2013;54:936-43). Alternatively, {sup 89}Zr-Pertuzumab which binds to a different epitope than trastuzumab on the HER2 receptor has shown high selectively in imaging variations in HER2 expression in breast cancer xenograft models (Marquez BV, Ikotun OF, Zheleznyak A, Wright B et al. Mol Pharm 2014;11:3988-95). Therefore, in this work, we investigated the specificity of {sup 89}Zr-Pertuzumab compared to {sup 18}F-FDG to identify early response to ado-trastuzumab emtansine (T-DM1) in a breast cancer xenograft model. Methods: Pertuzumab was conjugated top-NCS-Bz-DFO at varying molar ratios and labeled with {sup 89}Zr in different conditions. The optimal conditions were used in further in vitro and in vivo studies. In vivo PET imaging was conducted in nude female mice implanted with 17β-estradiol pellets and inoculated with 1 x 107 BT-474 HER2 positive breast cancer cells. In order to acquire baseline images, mice were injected via tail-vein with 200 μCi of 18F-FDG and imaged after 1 hour. The following day, they were injected with 100 μCi of {sup 89}Zr-Pertuzumab (20 μCi/μg) imaged 5

  15. Expression of SRY-related HMG Box Transcription Factors (Sox) 2 and 9 in Craniopharyngioma Subtypes and Surrounding Brain Tissue.

    Science.gov (United States)

    Thimsen, Vivian; John, Nora; Buchfelder, Michael; Flitsch, Jörg; Fahlbusch, Rudolf; Stefanits, Harald; Knosp, Engelbert; Losa, Marco; Buslei, Rolf; Hölsken, Annett

    2017-11-20

    Stem cells have been discovered as key players in the genesis of different neoplasms including craniopharyngioma (CP), a rare tumour entity in the sellar region. Sox2 and Sox9 are well-known stem cell markers involved in pituitary development. In this study we analysed the expression of both transcription factors using immunohistochemistry in a large cohort of 64 adamantinomatous (aCP) and 9 papillary CP (pCP) and quantitative PCR in 26 aCP and 7 pCP. Whereas immunohistochemically Sox2+ cells were verifiable in only five aCP (7.8%) and in 39.1% of the respective surrounding cerebral tissue, pCP specimens appeared always negative. In contrast, Sox9 was detectable in all tumours with a significantly higher expression in aCP compared to pCP (protein, p < 0.0001; mRNA p = 0.0484) This was also true for the respective tumour adjacent CNS where 63 aCP (98.4%) and six pCP (66.7%) showed Sox9+ cells. We further confirmed absence of Sox9 expression in nuclear β-catenin accumulating cells of aCP. Our results point to the conclusion that Sox2 and Sox9, seem to play essential roles not only in the specific formation of aCP, but also in processes involving the cerebral tumour environment, which needs to be illuminated in the future.

  16. Hopanoid-free Methylobacterium extorquens DM4 overproduces carotenoids and has widespread growth impairment.

    Directory of Open Access Journals (Sweden)

    Alexander S Bradley

    Full Text Available Hopanoids are sterol-like membrane lipids widely used as geochemical proxies for bacteria. Currently, the physiological role of hopanoids is not well understood, and this represents one of the major limitations in interpreting the significance of their presence in ancient or contemporary sediments. Previous analyses of mutants lacking hopanoids in a range of bacteria have revealed a range of phenotypes under normal growth conditions, but with most having at least an increased sensitivity to toxins and osmotic stress. We employed hopanoid-free strains of Methylobacterium extorquens DM4, uncovering severe growth defects relative to the wild-type under many tested conditions, including normal growth conditions without additional stressors. Mutants overproduce carotenoids-the other major isoprenoid product of this strain-and show an altered fatty acid profile, pronounced flocculation in liquid media, and lower growth yields than for the wild-type strain. The flocculation phenotype can be mitigated by addition of cellulase to the medium, suggesting a link between the function of hopanoids and the secretion of cellulose in M. extorquens DM4. On solid media, colonies of the hopanoid-free mutant strain were smaller than wild-type, and were more sensitive to osmotic or pH stress, as well as to a variety of toxins. The results for M. extorquens DM4 are consistent with the hypothesis that hopanoids are important for membrane fluidity and lipid packing, but also indicate that the specific physiological processes that require hopanoids vary across bacterial lineages. Our work provides further support to emerging observations that the role of hopanoids in membrane robustness and barrier function may be important across lineages, possibly mediated through an interaction with lipid A in the outer membrane.

  17. Aberrant brain regional homogeneity and functional connectivity in middle-aged T2DM patients: a resting-state functional MRI study

    Directory of Open Access Journals (Sweden)

    Daihong Liu

    2016-09-01

    Full Text Available Type 2 diabetes mellitus (T2DM has been associated with cognitive impairment. However, its neurological mechanism remains elusive. Combining regional homogeneity (ReHo and functional connectivity (FC analyses, the present study aimed to investigate brain functional alterations in middle-aged T2DM patients, which could provide complementary information for the neural substrates underlying T2DM-associated brain dysfunction. Twenty-five T2DM patients and 25 healthy controls were involved in neuropsychological testing and structural and resting-state functional magnetic resonance imaging data acquisition. ReHo analysis was conducted to determine the peak coordinates of brain regions with abnormal local brain activity synchronization. Then, the identified brain regions were considered as seeds, and FC between these brain regions and global voxels was computed. Finally, the potential correlations between the imaging indices and neuropsychological data were also explored. Compared with healthy controls, T2DM patients exhibited higher ReHo values in the anterior cingulate gyrus and lower ReHo in right fusiform gyrus, right precentral gyrus and right medial orbit of the superior frontal gyrus. Considering these areas as seed regions, T2DM patients displayed aberrant FC, mainly in the frontal and parietal lobes. The pattern of FC alterations in T2DM patients was characterized by decreased connectivity and positive to negative or negative to positive converted connectivity. Digital Span Test forward scores revealed significant correlations with the ReHo values of the right precentral gyrus (ρ = 0.527, p = 0.014 and FC between the right fusiform gyrus and middle temporal gyrus (ρ = -0.437, p = 0.048. Our findings suggest that T2DM patients suffer from cognitive dysfunction related to spatially local and remote brain activity synchronization impairment. The patterns of ReHo and FC alterations shed light on the mechanisms underlying T2DM-associated brain

  18. Transcript levels of ten caste-related genes in adult diploid males of Melipona quadrifasciata (Hymenoptera, Apidae: a comparison with haploid males, queens and workers

    Directory of Open Access Journals (Sweden)

    Andreia A. Borges

    2011-01-01

    Full Text Available In Hymenoptera, homozygosity at the sex locus results in the production of diploid males. In social species, these pose a double burden by having low fitness and drawing resources normally spent for increasing the work force of a colony. Yet, diploid males are of academic interest as they can elucidate effects of ploidy (normal males are haploid, whereas the female castes, the queens and workers, are diploid on morphology and life history. Herein we investigated expression levels of ten caste-related genes in the stingless bee Melipona quadrifasciata, comparing newly emerged and 5-day-old diploid males with haploid males, queens and workers. In diploid males, transcript levels for dunce and paramyosin were increased during the first five days of adult life, while those for diacylglycerol kinase and the transcriptional co-repressor groucho diminished. Two general trends were apparent, (i gene expression patterns in diploid males were overall more similar to haploid ones and workers than to queens, and (ii in queens and workers, more genes were up-regulated after emergence until day five, whereas in diploid and especially so in haploid males more genes were down-regulated. This difference between the sexes may be related to longevity, which is much longer in females than in males.

  19. Transcript levels of ten caste-related genes in adult diploid males of Melipona quadrifasciata (Hymenoptera, Apidae) - A comparison with haploid males, queens and workers.

    Science.gov (United States)

    Borges, Andreia A; Humann, Fernanda C; Oliveira Campos, Lucio A; Tavares, Mara G; Hartfelder, Klaus

    2011-10-01

    In Hymenoptera, homozygosity at the sex locus results in the production of diploid males. In social species, these pose a double burden by having low fitness and drawing resources normally spent for increasing the work force of a colony. Yet, diploid males are of academic interest as they can elucidate effects of ploidy (normal males are haploid, whereas the female castes, the queens and workers, are diploid) on morphology and life history. Herein we investigated expression levels of ten caste-related genes in the stingless bee Melipona quadrifasciata, comparing newly emerged and 5-day-old diploid males with haploid males, queens and workers. In diploid males, transcript levels for dunce and paramyosin were increased during the first five days of adult life, while those for diacylglycerol kinase and the transcriptional co-repressor groucho diminished. Two general trends were apparent, (i) gene expression patterns in diploid males were overall more similar to haploid ones and workers than to queens, and (ii) in queens and workers, more genes were up-regulated after emergence until day five, whereas in diploid and especially so in haploid males more genes were down-regulated. This difference between the sexes may be related to longevity, which is much longer in females than in males.

  20. Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

    International Nuclear Information System (INIS)

    Adams, Scott V.; Barrick, Brian; Christopher, Emily P.; Shafer, Martin M.; Makar, Karen W.; Song, Xiaoling; Lampe, Johanna W.; Vilchis, Hugo; Ulery, April; Newcomb, Polly A.

    2015-01-01

    Background: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals. Methods: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd. Conclusions: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion. - Highlights: • Genetic variation in metallothionein (MT) genes was assessed in two diverse populations. • Single nucleotide polymorphisms (SNPs) in MT genes were associated with mean urinary Cd, Cu and Zn. • Genetic variation may influence biomarkers of exposure, and associations of exposure with health.

  1. Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Scott V., E-mail: sadams@fhcrc.org [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Barrick, Brian [Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003 (United States); Christopher, Emily P. [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Shafer, Martin M. [Environmental Chemistry and Technology, Wisconsin State Laboratory of Hygiene, University of Wisconsin, 2601 Agriculture Dr., Madison, WI 53718 (United States); Makar, Karen W.; Song, Xiaoling [Public Health Science Biomarker Laboratory, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Lampe, Johanna W. [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States); Vilchis, Hugo [Border Epidemiology and Environmental Health Center, New Mexico State University, Box 30001 MSC 3BEC, Las Cruces, NM 88003 (United States); Ulery, April [Department of Plant and Environmental Sciences, New Mexico State University, Box 30003 MSC 3Q, Las Cruces, NM 88003 (United States); Newcomb, Polly A. [Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA 98109 (United States)

    2015-12-15

    Background: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals. Methods: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd. Conclusions: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion. - Highlights: • Genetic variation in metallothionein (MT) genes was assessed in two diverse populations. • Single nucleotide polymorphisms (SNPs) in MT genes were associated with mean urinary Cd, Cu and Zn. • Genetic variation may influence biomarkers of exposure, and associations of exposure with health.

  2. The BPA-substitute bisphenol S alters the transcription of genes related to endocrine, stress response and biotransformation pathways in the aquatic midge Chironomus riparius (Diptera, Chironomidae.

    Directory of Open Access Journals (Sweden)

    Óscar Herrero

    Full Text Available Bisphenol S (BPS is an industrial alternative to the endocrine disruptor bisphenol A (BPA, and can be found in many products labeled "BPA-free". Its use has grown in recent years, and presently it is considered a ubiquitous emerging pollutant. To date there is a lack of information on the effects of BPS on invertebrates, although they represent more than 95% of known species in the animal kingdom and are crucial for the structure and proper function of ecosystems. In this study, real-time RT-PCR was used to determine the early detrimental effects of BPS on the transcriptional rate of genes in the model species Chironomus riparius, specifically those related to the ecdysone pathway (EcR, ERR, E74, Vtg, cyp18a1 crucial for insect development and metamorphosis, stress and biotransformation mechanisms (hsp70, hsp40, cyp4g, GPx, GSTd3 that regulate adaptive responses and determine survival, and ribosome biogenesis (its2, rpL4, rpL13 which is essential for protein synthesis and homeostasis. While 24-hour exposure to 0.5, 5, 50, and 500 μg/L BPS had no effect on larval survival, almost all the studied genes were upregulated following a non-monotonic dose-response curve. Genes with the greatest increases in transcriptional activity (fold change relative to control were EcR (3.8, ERR (2, E74 (2.4, cyp18a1 (2.5, hsp70 (1.7, hsp40 (2.5, cyp4g (6.4, GPx (1.8, and GST (2.1, while others including Vtg, GAPDH, and selected ribosomal genes remained stable. We also measured the transcriptional activity of these genes 24 hours after BPS withdrawal and a general downregulation compared to controls was observed, though not significant in most cases. Our findings showed that BPS exposure altered the transcriptional profile of these genes, which may have consequences for the hormone system and several metabolic pathways. Although further research is needed to elucidate its mode of action, these results raise new concerns about the safety of BPA alternatives.

  3. The BPA-substitute bisphenol S alters the transcription of genes related to endocrine, stress response and biotransformation pathways in the aquatic midge Chironomus riparius (Diptera, Chironomidae).

    Science.gov (United States)

    Herrero, Óscar; Aquilino, Mónica; Sánchez-Argüello, Paloma; Planelló, Rosario

    2018-01-01

    Bisphenol S (BPS) is an industrial alternative to the endocrine disruptor bisphenol A (BPA), and can be found in many products labeled "BPA-free". Its use has grown in recent years, and presently it is considered a ubiquitous emerging pollutant. To date there is a lack of information on the effects of BPS on invertebrates, although they represent more than 95% of known species in the animal kingdom and are crucial for the structure and proper function of ecosystems. In this study, real-time RT-PCR was used to determine the early detrimental effects of BPS on the transcriptional rate of genes in the model species Chironomus riparius, specifically those related to the ecdysone pathway (EcR, ERR, E74, Vtg, cyp18a1) crucial for insect development and metamorphosis, stress and biotransformation mechanisms (hsp70, hsp40, cyp4g, GPx, GSTd3) that regulate adaptive responses and determine survival, and ribosome biogenesis (its2, rpL4, rpL13) which is essential for protein synthesis and homeostasis. While 24-hour exposure to 0.5, 5, 50, and 500 μg/L BPS had no effect on larval survival, almost all the studied genes were upregulated following a non-monotonic dose-response curve. Genes with the greatest increases in transcriptional activity (fold change relative to control) were EcR (3.8), ERR (2), E74 (2.4), cyp18a1 (2.5), hsp70 (1.7), hsp40 (2.5), cyp4g (6.4), GPx (1.8), and GST (2.1), while others including Vtg, GAPDH, and selected ribosomal genes remained stable. We also measured the transcriptional activity of these genes 24 hours after BPS withdrawal and a general downregulation compared to controls was observed, though not significant in most cases. Our findings showed that BPS exposure altered the transcriptional profile of these genes, which may have consequences for the hormone system and several metabolic pathways. Although further research is needed to elucidate its mode of action, these results raise new concerns about the safety of BPA alternatives.

  4. Pulse shape analysis for germanium detectors used in DM searches

    International Nuclear Information System (INIS)

    Sagdeev, I.R.; Drukier, A.K.; Welsh, D.J.; Klimenko, A.A.; Osetrov, S.B.; Smolnikov, A.A.

    1994-01-01

    Progress in Ge detector technology has resulted in ultralow backgrounds of less than 0.3 countskeV -1 kg -1 d -1 at energies between 6 and 9keV and from 12 to 20keV. Between 4 and 6keV it is less than 2 countskeV -1 kg -1 d -1 . Coupled with good energy resolution, 0.4keV FWHM at 10keV, this allows searches for DM particles with m≥qslant8GeV/c 2 .Electromagnetic interference (EMI) and acoustical pick-up are the main sources of background in the best Ge detectors. A PC-based on-line pulse shape analysis system is presented which permits rejection of large fraction of the EMI/acoustical background. The hardware uses a low cost, commercially available digital storage oscilloscope (DSO). The software consists of about 40000 lines of code in Pascal and assembly language. We tested this system using a low radioactive background Ge-system at the Baksan observatory. For low energy events (<100keV) this system permits improvement in the background by about 20-30%. ((orig.))

  5. SERUM GAMMA-GLUTAMYL TRANSFERASE AS A BIOMARKER OF TYPE-2 DM AMONG CIGARETTE SMOKERS

    Directory of Open Access Journals (Sweden)

    K. Suganthy

    2017-03-01

    Full Text Available BACKGROUND Smoking is one of the most common addictions of modern times and needs to be studied in a community as a public health issue. Also, smoking is a modifiable risk factor for type-2 DM. The smoking-related diseases share common pathophysiologies of imbalance of systemic oxidants and antioxidant status, increased inflammatory reactions, insulin resistance and dyslipidaemia. Biochemical assay of serum Gamma-Glutamyl Transferase (GGT activity is a low cost and highly sensitive laboratory test. Studies have indicated GGT is moderately elevated before the onset of other traditional risk factors for type-2 DM. So, among hepatic markers, the baseline GGT analysis can be an early risk marker of type 2 diabetes in cigarette smokers has to be studied. MATERIALS AND METHODS This is a case-control study on male cigarette smokers. 57 smokers were studied clinically and biochemically for plasma insulin, glucose and liver enzymes including GGT using standard biochemical methods and compared with 42 age and sex matched non-smokers as controls. RESULTS The mean serum GGT in smokers (25.45 ± 10.8 was increased compared to non-smokers (18.8 ± 5.8. Smokers GGT (r=0.396 and HOMA-IR (r=0.352 showed significant positive association with duration of smoking (p24 IU/L. Regression analysis showed none of the diabetic risk factors were observed to be dependent on GGT including other liver enzymes. Regression analysis showed GGT is not an independent risk factor for DM. Although, the mean fasting blood glucose (91.4 ± 21.3, BMI (26.1 ± 9.3 and HOMA-IR (7.3 ± 2.3 was increased among cigarette smokers with GGT >24 IU/L. CONCLUSION The baseline GGT assay in cigarette smokers might be associated with the proinflammatory status or be a marker of oxidative stress of smoke toxins. Smokers with baseline GGT >24 IU/L develop insulin resistance should be investigated in future longitudinal studies for prediabetes to consider cigarette smoking as an important modifiable

  6. DM100 AND DM1200 MELTER TESTING WITH HIGH WASTE LOADING GLASS FORMULATIONS FOR HANFORD HIGH-ALUMINUM HLW STREAMS

    Energy Technology Data Exchange (ETDEWEB)

    KRUGER AA; MATLACK KS; KOT WK; PEGG IL; JOSEPH I

    2009-12-30

    This Test Plan describes work to support the development and testing of high waste loading glass formulations that achieve high glass melting rates for Hanford high aluminum high level waste (HLW). In particular, the present testing is designed to evaluate the effect of using low activity waste (LAW) waste streams as a source of sodium in place ofchemical additives, sugar or cellulose as a reductant, boehmite as an aluminum source, and further enhancements to waste processing rate while meeting all processing and product quality requirements. The work will include preparation and characterization of crucible melts in support of subsequent DuraMelter 100 (DM 100) tests designed to examine the effects of enhanced glass formulations, glass processing temperature, incorporation of the LAW waste stream as a sodium source, type of organic reductant, and feed solids content on waste processing rate and product quality. Also included is a confirmatory test on the HLW Pilot Melter (DM1200) with a composition selected from those tested on the DM100. This work builds on previous work performed at the Vitreous State Laboratory (VSL) for Department of Energy's (DOE's) Office of River Protection (ORP) to increase waste loading and processing rates for high-iron HLW waste streams as well as previous tests conducted for ORP on the same waste composition. This Test Plan is prepared in response to an ORP-supplied statement of work. It is currently estimated that the number of HLW canisters to be produced in the Hanford Tank Waste Treatment and Immobilization Plant (WTP) is about 12,500. This estimate is based upon the inventory ofthe tank wastes, the anticipated performance of the sludge treatment processes, and current understanding of the capability of the borosilicate glass waste form. The WTP HLW melter design, unlike earlier DOE melter designs, incorporates an active glass bubbler system. The bubblers create active glass pool convection and thereby improve heat

  7. Proposed Method for Estimating Health-Promoting Glucosinolates and Hydrolysis Products in Broccoli (Brassica oleracea var. italica) Using Relative Transcript Abundance.

    Science.gov (United States)

    Becker, Talon M; Jeffery, Elizabeth H; Juvik, John A

    2017-01-18

    Due to the importance of glucosinolates and their hydrolysis products in human nutrition and plant defense, optimizing the content of these compounds is a frequent breeding objective for Brassica crops. Toward this goal, we investigated the feasibility of using models built from relative transcript abundance data for the prediction of glucosinolate and hydrolysis product concentrations in broccoli. We report that predictive models explaining at least 50% of the variation for a number of glucosinolates and their hydrolysis products can be built for prediction within the same season, but prediction accuracy decreased when using models built from one season's data for prediction of an opposing season. This method of phytochemical profile prediction could potentially allow for lower phytochemical phenotyping costs and larger breeding populations. This, in turn, could improve selection efficiency for phase II induction potential, a type of chemopreventive bioactivity, by allowing for the quick and relatively cheap content estimation of phytochemicals known to influence the trait.

  8. Small Molecules that Enhance the Catalytic Efficiency of HLA-DM

    International Nuclear Information System (INIS)

    Nicholson, M.; Moradi, B.; Seth, N.; Xing, X.; Cuny, G.; Stein, R.; Wucherpfenning, K.

    2006-01-01

    HLA-DM (DM) plays a critical role in Ag presentation to CD4 T cells by catalyzing the exchange of peptides bound to MHC class II molecules. Large lateral surfaces involved in the DM:HLA-DR (DR) interaction have been defined, but the mechanism of catalysis is not understood. In this study, we describe four small molecules that accelerate DM-catalyzed peptide exchange. Mechanistic studies demonstrate that these small molecules substantially enhance the catalytic efficiency of DM, indicating that they make the transition state of the DM:DR/peptide complex energetically more favorable. These compounds fall into two functional classes: two compounds are active only in the presence of DM, and binding data for one show a direct interaction with DM. The remaining two compounds have partial activity in the absence of DM, suggesting that they may act at the interface between DM and DR/peptide. A hydrophobic ridge in the DMβ1 domain was implicated in the catalysis of peptide exchange because the activity of three of these enhancers was substantially reduced by point mutations in this area

  9. No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals.

    Science.gov (United States)

    Bannister, Richard; Beresford, Nicola; Granger, David W; Pounds, Nadine A; Rand-Weaver, Mariann; White, Roger; Jobling, Susan; Routledge, Edwin J

    2013-09-15

    Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p>0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10(-6)M for Gen and >10(-5)M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of genistein and

  10. No substantial changes in estrogen receptor and estrogen-related receptor orthologue gene transcription in Marisa cornuarietis exposed to estrogenic chemicals☆☆☆

    Science.gov (United States)

    Bannister, Richard; Beresford, Nicola; Granger, David W.; Pounds, Nadine A.; Rand-Weaver, Mariann; White, Roger; Jobling, Susan; Routledge, Edwin J.

    2013-01-01

    Estrogen receptor orthologues in molluscs may be targets for endocrine disruptors, although mechanistic evidence is lacking. Molluscs are reported to be highly susceptible to effects caused by very low concentrations of environmental estrogens which, if substantiated, would have a major impact on the risk assessment of many chemicals. The present paper describes the most thorough evaluation to-date of the susceptibility of Marisa cornuarietis ER and ERR gene transcription to modulation by vertebrate estrogens in vivo and in vitro. We investigated the effects of estradiol-17β and 4-tert-Octylphenol exposure on in vivo estrogen receptor (ER) and estrogen-related receptor (ERR) gene transcription in the reproductive and neural tissues of the gastropod snail M. cornuarietis over a 12-week period. There was no significant effect (p > 0.05) of treatment on gene transcription levels between exposed and non-exposed snails. Absence of a direct interaction of estradiol-17β and 4-tert-Octylphenol with mollusc ER and ERR protein was also supported by in vitro studies in transfected HEK-293 cells. Additional in vitro studies with a selection of other potential ligands (including methyl-testosterone, 17α-ethinylestradiol, 4-hydroxytamoxifen, diethylstilbestrol, cyproterone acetate and ICI182780) showed no interaction when tested using this assay. In repeated in vitro tests, however, genistein (with mcER-like) and bisphenol-A (with mcERR) increased reporter gene expression at high concentrations only (>10−6 M for Gen and >10−5 M for BPA, respectively). Like vertebrate estrogen receptors, the mollusc ER protein bound to the consensus vertebrate estrogen-response element (ERE). Together, these data provide no substantial evidence that mcER-like and mcERR activation and transcript levels in tissues are modulated by the vertebrate estrogen estradiol-17β or 4-tert-Octylphenol in vivo, or that other ligands of vertebrate ERs and ERRs (with the possible exception of

  11. AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals.

    Science.gov (United States)

    Fagard, M; Boutet, S; Morel, J B; Bellini, C; Vaucheret, H

    2000-10-10

    Introduction of transgene DNA may lead to specific degradation of RNAs that are homologous to the transgene transcribed sequence through phenomena named post-transcriptional gene silencing (PTGS) in plants, quelling in fungi, and RNA interference (RNAi) in animals. It was shown previously that PTGS, quelling, and RNAi require a set of related proteins (SGS2, QDE-1, and EGO-1, respectively). Here we report the isolation of Arabidopsis mutants impaired in PTGS which are affected at the Argonaute1 (AGO1) locus. AGO1 is similar to QDE-2 required for quelling and RDE-1 required for RNAi. Sequencing of ago1 mutants revealed one amino acid essential for PTGS that is also present in QDE-2 and RDE-1 in a highly conserved motif. Taken together, these results confirm the hypothesis that these processes derive from a common ancestral mechanism that controls expression of invading nucleic acid molecules at the post-transcriptional level. As opposed to rde-1 and qde-2 mutants, which are viable, ago1 mutants display several developmental abnormalities, including sterility. These results raise the possibility that PTGS, or at least some of its elements, could participate in the regulation of gene expression during development in plants.

  12. Light regimes differentially affect baseline transcript abundance of stress-axis and (neurodevelopment-related genes in zebrafish (Danio rerio, Hamilton 1822 AB and TL larvae

    Directory of Open Access Journals (Sweden)

    Ruud van den Bos

    2017-11-01

    Full Text Available Many strains of zebrafish (Danio rerio are readily available. Earlier we observed differences between AB and Tupfel long-fin (TL larvae regarding baseline hypothalamus-pituitary-interrenal (HPI axis activity and (neurodevelopment. Light regimes, i.e. 14 h light:10 h dark and 24 h continuous dark or light, affect hatching rate and larval growth. Here, we assessed baseline transcript abundance of HPI-axis-related genes and (neurodevelopment-related genes of AB and TL larvae (5 days post fertilisation using these light regimes. A principal component analysis revealed that in AB larvae the baseline expression of HPI-axis-related genes was higher the more hours of light, while the expression of (neurodevelopment-related genes was higher under 14 h light:10 h dark than under both continuous light or dark. In TL larvae, a complex pattern emerged regarding baseline expression of HPI-axis-related and (neurodevelopment-related genes. These data extend data of earlier studies by showing that light regimes affect gene-expression in larvae, and more importantly so, strengthen the notion of differences between larvae of the AB and TL strain. The latter finding adds to the growing database of phenotypical differences between zebrafish of the AB and TL strain.

  13. Efficacy and safety of insulin pump treatment in adult T1DM patients--influence of age and social environment.

    Science.gov (United States)

    Grzanka, Małgorzata; Matejko, Bartłomiej; Cyganek, Katarzyna; Kozek, Elżbieta; Małecki, Maciej T; Klupa, Tomasz

    2012-01-01

    Continuous subcutaneous insulin infusion (CSII) via personal insulin pump is a valuable therapeutic tool in T1DM patients. However, adherence to recommended CSII-related behaviours may be of concern to young adults with intensive, variable daily activities (students, young professionals). The aim of this observational study was to estimate treatment outcomes in young adult patients with T1DM, and compare them with older individuals. Overall, 140 adults with T1DM on CSII were examined, divided into 2 subgroups: 77 patients younger than 26 years of age (mean 20.6 years) and 63 older subjects (mean 39.0). We compared the glycaemic control in both groups of T1DM subjects and analyzed treatment attitudes to identify potentially modifiable behaviours influencing the efficacy of the treatment. The younger individuals were characterized by significantly worse treatment outcomes, compared to the older ones: the mean HbA1c levels were 7.6 ± 1.3% and 6.9±1.3% (p=0.00001), while the mean glucose levels based on glucometer downloads were 161±33.6 mg/dL and 136±21.8 mg/dL (p=0.00001), respectively. The frequency of self-monitoring of blood glucose (SMBG) was lower in younger individuals (5.3±2.1 vs. 7.0±2.8 daily, p=0.0005, respectively); they were also less frequently used advanced pump functions, e.g. the bolus calculator (48% vs. 67% users, p=0.0014, respectively). The efficacy of CSII treatment observed in young T1DM adults was worse than in older patients. The reason for this phenomenon remains unclear, it may be due simply to age-dependend behaviours, to social environment, or both.

  14. An Integrative Review of Self-Efficacy Measurement Instruments in Youth with Type 1 Diabetes (T1DM)

    Science.gov (United States)

    Rasbach, Lisa; Jenkins, Carolyn; Laffel, Lori

    2014-01-01

    Purpose The purpose of this study is to assess the extant literature on instruments used to measure self-efficacy in youth with type 1 diabetes (T1DM) and their caregivers and to critically evaluate these measurements. Methods An integrative review (2003–2013) was conducted searching PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and U.S. National Library of Medicine PubMed service (PubMed) databases using key words diabetes, type 1 diabetes, and self-efficacy. The authors reviewed the resulting294 references for inclusion criteria of (a) sample of youth with T1DM or sample of caregivers of youth with T1DM, (b) description of the self-efficacy instrument as primary research, and (c) the instrument measured self-efficacy specifically related to diabetes management. Forty-five articles out of the initial 294 met criteria. Results Of the 45 articles, 10 different self-efficacy instruments were identified. The primary theoretical framework used was Bandura’s social cognitive theory and model of self-efficacy. Most participants were white middle class T1DM youth. Evaluations to assess validity often were not reported; however, a majority of studies reported high internal consistency of the instruments. Conclusions Sample homogeneity could limit the applicability of results to certain patient populations. Further psychometric analysis, including validity assessments, should be conducted in more diverse samples. Development of valid and reliable instruments for measuring self-efficacy that are sensitive to change across a wider caregiver base over time is necessary. While this review examined reliable and valid instruments used in research, future opportunities include evaluation of measuring self-efficacy in T1DM youth exposed to recent advances in diabetes management technologies. PMID:25216655

  15. Murværk opmuret med vådmørtler

    DEFF Research Database (Denmark)

    Hansen, Klavs Feilberg

    dmørtler benyttes i størstedelen af det murede nybyggeri. Egenskaberne af murværk opmuret med vådmørtel er i dag kun mangelfuldt dokumenteret. Denne rapport beskriver en metode til bedre dokumentation af de styrkemæssige egenskaber ved murværk opmuret med vådmørtel. Første del af rapporten genn...

  16. Accumulation of defence-related transcripts and cloning of a chitinase mRNA from pea leaves (Pisum sativum L.) inoculated with Ascochyta pisi Lib

    DEFF Research Database (Denmark)

    Vad, Knud; de Neergaard, Eigil; Madriz-Ordeñana, Kenneth

    1993-01-01

    The race specific resistance of pea to Ascochyta pisi Lib. was shown to be exhibited as a hypersensitive response associated with the production of polyphenolic substances in epidermal and mesophyll cells. The levels of transcripts representing a pathogenesis-related (PR) protein (chitinase......) and an enzyme of phytoalexin biosynthesis (chalcone synthase) were shown to accumulate more rapidly during the hypersensitive response than during lesion development in the compatible interaction. A full-length (1143 bp) cDNA sequence of a pea chitinase (EC 3.2.1.14) (coding for an approx. 34 500 Da protein......) was deduced by combining the overlapping sequences of three clones obtained following PCR amplification of cDNA prepared from mRNA isolated 24 h after inoculation of pea leaves with Ascochyta pisi. The combined sequences were identified as a class I chitinase corresponding to the basic A1-chitinase enzyme...

  17. A transcriptional signature of "exercise resistance" in skeletal muscle of individuals with type 2 diabetes mellitus.

    Science.gov (United States)

    Stephens, Natalie A; Xie, Hui; Johannsen, Neil M; Church, Timothy S; Smith, Steven R; Sparks, Lauren M

    2015-09-01

    Exercise benefits most, but not all, individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to determine whether a proportion of individuals with T2DM would fail to demonstrate exercise-induced metabolic improvements. We hypothesized that this lack of response would be related to their skeletal muscle transcriptional profile. 42 participants with T2DM from the previously reported HART-D study underwent a 9-month supervised exercise intervention. We performed a principal components analysis to distinguish Responders from Non-Responders (n=9 each) based on: decreases in (1) HbA1c, (2) %fat (3) BMI and (4) increase in skeletal muscle mtDNA. mRNA expression patterns in muscle tissue at baseline were assessed by microarray and qRT-PCR analysis in both groups. Of 186 genes identified by microarray analysis, 70% were up-regulated in Responders and down-regulated in Non-Responders. Several genes involved in substrate metabolism and mitochondrial biogenesis were significantly different (fold-change>1.5, pexercise response in metabolic outcomes, thus allowing exercise interventions to be targeted to these individuals and aid in the identification of novel approaches to treat Non-Responders in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Increased expression of interleukin-6 (IL-6) gene transcript in relation to IL-6 promoter hypomethylation in gingival tissue from patients with chronic periodontitis.

    Science.gov (United States)

    Kobayashi, Tetsuo; Ishida, Kohei; Yoshie, Hiromasa

    2016-09-01

    DNA methylation of the cytokine genes may play a role in the pathogenesis of periodontitis. The aim of this study is to evaluate whether the alteration of interleukin-6 (IL-6) gene promoter methylation in the gingival tissue (GT) and peripheral blood (PB) is unique to chronic periodontitis (CP). DNA isolated from the GT and PB of 25 patients with (CP) and 20 healthy controls (H) was modified with sodium bisulfite and analyzed for IL-6 promoter methylation with direct sequencing. The levels of IL-6 mRNA and serum IL-6 protein were evaluated by a quantitative reverse transcription polymerase chain reaction and an enzyme-linked immunosorbent assay. The CP group showed that the overall methylation rates of IL-6 promoter that contained 19 cytosine-guanine dinucleotide (CpG) motifs were significantly decreased in GT in comparison to PB (p<0.001), which was significantly negatively correlated with the probing depth (p=0.003). The GT and PB of the H group displayed similar overall methylation rates. No significant difference was observed in the methylation rates at each CpG in GT in comparison to the PB in both groups. The levels of IL-6 mRNA in the GT and PB and serum IL-6 of the two groups were comparable. The ratio of IL-6 mRNA in the GT relative to the PB was significantly higher in the CP group than in the H group (p=0.03). The increased expression of IL-6 gene transcription may be related to IL-6 promoter hypomethylation in the GT from CP patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. RNA-seq for gene identification and transcript profiling in relation to root growth of bermudagrass (Cynodon dactylon) under salinity stress.

    Science.gov (United States)

    Hu, Longxing; Li, Huiying; Chen, Liang; Lou, Yanhong; Amombo, Erick; Fu, Jinmin

    2015-08-04

    Soil salinity is one of the most significant abiotic stresses affecting plant shoots and roots growth. The adjustment of root architecture to spatio-temporal heterogeneity in salinity is particularly critical for plant growth and survival. Bermudagrass (Cynodon dactylon) is a widely used turf and forage perennial grass with a high degree of salinity tolerance. Salinity appears to stimulate the growth of roots and decrease their mortality in tolerant bermudagrass. To estimate a broad spectrum of genes related to root elongation affected by salt stress and the molecular mechanisms that control the positive response of root architecture to salinity, we analyzed the transcriptome of bermudagrass root tips in response to salinity. RNA-sequencing was performed in root tips of two bermudagrass genotypes contrasting in salt tolerance. A total of 237,850,130 high quality clean reads were generated and 250,359 transcripts were assembled with an average length of 1115 bp. Totally, 103,324 unigenes obtained with 53,765 unigenes (52 %) successfully annotated in databases. Bioinformatics analysis indicated that major transcription factor (TF) families linked to stress responses and growth regulation (MYB, bHLH, WRKY) were differentially expressed in root tips of bermudagrass under salinity. In addition, genes related to cell wall loosening and stiffening (xyloglucan endotransglucosylase/hydrolases, peroxidases) were identified. RNA-seq analysis identified candidate genes encoding TFs involved in the regulation of lignin synthesis, reactive oxygen species (ROS) homeostasis controlled by peroxidases, and the regulation of phytohormone signaling that promote cell wall loosening and therefore root growth under salinity.

  20. Heme oxygenase up-regulation under ultraviolet-B radiation is not epigenetically restricted and involves specific stress-related transcriptions factors

    Directory of Open Access Journals (Sweden)

    Diego Santa-Cruz

    2017-08-01

    Full Text Available Heme oxygenase-1 (HO-1 plays a protective role against oxidative stress in plants. The mechanisms regulating its expression, however, remain unclear. Here we studied the methylation state of a GC rich HO-1 promoter region and the expression of several stress-related transcription factors (TFs in soybean plants subjected to ultraviolet-B (UV-B radiation. Genomic DNA and total RNA were isolated from leaves of plants irradiated with 7.5 and 15 kJ m-2 UV-B. A 304 bp HO-1 promoter region was amplified by PCR from sodium bisulfite-treated DNA, cloned into pGEMT plasmid vector and evaluated by DNA sequencing. Bisulfite sequencing analysis showed similar HO-1 promoter methylation levels in control and UV-B-treated plants (C: 3.4±1.3%; 7.5: 2.6±0.5%; 15: 3.1±1.1%. Interestingly, HO-1 promoter was strongly unmethylated in control plants. Quantitative RT-PCR analysis of TFs showed that GmMYB177, GmMYBJ6, GmWRKY21, GmNAC11, GmNAC20 and GmGT2A but not GmWRK13 and GmDREB were induced by UV-B radiation. The expression of several TFs was also enhanced by hemin, a potent and specific HO inducer, inferring that they may mediate HO-1 up-regulation. These results suggest that soybean HO-1 gene expression is not epigenetically regulated. Moreover, the low level of HO-1 promoter methylation suggests that this antioxidant enzyme can rapidly respond to environmental stress. Finally, this study has identified some stress-related TFs involved in HO-1 up-regulation under UV-B radiation. Keywords: Heme oxygenase, DNA methylation, Transcription factors, Ultraviolet-B radiation, Glycine max

  1. MBNL142 and MBNL143 gene isoforms, overexpressed in DM1-patient muscle, encode for nuclear proteins interacting with Src family kinases.

    Science.gov (United States)

    Botta, A; Malena, A; Tibaldi, E; Rocchi, L; Loro, E; Pena, E; Cenci, L; Ambrosi, E; Bellocchi, M C; Pagano, M A; Novelli, G; Rossi, G; Monaco, H L; Gianazza, E; Pantic, B; Romeo, V; Marin, O; Brunati, A M; Vergani, L

    2013-08-15

    Myotonic dystrophy type-1 (DM1) is the most prevalent form of muscular dystrophy in adults. This disorder is an RNA-dominant disease, caused by expansion of a CTG repeat in the DMPK gene that leads to a misregulation in the alternative splicing of pre-mRNAs. The longer muscleblind-like-1 (MBNL1) transcripts containing exon 5 and the respective protein isoforms (MBNL142-43) were found to be overexpressed in DM1 muscle and localized exclusively in the nuclei. In vitro assays showed that MBNL142-43 bind the Src-homology 3 domain of Src family kinases (SFKs) via their proline-rich motifs, enhancing the SFK activity. Notably, this association was also confirmed in DM1 muscle and myotubes. The recovery, mediated by an siRNA target to Ex5-MBNL142-43, succeeded in reducing the nuclear localization of both Lyn and MBNL142-43 proteins and in decreasing the level of tyrosine phosphorylated proteins. Our results suggest an additional molecular mechanism in the DM1 pathogenesis, based on an altered phosphotyrosine signalling pathway.

  2. UCP2 and UCP3 variants and gene-environment interaction associated with prediabetes and T2DM in a rural population: a case control study in China.

    Science.gov (United States)

    Su, Meifang; Chen, Xiaoying; Chen, Yue; Wang, Congyun; Li, Songtao; Ying, Xuhua; Xiao, Tian; Wang, Na; Jiang, Qingwu; Fu, Chaowei

    2018-03-12

    There are disparities for the association between uncoupling proteins (UCP) and type 2 diabetes (T2DM). The study was to examine the associations of genetic variants of UCP2 and UCP3 with prediabetes and T2DM in a rural Chinese population. A population-based case-control study of 397 adults with T2DM, 394 with prediabetes and 409 with normal glucose tolerance (NGT) was carried out in 2014 in a rural community in eastern China. Three groups were identified through a community survey and the prediabetes and NGT groups were frequently matched by age and gender with the T2DM group and they were not relatives of T2DM subjects. With r 2  ≥ 0.8 and minor allele frequency (MAF) ≥0.05 for tag single nucleotide polymorphisms (SNPs) with potential function, three (rs660339, rs45560234 and rs643064) and six (rs7930460, rs15763, rs647126, rs1800849, rs3781907 and rs1685356) SNPs were selected respectively for UCP2 and UCP3 and genotyped in real time using the MassARRAY system (Sequenom; USA). The haplotypes, gene-environmental interaction and association between genetic variants of UCP2 and UCP3 and prediabetes or T2DM were explored. There were no significant differences in age and sex among three study groups. After the adjustment for possible covariates, the A allele of rs1800849 in UCP3 was significantly associated with prediabetes (aOR AA vs GG  = 1.68, 95% CI: 1.02-2.78), and the association was also significant under the recessive model (aOR AA vs GA + GG  = 1.64, 95% CI: 1.02-2.66). Also, rs15763 was found to be marginally significantly associated with T2DM under dominant model (OR GA + AA vs GG  = 0.73, 95% CI: 0.52-1.03, P = 0.072). No haplotype was significantly associated with prediabetes or T2DM. Multiplicative interactions for rs660339-overweight on T2DM were observed. In addition, the AA genotype of rs660339 was associated with an increased risk of T2DM in overweight subjects (OR = 1.48, 95%CI: 0.87-2.52) but with a decreased

  3. Molecular effect of fenofibrate on PBMC gene transcription related to lipid metabolism in patients with metabolic syndrome.

    Science.gov (United States)

    Moreno-Indias, I; Tinahones, F J; Clemente-Postigo, M; Castellano-Castillo, D; Fernández-García, J C; Macias-Gonzalez, M; Queipo-Ortuño, M I; Cardona, F

    2017-06-01

    Both fasting and postprandial hypertriglyceridaemia are considered independent risk factors for atherosclerosis. Treatment of hypertriglyceridaemia is based on fibrates, which activate the peroxisome proliferator-activated receptor alpha (PPARα). However, the metabolic pathways that activate or inhibit fibrates, and how the postprandial triglyceride levels are modified, have not yet been fully described. Accordingly, the aim of this study was to determine the feasibility of peripheral blood mononuclear cells (PBMC) to study the effects of fenofibrate in patients with the metabolic syndrome. A fat overload was given to 50 patients before and after treatment with fenofibrate for 3 months. Anthropometric and biochemical variables as well as gene expression in PBMC were analysed. After treatment with fenofibrate, we observed a decrease in both baseline and postprandial (3 h after the fat overload) levels of serum triglycerides, cholesterol and uric acid and an increase in HDL cholesterol and apolipoprotein AI levels. After treatment, there was also a rise in PPARα and RXRα expression and changes in genes regulated by PPARα, both baseline and postprandial. Furthermore, in vitro experiments showed that a PPARα agonist changed the expression of genes related with lipid metabolism. Treatment with fenofibrate reduced fasting and postprandial serum triglyceride levels, possibly through a mechanism related with an increase in the expression of RXRα and PPARα, by activating the pathways involved in the uptake and degradation of triglycerides and increasing the synthesis of apolipoprotein. These results suggest that PBMC may be useful for the easy study of fenofibrate actions. © 2017 John Wiley & Sons Ltd.

  4. The Csr/Rsm system of Yersinia and related pathogens: a post-transcriptional strategy for managing virulence.

    Science.gov (United States)

    Heroven, Ann Kathrin; Böhme, Katja; Dersch, Petra

    2012-04-01

    This review emphasizes the function and regulation of the Csr regulatory system in the human enteropathogen Yersinia pseudotuberculosis and compares its features with the homologous Csr/Rsm systems of related pathogens. The Csr/Rsm systems of eubacteria form a complex regulatory network in which redundant non-translated Csr/Rsm-RNAs bind the RNA-binding protein CsrA/RsmA, thereby preventing its interaction with mRNA targets. The Csr system is controlled by the BarA/UvrY-type of two-component sensor-regulator systems. Apart from that, common or pathogen-specific regulators control the abundance of the Csr components. The coordinate control of virulence factors and infection-linked physiological traits by the Csr/Rsm systems helps the pathogens to adapt individually to rapidly changing conditions to which they are exposed during the different stages of an infection. As Csr/Rsm function is relevant for full virulence, it represents a target suitable for antimicrobial drug development.

  5. Deletion of the transcriptional coactivator PGC1α in skeletal muscles is associated with reduced expression of genes related to oxidative muscle function

    International Nuclear Information System (INIS)

    Hatazawa, Yukino; Minami, Kimiko; Yoshimura, Ryoji; Onishi, Takumi; Manio, Mark Christian; Inoue, Kazuo; Sawada, Naoki; Suzuki, Osamu; Miura, Shinji; Kamei, Yasutomi

    2016-01-01

    The expression of the transcriptional coactivator PGC1α is increased in skeletal muscles during exercise. Previously, we showed that increased PGC1α leads to prolonged exercise performance (the duration for which running can be continued) and, at the same time, increases the expression of branched-chain amino acid (BCAA) metabolism-related enzymes and genes that are involved in supplying substrates for the TCA cycle. We recently created mice with PGC1α knockout specifically in the skeletal muscles (PGC1α KO mice), which show decreased mitochondrial content. In this study, global gene expression (microarray) analysis was performed in the skeletal muscles of PGC1α KO mice compared with that of wild-type control mice. As a result, decreased expression of genes involved in the TCA cycle, oxidative phosphorylation, and BCAA metabolism were observed. Compared with previously obtained microarray data on PGC1α-overexpressing transgenic mice, each gene showed the completely opposite direction of expression change. Bioinformatic analysis of the promoter region of genes with decreased expression in PGC1α KO mice predicted the involvement of several transcription factors, including a nuclear receptor, ERR, in their regulation. As PGC1α KO microarray data in this study show opposing findings to the PGC1α transgenic data, a loss-of-function experiment, as well as a gain-of-function experiment, revealed PGC1α’s function in the oxidative energy metabolism of skeletal muscles. - Highlights: • Microarray analysis was performed in the skeletal muscle of PGC1α KO mice. • Expression of genes in the oxidative energy metabolism was decreased. • Bioinformatic analysis of promoter region of the genes predicted involvement of ERR. • PGC1α KO microarray data in this study show the mirror image of transgenic data.

  6. The related transcriptional enhancer factor-1 isoform, TEAD4(216, can repress vascular endothelial growth factor expression in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Binoy Appukuttan

    Full Text Available Increased cellular production of vascular endothelial growth factor (VEGF is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4 protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4(216, which represses VEGF promoter activity. The TEAD4(216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE, which is the sequence critical to hypoxia inducible factor (HIF-mediated effects. The TEAD4(216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4(216 isoform can competitively repress the stimulatory activity of the TEAD4(434 and TEAD4(148 enhancers. Synthesis of the native VEGF(165 protein and cellular proliferation is suppressed by the TEAD4(216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4(216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases.

  7. Immunohistochemical expression of Ets-related gene-transcriptional factor in adenocarcinoma prostate and its correlation with Gleason score

    Directory of Open Access Journals (Sweden)

    Rahul Mannan

    2016-01-01

    Full Text Available Background: Prostate carcinoma is the second leading cause of cancer-related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment. Out of these markers, Ets-related gene (ERG product is a proto-oncogene which participates in chromosomal translocations and is frequently over expressed in prostate carcinoma which harbors ERG-transmembrane protease, serine 2 fusion. Materials and Methods: Fifty cases of carcinoma prostate diagnosed in needle biopsies and prostatic chips, in the Department of Pathology of a tertiary care teaching hospital in Punjab, India, were included in the present study. The slides were observed under the light microscope, and Gleason scoring was done using the 2005 International Society of Urological Pathology modified Gleason system. IHC study for ERG expression was done on all the cases, for which anti-ERG monoclonal rabbit clone antibody EP111 (Dako, Denmark was used. Lymphocytes and endothelial cells were taken as in built positive controls for staining. The intensity of ERG positivity was scored as no staining (0, weak staining (+1, moderate staining (+2 and intense staining (+3. The H score was then calculated by multiplying the intensity of the stain with the percentage (0-100 of the cells showing that staining intensity. The H-score has a range of 0-300. The relationship between IHC expression and clinico-pathological parameters was compared and analyzed using Chi-square test. P < 0.05 was considered statistically significant. Results: Majority of patients included in the study were in the age group of 61-80 (84% of the

  8. Immunohistochemical expression of Ets-related gene-transcriptional factor in adenocarcinoma prostate and its correlation with Gleason score.

    Science.gov (United States)

    Mannan, Rahul; Bhasin, Tejinder Singh; Manjari, Mridu; Singh, Gagandeep; Bhatia, Puneet Kaur; Sharma, Sonam

    2016-01-01

    Prostate carcinoma is the second leading cause of cancer-related deaths in males worldwide. The burden is expected to grow 1.7 million new cases and 499,000 new deaths by 2030. In developing countries such as India, prostate carcinoma will show an increase by 140% in the next few years. Although the diagnosis of prostate carcinoma can usually be made on histological features, now a days many immunohistochemical (IHC) markers are used to distinguish it from benign mimickers as well as in predicting prognosis and treatment. Out of these markers, Ets-related gene (ERG product) is a proto-oncogene which participates in chromosomal translocations and is frequently over expressed in prostate carcinoma which harbors ERG-transmembrane protease, serine 2 fusion. Fifty cases of carcinoma prostate diagnosed in needle biopsies and prostatic chips, in the Department of Pathology of a tertiary care teaching hospital in Punjab, India, were included in the present study. The slides were observed under the light microscope, and Gleason scoring was done using the 2005 International Society of Urological Pathology modified Gleason system. IHC study for ERG expression was done on all the cases, for which anti-ERG monoclonal rabbit clone antibody EP111 (Dako, Denmark) was used. Lymphocytes and endothelial cells were taken as in built positive controls for staining. The intensity of ERG positivity was scored as no staining (0), weak staining (+1), moderate staining (+2) and intense staining (+3). The H score was then calculated by multiplying the intensity of the stain with the percentage (0-100) of the cells showing that staining intensity. The H-score has a range of 0-300. The relationship between IHC expression and clinico-pathological parameters was compared and analyzed using Chi-square test. P < 0.05 was considered statistically significant. Majority of patients included in the study were in the age group of 61-80 (84% of the total). When ERG expression was studied with age

  9. Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma.

    Directory of Open Access Journals (Sweden)

    Jin Choi

    Full Text Available Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF, the levels of total immunoglobulin (Ig E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues. ELISA analysis showed that picroside II down-regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13 and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNγ in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes and the transcription factor GATA3 in the lung tissues of HDM-induced mice. Finally, we demonstrated that picroside II significantly decreased the expression of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo results. Taken together, these results indicate that picroside II has protective effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias.

  10. Comparative experimental and theoretical investigations of the DM neutron moisture probe

    DEFF Research Database (Denmark)

    Ølgaard, Povl Lebeck; Haahr, Vagner

    1967-01-01

    Theoretical and experimental investigations of the Danish produced DM subsurface moisture probe have been carried out at the Research Establishment Risö, and the results obtained are presented in this paper. The DM probe contains an Am-Be fast neutron source and has a glass scintillator containing...

  11. Draft Genome Sequence of Lactobacillus paracasei DmW181, a Bacterium Isolated from Wild Drosophila

    OpenAIRE

    Hammer, Austin J.; Walters, Amber; Carroll, Courtney; Newell, Peter D.; Chaston, John M.

    2017-01-01

    ABSTRACT The draft genome sequence of Lactobacillus paracasei DmW181, an anaerobic bacterium isolate from wild Drosophila flies, is reported here. Strain DmW181 possesses genes for sialic acid and mannose metabolism. The assembled genome is 3,201,429?bp, with 3,454 predicted genes.

  12. Draft Genome Sequence of Lactobacillus paracasei DmW181, a Bacterium Isolated from Wild Drosophila.

    Science.gov (United States)

    Hammer, Austin J; Walters, Amber; Carroll, Courtney; Newell, Peter D; Chaston, John M

    2017-07-06

    The draft genome sequence of Lactobacillus paracasei DmW181, an anaerobic bacterium isolate from wild Drosophila flies, is reported here. Strain DmW181 possesses genes for sialic acid and mannose metabolism. The assembled genome is 3,201,429 bp, with 3,454 predicted genes. Copyright © 2017 Hammer et al.

  13. Prevalence of type 2 diabetes mellitus complications among palestinians with T2DM

    DEFF Research Database (Denmark)

    Abu Al-Halaweh, Ahmad; Davidovitch, Nadav; Almdal, Thomas Peter

    2017-01-01

    AIMS: To assess the prevalence of microvascular and macrovascular complications of type 2 diabetes (T2DM) among Palestinians. METHODS: 1308 diagnosed T2DM attending four main Primary Health Care Clinics on the Southern West Bank of Palestine examined by a Mobile Diabetes Clinic team. All diabetes...

  14. Interference effects of two scalar boson propagators on the LHC search for the singlet fermion DM

    Energy Technology Data Exchange (ETDEWEB)

    Ko, P., E-mail: pko@kias.re.kr; Li, Jinmian, E-mail: jmli@kias.re.kr

    2017-02-10

    A gauge invariant UV-completion for singlet fermion DM interacting with the standard model (SM) particles involves a new singlet scalar. Therefore the model contains two scalar mediators, mixtures of the SM Higgs boson and a singlet scalar boson. Collider phenomenology of the interference effect between these two scalar propagators is studied in this work. This interference effect can be either constructive or destructive in the DM production cross section depending on both singlet scalar and DM masses, and it will soften the final state jets in the full mass region. Applying the CMS mono-jet search to our model, we find the interference effect plays a very important role in the DM search sensitivity, and the DM production cross section of our model is more than one order of magnitude below the LHC sensitivity at current stage.

  15. Changes in endotoxin levels in T2DM subjects on anti-diabetic therapies

    Directory of Open Access Journals (Sweden)

    Kumar Sudhesh

    2009-04-01

    Full Text Available Abstract Introduction Chronic low-grade inflammation is a significant factor in the development of obesity associated diabetes. This is supported by recent studies suggesting endotoxin, derived from gut flora, may be key to the development of inflammation by stimulating the secretion of an adverse cytokine profile from adipose tissue. Aims The study investigated the relationship between endotoxin and various metabolic parameters of diabetic patients to determine if anti-diabetic therapies exerted a significant effect on endotoxin levels and adipocytokine profiles. Methods Fasting blood samples were collected from consenting Saudi Arabian patients (BMI: 30.2 ± (SD5.6 kg/m2, n = 413, consisting of non-diabetics (ND: n = 67 and T2DM subjects (n = 346. The diabetics were divided into 5 subgroups based on their 1 year treatment regimes: diet-controlled (n = 36, metformin (n = 141, rosiglitazone (RSG: n = 22, a combined fixed dose of metformin/rosiglitazone (met/RSG n = 100 and insulin (n = 47. Lipid profiles, fasting plasma glucose, insulin, adiponectin, resistin, TNF-α, leptin, C-reactive protein (CRP and endotoxin concentrations were determined. Results Regression analyses revealed significant correlations between endotoxin levels and triglycerides (R2 = 0.42; p 2 = 0.10; p 2 = 0.076; p 2 = 0.032; p 2 = 0.055; p Conclusion We conclude that sub-clinical inflammation in T2DM may, in part, be mediated by circulating endotoxin. Furthermore, that whilst the endotoxin and adipocytokine profiles of diabetic patients treated with different therapies were comparable, the RSG group demonstrated significant differences in both adiponectin and endotoxin levels. We confirm an association between endotoxin and serum insulin and triglycerides and an inverse relationship with HDL. Lower endotoxin and higher adiponectin in the groups treated with RSG may be related and indicate another mechanism for the effect of RSG on insulin sensitivity.

  16. Production of the 2400 kb Duchenne muscular dystrophy (DMD) gene transcript; transcription time and cotranscriptional splicing

    Energy Technology Data Exchange (ETDEWEB)

    Tennyson, C.N.; Worton, R.G. [Univ. of Toronto and the Hospital for Sick Children, Ontario (Canada)

    1994-09-01

    The largest known gene in any organism is the human DMD gene which has 79 exons that span 2400 kb. The extreme nature of the DMD gene raises questions concerning the time required for transcription and whether splicing begins before transcription is complete. DMD gene transcription is induced as cultured human myoblasts differentiate to form multinucleated myotubes, providing a system for studying the kinetics of transcription and splicing. Using quantitative RT-PCR, transcript accumulation was monitored from four different regions within the gene following induction of expression. By comparing the accumulation of transcripts from the 5{prime} and 3{prime} ends of the gene we have shown that approximately 12 hours are required to transcribe 1770 kb of the gene, extrapolating to a time of 16 hours for the transcription unit expressed in muscle. Comparison of accumulation profiles for spliced and total transcript demonstrated that transcripts are spliced at the 5{prime} end before transcription is complete, providing strong evidence for cotranscriptional splicing of DMD gene transcripts. Finally, the rate of transcript accumulation was reduced at the 3{prime} end of the gene relative to the 5{prime} end, perhaps due to premature termination of transcription complexes as they traverse this enormous transcription unit. The lag between transcription initiation and the appearance of complete transcripts could be important in limiting transcript production in dividing cells and to the timing of mRNA appearance in differentiating muscle.

  17. Discovery of novel transcripts of the human tissue kallikrein (KLK1) and kallikrein-related peptidase 2 (KLK2) in human cancer cells, exploiting Next-Generation Sequencing technology.

    Science.gov (United States)

    Adamopoulos, Panagiotis G; Kontos, Christos K; Scorilas, Andreas

    2018-03-31

    Tissue kallikrein, kallikrein-related peptidases (KLKs), and plasma kallikrein form the largest group of serine proteases in the human genome, sharing many structural and functional properties. Several KLK transcripts have been found aberrantly expressed in numerous human malignancies, confirming their prognostic or/and diagnostic values. However, the process of alternative splicing can now be studied in-depth due to the development of Next-Generation Sequencing (NGS). In the present study, we used NGS to discover novel transcripts of the KLK1 and KLK2 genes, after nested touchdown PCR. Bioinformatics analysis and PCR experiments revealed a total of eleven novel KLK transcripts (two KLK1 and nine KLK2 transcripts). In addition, the expression profiles of each novel transcript were investigated with nested PCR experiments using variant-specific primers. Since KLKs are implicated in human malignancies, qualifying as potential biomarkers, the quantification of the presented novel transcripts in human samples may have clinical applications in different types of cancer. Copyright © 2018. Published by Elsevier Inc.

  18. FACT, the Bur kinase pathway, and the histone co-repressor HirC have overlapping nucleosome-related roles in yeast transcription elongation.

    Directory of Open Access Journals (Sweden)

    Jennifer R Stevens

    Full Text Available Gene transcription is constrained by the nucleosomal nature of chromosomal DNA. This nucleosomal barrier is modulated by FACT, a conserved histone-binding heterodimer. FACT mediates transcription-linked nucleosome disassembly and also nucleosome reassembly in the wake of the RNA polymerase II transcription complex, and in this way maintains the repression of 'cryptic' promoters found within some genes. Here we focus on a novel mutant version of the yeast FACT subunit Spt16 that supplies essential Spt16 activities but impairs transcription-linked nucleosome reassembly in dominant fashion. This Spt16 mutant protein also has genetic effects that are recessive, which we used to show that certain Spt16 activities collaborate with histone acetylation and the activities of a Bur-kinase/Spt4-Spt5/Paf1C pathway that facilitate transcription elongation. These collaborating activities were opposed by the actions of Rpd3S, a histone deacetylase that restores a repressive chromatin environment in a transcription-linked manner. Spt16 activity paralleling that of HirC, a co-repressor of histone gene expression, was also found to be opposed by Rpd3S. Our findings suggest that Spt16, the Bur/Spt4-Spt5/Paf1C pathway, and normal histone abundance and/or stoichiometry, in mutually cooperative fashion, facilitate nucleosome disassembly during transcription elongation. The recessive nature of these effects of the mutant Spt16 protein on transcription-linked nucleosome disassembly, contrasted to its dominant negative effect on transcription-linked nucleosome reassembly, indicate that mutant FACT harbouring the mutant Spt16 protein competes poorly with normal FACT at the stage of transcription-linked nucleosome disassembly, but effectively with normal FACT for transcription-linked nucleosome reassembly. This functional difference is consistent with the idea that FACT association with the transcription elongation complex depends on nucleosome disassembly, and that the

  19. Heterologous expression of the antimyotoxic protein DM64 in Pichia pastoris.

    Directory of Open Access Journals (Sweden)

    Saulo Martins Vieira

    2017-07-01

    Full Text Available Snakebite envenomation is a neglected condition that constitutes a public health problem in tropical and subtropical countries, including Brazil. Interestingly, some animals are resistant to snake envenomation due to the presence of inhibitory glycoproteins in their serum that target toxic venom components. DM64 is an acidic glycoprotein isolated from Didelphis aurita (opossum serum that has been characterized as an inhibitor of the myotoxicity induced by bothropic toxins bearing phospholipase A2 (PLA2 structures. This antitoxic protein can serve as an excellent starting template for the design of novel therapeutics against snakebite envenomation, particularly venom-induced local tissue damage. Therefore, the aim of this work was to produce a recombinant DM64 (rDM64 in the methylotrophic yeast Pichia pastoris and to compare its biological properties with those of native DM64. Yeast fermentation in the presence of Pefabloc, a serine protease inhibitor, stimulated cell growth (~1.5-fold, increased the rDM64 production yield approximately 10-fold and significantly reduced the susceptibility of rDM64 to proteolytic degradation. P. pastoris fermentation products were identified by mass spectrometry and Western blotting. The heterologous protein was efficiently purified from the culture medium by affinity chromatography (with immobilized PLA2 myotoxin and/or an ion exchange column. Although both native and recombinant DM64 exhibit different glycosylation patterns, they show very similar electrophoretic mobilities after PNGase F treatment. rDM64 formed a noncovalent complex with myotoxin II (Lys49-PLA2 from Bothrops asper and displayed biological activity that was similar to that of native DM64, inhibiting the cytotoxicity of myotoxin II by 92% at a 1:1 molar ratio.

  20. Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster

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    Wolfgang Blenau

    2017-05-01

    Full Text Available Serotonin (5-hydroxytryptamine, 5-HT is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects and deuterostomes (e.g., mammals. In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster, a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT1A, Dm5-HT1B, and Dm5-HT7 couple to cAMP signaling cascades, the Dm5-HT2A receptor leads to Ca2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT2B receptor. Knowledge about this receptor’s pharmacological properties is very limited. This is quite surprising because Dm5-HT2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT2B’s pharmacology, we evaluated the receptor’s response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT2B signaling in vitro and in vivo.

  1. Dm5-HT2B: Pharmacological Characterization of the Fifth Serotonin Receptor Subtype of Drosophila melanogaster.

    Science.gov (United States)

    Blenau, Wolfgang; Daniel, Stöppler; Balfanz, Sabine; Thamm, Markus; Baumann, Arnd

    2017-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) is an important regulator of physiological and behavioral processes in both protostomes (e.g., insects) and deuterostomes (e.g., mammals). In insects, serotonin has been found to modulate the heart rate and to control secretory processes, development, circadian rhythms, aggressive behavior, as well as to contribute to learning and memory. Serotonin exerts its activity by binding to and activating specific membrane receptors. The clear majority of these receptors belong to the superfamily of G-protein-coupled receptors. In Drosophila melanogaster , a total of five genes have been identified coding for 5-HT receptors. From this family of proteins, four have been pharmacologically examined in greater detail, so far. While Dm5-HT 1A , Dm5-HT 1B , and Dm5-HT 7 couple to cAMP signaling cascades, the Dm5-HT 2A receptor leads to Ca 2+ signaling in an inositol-1,4,5-trisphosphate-dependent manner. Based on sequence similarity to homologous genes in other insects, a fifth D. melanogaster gene was uncovered coding for a Dm5-HT 2B receptor. Knowledge about this receptor's pharmacological properties is very limited. This is quite surprising because Dm5-HT 2B has been attributed to distinct physiological functions based on genetic interference with its gene expression. Mutations were described reducing the response of the larval heart to 5-HT, and specific knockdown of Dm5-HT 2B mRNA in hemocytes resulted in a higher susceptibility of the flies to bacterial infection. To gain deeper understanding of Dm5-HT 2B 's pharmacology, we evaluated the receptor's response to a series of established 5-HT receptor agonists and antagonists in a functional cell-based assay. Metoclopramide and mianserin were identified as two potent antagonists that may allow pharmacological interference with Dm5-HT 2B signaling in vitro and in vivo .

  2. Expression profile of doublesex/male abnormal-3-related transcription factor-1 during gonadal sex change in the protogynous wrasse, Halichoeres trimaculatus.

    Science.gov (United States)

    Nozu, Ryo; Horiguchi, Ryo; Kobayashi, Yasuhisa; Nakamura, Masaru

    2015-11-01

    Sex change in fish involves a dramatic transformation of gonadal tissue and a switch in gametogenesis. Doublesex/male abnormal-3-related transcription factor-1 (DMRT1), encoded by the DMRT1 gene, is involved in testicular differentiation in a wide range of vertebrates as well as in sexual differentiation and gonadal sex change. In the present study, we investigated changes in the expression of dmrt1 during artificial gonadal sex change in the three-spot wrasse, Halichoeres trimaculatus, by real-time quantitative PCR and immunolocalization, using an anti-wrasse-Dmrt1 antibody that we prepared. We found that dmrt1 expression was predominantly observed in the testes, and that Dmrt1 was expressed in Sertoli cells of testes and a few granulosa cells surrounding vitellogenic oocytes of the ovary. Additionally, the upregulation of dmrt1 expression was consistent with an increase in spermatogenic cyst quantity rather than proliferation of presumptive spermatogonia, suggesting that dmrt1 is involved in the progression of spermatogenesis during sex change. Changes in the localization of Dmrt1 during gonadal sex change further implied that Sertoli cells originate from somatic cells adjacent to gonial germ cells during testicular formation in the three-spot wrasse. © 2015 Wiley Periodicals, Inc.

  3. Increased Energy Expenditure, Ucp1 Expression, and Resistance to Diet-induced Obesity in Mice Lacking Nuclear Factor-Erythroid-2-related Transcription Factor-2 (Nrf2).

    Science.gov (United States)

    Schneider, Kevin; Valdez, Joshua; Nguyen, Janice; Vawter, Marquis; Galke, Brandi; Kurtz, Theodore W; Chan, Jefferson Y

    2016-04-01

    The NRF2 (also known as NFE2L2) transcription factor is a critical regulator of genes involved in defense against oxidative stress. Previous studies suggest thatNrf2plays a role in adipogenesisin vitro, and deletion of theNrf2gene protects against diet-induced obesity in mice. Here, we demonstrate that resistance to diet-induced obesity inNrf2(-/-)mice is associated with a 20-30% increase in energy expenditure. Analysis of bioenergetics revealed thatNrf2(-/-)white adipose tissues exhibit greater oxygen consumption. White adipose tissue showed a >2-fold increase inUcp1gene expression. Oxygen consumption is also increased nearly 2.5-fold inNrf2-deficient fibroblasts. Oxidative stress induced by glucose oxidase resulted in increasedUcp1expression. Conversely, antioxidant chemicals (such asN-acetylcysteine and Mn(III)tetrakis(4-benzoic acid)porphyrin chloride) and SB203580 (a known suppressor ofUcp1expression) decreasedUcp1and oxygen consumption inNrf2-deficient fibroblasts. These findings suggest that increasing oxidative stress by limitingNrf2function in white adipocytes may be a novel means to modulate energy balance as a treatment of obesity and related clinical disorders. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Differential transcript induction of parsley pathogenesis-related proteins and of a small heat shock protein by ozone and heat shock

    International Nuclear Information System (INIS)

    Eckey-Kaltenbach, H.; Kiefer, E.; Grosskopf, E.; Ernst, D.; Sandermann, H. Jr

    1997-01-01

    Parsley (Petroselinum (crispum L.) is known to respond to pathogen attack by the synthesis of furanocoumarins and to UV irradiation by the synthesis of flavone glycosides whereas ozone treatment results in the induction of both pathways. A cDNA library from parsley plants was differentially screened using labelled reverse-transcribed poly(A)+ RNA isolated from ozone-treated parsley plants. This resulted in the isolation of 13 independent cDNA clones representing ozone-induced genes and of 11 cDNA clones representing ozone-repressed genes. DNA sequencing of several clones resulted in the identification of pathogenesis-related protein 1-3 (PR1-3), of a new member of PR1 cDNAs (PRI-4) and of a small heat shock protein (sHSP). Northern blot analyses showed a transient induction of the three mRNA species after ozone fumigation. In contrast, heat shock treatment of parsley plants resulted in an increase of sHSP mRNA whereas no increase for transcripts of PR1-3 and PR1-4 could be observed. This is the first characterized sHSP cDNA clone for plants induced by heat shock, as well as by oxidative stress caused by ozone. (author)

  5. Alteration of runt-related transcription factor 3 gene expression and biologic behavior of esophageal carcinoma TE-1 cells after 5-azacytidine intervention.

    Science.gov (United States)

    Wang, Shuai; Liu, Hong; Akhtar, Javed; Chen, Hua-Xia; Wang, Zhou

    2013-01-01

    5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at 50 μM had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.

  6. Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) and inhibits pro-survival function of Nrf1

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Madhurima; Kwong, Erick K.; Park, Eujean; Nagra, Parminder; Chan, Jefferson Y., E-mail: jchan@uci.edu

    2013-08-01

    Nuclear factor E2-related factor-1 (Nrf1) is a basic leucine zipper transcription factor that is known to regulate antioxidant and cytoprotective gene expression. It was recently shown that Nrf1 is regulated by SCF–Fbw7 ubiquitin ligase. However our knowledge of upstream signals that targets Nrf1 for degradation by the UPS is not known. We report here that Nrf1 expression is negatively regulated by glycogen synthase kinase 3 (GSK3) in Fbw7-dependent manner. We show that GSK3 interacts with Nrf1 and phosphorylates the Cdc4 phosphodegron domain (CPD) in Nrf1. Mutation of serine residue in the CPD of Nrf1 to alanine (S350A), blocks Nrf1 from phosphorylation by GSK3, and stabilizes Nrf1. Knockdown of Nrf1 and expression of a constitutively active form of GSK3 results in increased apoptosis in neuronal cells in response to ER stress, while expression of the GSK3 phosphorylation resistant S350A–Nrf1 attenuates apoptotic cell death. Together these data suggest that GSK3 regulates Nrf1 expression and cell survival function in response to stress activation. Highlights: • The effect of GSK3 on Nrf1 expression was examined. • GSK3 destabilizes Nrf1 protein via Fbw7 ubiquitin ligase. • GSK3 binds and phosphorylates Nrf1. • Protection from stress-induced apoptosis by Nrf1 is inhibited by GSK3.

  7. A module of human peripheral blood mononuclear cell transcriptional network containing primitive and differentiation markers is related to specific cardiovascular health variables.

    Directory of Open Access Journals (Sweden)

    Leni Moldovan

    Full Text Available Peripheral blood mononuclear cells (PBMCs, including rare circulating stem and progenitor cells (CSPCs, have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene, defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03 with age (R2 = -0.23, vascular stiffness (R2 = -0.24, and central aortic pressure (R2 = -0.19 and positively correlated with body mass index (R2 = 0.72, in women. The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional

  8. Transcription, Signaling Receptor Activity, Oxidative Phosphorylation, and Fatty Acid Metabolism Mediate the Presence of Closely Related Species in Distinct Intertidal and Cold-Seep Habitats.

    Science.gov (United States)

    Van Campenhout, Jelle; Vanreusel, Ann; Van Belleghem, Steven; Derycke, Sofie

    2015-12-03

    Bathyal cold seeps are isolated extreme deep-sea environments characterized by low species diversity while biomass can be high. The Håkon Mosby mud volcano (Barents Sea, 1,280 m) is a rather stable chemosynthetic driven habitat characterized by prominent surface bacterial mats with high sulfide concentrations and low oxygen levels. Here, the nematode Halomonhystera hermesi thrives in high abundances (11,000 individuals 10 cm(-2)). Halomonhystera hermesi is a member of the intertidal Halomonhystera disjuncta species complex that includes five cryptic species (GD1-5). GD1-5's common habitat is characterized by strong environmental fluctuations. Here, we compared the transcriptomes of H. hermesi and GD1, H. hermesi's closest relative. Genes encoding proteins involved in oxidative phosphorylation are more strongly expressed in H. hermesi than in GD1, and many genes were only observed in H. hermesi while being completely absent in GD1. Both observations could in part be attributed to high sulfide concentrations and low oxygen levels. Additionally, fatty acid elongation was also prominent in H. hermesi confirming the importance of highly unsaturated fatty acids in this species. Significant higher amounts of transcription factors and genes involved in signaling receptor activity were observed in GD1 (many of which were completely absent in H. hermesi), allowing fast signaling and transcriptional reprogramming which can mediate survival in dynamic intertidal environments. GC content was approximately 8% higher in H. hermesi coding unigenes resulting in differential codon usage between both species and a higher proportion of amino acids with GC-rich codons in H. hermesi. In general our results showed that most pathways were active in both environments and that only three genes are under natural selection. This indicates that also plasticity should be taken in consideration in the evolutionary history of Halomonhystera species. Such plasticity, as well as possible

  9. runDM: Running couplings of Dark Matter to the Standard Model

    Science.gov (United States)

    D'Eramo, Francesco; Kavanagh, Bradley J.; Panci, Paolo

    2018-02-01

    runDM calculates the running of the couplings of Dark Matter (DM) to the Standard Model (SM) in simplified models with vector mediators. By specifying the mass of the mediator and the couplings of the mediator to SM fields at high energy, the code can calculate the couplings at low energy, taking into account the mixing of all dimension-6 operators. runDM can also extract the operator coefficients relevant for direct detection, namely low energy couplings to up, down and strange quarks and to protons and neutrons.

  10. Studies on the s_dm.t=f verb form in Classical Egyptian

    OpenAIRE

    Zonhoven, Ludovicus Martinus Johannes

    1997-01-01

    This study is devoted to some synchronic aspects of the sDm.t=f verb form, primarily its meaning and uses in Classical Egyptian. In the introduction some attention is paid to the history of the studies of the form and its origin, an aspect which will receive no further consideration. In accordance with present common opinion the sDm.t=f is here considered to belong to the suffix conjugation. Ch. I is primarily concerned with the active Dr sDm.t=f construction, but begins with a general introd...

  11. THE DISTRIBUTION AND CHEMISTRY OF H2CO IN THE DM TAU PROTOPLANETARY DISK

    International Nuclear Information System (INIS)

    Loomis, Ryan A.; Öberg, Karin I.; Guzman, Viviana V.; Cleeves, L. Ilsedore; Andrews, Sean M.

    2015-01-01

    H 2 CO ice on dust grains is an important precursor of complex organic molecules (COMs). H 2 CO gas can be readily observed in protoplanetary disks and may be used to trace COM chemistry. However, its utility as a COM probe is currently limited by a lack of constraints on the relative contributions of two different formation pathways: on icy grain surfaces and in the gas phase. We use archival Atacama Large (sub-)Millimeter Array observations of the resolved distribution of H 2 CO emission in the disk around the young low-mass star DM Tau to assess the relative importance of these formation routes. The observed H 2 CO emission has a centrally peaked and radially broad brightness profile (extending out to 500 AU). We compare these observations with disk chemistry models with and without grain-surface formation reactions and find that both gas and grain-surface chemistry are necessary to explain the spatial distribution of the emission. Gas-phase H 2 CO production is responsible for the observed central peak, while grain-surface chemistry is required to reproduce the emission exterior to the CO snow line (where H 2 CO mainly forms through the hydrogenation of CO ice before being non-thermally desorbed). These observations demonstrate that both gas and grain-surface pathways contribute to the observed H 2 CO in disks and that their relative contributions depend strongly on distance from the host star

  12. Risk of cancer in relatives of patients with myotonic dystrophy

    DEFF Research Database (Denmark)

    Lund, M; Diaz, L J; Gørtz, S

    2014-01-01

    BACKGROUND AND PURPOSE: Myotonic dystrophies (DM) are autosomal dominantly inherited neuromuscular disorders caused by unstable nucleotide repeat expansions. DM and cancer have been associated, but the pathogenesis behind the association remains unclear. It could relate to derived effects of the DM...... genotype in which case non-DM relatives of DM patients would not be expected to be at increased risk of cancer. To elucidate this, a population-based cohort study investigating risk of cancer in relatives of DM patients was conducted. METHODS: DM was identified using the National Danish Patient Registry...

  13. Genome-wide analysis of brain and gonad transcripts reveals changes of key sex reversal-related genes expression and signaling pathways in three stages of Monopterus albus.

    Directory of Open Access Journals (Sweden)

    Wei Chi

    Full Text Available The natural sex reversal severely affects the sex ratio and thus decreases the productivity of the rice field eel (Monopterus albus. How to understand and manipulate this process is one of the major issues for the rice field eel stocking. So far the genomics and transcriptomics data available for this species are still scarce. Here we provide a comprehensive study of transcriptomes of brain and gonad tissue in three sex stages (female, intersex and male from the rice field eel to investigate changes in transcriptional level during the sex reversal process.Approximately 195 thousand unigenes were generated and over 44.4 thousand were functionally annotated. Comparative study between stages provided multiple differentially expressed genes in brain and gonad tissue. Overall 4668 genes were found to be of unequal abundance between gonad tissues, far more than that of the brain tissues (59 genes. These genes were enriched in several different signaling pathways. A number of 231 genes were found with different levels in gonad in each stage, with several reproduction-related genes included. A total of 19 candidate genes that could be most related to sex reversal were screened out, part of these genes' expression patterns were validated by RT-qPCR. The expression of spef2, maats1, spag6 and dmc1 were abundant in testis, but was barely detected in females, while the 17β-hsd12, zpsbp3, gal3 and foxn5 were only expressed in ovary.This study investigated the complexity of brain and gonad transcriptomes in three sex stages of the rice field eel. Integrated analysis of different gene expression and changes in signaling pathways, such as PI3K-Akt pathway, provided crucial data for further study of sex transformation mechanisms.

  14. Perencanaan Sistem Persediaan Bahan Baku Industri Garmen di PT. DM

    OpenAIRE

    Nunung Nurhasanah; Syarif Hidayat; Ajeng Putri Listianingsih; Devi Utami Agustini; Faikar Zakky Haidar; Nida'ul Hasanati

    2016-01-01

    One of the effort to presence with global competition in the era of the Asean Economic Community (AEC) in 2015, making it the various parties, both government, private, and Small and Medium Industries (SMEs) to compete with products made in ASEAN countries. One of the things that can be done is to make the efficiency of the production costs. For that, we need a production planning and control are very closely related to the raw material. The presence of raw materials becomes important because...

  15. The Drosophila DmGluRA is required for social interaction and memory

    Directory of Open Access Journals (Sweden)

    Brian P. Schoenfeld

    2013-05-01

    Full Text Available Metabotropic glutamate receptors (mGluRs have well established roles in cognition andsocial behavior in mammals. Whether or not these roles have been conserved throughoutevolution from invertebrate species is less clear. Mammals have 8 mGluRs whereasDrosophila have a single DmGluRA, which has both Gi and Gq coupled signalingactivity. We have utilized Drosophila to examine the role of DmGluRA in social behaviorand various phases of memory. We have found that flies that are homozygous orheterozygous for loss of function mutations of DmGluRA have impaired social behaviorin male Drosophila. Futhermore, flies that are homozygous or heterozygous for loss offunction mutations of DmGluRA have impaired learning during training, immediate recallmemory, short-term memory and long-term memory as young adults. This workdemonstrates a role for metabotropic glutamate receptor activity in both social behaviorand memory in Drosophila.

  16. Poor glycemic control impacts linear and non-linear dynamics of heart rate in DM type 2

    Directory of Open Access Journals (Sweden)

    Daniela Bassi

    2015-08-01

    Full Text Available INTRODUCTION: It is well known that type 2 diabetes mellitus (T2DM produces cardiovascular autonomic neuropathy (CAN, which may affect the cardiac autonomic modulation. However, it is unclear whether the lack of glycemic control in T2DM without CAN could impact negatively on cardiac autonomic modulation. Objective: To evaluate the relationship between glycemic control and cardiac autonomic modulation in individuals with T2DM without CAN. Descriptive, prospective and cross sectional study.METHODS: Forty-nine patients with T2DM (51±7 years were divided into two groups according to glycosylated hemoglobin (HbA1c: G1≤7% and G2>7.0%. Resting heart rate (HR and RR interval (RRi were obtained and calculated by linear (Mean iRR; Mean HR; rMSSD; STD RR; LF; HF; LF/HF, TINN and RR Tri, and non-linear (SD1; SD2; DFα1; DFα2, Shannon entropy; ApEn; SampEn and CD methods of heart rate variability (HRV. Insulin, HOMA-IR, fasting glucose and HbA1c were obtained by blood tests.RESULTS: G2 (HbA1c≤7% showed lower values for the mean of iRR; STD RR; RR Tri, TINN, SD2, CD and higher mean HR when compared with G1 (HbA1c > 7%. Additionally, HbA1c correlated negatively with mean RRi (r=0.28, p=0.044; STD RR (r=0.33, p=0.017; RR Tri (r=-0.35, p=0.013, SD2 (r=-0.39, p=0.004 and positively with mean HR (r=0.28, p=0.045. Finally, fasting glucose correlated negatively with STD RR (r=-0.36, p=0.010; RR Tri (r=-0.36, p=0.010; TINN (r=-0.33, p=0.019 and SD2 (r=-0.42, p=0.002.CONCLUSION: We concluded that poor glycemic control is related to cardiac autonomic modulation indices in individuals with T2DM even if they do not present cardiovascular autonomic neuropathy.

  17. Changes in transcription of cytokinin metabolism and signalling genes in grape (Vitis vinifera L.) berries are associated with the ripening-related increase in isopentenyladenine.

    Science.gov (United States)

    Böttcher, Christine; Burbidge, Crista A; Boss, Paul K; Davies, Christopher

    2015-09-16

    Cytokinins are known to play an important role in fruit set and early fruit growth, but their involvement in later stages of fruit development is less well understood. Recent reports of greatly increased cytokinin concentrations in the flesh of ripening kiwifruit (Actinidia deliciosa (A. Chev.) C.F. Liang & A.R. Ferguson) and grapes (Vitis vinifera L.) have suggested that these hormones are implicated in the control of ripening-related processes. A similar pattern of isopentenyladenine (iP) accumulation was observed in the ripening fruit of several grapevine cultivars, strawberry (Fragaria ananassa Duch.) and tomato (Solanum lycopersicum Mill.), suggesting a common, ripening-related role for this cytokinin. Significant differences in maximal iP concentrations between grapevine cultivars and between fruit species might reflect varying degrees of relevance or functional adaptations of this hormone in the ripening process. Grapevine orthologues of five Arabidopsis (Arabidopsis thaliana L.) gene families involved in cytokinin metabolism and signalling were identified and analysed for their expression in developing grape berries and a range of other grapevine tissues. Members of each gene family were characterised by distinct expression profiles during berry development and in different grapevine organs, suggesting a complex regulation of cellular cytokinin activities throughout the plant. The post-veraison-specific expression of a set of biosynthesis, activation, perception and signalling genes together with a lack of expression of degradation-related genes during the ripening phase were indicative of a local control of berry iP concentrations leading to the observed accumulation of iP in ripening grapes. The transcriptional analysis of grapevine genes involved in cytokinin production, degradation and response has provided a possible explanation for the ripening-associated accumulation of iP in grapes and other fruit. The pre- and post-veraison-specific expression of

  18. Serum metabonomics of NAFLD plus T2DM based on liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Chen, Yang; Li, Chunlong; Liu, Liyan; Guo, Fuchuan; Li, Songtao; Huang, Lina; Sun, Changhao; Feng, Rennan

    2016-09-01

    Nonalcoholic fatty liver disease (NAFLD), a main liver disease around the world, is closely associated with insulin resistance, type 2 diabetes mellitus (T2DM) and other metabolic diseases. The objective of this study is to identify distinct metabolites of NAFLD patients with or without T2DM. We used a biomarker-discovery population to find distinct metabolites of NAFLD patients with or without T2DM. Then, a validation population was applied to test the model of the biomarker-discovery population. All the individuals received anthropometric and common biochemical measurements. The metabolic data were analyzed by multivariable statistical analyses using ultra-high-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry. There were 7, 7, 2 metabolites in the positive electrospray ionization (ESI(+)) mode, which were identified between groups from both the biomarker-discovery and validation population. The NAFLD group showed higher concentrations of oleamide, l-phenylalanine, l-proline, bilirubin, l-palmitoylcarnitine, and PC (20:5) and a lower concentration of Lyso-PAF C-18 than those of control. Compared with the control group, the NAFLD+T2DM group displayed higher oleamide, l-leucine, LysoPC (14:0), bilirubin, tetradecenoylcarnitine, linoleyl carnitine, and tetradecadiencarnitine in serum. Tetradecenoylcarnitine and tetradecadiencarnitine were more elevated in patients with NAFLD+T2DM than in the NAFLD group. Serum metabonomic analyses displayed great metabolic changes in patients with NAFLD and NAFLD plus T2DM. Our study is beneficial in providing a further view into the pathogenesis and pathophysiology of NAFLD and NAFLD plus T2DM, which might be useful for the prevention and therapy of NAFLD and NAFLD plus T2DM. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  19. Characterization of a Fasciola gigantica protein carrying two DM9 domains reveals cellular relocalization property.

    Science.gov (United States)

    Phadungsil, Wansika; Smooker, Peter M; Vichasri-Grams, Suksiri; Grams, Rudi

    2016-01-01

    Even at the present age of whole-organism analysis, e.g., genomics, transcriptomics, and proteomics, the biological roles of many proteins remain unresolved. Classified among the proteins of unknown function is a family of proteins harboring repeats of the DM9 domain, a 60-75 amino acids motif first described in a small number of Drosophila melanogaster proteins. Proteins may carry two or more DM9 domains either in combination with other domains or as their sole constituent. Here we have characterized a 16.8 kDa Fasciola gigantica protein comprising two tandem repeated DM9 domains (FgDM9-1). The protein was located in the parenchyma of the immature and mature parasite and consequently it was not detected in the ES product of the parasite but only in the whole worm extract. Interestingly, extraction with SDS yielded a substantially higher amount of the protein suggesting association with insoluble cell components. In Sf9 insect cells a heterologously expressed EGFP-FgDM9-1 chimera showed cell-wide distribution but relocated to vesicle-like structures in the cytoplasm after stimulating cellular stress by bacteria, heat shock or chloroquine. These structures did not colocalize with the markers of endocytosis/phagocytosis ubiquitin, RAB7, GABARAP. The same behavior was noted for Aedes aegypti PRS1, a homologous mosquito DM9 protein as a positive control while EGFP did not exhibit such relocation in the insect cells. Cross-linking experiments on soluble recombinant FgDM9-1 indicated that the protein can undergo specific oligomerization. It is speculated that proteins carrying the DM9 domain have a role in vesicular transport in flatworms and insects. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. The clinical significance of serum Leptin in the pathogenesis of 2DM and obesity

    International Nuclear Information System (INIS)

    Liu Chunyu; Lu Kuan; Gao Yanyan

    2001-01-01

    Objective: To study the relationship between serum Leptin ad insulin, body fat distribution and testosterone in 2-DM patients. Methods: The fasting blood serum Leptin and insulin levels in 65 2DM patients and 42 controls were measured by radioimmunoassay. Abdominal subcutaneous adipose tissue volume (ASF) and abdominal visceral adipose tissue volume (AVF) were measured by spiral CT SSD soft-ware in 32 2DM patients. The authors also measured the Leptin before and 2h after a 75 g OGTT in 34 2DM patients and fasting plasma testosterone in 30 2DM males. Results: DM group and normal group had equal number of females and were matched in BMI. Baseline plasma Leptin concentrations were not significantly different between the groups (P 14 mmol/L) had lower Leptin levels (P < 0.05). Sex, BMI, ASF were important factors contributing to the serum Leptin. The Leptin concentrations were significantly positively correlated with BMI (r 0.57, P0.0001), ASF(r = 0.67 P0.025) and insulin (r = 0.47, P0.0013) and was negative correlated with the serum testosterone (r = -0.061, P0.025). Conclusion: There were no abnormal Leptin levels in 2DM implies, suggesting that Leptin might not be the main causing factor in 2DM. The poorly metabolic controlled patients might have lack of Leptin. The lower Leptin levels in men might be caused by testosterone, sex BMI, ASF were important factors contributing to the serum Leptin levels

  1. Hubungan Lama Menderita DM dengan Perilaku Perawatan Kaki secara Mandiri untuk Mencegah Ulkus Diabetikum

    OpenAIRE

    Apriliyasari, Renny Wulan

    2015-01-01

    Diabetes Mellitus (DM) atau yang biasa disebut kencing manis merupakan suatu kelompok penyakit metabolik dengan karakteristik gula darah melebihi nilai normal. Data dari Dinas Kesehatan Kabupaten Pati jumlah penderita DM meningkat, dengan rata-rata pada 2 tahun 2008-2009 sebanyak 1950 orang. Hasil survey di RSUD RAA Soewondo Pati, penyakit diabetes mellitus menempati peringkat pertama penyakit rawat jalan 2013 dengan 3893 total kunjungan atau sebesar 4,83%. Salah satu hal penting pada pasien ...

  2. DNA topoisomerase 1α promotes transcriptional silencing of transposable elements through DNA methylation and histone lysine 9 dimethylation in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Thanh Theresa Dinh

    2014-07-01

    Full Text Available RNA-directed DNA methylation (RdDM and histone H3 lysine 9 dimethylation (H3K9me2 are related transcriptional silencing mechanisms that target transposable elements (TEs and repeats to maintain genome stability in plants. RdDM is mediated by small and long noncoding RNAs produced by the plant-specific RNA polymerases Pol IV and Pol V, respectively. Through a chemical genetics screen with a luciferase-based DNA methylation reporter, LUCL, we found that camptothecin, a compound with anti-cancer properties that targets DNA topoisomerase 1α (TOP1α was able to de-repress LUCL by reducing its DNA methylation and H3K9me2 levels. Further studies with Arabidopsis top1α mutants showed that TOP1α silences endogenous RdDM loci by facilitating the production of Pol V-dependent long non-coding RNAs, AGONAUTE4 recruitment and H3K9me2 deposition at TEs and repeats. This study assigned a new role in epigenetic silencing to an enzyme that affects DNA topology.

  3. Association between the NF-E2 Related Factor 2 Gene Polymorphism and Oxidative Stress, Anti-Oxidative Status, and Newly-Diagnosed Type 2 Diabetes Mellitus in a Chinese Population

    Directory of Open Access Journals (Sweden)

    Xia Wang

    2015-07-01

    Full Text Available Oxidative stress is a major risk factor in the onset and progression of type 2 diabetes mellitus (T2DM. NF-E2 related factor 2 (NRF2 is a pivotal transcription factor in oxidative stress related illnesses. This study included 2174 subjects with 879 cases of newly-diagnosed T2DM and 1295 healthy controls. Compared to individuals with the CC genotype, those with the AA genotype had lower total anti-oxidative capacity, superoxide dismutase, catalase, glutathione, glutathione peroxidase activity; and lower homeostasis model assessment of β-cell function index. Those with the AA genotype also had a higher malondialdehyde concentration and homeostasis model assessment of insulin resistance index values. The frequency of allele A was significantly higher in T2DM subjects (29.4%, compared to control subjects (26.1%; p = 0.019. Individuals with the AA genotype had a significantly higher risk of developing T2DM (OR 1.56; 95% CI 1.11, 2.20; p = 0.011, relative to those with the CC genotype, even after adjusting for known T2DM risk factors. Our results suggest that the NRF2 rs6721961 polymorphism was significantly associated with oxidative stress, anti-oxidative status, and risk of newly-diagnosed T2DM. This polymorphism may also contribute to impaired insulin secretory capacity and increased insulin resistance in a Chinese population.

  4. Growth arrest-specific transcript 5 associated snoRNA levels are related to p53 expression and DNA damage in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Jonathan Krell

    Full Text Available The growth arrest-specific transcript 5 gene (GAS5 encodes a long noncoding RNA (lncRNA and hosts a number of small nucleolar RNAs (snoRNAs that have recently been implicated in multiple cellular processes and cancer. Here, we investigate the relationship between DNA damage, p53, and the GAS5 snoRNAs to gain further insight into the potential role of this locus in cell survival and oncogenesis both in vivo and in vitro.We used quantitative techniques to analyse the effect of DNA damage on GAS5 snoRNA expression and to assess the relationship between p53 and the GAS5 snoRNAs in cancer cell lines and in normal, pre-malignant, and malignant human colorectal tissue and used biological techniques to suggest potential roles for these snoRNAs in the DNA damage response.GAS5-derived snoRNA expression was induced by DNA damage in a p53-dependent manner in colorectal cancer cell lines and their levels were not affected by DICER. Furthermore, p53 levels strongly correlated with GAS5-derived snoRNA expression in colorectal tissue.In aggregate, these data suggest that the GAS5-derived snoRNAs are under control of p53 and that they have an important role in mediating the p53 response to DNA damage, which may not relate to their function in the ribosome. We suggest that these snoRNAs are not processed by DICER to form smaller snoRNA-derived RNAs with microRNA (miRNA-like functions, but their precise role requires further evaluation. Furthermore, since GAS5 host snoRNAs are often used as endogenous controls in qPCR quantifications we show that their use as housekeeping genes in DNA damage experiments can lead to inaccurate results.

  5. Activated nuclear transcription factor κB in patients with myocarditis and dilated cardiomyopathy-relation to inflammation and cardiac function

    International Nuclear Information System (INIS)

    Alter, Peter; Rupp, Heinz; Maisch, Bernhard

    2006-01-01

    Objectives and background: Myocarditis is caused by various agents and autoimmune processes. It is unknown whether viral genome persistence represents inactive remnants of previous infections or whether it is attributed to ongoing adverse processes. The latter also applies to the course of autoimmune myocarditis. One principal candidate for an adverse remodeling is nuclear factor-κB (NFκB). Methods: A total of 93 patients with suspected myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by echocardiography as well as right and left heart catheterization. Endomyocardial biopsies were taken from the left ventricle. Biopsies were examined by immunohistochemistry and PCR for viral genomes. Selective immunostaining of activated NFκB was performed. Results: NFκB was increased in patients with myocarditis when compared with controls (11.1 ± 7.1% vs. 5.0 ± 5.3%, P 2 = 0.72, P 2 = 0.43, P < 0.02). Increased activated NFκB was found in adenovirus persistence when compared with controls (P = 0.001). Only a trend of increased NFκB activation was seen in cytomegalovirus persistence. Parvovirus B19 persistence did not affect NFκB activation. Conclusions: Increased activation of NFκB is related to inflammatory processes in myocarditis. Since activated NFκB correlates with left ventricular function, it could be assumed that NFκB activation occurs at early stages of inflammation. Potentially, NFκB could inhibit loss of cardiomyocytes by apoptosis and protect from cardiac dilation. Since NFκB is a crucial key transcription factor of inflammation, its prognostic and future therapeutic relevance should be addressed

  6. Comparative evaluation of average glandular dose and breast cancer detection between single-view digital breast tomosynthesis (DBT) plus single-view digital mammography (DM) and two-view DM: correlation with breast thickness and density

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Sung Ui; Chang, Jung Min; Bae, Min Sun; Lee, Su Hyun; Cho, Nariya; Seo, Mirinae; Kim, Won Hwa; Moon, Woo Kyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of)

    2015-01-15

    To compare the average glandular dose (AGD) and diagnostic performance of mediolateral oblique (MLO) digital breast tomosynthesis (DBT) plus cranio-caudal (CC) digital mammography (DM) with two-view DM, and to evaluate the correlation of AGD with breast thickness and density. MLO and CC DM and DBT images of both breasts were obtained in 149 subjects. AGDs of DBT and DM per exposure were recorded, and their correlation with breast thickness and density were evaluated. Paired data of MLO DBT plus CC DM and two-view DM were reviewed for presence of malignancy in a jack-knife alternative free-response ROC (JAFROC) method. The AGDs of both DBT and DM, and differences in AGD between DBT and DM (ΔAGD), were correlated with breast thickness and density. The average JAFROC figure of merit (FOM) was significantly higher on the combined technique than two-view DM (P = 0.005). In dense breasts, the FOM and sensitivity of the combined technique was higher than that of two-view DM (P = 0.003) with small ΔAGD. MLO DBT plus CC DM provided higher diagnostic performance than two-view DM in dense breasts with a small increase in AGD. (orig.)

  7. Comparative evaluation of average glandular dose and breast cancer detection between single-view digital breast tomosynthesis (DBT) plus single-view digital mammography (DM) and two-view DM: correlation with breast thickness and density

    International Nuclear Information System (INIS)

    Shin, Sung Ui; Chang, Jung Min; Bae, Min Sun; Lee, Su Hyun; Cho, Nariya; Seo, Mirinae; Kim, Won Hwa; Moon, Woo Kyung

    2015-01-01

    To compare the average glandular dose (AGD) and diagnostic performance of mediolateral oblique (MLO) digital breast tomosynthesis (DBT) plus cranio-caudal (CC) digital mammography (DM) with two-view DM, and to evaluate the correlation of AGD with breast thickness and density. MLO and CC DM and DBT images of both breasts were obtained in 149 subjects. AGDs of DBT and DM per exposure were recorded, and their correlation with breast thickness and density were evaluated. Paired data of MLO DBT plus CC DM and two-view DM were reviewed for presence of malignancy in a jack-knife alternative free-response ROC (JAFROC) method. The AGDs of both DBT and DM, and differences in AGD between DBT and DM (ΔAGD), were correlated with breast thickness and density. The average JAFROC figure of merit (FOM) was significantly higher on the combined technique than two-view DM (P = 0.005). In dense breasts, the FOM and sensitivity of the combined technique was higher than that of two-view DM (P = 0.003) with small ΔAGD. MLO DBT plus CC DM provided higher diagnostic performance than two-view DM in dense breasts with a small increase in AGD. (orig.)

  8. A Protein Complex Required for Polymerase V Transcripts and RNA- Directed DNA Methylation in Arabidopsis

    KAUST Repository

    Law, Julie A.

    2010-05-01

    DNA methylation is an epigenetic modification associated with gene silencing. In Arabidopsis, DNA methylation is established by DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), which is targeted by small interfering RNAs through a pathway termed RNA-directed DNA methylation (RdDM) [1, 2]. Recently, RdDM was shown to require intergenic noncoding (IGN) transcripts that are dependent on the Pol V polymerase. These transcripts are proposed to function as scaffolds for the recruitment of downstream RdDM proteins, including DRM2, to loci that produce both siRNAs and IGN transcripts [3]. However, the mechanism(s) through which Pol V is targeted to specific genomic loci remains largely unknown. Through affinity purification of two known RdDM components, DEFECTIVE IN RNA-DIRECTED DNA METHYLATION 1 (DRD1) [4] and DEFECTIVE IN MERISTEM SILENCING 3 (DMS3) [5, 6], we found that they copurify with each other and with a novel protein, RNA-DIRECTED DNA METHYLATION 1 (RDM1), forming a complex we term DDR. We also found that DRD1 copurified with Pol V subunits and that RDM1, like DRD1 [3] and DMS3 [7], is required for the production of Pol V-dependent transcripts. These results suggest that the DDR complex acts in RdDM at a step upstream of the recruitment or activation of Pol V. © 2010 Elsevier Ltd. All rights reserved.

  9. A Protein Complex Required for Polymerase V Transcripts and RNA- Directed DNA Methylation in Arabidopsis

    KAUST Repository

    Law, Julie A.; Ausí n, Israel; Johnson, Lianna M.; Vashisht, Ajay  A Amar; Zhu, Jian-Kang; Wohlschlegel, James  A A.; Jacobsen, Steven E.

    2010-01-01

    DNA methylation is an epigenetic modification associated with gene silencing. In Arabidopsis, DNA methylation is established by DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), which is targeted by small interfering RNAs through a pathway termed RNA-directed DNA methylation (RdDM) [1, 2]. Recently, RdDM was shown to require intergenic noncoding (IGN) transcripts that are dependent on the Pol V polymerase. These transcripts are proposed to function as scaffolds for the recruitment of downstream RdDM proteins, including DRM2, to loci that produce both siRNAs and IGN transcripts [3]. However, the mechanism(s) through which Pol V is targeted to specific genomic loci remains largely unknown. Through affinity purification of two known RdDM components, DEFECTIVE IN RNA-DIRECTED DNA METHYLATION 1 (DRD1) [4] and DEFECTIVE IN MERISTEM SILENCING 3 (DMS3) [5, 6], we found that they copurify with each other and with a novel protein, RNA-DIRECTED DNA METHYLATION 1 (RDM1), forming a complex we term DDR. We also found that DRD1 copurified with Pol V subunits and that RDM1, like DRD1 [3] and DMS3 [7], is required for the production of Pol V-dependent transcripts. These results suggest that the DDR complex acts in RdDM at a step upstream of the recruitment or activation of Pol V. © 2010 Elsevier Ltd. All rights reserved.

  10. Contribution of the drought tolerance-related Stress-responsive NAC1 transcription factor to resistance of barley to Ramularia leaf spot

    OpenAIRE

    MCGRANN, GRAHAM R D; STEED, ANDREW; BURT, CHRISTOPHER; GODDARD, RACHEL; LACHAUX, CLEA; BANSAL, ANURADHA; CORBITT, MARGARET; GORNIAK, KALINA; NICHOLSON, PAUL; BROWN, JAMES K M

    2014-01-01

    NAC proteins are plant transcription factors that are involved in tolerance to abiotic and biotic stresses, as well as in many developmental processes. Stress-responsive NAC1 (SNAC1) transcription factor is involved in drought tolerance in barley and rice, but has not been shown previously to have a role in disease resistance. Transgenic over-expression of HvSNAC1 in barley cv. Golden Promise reduced the severity of Ramularia leaf spot (RLS), caused by the fungus Ramularia collo-cygni, but ha...

  11. Attitudes and barriers to exercise in adults with type 1 diabetes (T1DM and how best to address them: a qualitative study.

    Directory of Open Access Journals (Sweden)

    Nadia Lascar

    Full Text Available Regular physical activity has recognised health benefits for people with T1DM. However a significant proportion of them do not undertake the recommended levels of activity. Whilst questionnaire-based studies have examined barriers to exercise in people with T1DM, a formal qualitative analysis of these barriers has not been undertaken. Our aims were to explore attitudes, barriers and facilitators to exercise in patients with T1DM.A purposeful sample of long standing T1DM patients were invited to participate in this qualitative study. Twenty-six adults were interviewed using a semi-structured interview schedule to determine their level of exercise and barriers to initiation and maintenance of an exercise programme.Six main barriers to exercise were identified: lack of time and work related factors; access to facilities; lack of motivation; embarrassment and body image; weather; and diabetes specific barriers (low levels of knowledge about managing diabetes and its complications around exercise. Four motivators to exercise were identified: physical benefits from exercise; improvements in body image; enjoyment and the social interaction of exercising at gym or in groups. Three facilitators to exercise were identified: free or reduced admission to gyms and pools, help with time management, and advice and encouragement around managing diabetes for exercise.Many of the barriers to exercise in people with T1DM are shared with the non-diabetic population. The primary difference is the requirement for education about the effect of exercise on diabetes control and its complications. There was a preference for support to be given on a one to one basis rather than in a group environment. This suggests that with the addition of the above educational requirements, one to one techniques that have been successful in increasing activity in patients with other chronic disease and the general public should be successful in increasing activity in patients with T1DM.

  12. Attitudes and barriers to exercise in adults with type 1 diabetes (T1DM) and how best to address them: a qualitative study.

    Science.gov (United States)

    Lascar, Nadia; Kennedy, Amy; Hancock, Beverley; Jenkins, David; Andrews, Robert C; Greenfield, Sheila; Narendran, Parth

    2014-01-01

    Regular physical activity has recognised health benefits for people with T1DM. However a significant proportion of them do not undertake the recommended levels of activity. Whilst questionnaire-based studies have examined barriers to exercise in people with T1DM, a formal qualitative analysis of these barriers has not been undertaken. Our aims were to explore attitudes, barriers and facilitators to exercise in patients with T1DM. A purposeful sample of long standing T1DM patients were invited to participate in this qualitative study. Twenty-six adults were interviewed using a semi-structured interview schedule to determine their level of exercise and barriers to initiation and maintenance of an exercise programme. Six main barriers to exercise were identified: lack of time and work related factors; access to facilities; lack of motivation; embarrassment and body image; weather; and diabetes specific barriers (low levels of knowledge about managing diabetes and its complications around exercise). Four motivators to exercise were identified: physical benefits from exercise; improvements in body image; enjoyment and the social interaction of exercising at gym or in groups. Three facilitators to exercise were identified: free or reduced admission to gyms and pools, help with time management, and advice and encouragement around managing diabetes for exercise. Many of the barriers to exercise in people with T1DM are shared with the non-diabetic population. The primary difference is the requirement for education about the effect of exercise on diabetes control and its complications. There was a preference for support to be given on a one to one basis rather than in a group environment. This suggests that with the addition of the above educational requirements, one to one techniques that have been successful in increasing activity in patients with other chronic disease and the general public should be successful in increasing activity in patients with T1DM.

  13. Induction of dexamethasone (DM) of histidine decarboxylase (HDC) in mast cells

    International Nuclear Information System (INIS)

    Ichikawa, A.; Imanishi, N.; Nakayama, T.; Asano, M.; Tomita, K.

    1986-01-01

    Effects of glucocorticoids on HDC in cultured mouse mastocytoma P-815 cells and rat peritoneal mast cells (RPMC) were investigated to explore the role of steroids in inflammatory tissues. DM (1 nM to 10 μM) significantly elevated the histamine content and HDC activity of P-815 cells (37 0 C, 24 hrs), accompanying with a growth retardation of the cells by about 40%. In contrast to histamine, serotonin levels of P-815 cells were decreased by treatment with DM. However, DM had no significant effects on the activities of various enzymes other than HDC present in granules or membrane of P-815 cells. DM-induced increases of histamine and HDC activity were completely suppressed by the addition of cycloheximide and actinomycin D. P-815 cells were found to have the binding sites for 3 H-DM in the cytosol (Kd=2.2 nM, 450 sites/cell) and in the nuclei (Kd=0.1 nM, 39 sites/nucleus). Purified HDC from P-815 cells was identified to be an isozyme of mast cell type enzyme (MW=110K, pI=5.4). In contrast, the basal histamine level of cultured RPMC was not affected by treatment of DM, which suppressed histamine release activity induced by DNP-ascaris antiserum by 40%-50%. Histamine-depleted RPMC after degranulation partially recovered histamine level by 50%-60% in the presence of DM. These results showed that glucocorticoids specifically stimulated histamine formation with the increased de novo synthesis of HDC in mast cells

  14. De novo transcriptome sequence assembly and identification of AP2/ERF transcription factor related to abiotic stress in parsley (Petroselinum crispum.

    Directory of Open Access Journals (Sweden)

    Meng-Yao Li

    Full Text Available Parsley is an important biennial Apiaceae species that is widely cultivated as herb, spice, and vegetable. Previous studies on parsley principally focused on its physiological and biochemical properties, including phenolic compound and volatile oil contents. However, little is known about the molecular and genetic properties of parsley. In this study, 23,686,707 high-quality reads were obtained and assembled into 81,852 transcripts and 50,161 unigenes for the first time. Functional annotation showed that 30,516 unigenes had sequence similarity to known genes. In addition, 3,244 putative simple sequence repeats were detected in curly parsley. Finally, 1,569 of the identified unigenes belonged to 58 transcription factor families. Various abiotic stresses have a strong detrimental effect on the yield and quality of parsley. AP2/ERF transcription factors have important functions in plant development, hormonal regulation, and abiotic response. A total of 88 putative AP2/ERF factors were identified from the transcriptome sequence of parsley. Seven AP2/ERF transcription factors were selected in this study to analyze the expression profiles of parsley under different abiotic stresses. Our data provide a potentially valuable resource that can be used for intensive parsley research.

  15. De novo transcriptome sequence assembly and identification of AP2/ERF transcription factor related to abiotic stress in parsley (Petroselinum crispum).

    Science.gov (United States)

    Li, Meng-Yao; Tan, Hua-Wei; Wang, Feng; Jiang, Qian; Xu, Zhi-Sheng; Tian, Chang; Xiong, Ai-Sheng

    2014-01-01

    Parsley is an important biennial Apiaceae species that is widely cultivated as herb, spice, and vegetable. Previous studies on parsley principally focused on its physiological and biochemical properties, including phenolic compound and volatile oil contents. However, little is known about the molecular and genetic properties of parsley. In this study, 23,686,707 high-quality reads were obtained and assembled into 81,852 transcripts and 50,161 unigenes for the first time. Functional annotation showed that 30,516 unigenes had sequence similarity to known genes. In addition, 3,244 putative simple sequence repeats were detected in curly parsley. Finally, 1,569 of the identified unigenes belonged to 58 transcription factor families. Various abiotic stresses have a strong detrimental effect on the yield and quality of parsley. AP2/ERF transcription factors have important functions in plant development, hormonal regulation, and abiotic response. A total of 88 putative AP2/ERF factors were identified from the transcriptome sequence of parsley. Seven AP2/ERF transcription factors were selected in this study to analyze the expression profiles of parsley under different abiotic stresses. Our data provide a potentially valuable resource that can be used for intensive parsley research.

  16. Complementarity of DM Searches in a Consistent Simplified Model: the Case of Z'

    CERN Document Server

    Jacques, Thomas; Morgante, Enrico; Racco, Davide; Rameez, Mohamed; Riotto, Antonio

    2016-01-01

    We analyze the constraints from direct and indirect detection on fermionic Majorana Dark Matter (DM). Because the interaction with the Standard Model (SM) particles is spin-dependent, a priori the constraints that one gets from neutrino telescopes, the LHC and direct detection experiments are comparable. We study the complementarity of these searches in a particular example, in which a heavy $Z'$ mediates the interactions between the SM and the DM. We find that in most cases IceCube provides the strongest bounds on this scenario, while the LHC constraints are only meaningful for smaller dark matter masses. These light masses are less motivated by thermal relic abundance considerations. We show that the dominant annihilation channels of the light DM in the Sun are either $b \\bar b$ or $t \\bar t$, while the heavy DM annihilation is completely dominated by $Zh$ channel. The latter produces a hard neutrino spectrum which has not been previously analyzed. We study the neutrino spectrum yielded by DM and recast Ice...

  17. Complementarity of DM searches in a consistent simplified model: the case of Z′

    International Nuclear Information System (INIS)

    Jacques, Thomas; Katz, Andrey; Morgante, Enrico; Racco, Davide; Rameez, Mohamed; Riotto, Antonio

    2016-01-01

    We analyze the constraints from direct and indirect detection on fermionic Majorana Dark Matter (DM). Because the interaction with the Standard Model (SM) particles is spin-dependent, a priori the constraints that one gets from neutrino telescopes, the LHC, direct and indirect detection experiments are comparable. We study the complementarity of these searches in a particular example, in which a heavy Z ′ mediates the interactions between the SM and the DM. We find that for heavy dark matter indirect detection provides the strongest bounds on this scenario, while IceCube bounds are typically stronger than those from direct detection. The LHC constraints are dominant for smaller dark matter masses. These light masses are less motivated by thermal relic abundance considerations. We show that the dominant annihilation channels of the light DM in the Sun and the Galactic Center are either bb̄ or tt̄, while the heavy DM annihilation is completely dominated by Zh channel. The latter produces a hard neutrino spectrum which has not been previously analyzed. We study the neutrino spectrum yielded by DM and recast IceCube constraints to allow proper comparison with constraints from direct and indirect detection experiments and LHC exclusions.

  18. Replacing single-view mediolateral oblique (MLO) digital mammography (DM) with synthesized mammography (SM) with digital breast tomosynthesis (DBT) images: Comparison of the diagnostic performance and radiation dose with two-view DM with or without MLO-DBT

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hyo-Jin [Department of Radiology, Seoul National University Hospital, 03080 (Korea, Republic of); Chang, Jung Min, E-mail: imchangjm@gmail.com [Department of Radiology, Seoul National University Hospital, 03080 (Korea, Republic of); Department of Radiology, Seoul National University College of Medicine, 03080 (Korea, Republic of); Lee, Joongyub [Medical Research Collaborating Center, Biomedical Research Institution, Seoul National University Hospital, 03080 (Korea, Republic of); Song, Sung Eun; Shin, Sung Ui [Department of Radiology, Seoul National University Hospital, 03080 (Korea, Republic of); Kim, Won Hwa [Department of Radiology, Kyungpook National University Hospital, 41944 (Korea, Republic of); Bae, Min Sun [Department of Radiology, Seoul National University Hospital, 03080 (Korea, Republic of); Moon, Woo Kyung [Department of Radiology, Seoul National University Hospital, 03080 (Korea, Republic of); Department of Radiology, Seoul National University College of Medicine, 03080 (Korea, Republic of); Institute of Radiation Medicine, Seoul National University College Medical Research Center, 03080 (Korea, Republic of)

    2016-11-15

    Objectives: To evaluate the diagnostic performance and radiation dose of single view cranio-caudal (CC) digital mammography (DM) plus mediolateral oblique (MLO) digital breast tomosynthesis (DBT) combined with synthesized mammography (SM) in comparison with two-view DM with or without DBT. Material and methods: This study was approved by our institutional review board, and informed consent was obtained from 130 women. Paired two-view DM and single MLO-DBT with SM images were acquired, and four independent retrospective reading sessions of different combinations of DM, SM and DBT were performed for the presence of malignant tumors using jackknife alternative free-response receiver operator curve (JAFROC) methods. The diagnostic performances and average glandular dose (AGD) were compared between different combinations of DM, SM and DBT. Results: Of 159 lesions in 130 patients, 27 were malignant. When using MLO-DBT with SM instead of MLO-DM, a significantly higher sensitivity (P = 0.016) and specificity (P = 0.012) were noted than with two-view DM, and comparable figure of merit (FOM), sensitivity, and specificity to two-view DM with DBT were noted. The mean AGD of CC-DM plus MLO-DBT with SM was 5.78mGy ± 1.06 per patient, which was significantly lower than that with two-view DM with MLO-DBT (8.45mGy ± 1.32; P <0.001) and slightly higher than that with two-view DM (5.30mGy ± 0.63). Conclusions: The combined use of CC-DM plus MLO-DBT with SM showed higher sensitivity and specificity to two-view DM with a smaller AGD increment and comparable diagnostic performance to that of two-view DM with MLO-DBT with a significantly lower mean AGD.

  19. [HDL-C/apoA-I]: A multivessel cardiometabolic risk marker in women with T2DM.

    Science.gov (United States)

    Hermans, Michel P; Valensi, Paul; Ahn, Sylvie A; Rousseau, Michel F

    2018-01-01

    Although women have higher high-density lipoprotein cholesterol (HDL-C) than have men, their HDL particles are also prone to become small, dense, and dysfunctional in case of type 2 diabetes mellitus (T2DM). To assess the vascular risk related to HDLs of different sizes/densities without direct measurement, we adjusted HDL-C to its main apolipoprotein (apoA-I) as [HDL-C/apoA-I]. This ratio estimates HDL sizes and provides indices as to their number, cholesterol load, and density. We stratified 280 Caucasian T2DM women according to [HDL-C/apoA-I] quartiles (Q) to determine how they are segregated according to cardiometabolic risk, β-cell function, glycaemic control, and vascular complications. Five parameters were derived from combined determination of HDL-C and apoA-I: HDL size, HDL number, cholesterol load per particle (pP), apoA-I pP, and HDL density. An adverse cardiometabolic profile characterized QI and QII patients whose HDLs were denser and depleted in apoA-I, whereas QIII patients had HDLs with characteristics closer to those of controls. QIV patients had HDLs of supernormal size/composition and a more favourable phenotype in terms of fat distribution; insulin sensitivity (64% vs 41%), metabolic syndrome, and β-cell function (32% vs 23%); exogenous insulin (44 vs 89 U·d -1 ); and glycaemic control (glycated haemoglobin, 56 vs 61 mmol·mol -1 ), associated with lower prevalence of microvascular/macrovascular complications: all-cause microangiopathy 47% vs 61%; retinopathy 22% vs 34%; all-cause macroangiopathy 19% vs 31%; and coronary artery disease 6% vs 24% (P women according to metabolic phenotype, macrovascular and coronary damage, β-cell function, microangiopathic risk, and retinopathy. This ratio is a versatile and readily available marker of cardiometabolic status and vascular complications in T2DM women. Copyright © 2017 John Wiley & Sons, Ltd.

  20. bZIP transcription factor SmJLB1 regulates autophagy-related genes Smatg8 and Smatg4 and is required for fruiting-body development and vegetative growth in Sordaria macrospora.

    Science.gov (United States)

    Voigt, Oliver; Herzog, Britta; Jakobshagen, Antonia; Pöggeler, Stefanie

    2013-12-01

    Autophagy is a precisely controlled degradation process in eukaryotic cells, during which the bulk of the cytoplasm is engulfed by a double membrane vesicle, the autophagosome. Fusion of the autophagosome with the vacuole leads to breakdown of its contents, such as proteins and organelles, and the recycling of nutrients. Earlier studies of autophagic genes of the core autophagic machinery in the filamentous ascomycete Sordaria macrospora elucidated the impact of autophagy on fungal viability, vegetative growth and fruiting-body development. To gain further knowledge about the regulation of autophagy in S. macrospora, we analyzed the function of the bZIP transcription factor SmJLB1, a homolog of the Podospora anserina basic zipper-type transcription factor induced during incompatibility 4 (IDI-4) and the Aspergillus nidulans transcription factor jun-like bZIP A (JlbA). Generation of the homokaryotic deletion mutant demonstrated S. macrospora Smjlb1 is associated with autophagy-dependent processes. Deletion of Smjlb1 abolished fruiting-body formation and impaired vegetative growth. SmJLB1 is localized to the cytoplasm and to nuclei. Quantitative real-time PCR experiments revealed an upregulated expression of autophagy-related genes Smatg8 and Smatg4 in the Smjlb1 deletion mutant, suggesting a transcriptional repression function of SmJLB1. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Production and processing of siRNA precursor transcripts from the highly repetitive maize genome.

    Directory of Open Access Journals (Sweden)

    Christopher J Hale

    2009-08-01

    Full Text Available Mutations affecting the maintenance of heritable epigenetic states in maize identify multiple RNA-directed DNA methylation (RdDM factors including RMR1, a novel member of a plant-specific clade of Snf2-related proteins. Here we show that RMR1 is necessary for the accumulation of a majority of 24 nt small RNAs, including those derived from Long-Terminal Repeat (LTR retrotransposons, the most common repetitive feature in the maize genome. A genetic analysis of DNA transposon repression indicates that RMR1 acts upstream of the RNA-dependent RNA polymerase, RDR2 (MOP1. Surprisingly, we show that non-polyadenylated transcripts from a sampling of LTR retrotransposons are lost in both rmr1 and rdr2 mutants. In contrast, plants deficient for RNA Polymerase IV (Pol IV function show an increase in polyadenylated LTR RNA transcripts. These findings support a model in which Pol IV functions independently of the small RNA accumulation facilitated by RMR1 and RDR2 and support that a loss of Pol IV leads to RNA Polymerase II-based transcription. Additionally, the lack of changes in general genome homeostasis in rmr1 mutants, despite the global loss of 24 nt small RNAs, challenges the perceived roles of siRNAs in maintaining functional heterochromatin in the genomes of outcrossing grass species.

  2. SGLT-2 Inhibitors: Are They a Promising Treatment Option in T2DM Patients with NAFLD?

    Directory of Open Access Journals (Sweden)

    Dimitrios Patoulias

    2018-04-01

    Full Text Available Sodium glucose co-transporter type 2 inhibitors (SGLT-2 inhibitors are a class of antidiabetics, recently approved for the treatment of patients with T2DM. They feature cardioprotective and renoprotective action, while they exert beneficial effects on metabolic parameters. Non-alcoholic fatty liver disease (NAFLD is a frequent co-morbidity in diabetic patients. Its prevalence reaches up to 70%. Since there is no specific treatment approved for NAFLD, both experimental and clinical studies have been recently conducted highlighting the efficacy and safety of SGLT-2 inhibitors mainly in animal models and secondarily in patients with T2DM and NAFLD. This class of antidiabetics seems very attractive, improving both glycemic control and liver function tests, while inhibiting NAFLD progression. However, further investigation is required to establish them as a first-line treatment option in T2DM patients with NAFLD, after thorough assessment of their efficacy and safety in clinical practice.

  3. Plant insecticide L-canavanine repels Drosophila via the insect orphan GPCR DmX.

    Directory of Open Access Journals (Sweden)

    Christian Mitri

    2009-06-01

    Full Text Available For all animals, the taste sense is crucial to detect and avoid ingesting toxic molecules. Many toxins are synthesized by plants as a defense mechanism against insect predation. One example of such a natural toxic molecule is L-canavanine, a nonprotein amino acid found in the seeds of many legumes. Whether and how insects are informed that some plants contain L-canavanine remains to be elucidated. In insects, the taste sense relies on gustatory receptors forming the gustatory receptor (Gr family. Gr proteins display highly divergent sequences, suggesting that they could cover the entire range of tastants. However, one cannot exclude the possibility of evolutionarily independent taste receptors. Here, we show that L-canavanine is not only toxic, but is also a repellent for Drosophila. Using a pharmacogenetic approach, we find that flies sense food containing this poison by the DmX receptor. DmXR is an insect orphan G-protein-coupled receptor that has partially diverged in its ligand binding pocket from the metabotropic glutamate receptor family. Blockade of DmXR function with an antagonist lowers the repulsive effect of L-canavanine. In addition, disruption of the DmXR encoding gene, called mangetout (mtt, suppresses the L-canavanine repellent effect. To avoid the ingestion of L-canavanine, DmXR expression is required in bitter-sensitive gustatory receptor neurons, where it triggers the premature retraction of the proboscis, thus leading to the end of food searching. These findings show that the DmX receptor, which does not belong to the Gr family, fulfills a gustatory function necessary to avoid eating a natural toxin.

  4. Transcription of Byzantine Chant - Problems, Possibilities, Formats

    DEFF Research Database (Denmark)

    Troelsgård, Christian

    2007-01-01

    Discusses the problems and possibilities for transsription of Byzantine chant on the basis of medieval musical manuscripts. A relatively 'neutral' style of transcription is suggested for musicological purposes.......Discusses the problems and possibilities for transsription of Byzantine chant on the basis of medieval musical manuscripts. A relatively 'neutral' style of transcription is suggested for musicological purposes....

  5. Contribution of the drought tolerance-related Stress-responsive NAC1 transcription factor to resistance of barley to Ramularia leaf spot

    Science.gov (United States)

    MCGRANN, GRAHAM R D; STEED, ANDREW; BURT, CHRISTOPHER; GODDARD, RACHEL; LACHAUX, CLEA; BANSAL, ANURADHA; CORBITT, MARGARET; GORNIAK, KALINA; NICHOLSON, PAUL; BROWN, JAMES K M

    2015-01-01

    NAC proteins are plant transcription factors that are involved in tolerance to abiotic and biotic stresses, as well as in many developmental processes. Stress-responsive NAC1 (SNAC1) transcription factor is involved in drought tolerance in barley and rice, but has not been shown previously to have a role in disease resistance. Transgenic over-expression of HvSNAC1 in barley cv. Golden Promise reduced the severity of Ramularia leaf spot (RLS), caused by the fungus Ramularia collo-cygni, but had no effect on disease symptoms caused by Fusarium culmorum, Oculimacula yallundae (eyespot), Blumeria graminis f. sp. hordei (powdery mildew) or Magnaporthe oryzae (blast). The HvSNAC1 transcript was weakly induced in the RLS-susceptible cv. Golden Promise during the latter stages of R. collo-cygni symptom development when infected leaves were senescing. Potential mechanisms controlling HvSNAC1-mediated resistance to RLS were investigated. Gene expression analysis revealed no difference in the constitutive levels of antioxidant transcripts in either of the over-expression lines compared with cv. Golden Promise, nor was any difference in stomatal conductance or sensitivity to reactive oxygen species-induced cell death observed. Over-expression of HvSNAC1 delayed dark-induced leaf senescence. It is proposed that mechanisms controlled by HvSNAC1 that are involved in tolerance to abiotic stress and that inhibit senescence also confer resistance to R. collo-cygni and suppress RLS symptoms. This provides further evidence for an association between abiotic stress and senescence in barley and the development of RLS. PMID:25040333

  6. De Novo Transcriptome Sequence Assembly and Identification of AP2/ERF Transcription Factor Related to Abiotic Stress in Parsley (Petroselinum crispum)

    OpenAIRE

    Li, Meng-Yao; Tan, Hua-Wei; Wang, Feng; Jiang, Qian; Xu, Zhi-Sheng; Tian, Chang; Xiong, Ai-Sheng

    2014-01-01

    Parsley is an important biennial Apiaceae species that is widely cultivated as herb, spice, and vegetable. Previous studies on parsley principally focused on its physiological and biochemical properties, including phenolic compound and volatile oil contents. However, little is known about the molecular and genetic properties of parsley. In this study, 23,686,707 high-quality reads were obtained and assembled into 81,852 transcripts and 50,161 unigenes for the first time. Functional annotation...

  7. The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study

    Directory of Open Access Journals (Sweden)

    Yamakawa-Kobayashi Kimiko

    2012-02-01

    Full Text Available Abstract Background Type 2 diabetes mellitus (T2DM is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese. Methods Single nucleotide polymorphisms (SNPs in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects. Results We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (P P P = 0.88 for trend. Conclusions Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.

  8. The Transcriptome of the Reference Potato Genome Solanum tuberosum Group Phureja Clone DM1-3 516R44

    Science.gov (United States)

    Massa, Alicia N.; Childs, Kevin L.; Lin, Haining; Bryan, Glenn J.; Giuliano, Giovanni; Buell, C. Robin

    2011-01-01

    Advances in molecular breeding in potato have been limited by its complex biological system, which includes vegetative propagation, autotetraploidy, and extreme heterozygosity. The availability of the potato genome and accompanying gene complement with corresponding gene structure, location, and functional annotation are powerful resources for understanding this complex plant and advancing molecular breeding efforts. Here, we report a reference for the potato transcriptome using 32 tissues and growth conditions from the doubled monoploid Solanum tuberosum Group Phureja clone DM1-3 516R44 for which a genome sequence is available. Analysis of greater than 550 million RNA-Seq reads permitted the detection and quantification of expression levels of over 22,000 genes. Hierarchical clustering and principal component analyses captured the biological variability that accounts for gene expression differences among tissues suggesting tissue-specific gene expression, and genes with tissue or condition restricted expression. Using gene co-expression network analysis, we identified 18 gene modules that represent tissue-specific transcriptional networks of major potato organs and developmental stages. This information provides a powerful resource for potato research as well as studies on other members of the Solanaceae family. PMID:22046362

  9. Eukaryotic transcription factors

    DEFF Research Database (Denmark)

    Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

    2017-01-01

    Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... regions with function-related, short sequence motifs and molecular recognition features with structural propensities. This review focuses on molecular aspects of TFs, which represent paradigms of ID-related features. Through specific examples, we review how the ID-associated flexibility of TFs enables....... It is furthermore emphasized how classic biochemical concepts like allostery, conformational selection, induced fit, and feedback regulation are undergoing a revival with the appreciation of ID. The review also describes the most recent advances based on computational simulations of ID-based interaction mechanisms...

  10. Identification of individualised empirical models of carbohydrate and insulin effects on T1DM blood glucose dynamics

    Science.gov (United States)

    Cescon, Marzia; Johansson, Rolf; Renard, Eric; Maran, Alberto

    2014-07-01

    One of the main limiting factors in improving glucose control for type 1 diabetes mellitus (T1DM) subjects is the lack of a precise description of meal and insulin intake effects on blood glucose. Knowing the magnitude and duration of such effects would be useful not only for patients and physicians, but also for the development of a controller targeting glycaemia regulation. Therefore, in this paper we focus on estimating low-complexity yet physiologically sound and individualised multi-input single-output (MISO) models of the glucose metabolism in T1DM able to reflect the basic dynamical features of the glucose-insulin metabolic system in response to a meal intake or an insulin injection. The models are continuous-time second-order transfer functions relating the amount of carbohydrate of a meal and the insulin units of the accordingly administered dose (inputs) to plasma glucose evolution (output) and consist of few parameters clinically relevant to be estimated. The estimation strategy is continuous-time data-driven system identification and exploits a database in which meals and insulin boluses are separated in time, allowing the unique identification of the model parameters.

  11. On the singular set of harmonic maps into DM-complexes

    CERN Document Server

    Daskalopoulos, Georgios

    2016-01-01

    The authors prove that the singular set of a harmonic map from a smooth Riemammian domain to a Riemannian DM-complex is of Hausdorff codimension at least two. They also explore monotonicity formulas and an order gap theorem for approximately harmonic maps. These regularity results have applications to rigidity problems examined in subsequent articles.

  12. DISCOVERY OF LOW DM FAST RADIO TRANSIENTS: GEMINGA PULSAR CAUGHT IN THE ACT

    International Nuclear Information System (INIS)

    Maan, Yogesh

    2015-01-01

    We report the discovery of several energetic radio bursts at 34 MHz, using the Gauribidanur radio telescope. The radio bursts exhibit two important properties associated with the propagation of astronomical signals through the interstellar medium: (i) frequency dependent dispersive delays across the observing bandwidth and (ii) Faraday rotation of the plane of linear polarization. These bursts sample a range of dispersion measures (DM; 1.4–3.6 pc cm −3 ) and show DM-variation at timescales of the order of a minute. Using groups of bursts having a consistent DM, we show that the bursts have originated from the radio-quiet gamma-ray pulsar Geminga. Detection of these bursts supports the existence of occasional radio emission from Geminga. The rare occurrence of these bursts, and the short timescale variation in their DM (if really caused by the intervening medium or the pulsar magnetosphere), might provide clues as to why the pulsar has not been detected in earlier sensitive searches. We present details of the observations and search procedure used to discover these bursts, a detailed analysis of their properties, and evidences of these bursts being associated with Geminga pulsar, and briefly discuss the possible emission mechanism of these bursts

  13. MIMO-OFDM WDM PON with DM-VCSEL for femtocells application

    DEFF Research Database (Denmark)

    Binti Othman, Maisara; Deng, Lei; Pang, Xiaodan

    2011-01-01

    We report on experimental demonstration of 2x2 MIMO-OFDM 5.6-GHz radio over fiber signaling over 20 km WDM-PON with directly modulated (DM) VCSELs for femtocells application. MIMO-OFDM algorithms effectively compensate for impairments in the wireless link. Error-free signal demodulation of 64...

  14. Effect of DM Actuator Errors on the WFIRST/AFTA Coronagraph Contrast Performance

    Science.gov (United States)

    Sidick, Erkin; Shi, Fang

    2015-01-01

    The WFIRST/AFTA 2.4 m space telescope currently under study includes a stellar coronagraph for the imaging and the spectral characterization of extrasolar planets. The coronagraph employs two sequential deformable mirrors (DMs) to compensate for phase and amplitude errors in creating dark holes. DMs are critical elements in high contrast coronagraphs, requiring precision and stability measured in picometers to enable detection of Earth-like exoplanets. Working with a low-order wavefront-sensor the DM that is conjugate to a pupil can also be used to correct low-order wavefront drift during a scientific observation. However, not all actuators in a DM have the same gain. When using such a DM in low-order wavefront sensing and control subsystem, the actuator gain errors introduce high-spatial frequency errors to the DM surface and thus worsen the contrast performance of the coronagraph. We have investigated the effects of actuator gain errors and the actuator command digitization errors on the contrast performance of the coronagraph through modeling and simulations, and will present our results in this paper.

  15. DISCOVERY OF LOW DM FAST RADIO TRANSIENTS: GEMINGA PULSAR CAUGHT IN THE ACT

    Energy Technology Data Exchange (ETDEWEB)

    Maan, Yogesh, E-mail: ymaan@ncra.tifr.res.in [National Centre for Radio Astrophysics, Pune 411007 (India)

    2015-12-20

    We report the discovery of several energetic radio bursts at 34 MHz, using the Gauribidanur radio telescope. The radio bursts exhibit two important properties associated with the propagation of astronomical signals through the interstellar medium: (i) frequency dependent dispersive delays across the observing bandwidth and (ii) Faraday rotation of the plane of linear polarization. These bursts sample a range of dispersion measures (DM; 1.4–3.6 pc cm{sup −3}) and show DM-variation at timescales of the order of a minute. Using groups of bursts having a consistent DM, we show that the bursts have originated from the radio-quiet gamma-ray pulsar Geminga. Detection of these bursts supports the existence of occasional radio emission from Geminga. The rare occurrence of these bursts, and the short timescale variation in their DM (if really caused by the intervening medium or the pulsar magnetosphere), might provide clues as to why the pulsar has not been detected in earlier sensitive searches. We present details of the observations and search procedure used to discover these bursts, a detailed analysis of their properties, and evidences of these bursts being associated with Geminga pulsar, and briefly discuss the possible emission mechanism of these bursts.

  16. Studies on the s_dm.t=f verb form in Classical Egyptian

    NARCIS (Netherlands)

    Zonhoven, Ludovicus Martinus Johannes

    1997-01-01

    This study is devoted to some synchronic aspects of the sDm.t=f verb form, primarily its meaning and uses in Classical Egyptian. In the introduction some attention is paid to the history of the studies of the form and its origin, an aspect which will receive no further consideration. In accordance

  17. PPARγ transcriptionally regulates the expression of insulin-degrading enzyme in primary neurons

    International Nuclear Information System (INIS)

    Du, Jing; Zhang, Lang; Liu, Shubo; Zhang, Chi; Huang, Xiuqing; Li, Jian; Zhao, Nanming; Wang, Zhao

    2009-01-01

    Insulin-degrading enzyme (IDE) is a protease that has been demonstrated to play a key role in degrading both Aβ and insulin and deficient in IDE function is associated with Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2) pathology. However, little is known about the cellular and molecular regulation of IDE expression. Here we show IDE levels are markedly decreased in DM2 patients and positively correlated with the peroxisome proliferator-activated receptor γ (PPARγ) levels. Further studies show that PPARγ plays an important role in regulating IDE expression in rat primary neurons through binding to a functional peroxisome proliferator-response element (PPRE) in IDE promoter and promoting IDE gene transcription. Finally, we demonstrate that PPARγ participates in the insulin-induced IDE expression in neurons. These results suggest that PPARγ transcriptionally induces IDE expression which provides a novel mechanism for the use of PPARγ agonists in both DM2 and AD therapies.

  18. The Transcriptional Repressor TupA in Aspergillus niger Is Involved in Controlling Gene Expression Related to Cell Wall Biosynthesis, Development, and Nitrogen Source Availability

    DEFF Research Database (Denmark)

    Schachtschabel, Doreen; Arentshorst, Mark; Nitsche, Benjamin M

    2013-01-01

    The Tup1-Cyc8 (Ssn6) complex is a well characterized and conserved general transcriptional repressor complex in eukaryotic cells. Here, we report the identification of the Tup1 (TupA) homolog in the filamentous fungus Aspergillus niger in a genetic screen for mutants with a constitutive expression...... of the agsA gene. The agsA gene encodes a putative alpha-glucan synthase, which is induced in response to cell wall stress in A. niger. Apart from the constitutive expression of agsA, the selected mutant was also found to produce an unknown pigment at high temperatures. Complementation analysis...

  19. Management of newly diagnosed type 2 Diabetes Mellitus (T2DM) in children and adolescents.

    Science.gov (United States)

    Copeland, Kenneth C; Silverstein, Janet; Moore, Kelly R; Prazar, Greg E; Raymer, Terry; Shiffman, Richard N; Springer, Shelley C; Thaker, Vidhu V; Anderson, Meaghan; Spann, Stephen J; Flinn, Susan K

    2013-02-01

    Over the past 3 decades, the prevalence of childhood obesity has increased dramatically in North America, ushering in a variety of health problems, including type 2 diabetes mellitus (T2DM), which previously was not typically seen until much later in life. The rapid emergence of childhood T2DM poses challenges to many physicians who find themselves generally ill-equipped to treat adult diseases encountered in children. This clinical practice guideline was developed to provide evidence-based recommendations on managing 10- to 18-year-old patients in whom T2DM has been diagnosed. The American Academy of Pediatrics (AAP) convened a Subcommittee on Management of T2DM in Children and Adolescents with the support of the American Diabetes Association, the Pediatric Endocrine Society, the American Academy of Family Physicians, and the Academy of Nutrition and Dietetics (formerly the American Dietetic Association). These groups collaborated to develop an evidence report that served as a major source of information for these practice guideline recommendations. The guideline emphasizes the use of management modalities that have been shown to affect clinical outcomes in this pediatric population. Recommendations are made for situations in which either insulin or metformin is the preferred first-line treatment of children and adolescents with T2DM. The recommendations suggest integrating lifestyle modifications (ie, diet and exercise) in concert with medication rather than as an isolated initial treatment approach. Guidelines for frequency of monitoring hemoglobin A1c (HbA1c) and finger-stick blood glucose (BG) concentrations are presented. Decisions were made on the basis of a systematic grading of the quality of evidence and strength of recommendation. The clinical practice guideline underwent peer review before it was approved by the AAP. This clinical practice guideline is not intended to replace clinical judgment or establish a protocol for the care of all children with T2

  20. Asupan vitamin C berhubungan dengan kadar glukosa darah pada pasien rawat jalan DM tipe 2

    Directory of Open Access Journals (Sweden)

    Riya Purwaningtyastuti

    2018-01-01

    Full Text Available ABSTRACKBackground: High sugar levels in people with diabetes mellitus causes changes in the body. One of its detrimental process called oxidation reaction that causes the increased formation of harmful substances called free radicals. Antioxidant vitamin A, C, and E helpful to reduce oxidative damage in people with diabetes mellitus and prevent complications. Objectives: The know relationship intake antioxidant with blood glocuse level outpatient type 2 diabetes mellitus in RSUD Panembahan Senopati Bantul Yogyakarta. Methods: This study was observasional with of cross sectional. The subjects in this study were outpatients with diabetes mellitus type 2 with sampels of 89 respondents. Purposive sampling technique. Data consumption pattern of antioxidant, used semi quantitative food frequency (SQFFQ laboratories to examination and blood glucose levels. Data analysis used Fisher’s Exact Test. Results: There is significant association between vitamin C intake with blood sugar levels in patients diabetes mellitus the value of p = 0.004. The existence of a no signifi cant association between vitamin E intake with blood sugar levels in patients diabetes mellitus the value of p = 0.073 and there is no signifi cant association between vitamin A intake with blood sugar levels in patients diabetes mellitus the value of p = 0.252. Conclusion: There is a relationship between vitamin C intake with blood sugar levels, while the intake of vitamin A and E are not related to blood sugar levels KEYWORDS: type 2 diabetes mellitus, blood glucose level, vitamin C intake, vitamin A intake, vitamin E intake. ABSTRAK Latar Belakang : Kadar glukosa yang tinggi pada penderita kencing manis/DM menyebabkan berbagai perubahan di dalam tubuh. Salah satu proses merugikan dinamakan reaksi oksidasi yang menyebabkan peningkatan pembentukan zat berbahaya yang disebut radikal bebas. Antioksidan vitamin A,C dan E bermanfaat dapat menurunkan kadar glukosa darah. Tujuan: Untuk

  1. Development of an HTS-Compatible Assay for Discovery of Melanoma-Related Microphthalmia Transcription Factor Disruptors Using AlphaScreen Technology.

    Science.gov (United States)

    Wang, Jing; Fang, Pengfei; Chase, Peter; Tshori, Sagi; Razin, Ehud; Spicer, Timothy P; Scampavia, Louis; Hodder, Peter; Guo, Min

    2017-01-01

    Microphthalmia transcription factor (MITF) is a master transcription factor expressed in melanocytes, essential for melanocyte survival, differentiation, and pigment formation, and is a key oncogenic factor in melanoma initiation, migration, and treatment resistance. Although identified as an important therapeutic target for melanoma, clinical inhibitors directly targeting the MITF protein are not available. Based on the functional state of MITF, we have designed an MITF dimerization-based AlphaScreen (MIDAS) assay that sensitively and specifically mirrors the dimerization of MITF in vitro. This assay is further exploited for identification of the MITF dimer disruptor for high-throughput screening. A pilot screen against a library of 1280 pharmacologically active compounds indicates that the MIDAS assay performance exhibits exceptional results with a Z' factor of 0.81 and a signal-to-background (S/B) ratio of 3.92 while identifying initial hit compounds that yield an ability to disrupt MITF-DNA interaction. The results presented demonstrate that the MIDAS assay is ready to screen large chemical libraries in order to discover novel modulators of MITF for potential melanoma treatment.

  2. WRKY2/34–VQ20 Modules in Arabidopsis thaliana Negatively Regulate Expression of a Trio of Related MYB Transcription Factors During Pollen Development

    Directory of Open Access Journals (Sweden)

    Rihua Lei

    2018-03-01

    Full Text Available Male gametogenesis in plants is tightly controlled and involves the complex and precise regulation of transcriptional reprogramming. Interactions between WRKY proteins and VQ motif-containing proteins are required to control these complicated transcriptional networks. However, our understanding of the mechanisms by which these complexes affect downstream gene expression is quite limited. In this study, we found that WRKY2 and WKRY34 repress MYB97, MYB101, and MYB120 expression during male gametogenesis. MYB expression was up-regulated in the wrky2-1 wrky34-1 vq20-1 triple mutant during male gametogenesis. The expression levels of six potential targets of the three MYBs increased the most in the wrky2-1 wrky34-1 vq20-1 triple mutant, followed by the wrky2-1 wrky34-1 double mutant, compared with in wild-type. Yeast one-hybrid and dual luciferase reporter assays indicated that WRKY2 and WRKY34 recognized the MYB97 promoter by binding to its W-boxes. MYB97 overexpression caused defects in pollen germination and pollen tube length, which impacted male fertility. Thus, WRKY2/34–VQ20 complexes appear to negatively regulate the expression of certain MYBs during plant male gametogenesis.

  3. Two variants on T2DM susceptible gene HHEX are associated with CRC risk in a Chinese population.

    Science.gov (United States)

    Sun, Rui; Liu, Jian-Ping; Gao, Chang; Xiong, Ying-Ying; Li, Min; Wang, Ya-Ping; Su, Yan-Wei; Lin, Mei; Jiang, An-Li; Xiong, Ling-Fan; Xie, Yan; Feng, Jue-Ping

    2016-05-17

    Increasing amounts of evidence has demonstrated that T2DM (Type 2 Diabetes Mellitus) patients have increased susceptibility to CRC (colorectal cancer). As HHEX is a recognized susceptibility gene in T2DM, this work was focused on two SNPs in HHEX, rs1111875 and rs7923837, to study their association with CRC. T2DM patients without CRC (T2DM-only, n=300), T2DM with CRC (T2DM/CRC, n=135), cancer-free controls (Control, n=570), and CRC without T2DM (CRC-only, n=642) cases were enrolled. DNA samples were extracted from the peripheral blood leukocytes of the patients and sequenced by direct sequencing. The χ2 test was used to compare categorical data. We found that in T2DM patients, rs1111875 but not the rs7923837 in HHEX gene was associated with the occurrence of CRC (p= 0.006). for rs1111875, TC/CC patients had an increased risk of CRC (p=0.019, OR=1.592, 95%CI=1.046-2.423). Moreover, our results also indicated that the two variants of HEEX gene could be risk factors for CRC in general population, independent on T2DM (pCRC was observed in TC or TC/CC than CC individuals (pCRC risk was observed in AG, GG, and AG/GG than AA individuals (pCRC susceptibility. Risk effects and the functional impact of these polymorphisms need further validation.

  4. 17β-estradiol-induced regulation of the novel 5-HT1A-related transcription factors NUDR and Freud-1 in SH SY5Y cells.

    Science.gov (United States)

    Adeosun, Samuel O; Albert, Paul R; Austin, Mark C; Iyo, Abiye H

    2012-05-01

    Nuclear deformed epidermal autoregulatory factor-1 (NUDR/Deaf-1) and five prime repressor element under dual repression (Freud-1) are novel transcriptional regulators of the 5-HT(1A) receptor, a receptor that has been implicated in the pathophysiology of various psychiatric illnesses. The antidepressant effect of 17β-Estradiol (17βE(2)) is purported to involve the downregulation of this receptor. We investigated the possible role of NUDR and Freud-1 in 17βE(2)-induced downregulation of the 5-HT(1A) receptor in the neuroblastoma cell line SH SY5Y. Cells were treated with 10 nM of 17βE(2) for 3 or 48 h, followed by a 24-h withdrawal period. Proteins were isolated and analyzed by western blotting. 17βE(2) treatment increased NUDR immunoreactivity while Freud-1 and the 5-HT(1A) receptor showed significant decreases. Upon withdrawal of 17βE(2), protein expression returned to control levels, except for NUDR, which remained significantly elevated in the 3-h treatment. Taken together, these data support a non-genomic downregulation of 5-HT(1A) receptor protein by 17βE(2), which does not involve NUDR and Freud-1. Rather, changes in both transcription factors seem to be compensatory/homeostatic responses to changes in 5-HT(1A) receptor induced by 17βE(2). These observations further highlight the importance of NUDR and Freud-1 in regulating 5-HT(1A) receptor expression.

  5. Abrogation of cisplatin-induced hepatotoxicity in mice by xanthorrhizol is related to its effect on the regulation of gene transcription

    International Nuclear Information System (INIS)

    Hwan Kim, Seong; Ok Hong, Kyoung; Chung, Won-Yoon; Kwan Hwang, Jae; Park, Kwang-Kyun

    2004-01-01

    Cisplatin is a widely used anticancer drug, but at high dose, it can produce undesirable side effects such as hepatotoxicity. Because Curcuma xanthorrhiza Roxb. (Zingiberaceae) has been traditionally used to treat liver disorders, the protective effect of xanthorrhizol, which is isolated from C. xanthorrhiza, on cisplatin-induced hepatotoxicity was evaluated in mice. The pretreatment of xanthorrhizol (200 mg/kg/day, po) for 4 days prevented the hepatotoxicity induced by cisplatin (45 mg/kg, ip) with statistical significance. Interestingly, it abrogated cisplatin-induced DNA-binding activity of nuclear factor-kappaB (NF-κB), which consequently affected mRNA expression levels of NF-κB-dependent genes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), even in part. It also attenuated the cisplatin-suppressed DNA-binding activity of activator protein 1 (AP-1). Using differential display reverse transcription-polymerase chain reaction (DDRT-PCR), seven upregulated genes including S100 calcium binding protein A9 (S100A9) mRNA and antigenic determinant for rec-A protein mRNA and five downregulated genes including caseinolytic protease X (ClpX) mRNA and ceruloplasmin (CP) mRNA by cisplatin were identified. Although these mRNA expression patterns were not totally consistent with gel shift patterns, altered expression levels by cisplatin were reversed by the pretreatment of xanthorrhizol. In conclusion, the ability of xanthorrhizol to regulate the DNA-binding activities of transcription factors, NF-κB and AP-1, could be one possible mechanism to elucidate the preventive effect of xanthorrhizol on cisplatin-induced hepatotoxicity. Furthermore, genes identified in this study could be helpful to understand the mechanism of cisplatin-induced hepatotoxicity. Finally, the combination treatment of xanthorrhizol and cisplatin may provide more advantage than single treatment of cisplatin in cancer therapy

  6. WRKY transcription factors

    Science.gov (United States)

    Bakshi, Madhunita; Oelmüller, Ralf

    2014-01-01

    WRKY transcription factors are one of the largest families of transcriptional regulators found exclusively in plants. They have diverse biological functions in plant disease resistance, abiotic stress responses, nutrient deprivation, senescence, seed and trichome development, embryogenesis, as well as additional developmental and hormone-controlled processes. WRKYs can act as transcriptional activators or repressors, in various homo- and heterodimer combinations. Here we review recent progress on the function of WRKY transcription factors in Arabidopsis and other plant species such as rice, potato, and parsley, with a special focus on abiotic, developmental, and hormone-regulated processes. PMID:24492469

  7. Narrowband dm-spikes, intermediate drift bursts and pulsations in the solar flare of August 19, 1981

    International Nuclear Information System (INIS)

    Karlicky, M.

    1986-01-01

    In the initial phase (1251-1253 UT) of the flare of Aug. 19, 1981, an interesting group of narrowband dm-spikes, intermediate drift bursts and pulsations was observed. The paper tries to explain this group of bursts by a uniform model. It is shown that all these bursts are associated with acceleration and trapping of superthermal electrons in the flare loop. The parameters of the flare loop and the electric field in the acceleration process are estimated. An explanation is given of why the ''period'' of intermediate drift bursts and of pulsations is the same. Later the flare loop under study explodes and a shock wave (type II radio burst) is generated at a relatively high altitude of ∼ 100,000 km above the photosphere. This process is connected with the 10 cm radio flux decrease. (author)

  8. Resistance to Downy Mildew in Lettuce 'La Brillante' is Conferred by Dm50 Gene and Multiple QTL.

    Science.gov (United States)

    Simko, Ivan; Ochoa, Oswaldo E; Pel, Mathieu A; Tsuchida, Cayla; Font I Forcada, Carolina; Hayes, Ryan J; Truco, Maria-Jose; Antonise, Rudie; Galeano, Carlos H; Michelmore, Richard W

    2015-09-01

    Many cultivars of lettuce (Lactuca sativa L.) are susceptible to downy mildew, a nearly globally ubiquitous disease caused by Bremia lactucae. We previously determined that Batavia type cultivar 'La Brillante' has a high level of field resistance to the disease in California. Testing of a mapping population developed from a cross between 'Salinas 88' and La Brillante in multiple field and laboratory experiments revealed that at least five loci conferred resistance in La Brillante. The presence of a new dominant resistance gene (designated Dm50) that confers complete resistance to specific isolates was detected in laboratory tests of seedlings inoculated with multiple diverse isolates. Dm50 is located in the major resistance cluster on linkage group 2 that contains at least eight major, dominant Dm genes conferring resistance to downy mildew. However, this Dm gene is ineffective against the isolates of B. lactucae prevalent in the field in California and the Netherlands. A quantitative trait locus (QTL) located at the Dm50 chromosomal region (qDM2.2) was detected, though, when the amount of disease was evaluated a month before plants reached harvest maturity. Four additional QTL for resistance to B. lactucae were identified on linkage groups 4 (qDM4.1 and qDM4.2), 7 (qDM7.1), and 9 (qDM9.2). The largest effect was associated with qDM7.1 (up to 32.9% of the total phenotypic variance) that determined resistance in multiple field experiments. Markers identified in the present study will facilitate introduction of these resistance loci into commercial cultivars of lettuce.

  9. Dynamics of the diffusive DM-DE interaction – Dynamical system approach

    Energy Technology Data Exchange (ETDEWEB)

    Haba, Zbigniew [Institute of Theoretical Physics, University of Wroclaw, Plac Maxa Borna 9, 50-204 Wrocław (Poland); Stachowski, Aleksander; Szydłowski, Marek, E-mail: zhab@ift.uni.wroc.pl, E-mail: aleksander.stachowski@uj.edu.pl, E-mail: marek.szydlowski@uj.edu.pl [Astronomical Observatory, Jagiellonian University, Orla 171, 30-244 Krakow (Poland)

    2016-07-01

    We discuss dynamics of a model of an energy transfer between dark energy (DE) and dark matter (DM) . The energy transfer is determined by a non-conservation law resulting from a diffusion of dark matter in an environment of dark energy. The relativistic invariance defines the diffusion in a unique way. The system can contain baryonic matter and radiation which do not interact with the dark sector. We treat the Friedman equation and the conservation laws as a closed dynamical system. The dynamics of the model is examined using the dynamical systems methods for demonstration how solutions depend on initial conditions. We also fit the model parameters using astronomical observation: SNIa, H ( z ), BAO and Alcock-Paczynski test. We show that the model with diffuse DM-DE is consistent with the data.

  10. Role of miRNAs in Epicardial Adipose Tissue in CAD Patients with T2DM

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2016-01-01

    Full Text Available Background. Epicardial adipose tissue (EAT is identified as an atypical fat depot surrounding the heart with a putative role in the involvement of metabolic disorders, including obesity, type-2 diabetes mellitus, and atherosclerosis. We profiled miRNAs in EAT of metabolic patients with coronary artery disease (CAD and type-2 diabetes mellitus (T2DM versus metabolically healthy patients by microarray. Compared to metabolically healthy patients, we identified forty-two miRNAs that are differentially expressed in patients with CAD and T2DM from Xinjiang, China. Eleven miRNAs were selected as potential novel miRNAs according to P value and fold change. Then the potential novel miRNAs targeted genes were predicted via TargetScan, PicTar, and miRTarbase, and the function of the target genes was predicted via Gene Ontology (GO analysis while the enriched KEGG pathway analyses of the miRNAs targeted genes were performed by bioinformatics software DAVID. Then protein-protein interaction networks of the targeted gene were conducted by online software STRING. Finally, using microarray, bioinformatics approaches revealed the possible molecular mechanisms pathogenesis of CAD and T2DM. A total of 11 differentially expressed miRNAs were identified and among them, hsa-miR-4687-3p drew specific attention. Bioinformatics analysis revealed that insulin signaling pathway is the central way involved in the progression of metabolic disorders. Conclusions. The current findings support the fact that miRNAs are involved in the pathogenesis of metabolic disorders in EAT of CAD patients with T2DM, and validation of the results of these miRNAs by independent and prospective study is certainly warranted.

  11. Ekologický marketing ve společnosti DM drogeriemarkt

    OpenAIRE

    Bakalářová, Jana

    2014-01-01

    The Bachelor's thesis entitled Green Marketing in DM drogeriemarkt company deals with the analysis of a new marketing approach/attitude also known as an environmental or green marketing, which has become very popular. The two preliminary chapters of my bachelor thesis are devoted to theoretical explanations, terms and definitions on the basis we can more develop it to a deeper description of marketing terms. The following part introduces a green marketing itself from it's definition through h...

  12. Sensitive limits on the abundance of cold water vapor in the DM Tauri protoplanetary disk

    NARCIS (Netherlands)

    Bergin, E. A.; Hogerheijde, M. R.; Brinch, C.; Fogel, J.; Yildiz, U. A.; Kristensen, L. E.; van Dishoeck, E. F.; Bell, T. A.; Blake, G.A.; Cernicharo, J.; Dominik, C.; Lis, D.; Melnick, G.; Neufeld, D.; Panic, O.; Pearson, J. C.; Bachiller, R.; Baudry, A.; Benedettini, M.; Benz, A. O.; Bjerkeli, P.; Bontemps, S.; Braine, J.; Bruderer, S.; Caselli, P.; Codella, C.; Daniel, F.; di Giorgio, A. M.; Doty, S. D.; Encrenaz, P.; Fich, M.; Fuente, A.; Giannini, T.; Goicoechea, J. R.; de Graauw, Th.; Helmich, F.; Herczeg, G. J.; Herpin, F.; Jacq, T.; Johnstone, D.; Jorgensen, J. K.; Larsson, B.; Liseau, R.; Marseille, M.; Mc Coey, C.; Nisini, B.; Olberg, M.; Parise, B.; Plume, R.; Risacher, C.; Santiago-Garcia, J.; Saraceno, P.; Shipman, R.; Tafalla, M.; van Kempen, T. A.; Visser, R.; Wampfler, S. F.; Wyrowski, F.; van der Tak, F.; Jellema, W.; Tielens, A. G. G. M.; Hartogh, P.; Stuetzki, J.; Szczerba, R.

    2010-01-01

    We performed a sensitive search for the ground-state emission lines of ortho-and para-water vapor in the DM Tau protoplanetary disk using the Herschel/HIFI instrument. No strong lines are detected down to 3 sigma levels in 0.5 km s(-1) channels of 4.2 mK for the 1(10)-1(01) line and 12.6 mK for the

  13. PROFIL URINALISIS PENGGUNAAN IMUNAX PADA PASIEN DIABETES MELITUS (DM RAWAT JALAN DI RSU PKU MUHAMMADIYAH BANTUL

    Directory of Open Access Journals (Sweden)

    Adnan

    2018-03-01

    Full Text Available Diabetes mellitus (DM is a metabolic disease characterized by the onset of hyperglycemia due to secretion disorders, as well as resistance of insulin. Chronic hyperglycemic and other DM metabolic disorders will cause tissue and organ damage, such as the eyes, kidneys and vascular system. Some studies show that immunax (MBJH: minyak biji jinten hitam has antidibetic benefits. This study aims to determine the description of urinalysis and proteinuria in DM patients who get immunax. The study design was randomized controlled trial. MBJH is given in 2 dosage levels, 2x1 soft capsule and 2x2 soft capsul given for 20 days on the subject. Urine data taken before and after administration of immunax preparations. The results showed that based on sex, age, education, occupation, marital status and the type of therapy used there was no significant difference in the characteristics and types of therapy used by the study subjects (patients at risk of metabolic syndrome between the treatment groups and the placebo group. The result of urinalysis test showed that there was no difference of urinalysis image in the three groups. The conclusion of this study was that there was no significant effect (p value> 0,05 on immunax (MBJH on the urinalysis profile in patients with metabolic syndrome risk, both dose 2x1, 2x2, and control group

  14. Polyuria with the Concurrent manifestation of Central Diabetes Insipidus (CDI) & Type 2 Diabetes Mellitus (DM).

    Science.gov (United States)

    Shin, Hyun-Jong; Kim, Jae-Ha; Yi, Joo-Hark; Han, Sang-Woong; Kim, Ho-Jung

    2012-12-01

    We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 µg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature.

  15. Protective mechanisms against oxidative stress and angiopathy in young patients with diabetes type 1 (DM1).

    Science.gov (United States)

    Koutroumani, Nikolitsa; Partsalaki, Ioanna; Lamari, Fotini; Dettoraki, Athina; Gil, Andrea Paola Rojas; Karvela, Alexia; Kostopoulou, Eirini; Spiliotis, Bessie E

    2013-01-01

    Advanced glycation end-products (AGEs) via their receptor, RAGE, are involved in diabetic angiopathy. Soluble RAGE, an inhibitor of this axis, is formed by enzymatic catalysis (sRAGE) or alternative splicing (esRAGE). Malondialdehyde (MDA) is an oxidative stress marker, and ferric reducing ability of plasma (FRAP) is an anti-oxidant capacity marker. In isolated mononuclear blood cells from 110 DM1-patients (P) and 124 controls (C) (4-29 years) RAGE mRNA (g) and protein expression (pe) were measured by RT-PCR and Western immunoblotting, respectively. Plasma levels of CML (AGEs) and sRAGE were measured by ELISA, MDA by flurometry and FRAP according to 'Benzie and Strain'. P showed: (i) higher g of RAGE, especially in p>13 years of age and >5 years DM1, (ii) increased pe of esRAGE in DM1>5 years and (iii) increased FRAP and MDA. The increased esRAGE and FRAP with increased levels of CML and MDA possibly reflects a protective response against the formation of diabetic complications in these young diabetic patients.

  16. Effect of Exercise on Psychological Well-being in T2DM

    Directory of Open Access Journals (Sweden)

    Farzad Najafipoor

    2011-09-01

    Full Text Available Background: Type 2 diabetic patients (T2DM experience health problems including psychiatric and psychological complications that influence their general health. Since exercise has an additional effect on psychological improvement, we aimed to establish the role of exercise as improvement of psychological problems. Methods: 80 subjects with T2DM were assigned to take exercise for 90 minutes per session, 3 times a week for a period of 4 months. They answered the GHQ-12 questionnaire before and after the study project. Results: Questionnaires were scored by Likert model and entered the statistical analysis. Our findings demonstrate a significant decrease in the mean GHQ-12 scores. [13.39 ± 5.89 to 8.52 ± 5.12 (p < 0.001]. Factor analysis by Graetz's three-factor model suggests that factor I (anxiety and depression associates with more improvement than the other factors.Conclusion: Exercise improves psychological distress in T2DM and results in improved well-being.

  17. Insulin initiation and intensification in patients with T2DM for the primary care physician

    Directory of Open Access Journals (Sweden)

    Unger J

    2011-06-01

    Full Text Available Jeff UngerCatalina Research Institute, Chino, CA, USAAbstract: Type 2 diabetes mellitus (T2DM is characterized by both insulin resistance and inadequate insulin secretion. All patients with the disease require treatment to achieve and maintain the target glycosylated hemoglobin (A1C level of 6.5%–7%. Pharmacological management of T2DM typically begins with the introduction of oral medications, and the majority of patients require exogenous insulin therapy at some point in time. Primary care physicians play an essential role in the management of T2DM since they often initiate insulin therapy and intensify regimens over time as needed. Although insulin therapy is prescribed on an individualized basis, treatment usually begins with basal insulin added to a background therapy of oral agents. Prandial insulin injections may be added if glycemic targets are not achieved. Treatments may be intensified over time using patient-friendly titration algorithms. The goal of insulin intensification within the primary care setting is to minimize patients' exposure to chronic hyperglycemia and weight gain, and reduce patients' risk of hypoglycemia, while achieving individualized fasting, postprandial, and A1C targets. Simplified treatment protocols and insulin delivery devices allow physicians to become efficient prescribers of insulin intensification within the primary care arena.Keywords: diabetes, basal, bolus, regimens, insulin analogs, structured glucose testing

  18. Anti-listerial Bactericidal Activity of Lactobacillus plantarum DM5 Isolated from Fermented Beverage Marcha.

    Science.gov (United States)

    Das, Deeplina; Goyal, Arun

    2013-09-01

    The strain Lactobacillus plantarum DM5 was isolated from fermented beverage Marcha of Sikkim and explored for its antagonistic activity against food-borne pathogens. The cell-free supernatant of L. plantarum DM5 showed antibacterial activity of 6,400 AU/mL in MRS medium (pH 6.0) against the indicator strain Staphylococcus aureus. MRS medium supplemented with 15 g/L of maltose at 37 °C under static condition yielded highest antimicrobial activity (6,400 AU/mL) with 3 % increase in specific activity when compared to 20 g/L glucose. The antimicrobial compound was heat stable (60 min at 100 °C) and was active over a wide pH range. It showed bactericidal effect on S. aureus and Listeria monocytogenes by causing 96 and 98 % of cell lysis, respectively. The cell morphology of the treated S. aureus and L. monocytogenes was completely deformed as revealed by scanning electron microscopy, suggesting the high potential of L. plantarum DM5 as natural preservatives in food industry. The antimicrobial compound was purified by 80 % ammonium sulphate precipitation and showed antimicrobial activity of 12,800 AU/mL with 19-fold purification and a molecular mass of 15.2 kDa, indicating the proteinaceous nature of the compound.

  19. IMPROVING SELF-CARE INDEPENDENCY OF TYPE 2 DM PATIENTS BASED ON LASALLIAN EDUCATION MODEL

    Directory of Open Access Journals (Sweden)

    Annastasia Sintia Lamonge

    2016-09-01

    Full Text Available Abstract The specific objectives of this study were: (1 Analyze the effectiveness of Lasallian health education in order to increased knowledge and attitude. (2 Analyze the effectiveness of Lasallian health education in order to increase the self-care independency of people with type 2 diabetes mellitus (DM. Research design of this study was  Pre-Experiment with target population patients with type 2 DM. 12 participants were recruited in the study with  purposive sampling technique. Bivariate test results of knowledge and attitudes before and after giving the Lasallian health education showed significant results with ρ-value of 0.016 (p-value <ά 0.05. Research result of self-care independency of type 2 diabetic patients in before and after giving Lasallian health education show significant result with ρ-value of 0.001 (p-value <ά 0:01. Transformation of people behavior or habit by a health education program should have three important determinant, there are cognitive,  affective and psychomotor aspects of participants to motivate and increase self-awareness, and adherence of self-care management and improving of quality of life. Keywords: Type 2 DM, Lasallian Health Education, Knowledge, Attitude, Self-care independency.

  20. CCAAT/Enhancer-Binding Protein α Is a Crucial Regulator of Human Fat Mass and Obesity Associated Gene Transcription and Expression

    Directory of Open Access Journals (Sweden)

    Wei Ren

    2014-01-01

    Full Text Available Several susceptibility loci have been reported associated with obesity and T2DM in GWAS. Fat mass and obesity associated gene (FTO is the first gene associated with body mass index (BMI and risk for diabetes in diverse patient populations. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. While much is known about the epigenetic mutations contributing to obesity and T2DM, less is certain with the expression regulation of FTO gene. In this study, a highly conserved canonical C/EBPα binding site was located around position −45~−54 bp relative to the human FTO gene transcriptional start site. Site-directed mutagenesis of the putative C/EBPα binding sites decreased FTO promoter activity. Overexpression and RNAi studies also indicated that C/EBPα was required for the expression of FTO. Chromatin immunoprecipitation (ChIP experiment was carried out and the result shows direct binding of C/EBPα to the putative binding regions in the FTO promoter. Collectively, our data suggest that C/EBPα may act as a positive regulator binding to FTO promoter and consequently, activates the gene transcription.

  1. Small RNA-Sequencing Links Physiological Changes and RdDM Process to Vegetative-to-Floral Transition in Apple

    Directory of Open Access Journals (Sweden)

    Xinwei Guo

    2017-05-01

    Full Text Available Transition from vegetative to floral buds is a critical physiological change during flower induction that determines fruit productivity. Small non-coding RNAs (sRNAs including microRNAs (miRNAs and small interfering RNAs (siRNAs are pivotal regulators of plant growth and development. Although the key role of sRNAs in flowering regulation has been well-described in Arabidopsis and some other annual plants, their relevance to vegetative-to-floral transition (hereafter, referred to floral transition in perennial woody trees remains under defined. Here, we performed Illumina sequencing of sRNA libraries prepared from vegetative and floral bud during flower induction of the apple trees. A large number of sRNAs exemplified by 33 previously annotated miRNAs and six novel members display significant differential expression (DE patterns. Notably, most of these DE-miRNAs in floral transition displayed opposite expression changes in reported phase transition in apple trees. Bioinformatics analysis suggests most of the DE-miRNAs targeted transcripts involved in SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL gene regulation, stress responses, and auxin and gibberellin (GA pathways, with further suggestion that there is an inherent link between physiological stress response and metabolism reprogramming during floral transition. We also observed significant changes in 24 nucleotide (nt sRNAs that are hallmarks for RNA-dependent DNA methylation (RdDM pathway, suggestive of the correlation between epigenetic modifications and the floral transition. The study not only provides new insight into our understanding of fundamental mechanism of poorly studied floral transition in apple and other woody plants, but also presents important sRNA resource for future in-depth research in the apple flowering physiology.

  2. JST Thesaurus Headwords and Synonyms: T1DM [MeCab user dictionary for science technology term[Archive

    Lifescience Database Archive (English)

    Full Text Available MeCab user dictionary for science technology term T1DM 名詞 一般 * * * * 1型糖尿病 1ガタトウニョウビョウ イチガタトーニョービョー Thesaurus2015 200906052809193540 C LS51 UNKNOWN_2 T 1 DM

  3. Relative expression of rRNA transcripts and 45S rDNA promoter methylation status are dysregulated in tumors in comparison with matched-normal tissues in breast cancer.

    Science.gov (United States)

    Karahan, Gurbet; Sayar, Nilufer; Gozum, Gokcen; Bozkurt, Betul; Konu, Ozlen; Yulug, Isik G

    2015-06-01

    Ribosomal RNA (rRNA) expression, one of the most important factors regulating ribosome production, is primarily controlled by a CG-rich 45 S rDNA promoter. However, the DNA methylation state of the 45 S rDNA promoter, as well as its effect on rRNA gene expression in types of human cancers is controversial. In the present study we analyzed the methylation status of the rDNA promoter (-380 to +53 bp) as well as associated rRNA expression levels in breast cancer cell lines and breast tumor-normal tissue pairs. We found that the aforementioned regulatory region was extensively methylated (74-96%) in all cell lines and in 68% (13/19 tumor-normal pairs) of the tumors. Expression levels of rRNA transcripts 18 S, 28 S, 5.8 S and 45 S external transcribed spacer (45 S ETS) greatly varied in the breast cancer cell lines regardless of their methylation status. Analyses of rRNA transcript expression levels in the breast tumor and normal matched tissues showed no significant difference when normalized with TBP. On the other hand, using the geometric mean of the rRNA expression values (GM-rRNA) as reference enabled us to identify significant changes in the relative expression of rRNAs in the tissue samples. We propose GM-rRNA normalization as a novel strategy to analyze expression differences between rRNA transcripts. Accordingly, the 18S rRNA/GM-rRNA ratio was significantly higher whereas the 5.8S rRNA/GM-rRNA ratio was significantly lower in breast tumor samples than this ratio in the matched normal samples. Moreover, the 18S rRNA/GM-rRNA ratio was negatively correlated with the 45 S rDNA promoter methylation level in the normal breast tissue samples, yet not in the breast tumors. Significant correlations observed between the expression levels of rRNA transcripts in the normal samples were lost in the tumor samples. We showed that the expression of rRNA transcripts may not be based solely on promoter methylation. Carcinogenesis may cause dysregulation of the correlation

  4. Transcription Factor Activating Protein-2β (TFAP-2β) genotype and symptoms of attention deficit hyperactivity disorder in relation to symptoms of depression in two independent samples.

    Science.gov (United States)

    Nilsson, Kent W; Sonnby, Karin; Nordquist, Niklas; Comasco, Erika; Leppert, Jerzy; Oreland, Lars; Sjöberg, Rickard L

    2014-04-01

    The Transcription Factor Activating Protein-2β (TFAP-2β) gene has been shown to influence monoaminergic neurotransmission, and several genes important for monoaminergic function have binding sites for TFAP-2β. Familial studies of attention deficit hyperactivity disorder (ADHD) suggest a hereditary-determined subtype of ADHD with comorbid depression. We examined a functional variation of the TFAP-2β gene in the context of co-occurring symptoms of ADHD and depression in two independent population-based samples of adolescents (Group A, n = 175 and Group B, n = 1,506) from Sweden. Results indicated 6.1 to 7.8% of adolescents screened positively for ADHD and depression symptoms. Symptoms of depression were more common among girls who screened positively for ADHD and did not carry the nine-repeat allele of the TFAP-2β intron 1 Variable Number Tandem Repeat (VNTR) polymorphism. The presence of the nine-repeat variant of the TFAP-2β intron 1 VNTR appears to protect girls with ADHD symptoms from the co-expression of symptoms of depression.

  5. Isolation and Identification of Post-Transcriptional Gene Silencing-Related Micro-RNAs by Functionalized Silicon Nanowire Field-effect Transistor

    Science.gov (United States)

    Chen, Kuan-I.; Pan, Chien-Yuan; Li, Keng-Hui; Huang, Ying-Chih; Lu, Chia-Wei; Tang, Chuan-Yi; Su, Ya-Wen; Tseng, Ling-Wei; Tseng, Kun-Chang; Lin, Chi-Yun; Chen, Chii-Dong; Lin, Shih-Shun; Chen, Yit-Tsong

    2015-11-01

    Many transcribed RNAs are non-coding RNAs, including microRNAs (miRNAs), which bind to complementary sequences on messenger RNAs to regulate the translation efficacy. Therefore, identifying the miRNAs expressed in cells/organisms aids in understanding genetic control in cells/organisms. In this report, we determined the binding of oligonucleotides to a receptor-modified silicon nanowire field-effect transistor (SiNW-FET) by monitoring the changes in conductance of the SiNW-FET. We first modified a SiNW-FET with a DNA probe to directly and selectively detect the complementary miRNA in cell lysates. This SiNW-FET device has 7-fold higher sensitivity than reverse transcription-quantitative polymerase chain reaction in detecting the corresponding miRNA. Next, we anchored viral p19 proteins, which bind the double-strand small RNAs (ds-sRNAs), on the SiNW-FET. By perfusing the device with synthesized ds-sRNAs of different pairing statuses, the dissociation constants revealed that the nucleotides at the 3‧-overhangs and pairings at the terminus are important for the interactions. After perfusing the total RNA mixture extracted from Nicotiana benthamiana across the device, this device could enrich the ds-sRNAs for sequence analysis. Finally, this bionanoelectronic SiNW-FET, which is able to isolate and identify the interacting protein-RNA, adds an additional tool in genomic technology for the future study of direct biomolecular interactions.

  6. Method to determine transcriptional regulation pathways in organisms

    Science.gov (United States)

    Gardner, Timothy S.; Collins, James J.; Hayete, Boris; Faith, Jeremiah

    2012-11-06

    The invention relates to computer-implemented methods and systems for identifying regulatory relationships between expressed regulating polypeptides and targets of the regulatory activities of such regulating polypeptides. More specifically, the invention provides a new method for identifying regulatory dependencies between biochemical species in a cell. In particular embodiments, provided are computer-implemented methods for identifying a regulatory interaction between a transcription factor and a gene target of the transcription factor, or between a transcription factor and a set of gene targets of the transcription factor. Further provided are genome-scale methods for predicting regulatory interactions between a set of transcription factors and a corresponding set of transcriptional target substrates thereof.

  7. DM100 AND DM1200 MELTER TESTING WITH HIGH WASTE LOADING FORMULATIONS FOR HANFORD HIGH-ALUMINUM HLW STREAMS, TEST PLAN 09T1690-1

    International Nuclear Information System (INIS)

    Kruger, A.A.; Matlack, K.S.; Kot, W.K.; Pegg, I.L.; Joseph, I.

    2009-01-01

    This Test Plan describes work to support the development and testing of high waste loading glass formulations that achieve high glass melting rates for Hanford high aluminum high level waste (HLW). In particular, the present testing is designed to evaluate the effect of using low activity waste (LAW) waste streams as a source of sodium in place ofchemical additives, sugar or cellulose as a reductant, boehmite as an aluminum source, and further enhancements to waste processing rate while meeting all processing and product quality requirements. The work will include preparation and characterization of crucible melts in support of subsequent DuraMelter 100 (DM 100) tests designed to examine the effects of enhanced glass formulations, glass processing temperature, incorporation of the LAW waste stream as a sodium source, type of organic reductant, and feed solids content on waste processing rate and product quality. Also included is a confirmatory test on the HLW Pilot Melter (DM1200) with a composition selected from those tested on the DM100. This work builds on previous work performed at the Vitreous State Laboratory (VSL) for Department of Energy's (DOE's) Office of River Protection (ORP) to increase waste loading and processing rates for high-iron HLW waste streams as well as previous tests conducted for ORP on the same waste composition. This Test Plan is prepared in response to an ORP-supplied statement of work. It is currently estimated that the number of HLW canisters to be produced in the Hanford Tank Waste Treatment and Immobilization Plant (WTP) is about 12,500. This estimate is based upon the inventory ofthe tank wastes, the anticipated performance of the sludge treatment processes, and current understanding of the capability of the borosilicate glass waste form. The WTP HLW melter design, unlike earlier DOE melter designs, incorporates an active glass bubbler system. The bubblers create active glass pool convection and thereby improve heat transfer and

  8. Selenium Biofortification in Radish Enhances Nutritional Quality via Accumulation of Methyl-Selenocysteine and Promotion of Transcripts and Metabolites Related to Glucosinolates, Phenolics, and Amino Acids

    Science.gov (United States)

    Schiavon, Michela; Berto, Chiara; Malagoli, Mario; Trentin, Annarita; Sambo, Paolo; Dall'Acqua, Stefano; Pilon-Smits, Elizabeth A. H.

    2016-01-01

    Two selenium (Se) fertilization methods were tested for their effects on levels of anticarcinogenic selenocompounds in radish (Raphanus sativus), as well as other nutraceuticals. First, radish was grown on soil and foliar selenate applied 7 days before harvest at 0, 5, 10, and 20 mg Se per plant. Selenium levels were up to 1200 mg Se/kg DW in leaves and 120 mg Se/kg DW in roots. The thiols cysteine and glutathione were present at 2–3-fold higher levels in roots of Se treated plants, and total glucosinolate levels were 35% higher, due to increases in glucoraphanin. The only seleno-aminoacid detected in Se treated plants was Se-methyl-SeCys (100 mg/kg FW in leaves, 33 mg/kg FW in roots). The levels of phenolic aminoacids increased with selenate treatment, as did root total nitrogen and protein content, while the level of several polyphenols decreased. Second, radish was grown in hydroponics and supplied with 0, 5, 10, 20, or 40 μM selenate for 1 week. Selenate treatment led to a 20–30% increase in biomass. Selenium concentration was 242 mg Se/kg DW in leaves and 85 mg Se/kg DW in roots. Cysteine levels decreased with Se in leaves but increased in roots; glutatione levels decreased in both. Total glucosinolate levels in leaves decreased with Se treatment due to repression of genes involved in glucosinolates metabolism. Se-methyl-SeCys concentration ranged from 7–15 mg/kg FW. Aminoacid concentration increased with Se treatment in leaves but decreased in roots. Roots of Se treated plants contained elevated transcript levels of sulfate transporters (Sultr) and ATP sulfurylase, a key enzyme of S/Se assimilation. No effects on polyphenols were observed. In conclusion, Se biofortification of radish roots may be achieved via foliar spray or hydroponic supply. One to ten radishes could fulfill the daily human requirement (70 μg) after a single foliar spray of 5 mg selenate per plant or 1 week of 5–10 μM selenate supply in hydroponics. The radishes metabolized

  9. Selenium biofortification in radish enhances nutritional quality via accumulation of methyl-selenocysteine and promotion of transcripts and metabolites related to glucosinolates, phenolics and amino acids

    Directory of Open Access Journals (Sweden)

    Michela Schiavon

    2016-09-01

    Full Text Available Two selenium (Se fertilization methods were tested for their effects on levels of anticarcinogenic selenocompounds in radish (Raphanus sativus, as well as other nutraceuticals. First, radish was grown on soil and foliar selenate applied 7d before harvest at 0, 5, 10 and 20 mg Se per plant. Selenium levels were up to 1,200 mg Se/kg DW in leaves and 120 mg Se/kg DW in roots. The thiols cysteine and glutathione were present at 2-3 fold higher levels in roots of Se treated plants, and total glucosinolate levels were 35% higher, due to increases in glucoraphanin. The only seleno-aminoacid detected in Se treated plants was Se-methyl-SeCys (100 mg/kg FW in leaves, 33 mg/kg FW in roots. The levels of phenolic aminoacids increased with selenate treatment, as did root total nitrogen and protein content, while the level of several polyphenols decreased. Second, radish was grown in hydroponics and supplied with 0, 5, 10, 20, or 40 microM selenate for one week. Selenate treatment led to a 20-30% increase in biomass. Selenium concentration was 242 mg Se/kg DW in leaves and 85 mg Se/kg DW in roots. Cysteine levels decreased with Se in leaves but increased in roots; glutatione levels decreased in both. Total glucosinolate levels in leaves decreased with Se treatment due to repression of genes involved in glucosinolates metabolism. Se-methyl-SeCys concentration ranged from 7-15 mg/kg FW. Aminoacid concentration increased with Se treatment in leaves but decreased in roots. Roots of Se treated plants contained elevated transcript levels of sulfate transporters (Sultr and ATP sulfurylase, a key enzyme of S/Se assimilation. No effects on polyphenols were observed. In conclusion, Se biofortification of radish roots may be achieved via foliar spray or hydroponic supply. One to ten radishes could fulfill the daily human requirement (70 microg after a single foliar spray of 5 mg selenate per plant or one week of 5-10 microM selenate supply in hydroponics. The radishes

  10. PPPC 4 DM secondary: a Poor Particle Physicist Cookbook for secondary radiation from Dark Matter

    Energy Technology Data Exchange (ETDEWEB)

    Buch, Jatan [Institut de Physique Théorique, Université Paris Saclay, CNRS, CEA,F-91191 Gif-sur-Yvette (France); Department of Physics, Indian Institute of Technology,Kharagpur, West Bengal - 721302 (India); Cirelli, Marco; Giesen, Gaëlle; Taoso, Marco [Institut de Physique Théorique, Université Paris Saclay, CNRS, CEA,F-91191 Gif-sur-Yvette (France)

    2015-09-11

    We enlarge the set of recipes and ingredients at disposal of any poor particle physicist eager to cook up signatures from weak-scale Dark Matter models by computing two secondary emissions due to DM particles annihilating or decaying in the galactic halo, namely the radio signals from synchrotron emission and the gamma rays from bremsstrahlung. We consider several magnetic field configurations and propagation scenarios for electrons and positrons. We also provide an improved energy loss function for electrons and positrons in the Galaxy, including synchrotron losses in the different configurations, bremsstrahlung losses, ionization losses and Inverse Compton losses with an updated InterStellar Radiation Field.

  11. PPPC 4 DM secondary: a Poor Particle Physicist Cookbook for secondary radiation from Dark Matter

    Energy Technology Data Exchange (ETDEWEB)

    Buch, Jatan; Cirelli, Marco; Giesen, Gaëlle; Taoso, Marco, E-mail: jbuch.iitkgp@gmail.com, E-mail: marco.cirelli@cea.fr, E-mail: gaelle.giesen@cea.fr, E-mail: marco.taoso@cea.fr [Institut de Physique Théorique, Université Paris Saclay, CNRS, CEA, F-91191 Gif-sur-Yvette (France)

    2015-09-01

    We enlarge the set of recipes and ingredients at disposal of any poor particle physicist eager to cook up signatures from weak-scale Dark Matter models by computing two secondary emissions due to DM particles annihilating or decaying in the galactic halo, namely the radio signals from synchrotron emission and the gamma rays from bremsstrahlung. We consider several magnetic field configurations and propagation scenarios for electrons and positrons. We also provide an improved energy loss function for electrons and positrons in the Galaxy, including synchrotron losses in the different configurations, bremsstrahlung losses, ionization losses and Inverse Compton losses with an updated InterStellar Radiation Field.

  12. High-contrast coronagraph performance in the presence of DM actuator defects

    Science.gov (United States)

    Sidick, Erkin; Shaklan, Stuart; Cady, Eric

    2015-09-01

    Deformable Mirrors (DMs) are critical elements in high contrast coronagraphs, requiring precision and stability measured in picometers to enable detection of Earth-like exoplanets. Occasionally DM actuators or their associated cables or electronics fail, requiring a wavefront control algorithm to compensate for actuators that may be displaced from their neighbors by hundreds of nanometers. We have carried out experiments on our High-Contrast Imaging Testbed (HCIT) to study the impact of failed actuators in partial fulfilment of the Terrestrial Planet Finder Coronagraph optical model validation milestone. We show that the wavefront control algorithm adapts to several broken actuators and maintains dark-hole contrast in broadband light.

  13. PPPC 4 DM secondary: a Poor Particle Physicist Cookbook for secondary radiation from Dark Matter

    International Nuclear Information System (INIS)

    Buch, Jatan; Cirelli, Marco; Giesen, Gaëlle; Taoso, Marco

    2015-01-01

    We enlarge the set of recipes and ingredients at disposal of any poor particle physicist eager to cook up signatures from weak-scale Dark Matter models by computing two secondary emissions due to DM particles annihilating or decaying in the galactic halo, namely the radio signals from synchrotron emission and the gamma rays from bremsstrahlung. We consider several magnetic field configurations and propagation scenarios for electrons and positrons. We also provide an improved energy loss function for electrons and positrons in the Galaxy, including synchrotron losses in the different configurations, bremsstrahlung losses, ionization losses and Inverse Compton losses with an updated InterStellar Radiation Field

  14. High-Contrast Coronagraph Performance in the Presence of DM Actuator Defects

    Science.gov (United States)

    Sidick, Erkin; Shaklan, Stuart; Cady, Eric

    2015-01-01

    Deformable Mirrors (DMs) are critical elements in high contrast coronagraphs, requiring precision and stability measured in picometers to enable detection of Earth-like exoplanets. Occasionally DM actuators or their associated cables or electronics fail, requiring a wavefront control algorithm to compensate for actuators that may be displaced from their neighbors by hundreds of nanometers. We have carried out experiments on our High-Contrast Imaging Testbed (HCIT) to study the impact of failed actuators in partial fulfillment of the Terrestrial Planet Finder Coronagraph optical model validation milestone. We show that the wavefront control algorithm adapts to several broken actuators and maintains dark-hole contrast in broadband light.

  15. In vitro activity of DMG-Mino and DMG-DM Dot, two new glycylcyclines, against anaerobic bacteria.

    Science.gov (United States)

    Nord, C E; Lindmark, A; Persson, I

    1993-10-01

    The in vitro activity of DMG-Mino and DMG-DM Dot against 350 anaerobic bacterial strains including anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, other Bacteroides species and fusobacteria was determined by the agar dilution method. Their activity was compared with that of minocycline, doxycycline, piperacillin, cefoxitin, imipenem, clindamycin and metronidazole. DMG-Mino and DMG-DM Dot and imipenem were the most active agents tested. DMG-Mino and DMG-DM Dot had in vitro activity superior to that of minocycline and doxycycline.

  16. Relative mRNA expression of prostate-derived E-twenty-six factor and E-twenty-six variant 4 transcription factors, and of uridine phosphorylase-1 and thymidine phosphorylase enzymes, in benign and malignant prostatic tissue

    Science.gov (United States)

    CAVAZZOLA, LUCIANE ROSTIROLA; CARVALHAL, GUSTAVO FRANCO; DEVES, CANDIDA; RENCK, DAIANA; ALMEIDA, RICARDO; SANTOS, DIóGENES SANTIAGO

    2015-01-01

    Prostate cancer is the most frequent urological tumor, and the second most common cancer diagnosed in men. Incidence and mortality are variable and appear to depend on behavioral factors and genetic predisposition. The prostate-derived E-twenty-six factor (PDEF) and E-twenty-six variant 4 (ETV4) transcription factors, and the thymidine phosphorylase (TP) and uridine phosphorylase-1 (UP-1) enzymes, are reported to be components of the pathways leading to tumorigenesis and/or metastasis in a number of tumors. The present study aimed to analyze the mRNA expression levels of these proteins in prostatic cancerous and benign tissue, and their association with clinical and pathological variables. Using quantitative reverse transcription polymerase chain reaction, the mRNA expression levels of PDEF, ETV4, TP and UP-1 were studied in 52 tissue samples (31 of benign prostatic hyperplasia and 21 of prostate adenocarcinomas) obtained from patients treated by transurethral resection of the prostate or by radical prostatectomy. Relative expression was assessed using the ∆-CT method. Data was analyzed using Spearman's tests for correlation. Pbenign and malignant prostatic tissues. Further studies are necessary to define the role of these proteins as therapeutic targets in prostate cancer. PMID:26137165

  17. Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats.

    Directory of Open Access Journals (Sweden)

    Raul Hernandes Bortolin

    Full Text Available Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM, and T1DM plus zinc supplementation (T1DMS. Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young's modulus, and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic

  18. Metabolic Network Topology Reveals Transcriptional Regulatory Signatures of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Zelezniak, Aleksej; Pers, Tune Hannes; Pinho Soares, Simao Pedro

    2010-01-01

    mechanisms underlying these transcriptional changes and their impact on the cellular metabolic phenotype is a challenging task due to the complexity of transcriptional regulation and the highly interconnected nature of the metabolic network. In this study we integrate skeletal muscle gene expression datasets...... with human metabolic network reconstructions to identify key metabolic regulatory features of T2DM. These features include reporter metabolites—metabolites with significant collective transcriptional response in the associated enzyme-coding genes, and transcription factors with significant enrichment...... factor regulatory network connecting several parts of metabolism. The identified transcription factors include members of the CREB, NRF1 and PPAR family, among others, and represent regulatory targets for further experimental analysis. Overall, our results provide a holistic picture of key metabolic...

  19. DM ORI: A YOUNG STAR OCCULTED BY A DISTURBANCE IN ITS PROTOPLANETARY DISK

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Joseph E.; Stassun, Keivan G.; Lund, Michael B.; Weintraub, David A. [Department of Physics and Astronomy, Vanderbilt University, 6301 Stevenson Center, Nashville, TN 37235 (United States); Cargile, Phillip [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Shappee, Benjamin J. [Carnegie Observatories, 813 Santa Barbara Street, Pasadena, CA 91101 (United States); Siverd, Robert J. [Las Cumbres Observatory Global Telescope Network, 6740 Cortona Drive, Suite 102, Santa Barbara, CA 93117 (United States); Pepper, Joshua [Department of Physics, Lehigh University, 16 Memorial Drive East, Bethlehem, PA 18015 (United States); Kochanek, Christopher S.; Gaudi, B. Scott; Stanek, Krzysztof Z.; Holoien, Thomas W.-S. [Department of Astronomy, The Ohio State University, Columbus, OH 43210 (United States); James, David [Cerro Tololo InterAmerican Observatory, Casilla 603, La Serena (Chile); Kuhn, Rudolf B. [South African Astronomical Observatory, P.O. Box 9, Observatory 7935 (South Africa); Beatty, Thomas G. [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Prieto, Jose L. [Nucleo de Astronoma de la Facultad de Ingeniera, Universidad Diego Portales, Av. Ejercito 441, Santiago (Chile); Feldman, Daniel M.; Espaillat, Catherine C. [Department of Astronomy, Boston University, 725 Commonwealth Avenue, Boston, MA 02215 (United States)

    2016-11-01

    In some planet formation theories, protoplanets grow gravitationally within a young star’s protoplanetary disk, a signature of which may be a localized disturbance in the disk’s radial and/or vertical structure. Using time-series photometric observations by the Kilodegree Extremely Little Telescope South project and the All-Sky Automated Survey for SuperNovae, combined with archival observations, we present the discovery of two extended dimming events of the young star, DM Ori. This young system faded by ∼1.5 mag from 2000 March to 2002 August and then again in 2013 January until 2014 September (depth ∼1.7 mag). We constrain the duration of the 2000–2002 dimming to be < 860 days, and the event in 2013–2014 to be < 585 days, separated by ∼12.5 years. A model of the spectral energy distribution indicates a large infrared excess consistent with an extensive circumstellar disk. Using basic kinematic arguments, we propose that DM Ori is likely being periodically occulted by a feature (possibly a warp or perturbation) in its circumstellar disk. In this scenario, the occulting feature is located >6 au from the host star, moving at ∼14.6 km s{sup −1} and is ∼4.9 au in width. This localized structure may indicate a disturbance such as that which may be caused by a protoplanet early in its formation.

  20. Data Clustering Menggunakan Metodologi CRISP-DM Untuk Pengenalan Pola Proporsi Pelaksanaan Tridharma

    Directory of Open Access Journals (Sweden)

    Irwan Budiman

    2014-01-01

    Full Text Available Quality of human resources faculty can be reflected from the implementation of productivity and quality Tridharma (education, research, community service  and  supporting  field  activities.  Lecturer  Workload  and Evaluation of  Higher Education  Tridharma  (BKD  and theEPT-PT  aims  to  ensure  the  implementation  of  the  faculty  task  runs  according  to  the  criteria  set  out  in  legislation.  Data  clusteringTridharma  implementation is needed to  get  some  knowledge  of the  pattern of Tridharma  implementation  at  college.  Clustering  as a  data mining  technique  should be  scalable, reliable  and  meet  an  agreed  standard.  CRISP-DM is the standardization of  data mining  is  used  in this study. The results of data clustering found the pattern of proportion of Tridharma  into 3 clusters representing patterns: professionals, managers and teachers.Keywords : Clustering, CRISP-DM, K-Means, Tridharma

  1. PPPC 4 DM ID: a poor particle physicist cookbook for dark matter indirect detection

    Energy Technology Data Exchange (ETDEWEB)

    Cirelli, Marco; Panci, Paolo; Strumia, Alessandro [CERN Theory Division, CH-1211 Geneve (Switzerland); Corcella, Gennaro [Museo Storico della Fisica, Centro Studi e Ricerche E. Fermi, P. del Viminale 1, I-00185 Rome (Italy); Hektor, Andi; Kadastik, Mario; Raidal, Martti [National Institute of Chemical Physics and Biophysics, Ravala 10, 10143 Tallinn (Estonia); Hütsi, Gert [Tartu Observatory, Tõravere 61602 (Estonia); Sala, Filippo, E-mail: marco.cirelli@cea.fr [Scuola Normale Superiore, Piazza dei Cavalieri 7, I-56126 Pisa (Italy)

    2011-03-01

    We provide ingredients and recipes for computing signals of TeV-scale Dark Matter annihilations and decays in the Galaxy and beyond. For each DM channel, we present the energy spectra at production, computed by high-statistics simulations. We estimate the Monte Carlo uncertainty by comparing the results yielded by the Pythia and Herwig event generators. We then provide the propagation functions for charged particles in the Galaxy, for several DM distribution profiles and sets of propagation parameters. Propagation of e{sup ±} is performed with an improved semi-analytic method that takes into account position-dependent energy losses in the Milky Way. Using such propagation functions, we compute the energy spectra of e{sup ±}, p-bar and d-bar at the location of the Earth. We then present the gamma ray fluxes, both from prompt emission and from Inverse Compton scattering in the galactic halo. Finally, we provide the spectra of extragalactic gamma rays. All results are available in numerical form and ready to be consumed.

  2. PPPC 4 DM ID: a poor particle physicist cookbook for dark matter indirect detection

    International Nuclear Information System (INIS)

    Cirelli, Marco; Panci, Paolo; Strumia, Alessandro; Corcella, Gennaro; Hektor, Andi; Kadastik, Mario; Raidal, Martti; Hütsi, Gert; Sala, Filippo

    2011-01-01

    We provide ingredients and recipes for computing signals of TeV-scale Dark Matter annihilations and decays in the Galaxy and beyond. For each DM channel, we present the energy spectra at production, computed by high-statistics simulations. We estimate the Monte Carlo uncertainty by comparing the results yielded by the Pythia and Herwig event generators. We then provide the propagation functions for charged particles in the Galaxy, for several DM distribution profiles and sets of propagation parameters. Propagation of e ± is performed with an improved semi-analytic method that takes into account position-dependent energy losses in the Milky Way. Using such propagation functions, we compute the energy spectra of e ± , p-bar and d-bar at the location of the Earth. We then present the gamma ray fluxes, both from prompt emission and from Inverse Compton scattering in the galactic halo. Finally, we provide the spectra of extragalactic gamma rays. All results are available in numerical form and ready to be consumed

  3. A New Approach to the Long-Term Activity Behavior of DM UMa

    Directory of Open Access Journals (Sweden)

    Taş G.

    2012-12-01

    Full Text Available A long-term activity character of DM UMa (K0-1 IV-III, which is one of the most active members of the RS CVn type variables, is examined using the multicolor photometric observations which spread to the time interval between 1980 and 2009. In this work, we present a new approximation for the long-term light and color variation of DM UMa using data obtained by combining our own observations obtained in the Johnson broad-band U,B,V,R filters between the years 1997 and 2008 and data published in literature. Available light and color data were examined for the long-term and seasonal variations using PERIOD04 program. The period analysis of the V-band data reveals the period estimations of 51.2±2.8 years and 15.1±0.7 years superposed on it. The U-B, B-V and V-R colors do not show correlation with the longer period, but they show variations with a period similar to the shorter one, except for B-V color. The amplitude variation also does not exhibit any correlation with the V light and color curves. It is found that the movement of the spot minima phases in years also indicates the migration period of nearly 15 years, similar to the period derived from the analysis of the long-term photometric observations in V-band.

  4. Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in dutch Caucasians

    NARCIS (Netherlands)

    Meex, Steven J. R.; van Greevenbroek, Marleen M. J.; Ayoubi, Torik A.; Vlietinck, Robert; van Vliet-Ostaptchouk, Jana V.; Hofker, Martin H.; Vermeulen, Vicky M. M. -J.; Schalkwijk, Casper G.; Feskens, Edith J. M.; Boer, Jolanda M. A.; Stehouwer, Coen D. A.; van der Kallen, Carla J. H.; de Bruin, Tjerk W. A.

    Context: Activating transcription factor 6 (ATF6) is critical for initiation and full activation of the unfolded protein response. An association between genetic variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima Indians. Objectives: To investigate the broader significance of

  5. The interaction of the antitoxin DM43 with a snake venom metalloproteinase analyzed by mass spectrometry and surface plasmon resonance

    DEFF Research Database (Denmark)

    Brand, Guilherme D; Salbo, Rune; Jørgensen, Thomas J D

    2012-01-01

    DM43 is a circulating dimeric antitoxin isolated from Didelphis aurita, a South American marsupial naturally immune to snake envenomation. This endogenous inhibitor binds non-covalently to jararhagin, the main hemorrhagic metalloproteinase from Bothrops jararaca snake venom, and efficiently...

  6. Single Crystal Piezoelectric Stack Actuator DM with Integrated Low-Power HVA-Based Driver ASIC, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This SBIR Phase I project aims to develop an innovative batch fabrication technique to create single crystal PMN-PT stack actuator deformable mirrors (DM) at low...

  7. Downregulation of DmMANF in Glial Cells Results in Neurodegeneration and Affects Sleep and Lifespan in Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Lucyna Walkowicz

    2017-11-01

    Full Text Available In Drosophila melanogaster, mesencephalic astrocyte-derived neurotrophic factor (DmMANF is an evolutionarily conserved ortholog of mammalian MANF and cerebral dopamine neurotrophic factor (CDNF, which have been shown to promote the survival of dopaminergic neurons in the brain. We observed especially high levels of DmMANF in the visual system of Drosophila, particularly in the first optic neuropil (lamina. In the lamina, DmMANF was found in glial cells (surface and epithelial glia, photoreceptors and interneurons. Interestingly, silencing of DmMANF in all neurons or specifically in photoreceptors or L2 interneurons had no impact on the structure of the visual system. However, downregulation of DmMANF in glial cells induced degeneration of the lamina. Remarkably, this degeneration in the form of holes and/or tightly packed membranes was observed only in the lamina epithelial glial cells. Those membranes seem to originate from the endoplasmic reticulum, which forms autophagosome membranes. Moreover, capitate projections, the epithelial glia invaginations into photoreceptor terminals that are involved in recycling of the photoreceptor neurotransmitter histamine, were less numerous after DmMANF silencing either in neurons or glial cells. The distribution of the alpha subunit of Na+/K+-ATPase protein in the lamina cell membranes was also changed. At the behavioral level, silencing of DmMANF either in neurons or glial cells affected the daily activity/sleep pattern, and flies showed less activity during the day but higher activity during the night than did controls. In the case of silencing in glia, the lifespan of flies was also shortened. The obtained results showed that DmMANF regulates many functions in the brain, particularly those dependent on glial cells.

  8. Do Adolescents with T1DM Differ from Their Peers in Health, Eating Habits and Social Support?

    Science.gov (United States)

    Husárová, Daniela; Kostičová, Michaela; Kočišová, Denisa; Schusterová, Ingrid; Gecková, Andrea Madarasová

    2017-12-01

    The aim of this study was to analyse differences in health, eating habits and social support in adolescents with type 1 diabetes mellitus (T1DM) in comparison to peers with another long-term illness or without any medical condition. We used self-reported data from the cross-sectional Health Behaviour in School-aged Children study collected in 2014 among Slovak adolescents as well as data from adolescents with T1DM collected in outpatient settings (11 to 15 years old, N=8,910, 50.3% of boys). Logistic regression models and general linear models were used to analyse differences between adolescents with T1DM and their peers with and without long-term illness in self-rated health, life satisfaction, health complaints, regular breakfast, sweets and soft drink consumption, and perceived support from family, teachers and classmates. Adolescents with T1DM reported worse self-rated health and suffer from more health complaints, but they have lower chance of having breakfast irregularly in comparison to their peers with another long-term illness or without any medical condition. Moreover, compared with their peers, adolescents with T1DM perceived stronger support from teachers and classmates, but weaker support from their family. We did not confirm any differences in life satisfaction, sweets and soft drink consumption between adolescents with T1DM and their peers. Adolescents with T1DM reported more regular eating habits, no difference in life satisfaction and more social support outside the family in comparison to their peers. However, their worse self-rated health, more health complaints and weaker support from family should be considered in interventions targeting psychosocial adjustment of adolescents with T1DM. Copyright© by the National Institute of Public Health, Prague 2017

  9. "I Know that You Know that I Know": Neural Substrates Associated with Social Cognition Deficits in DM1 Patients.

    Directory of Open Access Journals (Sweden)

    Laura Serra

    Full Text Available Myotonic dystrophy type-1 (DM1 is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM. We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in the Eyes" and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients' "Theory of Mind-network", which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients' success in life.

  10. Concerted transcription of auxin and carbohydrate homeostasis-related genes underlies improved adventitious rooting of microcuttings derived from far-red treated Eucalyptus globulus Labill mother plants.

    Science.gov (United States)

    Ruedell, Carolina Michels; de Almeida, Márcia Rodrigues; Fett-Neto, Arthur Germano

    2015-12-01

    Economically important plant species, such as Eucalyptus globulus, are often rooting recalcitrant. We have previously shown that far-red light enrichment applied to E. globulus donor-plants improved microcutting rooting competence and increased rooting zone/shoot carbohydrate ratio. To better understand this developmental response, the relative expression profiles of genes involved in auxin signaling (ARF6, ARF8, AGO1), biosynthesis (YUC3) and transport (AUX1, PIN1, PIN2); sucrose cleavage (SUS1, CWINV1), transport (SUC5), hexose phosphorylation (HXK1, FLN1) and starch biosynthesis (SS3) were quantified during adventitious rooting of E. globulus microcuttings derived from donor plants exposed to far-red or white light. Expression of auxin transport-related genes increased in the first days of root induction. Far-red enrichment of donor plants induced ARF6, ARF8 and AGO1 in microcuttings. The first two gene products could activate GH3 and other rooting related genes, whereas AGO1 deregulation of the repressor ARF17 may relief rooting inhibition. Increased sink strength at the basal stem with sucrose unloading in root tissue mediated by SUC and subsequent hydrolysis by SUS1 were also supported by gene expression profile. Fructose phosphorylation and starch biosynthesis could also contribute to proper carbon allocation at the site of rooting, as evidenced by increased expression of related genes. These data are in good agreement with increased contents of hexoses and starch at the cutting base severed from far-red exposed donor plants. To sum up, pathways integrating auxin and carbohydrate metabolism were activated in microcuttings derived from donor plants exposed to far red light enrichment, thereby improving rooting response in E. globulus. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Characterization of a noncytotoxic bacteriocin from probiotic Lactobacillus plantarum DM5 with potential as a food preservative.

    Science.gov (United States)

    Das, Deeplina; Goyal, Arun

    2014-10-01

    The aim of this work was to purify and characterize the bacteriocin produced by probiotic Lactobacillus plantarum DM5 in order to evaluate its potential as nutraceuticals. Lb. plantarum DM5 exhibited in vitro probiotic properties such as high resistance to gastric juice and bile salt, adherence to human adenocarcinoma (HT-29) cells, bile salt hydrolase and cholesterol assimilation activity. Moreover, Lb. plantarum DM5 showed bacteriocin activity against several major food borne pathogens. Zymogram analysis of purified bacteriocin (plantaricin DM5) showed a molecular size of ∼15.2 kDa. Plantaricin DM5 was sensitive to proteolytic enzymes but stable in the pH range of 2.0-10.0, and it was heat resistant (121 °C for 15 min) and remained active upon treatment with surfactants and detergents. Cytotoxicity analysis of plantaricin DM5 on human embryonic kidney 293 (HEK 293) and human cervical cancer (HeLa) cell lines revealed its nontoxic and biocompatible nature. To the best of our knowledge, this is the first study on the isolated strain expressing probiotic properties and broad antimicrobial activity without any cytotoxic effect on mammalian cells from indigenous fermented beverage Marcha from India, and thus contributes to the food industry as a novel bio-preservant.

  12. Inhibition of HLA-DM mediated MHC class II peptide loading by HLA-DO promotes self tolerance

    Directory of Open Access Journals (Sweden)

    Lisa K. Denzin

    2013-12-01

    Full Text Available Major histocompatibility class II (MHCII molecules are loaded with peptides derived from foreign and self-proteins within the endosomes and lysosomes of antigen presenting cells (APCs. This process is mediated by interaction of MHCII with the conserved, nonpolymorphic MHCII-like molecule HLA-DM (DM. DM activity is directly opposed by HLA-DO (DO, another conserved, non-polymorphic MHCII like molecule. DO is an MHCII substrate mimic. Binding of DO to DM prevents MHCII from binding to DM, thereby inhibiting peptide loading. Inhibition of DM function enables low stability MHC complexes to survive and populate the surface of APCS. As a consequence, DO promotes the display of a broader pool of low abundance self-peptides. Broadening the peptide repertoire theoretically reduces the likelihood of inadvertently acquiring a density of self-ligands that is sufficient to activate self-reactive T cells. One function of DO, therefore, is to promote T cell tolerance by shaping the visible image of self. Recent data also shows that DO influences the adaptive immune response by controlling B cell entry into the germinal center reaction. This review explores the data supporting these concepts.

  13. Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases Intestinal Gluconeogenesis in a T2DM Rat Model.

    Science.gov (United States)

    Yan, Yong; Zhou, Zhou; Kong, Fanzhi; Feng, Suibin; Li, Xuzhong; Sha, Yanhua; Zhang, Guangjun; Liu, Haijun; Zhang, Haiqing; Wang, Shiguang; Hu, Cheng; Zhang, Xueli

    2016-11-01

    Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and intestinal morphological adaption, as well as hepatic and intestinal gluconeogenesis. Twenty adult male T2DM rats induced by high-fat diet and low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, and serum lipid profiles were assessed to evaluate metabolic changes. Intestinal sections were stained with hematoxylin and eosin (H&E) for light microscopy examination. The messenger RNA (mRNA) and protein expression levels of key regulatory enzymes of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase)] were determined through reverse-transcription PCR (RT-PCR) and Western blotting, respectively. RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum triglyceride (TG) and free fatty acid (FFA) levels. The jejunum and ileum exhibited a marked increase in the length and number of intestinal villi after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK and G6Pase in the liver and upregulated expression of these enzymes in the jejunum and ileum tissues. RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The small intestine shows hyperplasia and hypertrophy after RYGB. Meanwhile, our study demonstrated that the reduced hepatic gluconeogenesis and increased intestinal gluconeogenesis may contribute to improved glucose homeostasis after RYGB.

  14. Aboveground Whitefly Infestation Modulates Transcriptional Levels of Anthocyanin Biosynthesis and Jasmonic Acid Signaling-Related Genes and Augments the Cope with Drought Stress of Maize.

    Directory of Open Access Journals (Sweden)

    Yong-Soon Park

    Full Text Available Up to now, the potential underlying molecular mechanisms by which maize (Zea mays L. plants elicit defense responses by infestation with a phloem feeding insect whitefly [Bemisia tabaci (Genn.] have been barely elucidated against (abiotic stresses. To fill this gap of current knowledge maize plants were infested with whitefly and these plants were subsequently assessed the levels of water loss. To understand the mode of action, plant hormone contents and the stress-related mRNA expression were evaluated. Whitefly-infested maize plants did not display any significant phenotypic differences in above-ground tissues (infested site compared with controls. By contrast, root (systemic tissue biomass was increased by 2-fold by whitefly infestation. The levels of endogenous indole-3-acetic acid (IAA, jasmonic acid (JA, and hydrogen peroxide (H2O2 were significantly higher in whitefly-infested plants. The biosynthetic or signaling-related genes for JA and anthocyanins were highly up-regulated. Additionally, we found that healthier plants were obtained in whitefly-infested plants under drought conditions. The weight of whitefly-infested plants was approximately 20% higher than that of control plants at 14 d of drought treatment. The drought tolerance-related genes, ZmbZIP72, ZmSNAC1, and ZmABA1, were highly expressed in the whitefly-infected plants. Collectively, our results suggest that IAA/JA-derived maize physiological changes and correlation of H2O2 production and water loss are modulated by above-ground whitefly infestation in maize plants.

  15. Prevalence of diabetic retinopathy and its relationship with glomerular filtration rate and other risk factors in patients with type 2 diabetes mellitus in Spain. DM2 HOPE study

    Directory of Open Access Journals (Sweden)

    Maribel López

    2017-09-01

    Conclusion: Around one in seven patients with T2DM has DR after nine years since diagnosis. Time since diagnosis, insulin therapy, cardiovascular profile, and renal dysfunction are associated with DR in patients with T2DM in Spain.

  16. Riboflavin Depletion Promotes Tumorigenesis in HEK293T and NIH3T3 Cells by Sustaining Cell Proliferation and Regulating Cell Cycle-Related Gene Transcription.

    Science.gov (United States)

    Long, Lin; He, Jian-Zhong; Chen, Ye; Xu, Xiu-E; Liao, Lian-Di; Xie, Yang-Min; Li, En-Min; Xu, Li-Yan

    2018-05-07

    Riboflavin is an essential component of the human diet and its derivative cofactors play an established role in oxidative metabolism. Riboflavin deficiency has been linked with various human diseases. The objective of this study was to identify whether riboflavin depletion promotes tumorigenesis. HEK293T and NIH3T3 cells were cultured in riboflavin-deficient or riboflavin-sufficient medium and passaged every 48 h. Cells were collected every 5 generations and plate colony formation assays were performed to observe cell proliferation. Subcutaneous tumorigenicity assays in NU/NU mice were used to observe tumorigenicity of riboflavin-depleted HEK293T cells. Mechanistically, gene expression profiling and gene ontology analysis were used to identify abnormally expressed genes induced by riboflavin depletion. Western blot analyses, cell cycle analyses, and chromatin immunoprecipitation were used to validate the expression of cell cycle-related genes. Plate colony formation of NIH3T3 and HEK293T cell lines was enhanced >2-fold when cultured in riboflavin-deficient medium for 10-20 generations. Moreover, we observed enhanced subcutaneous tumorigenicity in NU/NU mice following injection of riboflavin-depleted compared with normal HEK293T cells (55.6% compared with 0.0% tumor formation, respectively). Gene expression profiling and gene ontology analysis revealed that riboflavin depletion induced the expression of cell cycle-related genes. Validation experiments also found that riboflavin depletion decreased p21 and p27 protein levels by ∼20%, and increased cell cycle-related and expression-elevated protein in tumor (CREPT) protein expression >2-fold, resulting in cyclin D1 and CDK4 levels being increased ∼1.5-fold, and cell cycle acceleration. We also observed that riboflavin depletion decreased intracellular riboflavin levels by 20% and upregulated expression of riboflavin transporter genes, particularly SLC52A3, and that the changes in CREPT and SLC52A3 correlated with

  17. Selected results on J/PSI hadronic decays from DM2 and Mark III

    International Nuclear Information System (INIS)

    Augustin, J.E.

    1985-01-01

    Results from the high statistics experiments Mark III and DM2 on J/PSI hadronic decays are reviewed. Special interest is given to SU3 violating decays into two pseudoscalars and baryon-antibaryon, especially the first observation of J/PSI → Ksub(S)sup(o)Ksub(L)sup(o). The complete measurement of the vector + pseudoscalar modes allows a new determination of the eta and eta' mixing parameters, indicating the presence of a new component in the eta' wave function. The iota(1440) and theta(1700) gluonium candidates have been searched for in hadronic decays, and the Mark III experiment observes a signal in J/PSI → ω iota (or ωE)

  18. Analysis and realization of a high resolution trigger for DM2 experiment

    International Nuclear Information System (INIS)

    Bertrand, J.L.

    1984-01-01

    The construction of a high resolution trigger has been carried out from its theoretical design to building. The term trigger is applied to an almost real-time system for track filtering in particle detection. Curved tracks are detected (with a magnetic field) and the detector is of a revolution symmetry type. The concept of a ''hybrid'' trigger with features in between those of the so-called ''CELLO R0'' and ''MARK II'' types is launched. It allows a positive versatility for the optimization of the different features. Besides a specific structure, some hardware and software implements have been designed for development and tests. The ''TRIGGER LENT'' is presently in operation in the DM2 experiment [fr

  19. Dynamics of Entanglement in Qubit-Qutrit with x-Component of DM Interaction

    International Nuclear Information System (INIS)

    Sharma, Kapil K.; Pandey, S.N.

    2016-01-01

    In this present paper, we study the entanglement dynamics in qubit A-qutrit B pair under x component of Dzyaloshinshkii–Moriya interaction (D x ) by taking an auxiliary qubit C. Here, we consider an entangled qubit-qutrit pair initially prepared in two parameter qubit-qutrit states and one auxiliary qubit prepared in pure state interacts with the qutrit of the pair through DM interaction. We trace away the auxiliary qubit and calculate the reduced dynamics in qubit A-qutrit B pair to study the influence of the state of auxiliary qubit C and D x on entanglement. We find that the state (probability amplitude) of auxiliary qubit does not influence the entanglement, only D x influences the same. The phenomenon of entanglement sudden death (ESD) induced by D x has also been observed. We also present the affected and unaffected two parameter qubit-qutrit states by D x . (paper)

  20. The prefabricated building risk decision research of DM technology on the basis of Rough Set

    Science.gov (United States)

    Guo, Z. L.; Zhang, W. B.; Ma, L. H.

    2017-08-01

    With the resources crises and more serious pollution, the green building has been strongly advocated by most countries and become a new building style in the construction field. Compared with traditional building, the prefabricated building has its own irreplaceable advantages but is influenced by many uncertainties. So far, a majority of scholars have been studying based on qualitative researches from all of the word. This paper profoundly expounds its significance about the prefabricated building. On the premise of the existing research methods, combined with rough set theory, this paper redefines the factors which affect the prefabricated building risk. Moreover, it quantifies risk factors and establish an expert knowledge base through assessing. And then reduced risk factors about the redundant attributes and attribute values, finally form the simplest decision rule. This simplest decision rule, which is based on the DM technology of rough set theory, provides prefabricated building with a controllable new decision-making method.

  1. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  2. Effect of some environmental parameters on fermentative hydrogen production by Enterobacter cloacae DM11

    Energy Technology Data Exchange (ETDEWEB)

    Nath, K.; Kumar, A.; Das, D. [Indian Inst. of Technology, Kharagpur (India). Dept. of Biotechnology, Fermentation Technology Laboratory

    2006-06-15

    This study addressed the issue of using biological systems for hydrogen production as an environmentally sound alternative to conventional thermochemical and electrochemical processes. In particular, it examined the potential for anaerobic fermentation for biological hydrogen production and the possibility of coupling gaseous energy generation with simultaneous treatment of biodegradable waste materials. The study focused on hydrogen production by anaerobic fermentation using Enterobacter cloacae DM11, a Gram-negative, motile facultative anaerobe. Although hydrogen production by these bacteria depends on many environmental parameters, there is very little information on the effects of these factors in the hydrogen production potential of this organism. For that reason, this study examined the effect of initial medium pH, reaction temperature, initial glucose concentration, and iron (Fe2+) concentration on the fermentative production of hydrogen. Fermentative hydrogen production was carried out by Enterobacter cloacae DM11, using glucose as the substrate. Batch cultivations were performed in a 500 ml custom-designed vertical tubular bioreactor. The maximum molar yield of hydrogen was 3.31 mol (mol glucose){sub 1}. The rate and cumulative volume of hydrogen production decreased at higher initial glucose concentration. The pH of 6.5 at a temperature of 37 degrees C was most suitable for maximum rate of production of hydrogen in batch fermentation. The addition of Fe2+ on hydrogen production had a marginal enhancing effect on total hydrogen production. A simple model developed from the modified Gompertz equation was used to fit the cumulative hydrogen production curve and to estimate the hydrogen production potential, maximum production rate, and lag time. It was concluded that these study results could be used in the development of a high rate continuous hydrogen production process. 30 refs., 4 tabs., 3 figs.

  3. The design of red-blue 3D video fusion system based on DM642

    Science.gov (United States)

    Fu, Rongguo; Luo, Hao; Lv, Jin; Feng, Shu; Wei, Yifang; Zhang, Hao

    2016-10-01

    Aiming at the uncertainty of traditional 3D video capturing including camera focal lengths, distance and angle parameters between two cameras, a red-blue 3D video fusion system based on DM642 hardware processing platform is designed with the parallel optical axis. In view of the brightness reduction of traditional 3D video, the brightness enhancement algorithm based on human visual characteristics is proposed and the luminance component processing method based on YCbCr color space is also proposed. The BIOS real-time operating system is used to improve the real-time performance. The video processing circuit with the core of DM642 enhances the brightness of the images, then converts the video signals of YCbCr to RGB and extracts the R component from one camera, so does the other video and G, B component are extracted synchronously, outputs 3D fusion images finally. The real-time adjustments such as translation and scaling of the two color components are realized through the serial communication between the VC software and BIOS. The system with the method of adding red-blue components reduces the lost of the chrominance components and makes the picture color saturation reduce to more than 95% of the original. Enhancement algorithm after optimization to reduce the amount of data fusion in the processing of video is used to reduce the fusion time and watching effect is improved. Experimental results show that the system can capture images in near distance, output red-blue 3D video and presents the nice experiences to the audience wearing red-blue glasses.

  4. Beam shaping by using small-aperture SLM and DM in a high power laser

    Science.gov (United States)

    Li, Sensen; Lu, Zhiwei; Du, Pengyuan; Wang, Yulei; Ding, Lei; Yan, Xiusheng

    2018-03-01

    High-power laser plays an important role in many fields, such as directed energy weapon, optoelectronic contermeasures, inertial confinement fusion, industrial processing and scientific research. The uniform nearfield and wavefront are the important part of the beam quality for high power lasers, which is conducive to maintaining the high spatial beam quality in propagation. We demonstrate experimentally that the spatial intensity and wavefront distribution at the output is well compensated in the complex high-power solid-state laser system by using the small-aperture spatial light modulator (SLM) and deformable mirror (DM) in the front stage. The experimental setup is a hundred-Joule-level Nd:glass laser system operating at three wavelengths at 1053 nm (1ω), 527 nm (2ω) and 351 nm (3ω) with 3 ns pulse duration with the final output beam aperture of 60 mm. While the clear arperture of the electrically addressable SLM is less than 20 mm and the effective diameter of the 52-actuators DM is about 15 mm. In the beam shaping system, the key point is that the two front-stage beam shaping devices needs to precompensate the gain nonuniform and wavefront distortion of the laser system. The details of the iterative algorithm for improving the beam quality are presented. Experimental results show that output nearfield and wavefont are both nearly flat-topped with the nearfield modulation of 1.26:1 and wavefront peak-to-valley value of 0.29 λ at 1053nm after beam shaping.

  5. T-1020 NaI crystal test for DM-Ice

    International Nuclear Information System (INIS)

    Maruyama, Reina; Heeger, Karsten; Pierpoint, Zachary; Pettus, Walter; Broerman, Benjamin; Hilgenberg, Chris; Webber, David

    2011-01-01

    This is a memorandum of understanding between the Fermi National Accelerator Laboratory (Fermilab) and the experiments of the NaI Crystal Test for DM-Ice from the University of Wisconsin who have committed to participate in detector tests to be carried out during the 2011-2012 Fermilab Neutrino program. The memorandum is intended primarily for the purpose of recording expectations for budget estimates and work allocations for Fermilab, the funding agencies and the participating institutions. It reflects an arrangement that currently is satisfactory to the parties; however, it is recognized and anticipated that changing circumstances of the evolving research program will necessitate revisions. The parties agree to modify this memorandum to reflect such required adjustments. Actual contractual obligations will be set forth in separate documents. The DM-Ice collaboration is designing a sodium-iodide (NaI) based detector for a direct dark matter search. The detectors should have low readout noise and background levels to carry out a sensitive search. A 17-kg version of the experiment is running at the South Pole, 2500 m deep in the Antarctic ice, and a large scale experiment is currently being designed. One of the keys to the success of the experiment is to have a good understanding of the background levels intrinsic in the NaI detectors. To measure the background level, the detectors have to be shielded against cosmic rays. The lead shielding used for DAMIC in the Minos Underground Areas is a well-suited location for this test since it offers enough overburden to shield against cosmic rays, lead shielding, and experimental infrastructure. The goal of the test is to assess the background levels in the detector and to assess the characteristics of phosphorescence induced by muons and 100 keV-3 MeV gamma rays.

  6. Transcriptional Profiling of Immune-Related Genes in Leishmania infantum-Infected Mice: Identification of Potential Biomarkers of Infection and Progression of Disease

    Directory of Open Access Journals (Sweden)

    Eduardo Ontoria

    2018-06-01

    Full Text Available Leishmania spp. is a protozoan parasite that affects millions of people around the world. At present, there is no effective vaccine to prevent leishmaniases in humans. A major limitation in vaccine development is the lack of precise understanding of the particular immunological mechanisms that allow parasite survival in the host. The parasite-host cell interaction induces dramatic changes in transcriptome patterns in both organisms, therefore, a detailed analysis of gene expression in infected tissues will contribute to the evaluation of drug and vaccine candidates, the identification of potential biomarkers, and the understanding of the immunological pathways that lead to protection or progression of disease. In this large-scale analysis, differential expression of 112 immune-related genes has been analyzed using high-throughput qPCR in spleens of infected and naïve Balb/c mice at four different time points. This analysis revealed that early response against Leishmania infection is characterized by the upregulation of Th1 markers and M1-macrophage activation molecules such as Ifng, Stat1, Cxcl9, Cxcl10, Ccr5, Cxcr3, Xcl1, and Ccl3. This activation doesn't protect spleen from infection, since parasitic burden rises along time. This marked difference in gene expression between infected and control mice disappears during intermediate stages of infection, probably related to the strong anti-inflammatory and immunosuppresory signals that are activated early upon infection (Ctla4 or remain activated throughout the experiment (Il18bp. The overexpression of these Th1/M1 markers is restored later in the chronic phase (8 wpi, suggesting the generation of a classical “protective response” against leishmaniasis. Nonetheless, the parasitic burden rockets at this timepoint. This apparent contradiction can be explained by the generation of a regulatory immune response characterized by overexpression of Ifng, Tnfa, Il10, and downregulation Il4 that

  7. Exposure of maternal mice to cis-bifenthrin enantioselectively disrupts the transcription of genes related to testosterone synthesis in male offspring.

    Science.gov (United States)

    Jin, Yuanxiang; Wang, Jiangcong; Sun, Xueqing; Ye, Yang; Xu, Minjie; Wang, Jianai; Chen, Shaoping; Fu, Zhengwei

    2013-12-01

    The commercial bifenthrin (BF) contains two cis isomers. In the present study, a dose of 15mg/kg of 1R-cis-BF or 1S-cis-BF was orally administered for 3 weeks to female mice before or during pregnancy. Then, the expression of steroidogenesis related genes which were considered as effective biomarkers of endocrine disruption were analyzed in the male offspring. Maternal exposure to 1S-cis-BF during pregnancy significantly reduced the mRNA levels of peripheral benzodiazepine receptor (PBR) and steroidogenic acute regulatory protein (StAR) in the testes of 3- or 6-week old male offspring. In addition, a significant decrease of cytochrome P450 17α-hydroxysteroid dehydrogenase (P450-17α) was also observed in the testes of 6-week old male offspring when dams were treated with 1S-cis-BF during pregnancy but not before pregnancy. Moreover, the scavenger receptor class B type 1 (SRB1) and cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc) decreased significantly in the testes of 6-week old male offspring when dams were treated with 1S-cis-BF during and before pregnancy. Thus, oral administration of the maternal mice to cis-BF for 3 weeks, particularly during pregnancy, resulted in endocrine disruption in the male offspring, with the 1S-cis-BF causing more significant alterations than the 1R-cis-BF form. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Clinical significance of changes of serum APN, plasma VEGF, Hcy and urine albumin levels in patients with DM2 nephrosis

    International Nuclear Information System (INIS)

    Zhang Yuejin; Zhang Xinfang; Hu Ying

    2011-01-01

    Objective: Explore type 2 diabetes mellitus (DM2) and complicating with kidney disease patients homocysteine (Hcy), adiponectin (APN), vascular endothelial growth factor (VEGF) and urine albumin change relations. Methods: A normal controls and no complications of diabetes groups, combined with nephropathy. A comparison were measured of serum APN, plasma VEGF, Hcy and urine albumin level among. Results: Two groups of patients with diabetes fasting blood glucose level were no significant difference. Also there is no difference of BUN and Cr in three groups urine albumin in diabetic-nephropathy albumin increased significantly (P<0.01), than without complications group. Three groups of Hcy concentrations were significantly higher than that of normal control group (P<0.01), serum APN, plasma VEGF level obviously lower than normal control group, which increased in patients with nephropathy increased or reduced more apparently no complications group also have obvious difference (P<0.01). Conclusion: In patients with diabetes in two groups, plasma Hcy and urine albumin were significantly higher APN, and VEGF decreased significantly. In patients with nephropathy manifested more apparently, but renal damage did not enter decompensated period, clinically necessary for people with diabetes testing serum APN, plasma VEGF, Hcy and urine Albumin level, promptly intervention to prevent or relieve the further development of diabetes. (authors)

  9. Patient-reported outcomes from EMILIA, a randomized phase 3 study of trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer.

    Science.gov (United States)

    Welslau, Manfred; Diéras, Veronique; Sohn, Joo-Hyuk; Hurvitz, Sara A; Lalla, Deepa; Fang, Liang; Althaus, Betsy; Guardino, Ellie; Miles, David

    2014-03-01

    This report describes the results of an analysis of patient-reported outcomes from EMILIA (TDM4370g/BO21977), a randomized phase 3 study of the antibody-drug conjugate trastuzumab emtansine (T-DM1) versus capecitabine and lapatinib in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer. A secondary endpoint of the EMILIA study was time to symptom worsening (time from randomization to the first documentation of a ≥ 5-point decrease from baseline) as measured by the Trial Outcome Index Physical/Functional/Breast (TOI-PFB) subset of the Functional Assessment of Cancer Therapy-Breast questionnaire. Predefined exploratory patient-reported outcome endpoints included proportion of patients with a clinically significant improvement in symptoms (per TOI-PFB) and proportion of patients with diarrhea symptoms (per Diarrhea Assessment Scale). In the T-DM1 arm, 450 of 495 patients had a baseline and ≥ 1 postbaseline TOI-PFB score versus 445 of 496 patients in the capecitabine-plus-lapatinib arm. Time to symptom worsening was delayed in the T-DM1 arm versus the capecitabine-plus-lapatinib arm (7.1 months versus 4.6 months, respectively; hazard ratio = 0.796; P = .0121). In the T-DM1 arm, 55.3% of patients developed clinically significant improvement in symptoms from baseline versus 49.4% in the capecitabine-plus-lapatinib arm (P = .0842). Although similar at baseline, the number of patients reporting diarrhea symptoms increased 1.5- to 2-fold during treatment with capecitabine and lapatinib but remained near baseline levels in the T-DM1 arm. Together with the EMILIA primary data, these results support the concept that T-DM1 has greater efficacy and tolerability than capecitabine plus lapatinib, which may translate into improvements in health-related quality of life. © 2013 American Cancer Society.

  10. Cytological and transcriptional dynamics analysis of host plant revealed stage-specific biological processes related to compatible rice-Ustilaginoidea virens interaction.

    Directory of Open Access Journals (Sweden)

    Jinquan Chao

    Full Text Available Rice false smut, a fungal disease caused by Ustilaginoidea virens is becoming a severe detriment to rice production worldwide. However, little is known about the molecular response of rice to attacks by the smut pathogen. In this article, we define the initial infection process as having three stages: initial colonization on the pistil (stage 1, S1, amplification on the anther (stage 2, S2 and sporulation in the anther chambers (stage 3, S3. Based on the transcriptome of rice hosts in response to U. virens in two separate years, we identified 126, 204, and 580 specific regulated genes in their respective stages S1, S2, and S3, respectively, by excluding common expression patterns in other openly biotic/abiotic databases using bioinformatics. As the disease progresses, several stage-specific biological processes (BP terms were distinctively enriched: "Phosphorylation" in stage S1, "PCD" in S2, and "Cell wall biogenesis" in S3, implying a concise signal cascade indicative of the tactics that smut pathogens use to control host rice cells during infection. 113 regulated genes were coexpressed among the three stages. They shared highly conserved promoter cis-element in the promoters in response to the regulation of WRKY and Myb for up-regulation, and ABA and Ca2+ for down regulation, indicating their potentially critical roles in signal transduction during rice-U. virens interaction. We further analyzed seven highly regulated unique genes; four were specific to pollen development, implying that pollen-related genes play critical roles in the establishment of rice susceptibility to U. virens. To my knowledge, this is the first report about probing of molecular response of rice to smut pathogen infection, which will greatly expand our understanding of the molecular events surrounding infection by rice false smut.

  11. Embryonic exposure to cis-bifenthrin enantioselectively induces the transcription of genes related to oxidative stress, apoptosis and immunotoxicity in zebrafish (Danio rerio).

    Science.gov (United States)

    Jin, Yuanxiang; Pan, Xiuhong; Cao, Limin; Ma, Bufang; Fu, Zhengwei

    2013-02-01

    Cis-bifenthrin (cis-BF) is used widely for agricultural and non-agricultural purpose. Thus, cis-BF is one of the most frequently detected insecticides in the aquatic ecosystem. As a chiral pesticide, the commercial cis-BF contained two enantiomers including 1R-cis-BF and 1S-cis-BF. However, the difference in inducing oxidative stress, apoptosis and immunotoxicity by the two enantiomers in zebrafish still remains unclear. In the present study, the zebrafish were exposed to environmental concentrations of cis-BF, 1R-cis-BF and 1S-cis-BF during the embryos developmental stage. We observed that the mRNA levels of the most genes related to oxidative stress, apoptosis and immunotoxicity including Cu/Zn-superoxide dismutase (Cu/Zn-Sod), catalase (Cat), P53, murine double minute 2 (Mdm2), B-cell lymphoma/leukaemia-2 gene (Bcl2), Bcl2 associated X protein (Bax), apoptotic protease activating factor-1 (Apaf1), Caspase 9 (Cas9), Caspase 3 (Cas3), interleukin-1 beta (IL-1β) and interleukin-8(Il-8) were much higher in 1S-cis-BF treated group than those in cis-BF or 1R-cis-BF treated ones, suggesting that 1S-cis-BF has higher risk to induced oxidative stress, apoptosis and immunotoxicity than 1R-cis-BF in zebrafish. The information presented in this study will help with elucidating the differences and environmental risk of the two enantiomers of cis-BF-induced toxicity in aquatic organisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Mitogen-activated protein kinase 1 from disk abalone (Haliotis discus discus): Roles in early development and immunity-related transcriptional responses.

    Science.gov (United States)

    Perera, N C N; Godahewa, G I; Lee, Jehee

    2016-12-01

    Mitogen-activated protein kinase (MAPK) is involved in the regulation of cellular events by mediating signal transduction pathways. MAPK1 is a member of the extracellular-signal regulated kinases (ERKs), playing roles in cell proliferation, differentiation, and development. This is mainly in response to growth factors, mitogens, and many environmental stresses. In the current study, we have characterized the structural features of a homolog of MAPK1 from disk abalone (AbMAPK1). Further, we have unraveled its expressional kinetics against different experimental pathogenic infections or related chemical stimulants. AbMAPK1 harbors a 5' untranslated region (UTR) of 23 bps, a coding sequence of 1104 bps, and a 3' UTR of 448 bp. The putative peptide comprises a predicted molecular mass of 42.2 kDa, with a theoretical pI of 6.28. Based on the in silico analysis, AbMAPK1 possesses two N-glycosylation sites, one S_TK catalytic domain, and a conserved His-Arg-Asp domain (HRD). In addition, a conservative glycine rich ATP-phosphate-binding loop and a threonine-x-tyrosine motif (TEY) important for the autophosphorylation were also identified in the protein. Homology assessment of AbMAPK1 showed several conserved regions, and ark clam (Aplysia californica) showed the highest sequence identity (87.9%). The phylogenetic analysis supported close evolutionary kinship with molluscan orthologs. Constitutive expression of AbMAPK1 was observed in six different tissues of disk abalone, with the highest expression in the digestive tract, followed by the gills and hemocytes. Highest AbMAPK1 mRNA expression level was detected at the trochophore developmental stage, suggesting its role in abalone cell differentiation and proliferation. Significant modulation of AbMAPK1 expression under pathogenic stress suggested its putative involvement in the immune defense mechanism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Distinct roles of the DmNav and DSC1 channels in the action of DDT and pyrethroids.

    Science.gov (United States)

    Rinkevich, Frank D; Du, Yuzhe; Tolinski, Josh; Ueda, Atsushi; Wu, Chun-Fang; Zhorov, Boris S; Dong, Ke

    2015-03-01

    Voltage-gated sodium channels (Nav channels) are critical for electrical signaling in the nervous system and are the primary targets of the insecticides DDT and pyrethroids. In Drosophila melanogaster, besides the canonical Nav channel, Para (also called DmNav), there is a sodium channel-like cation channel called DSC1 (Drosophila sodium channel 1). Temperature-sensitive paralytic mutations in DmNav (para(ts)) confer resistance to DDT and pyrethroids, whereas DSC1 knockout flies exhibit enhanced sensitivity to pyrethroids. To further define the roles and interaction of DmNav and DSC1 channels in DDT and pyrethroid neurotoxicology, we generated a DmNav/DSC1 double mutant line by introducing a para(ts1) allele (carrying the I265N mutation) into a DSC1 knockout line. We confirmed that the I265N mutation reduced the sensitivity to two pyrethroids, permethrin and deltamethrin of a DmNav variant expressed in Xenopus oocytes. Computer modeling predicts that the I265N mutation confers pyrethroid resistance by allosterically altering the second pyrethroid receptor site on the DmNav channel. Furthermore, we found that I265N-mediated pyrethroid resistance in para(ts1) mutant flies was almost completely abolished in para(ts1);DSC1(-/-) double mutant flies. Unexpectedly, however, the DSC1 knockout flies were less sensitive to DDT, compared to the control flies (w(1118A)), and the para(ts1);DSC1(-/-) double mutant flies were even more resistant to DDT compared to the DSC1 knockout or para(ts1) mutant. Our findings revealed distinct roles of the DmNav and DSC1 channels in the neurotoxicology of DDT vs. pyrethroids and implicate the exciting possibility of using DSC1 channel blockers or modifiers in the management of pyrethroid resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Clinical efficacy and safety of T-DM1 for patients with HER2-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Ma B

    2016-02-01

    Full Text Available Bo Ma,1 Qianqian Ma,2 Hongqiang Wang,3 Guolei Zhang,1 Huiying Zhang,1 Xiaohong Wang1 1Affiliated Central Hospital of Huzhou Teachers College, Huzhou, Zhejiang, People’s Republic of China; 2University Hospital of Tuebingen, Tuebingen, Germany; 3Department of Oncology, Hospital of Zhoushan, Zhoushan, Zhejiang, People’s Republic of China Purpose: The aim of this study was to evaluate the therapeutic efficacy and safety of trastuzumab emtansine (T-DM1 for the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer.  Methods: We performed a systemic review and meta-analysis of the relevant published clinical studies. A computerized search was performed for controlled clinical trials of T-DM1 in targeted treatment. Overall survival, progression-free survival, objective response rate, symptom progression free, and adverse events (AEs were evaluated.  Results: Eight eligible trials with a total of 2,016 patients with breast cancer were included in the present meta-analysis. The treatment of patients with breast cancer with T-DM1 was associated with significantly increased overall and progression-free survival when compared with controls (P<0.0001. An analysis of the objective response rate and symptom progression free also demonstrated favorable results for T-DM1 treatment (P≤0.0001. There was no significant difference between the T-DM1 and control groups with respect to nonhematologic or hematologic AEs (P=0.99 and P=0.30, respectively.  Conclusion: Overall, T-DM1 is efficacious in the treatment of patients with human epidermal growth factor receptor 2-positive breast cancer and low rates of AEs compared with controls. Keywords: breast cancer, meta-analysis, HER2, T-DM1, efficacy

  15. Basal transcription machinery

    Indian Academy of Sciences (India)

    2007-03-29

    Mar 29, 2007 ... The holoenzyme of prokaryotic RNA polymerase consists of the core enzyme, made of two , , ' and subunits, which lacks promoter selectivity and a sigma () subunit which enables the core enzyme to initiate transcription in a promoter dependent fashion. A stress sigma factor s, in prokaryotes ...

  16. Machine Dictation and Transcription.

    Science.gov (United States)

    Harvey, Evelyn; And Others

    This instructional package contains both an instructor's manual and a student's manual for a course in machine dictation and transcription. The instructor's manual contains an overview with tips on teaching the course, letters for dictation, and a key to the letters. The student's manual contains an overview of the course and of the skills needed…

  17. Transcriptional Regulation in Haematopoiesis:

    DEFF Research Database (Denmark)

    Lauridsen, Felicia K B

    with the capacity to both self-renew and differentiate. This thesis is built upon two studies, which investigate two different aspects of the haematopoietic system; heterogeneity within the HSC compartment (presented in manuscript I), and the interplay between transcription factors controlling granulocyte/ monocyte...

  18. A food additive with prebiotic properties of an α-d-glucan from lactobacillus plantarum DM5.

    Science.gov (United States)

    Das, Deeplina; Baruah, Rwivoo; Goyal, Arun

    2014-08-01

    An α-d-glucan produced by Lactobacillus plantarum DM5 was explored for in vitro prebiotic activities. Glucan-DM5 demonstrated 21.6% solubility, 316.9% water holding capacity, 86.2% flocculation activity, 71.4% emulsification activity and a degradation temperature (Td) of 292.2°C. Glucan-DM5 exhibited lowest digestibility of 0.54% by artificial gastric juice, 0.21% by intestinal fluid and 0.32% by α-amylase whereas the standard prebiotic inulin, showed 25.23%, 5.97% and 19.13%, hydrolysis, respectively. Prebiotic activity assay of glucan-DM5 displayed increased growth of probiotic bacteria such as Bifidobacterium infantis and Lactobacillus acidophilus, but did not support the growth of non-probiotic bacteria such as Escherichia coli and Enterobacter aerogenes. The overall findings indicated that glucan from L. plantarum DM5 can serve as a potential prebiotic additive for food products. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Quantification of HLA-DM-Dependent Major Histocompatibility Complex of Class II Immunopeptidomes by the Peptide Landscape Antigenic Epitope Alignment Utility

    Directory of Open Access Journals (Sweden)

    Miguel Álvaro-Benito

    2018-05-01

    Full Text Available The major histocompatibility complex of class II (MHCII immunopeptidome represents the repertoire of antigenic peptides with the potential to activate CD4+ T cells. An understanding of how the relative abundance of specific antigenic epitopes affects the outcome of T cell responses is an important aspect of adaptive immunity and offers a venue to more rationally tailor T cell activation in the context of disease. Recent advances in mass spectrometric instrumentation, computational power, labeling strategies, and software analysis have enabled an increasing number of stratified studies on HLA ligandomes, in the context of both basic and translational research. A key challenge in the case of MHCII immunopeptidomes, often determined for different samples at distinct conditions, is to derive quantitative information on consensus epitopes from antigenic peptides of variable lengths. Here, we present the design and benchmarking of a new algorithm [peptide landscape antigenic epitope alignment utility (PLAtEAU] allowing the identification and label-free quantification (LFQ of shared consensus epitopes arising from series of nested peptides. The algorithm simplifies the complexity of the dataset while allowing the identification of nested peptides within relatively short segments of protein sequences. Moreover, we apply this algorithm to the comparison of the ligandomes of cell lines with two different expression levels of the peptide-exchange catalyst HLA-DM. Direct comparison of LFQ intensities determined at the peptide level is inconclusive, as most of the peptides are not significantly enriched due to poor sampling. Applying the PLAtEAU algorithm for grouping of the peptides into consensus epitopes shows that more than half of the total number of epitopes is preferentially and significantly enriched for each condition. This simplification and deconvolution of the complex and ambiguous peptide-level dataset highlights the value of the PLAt

  20. T2DM Self-Management via Smartphone Applications: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Cui, Mingxuan; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

    2016-01-01

    Mobile health interventions (mHealth) based on smartphone applications (apps) are promising tools to help improve diabetes care and self-management; however, more evidence on the efficacy of mHealth in diabetes care is needed. The objective of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effect of mHealth apps on changes in hemoglobin A1c (HbA1c), blood glucose, blood pressure, serum lipids, and body weight in type 2 diabetes mellitus (T2DM) patients. Two independent reviewers searched three online databases (PubMed, the Cochrane Library, and EMBASE) to identify relevant studies published between January 2005 and June 2016. Of the 2,596 articles retrieved, 13 RCTs were included. We used random effects model to estimate the pooled results. Thirteen studies were selected for the systematic review, six of which with data available containing 1,022 patients were included for the meta-analysis. There was a moderate effect on glycemic control after the mHealth app-based interventions. The overall effect on HbA1c shown as mean difference (MD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.11% [-7.54 to -1.20 mmol/mol]; p = 0.007) and standardized mean differences (SMD) was -0.40% (-4.37 mmol/mol) (95% confidence interval [CI] -0.69 to -0.10% [-7.54 to -1.09 mmol/mol]; p = 0.008). A subgroup analysis showed a similar effect with -0.33% (-3.61 mmol/mol) (95% CI -0.59 to -0.06% [-6.45 to -0.66 mmol/mol]; p = 0.02) in MD and -0.38% (-4.15 mmol/mol) (95% CI -0.71 to -0.05% [-7.76 to -0.55 mmol/mol]; p = 0.02) in SMD in studies where patients' baseline HbA1c levels were less than 8.0%. No effects of mHealth app interventions were found on blood pressure, serum lipids, or weight. Assessment of overall study quality and publication bias demonstrated a low risk of bias among the six studies. Smartphone apps offered moderate benefits for T2DM self-management. However, more research with

  1. RESISTANCE-RELATED GENE TRANSCRIPTION AND ...

    African Journals Online (AJOL)

    jdx

    2014-02-05

    Feb 5, 2014 ... By 72 hpi, the pathogen switched to necrotrophic growth to avoid contact with the increasing ... A better understanding of the gene network underlying ... 5.0 software under default parameters and were custom-ordered.

  2. DNA Topoisomerases in Transcription

    DEFF Research Database (Denmark)

    Rødgaard, Morten Terpager

    2015-01-01

    This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most of the ex......This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most...... topoisomerase-DNA cleavage complex. The second study is an investigation of how topoisomerases influence gene regulation by keeping the genome in an optimal topological state....

  3. Deciphering Transcriptional Regulation

    DEFF Research Database (Denmark)

    Valen, Eivind

    The myriad of cells in the human body are all made from the same blueprint: the human genome. At the heart of this diversity lies the concept of gene regulation, the process in which it is decided which genes are used where and when. Genes do not function as on/off buttons, but more like a volume...... mostly near the start of the gene known as the promoter. This region contains patterns scattered in the DNA that the TFs can recognize and bind to. Such binding can prompt the assembly of the pre-initiation complex which ultimately leads to transcription of the gene. In order to achieve the regulation...... on what characterizes a hippocampus promoter. Pairing CAGE with TF binding site prediction we identi¿ed a likely key regulator of hippocampus. Finally, we developed a method for CAGE exploration. While the DeepCAGE library characterized a full 1.4 million transcription initiation events it did not capture...

  4. DNA Damage Observed in Unaffected Individuals with Family History of T2DM

    Science.gov (United States)

    Ramesh, Nikhila; Abilash, V. G.

    2017-11-01

    Diabetes has been documented to cause high levels of DNA fragmentation in some cases. As diabetes is inheritable and influenced by both genetic and environmental factors, an investigation into the genomic stability of individuals who are strongly at risk of inheriting diabetes was conducted by inducing oxidative stress, as DNA damage in unaffected individuals could be a sign of onset of the disease or the presence of genetic alterations that reduce cellular defences against reactive oxygen species. In this study, alkaline comet assay was performed on isolated human leukocytes to determine whether individuals with a family history of Type 2 Diabetes Mellitus (T2DM) are more prone to DNA damage under oxidative stress. Visual scoring of comets showed that these individuals have higher degree of DNA damage compared to a control individual with no family history of Type 2 Diabetes Mellitus. Further studies with large sample could determine the presence of disabled cellular defences against oxidative stress in unaffected individuals and intervention with antioxidants could prevent or manage Type 2 Diabetes Mellitus and its complications.

  5. Crystal Structure of Allophycocyanin from Marine Cyanobacterium Phormidium sp. A09DM.

    Directory of Open Access Journals (Sweden)

    Ravi Raghav Sonani

    Full Text Available Isolated phycobilisome (PBS sub-assemblies have been widely subjected to X-ray crystallography analysis to obtain greater insights into the structure-function relationship of this light harvesting complex. Allophycocyanin (APC is the phycobiliprotein always found in the PBS core complex. Phycocyanobilin (PCB chromophores, covalently bound to conserved Cys residues of α- and β- subunits of APC, are responsible for solar energy absorption from phycocyanin and for transfer to photosynthetic apparatus. In the known APC structures, heterodimers of α- and β- subunits (known as αβ monomers assemble as trimer or hexamer. We here for the first time report the crystal structure of APC isolated from a marine cyanobacterium (Phormidium sp. A09DM. The crystal structure has been refined against all the observed data to the resolution of 2.51 Å to Rwork (Rfree of 0.158 (0.229 with good stereochemistry of the atomic model. The Phormidium protein exists as a trimer of αβ monomers in solution and in crystal lattice. The overall tertiary structures of α- and β- subunits, and trimeric quaternary fold of the Phormidium protein resemble the other known APC structures. Also, configuration and conformation of the two covalently bound PCB chromophores in the marine APC are same as those observed in fresh water cyanobacteria and marine red algae. More hydrophobic residues, however, constitute the environment of the chromophore bound to α-subunit of the Phormidium protein, owing mainly to amino acid substitutions in the marine protein.

  6. Transcriptional networks controlling adipocyte differentiation

    DEFF Research Database (Denmark)

    Siersbæk, R; Mandrup, Susanne

    2011-01-01

    " of the transcription factor networks operating at specific time points during adipogenesis. Using such global "snapshots," we have demonstrated that dramatic remodeling of the chromatin template occurs within the first few hours following adipogenic stimulation and that many of the early transcription factors bind...... in a cooperative fashion to transcription factor hotspots. Such hotspots are likely to represent key chromatin nodes, where many adipogenic signaling pathways converge to drive the adipogenic transcriptional reprogramming....

  7. CTX Correlation to Disease Duration and Adiponectin in Egyptian Children with T1DM/ Korelacija između CTX-a i trajanja bolesti i adiponektina kod egipatske dece sa T1DM

    Directory of Open Access Journals (Sweden)

    Hashim Amel A.

    2016-01-01

    Full Text Available Uvod: U ovoj studiji istraživali smo odnos između adiponektina i markera koštanih promena kod egipatske dece i ado­lescenata sa T1DM, uticaj trajanja bolesti na ove markere, kao i potencijalne korelacije između adiponektina i ko­štanih markera kod ovih pacijenata.

  8. Differentiation of canine distemper virus isolates in fur animals from various vaccine strains by reverse transcription-polymerase chain reaction-restriction fragment length polymorphism according to phylogenetic relations in china

    Directory of Open Access Journals (Sweden)

    Zhao Jianjun

    2011-02-01

    Full Text Available Abstract In order to effectively identify the vaccine and field strains of Canine distemper virus (CDV, a new differential diagnostic test has been developed based on reverse transcription-polymerase chain reaction (RT-PCR and restriction fragment length polymorphism (RFLP. We selected an 829 bp fragment of the nucleoprotein (N gene of CDV. By RFLP analysis using BamHI, field isolates were distinguishable from the vaccine strains. Two fragments were obtained from the vaccine strains by RT-PCR-RFLP analysis while three were observed in the field strains. An 829 nucleotide region of the CDV N gene was analyzed in 19 CDV field strains isolated from minks, raccoon dogs and foxes in China between 2005 and 2007. The results suggest this method is precise, accurate and efficient. It was also determined that three different genotypes exist in CDV field strains in fur animal herds of the north of China, most of which belong to Asian type. Mutated field strains, JSY06-R1, JSY06-R2 and JDH07-F1 also exist in Northern China, but are most closely related to the standard virulent strain A75/17, designated in Arctic and America-2 genetype in the present study, respectively.

  9. Specific DNA binding of a potential transcriptional regulator, inosine 5'-monophosphate dehydrogenase-related protein VII, to the promoter region of a methyl coenzyme m reductase I-encoding operon retrieved from Methanothermobacter thermautotrophicus strain DeltaH.

    Science.gov (United States)

    Shinzato, Naoya; Enoki, Miho; Sato, Hiroaki; Nakamura, Kohei; Matsui, Toru; Kamagata, Yoichi

    2008-10-01

    Two methyl coenzyme M reductases (MCRs) encoded by the mcr and mrt operons of the hydrogenotrophic methanogen Methanothermobacter thermautotrophicus DeltaH are expressed in response to H(2) availability. In the present study, cis elements and trans-acting factors responsible for the gene expression of MCRs were investigated by using electrophoretic mobility shift assay (EMSA) and affinity particle purification. A survey of their operator regions by EMSA with protein extracts from mrt-expressing cultures restricted them to 46- and 41-bp-long mcr and mrt upstream regions, respectively. Affinity particle purification of DNA-binding proteins conjugated with putative operator regions resulted in the retrieval of a protein attributed to IMP dehydrogenase-related protein VII (IMPDH VII). IMPDH VII is predicted to have a winged helix-turn-helix DNA-binding motif and two cystathionine beta-synthase domains, and it has been suspected to be an energy-sensing module. EMSA with oligonucleotide probes with unusual sequences showed that the binding site of IMPDH VII mostly overlaps the factor B-responsible element-TATA box of the mcr operon. The results presented here suggest that IMPDH VII encoded by MTH126 is a plausible candidate for the transcriptional regulator of the mcr operon in this methanogen.

  10. A Widespread, Clumpy Starburst in the Isolated Ongoing Dwarf Galaxy Merger dm1647+21

    Energy Technology Data Exchange (ETDEWEB)

    Privon, G. C. [Instituto de Astrofśica, Facultad de Física, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 22 (Chile); Stierwalt, S.; Johnson, K. E.; Kallivayalil, N.; Liss, S. [Department of Astronomy, University of Virginia, 530 McCormick Road, Charlottesville, VA 22904 (United States); Patton, D. R. [Department of Physics and Astronomy, Trent University, 1600 West Bank Drive, Peterborough, ON K9L 0G2 (Canada); Besla, G. [Department of Astronomy, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Pearson, S.; Putman, M., E-mail: gprivon@astro.puc.cl [Department of Astronomy, Columbia University, 550 West 120th Street, New York, NY 10027 (United States); Collaboration: TiNy Titans

    2017-09-01

    Interactions between pairs of isolated dwarf galaxies provide a critical window into low-mass hierarchical, gas-dominated galaxy assembly and the build-up of stellar mass in low-metallicity systems. We present the first Very Large Telescope/Multi Unit Spectroscopic Explorer (VLT/MUSE) optical integral field unit (IFU) observations of the interacting dwarf pair dm1647+21 selected from the TiNy Titans survey. The H α emission is widespread and corresponds to a total unobscured star formation rate (SFR) of 0.44 M {sub ⊙} yr{sup −1}, which is 2.7 times higher than the SFR inferred from Sloan Digital Sky Survey (SDSS) data. The implied specific SFR (sSFR) for the system is elevated by more than an order of magnitude above non-interacting dwarfs in the same mass range. This increase is dominated by the lower-mass galaxy, which has a sSFR enhancement of >50. Examining the spatially resolved maps of classic optical line diagnostics, we find that the interstellar medium (ISM) excitation can be fully explained by star formation. The velocity field of the ionized gas is not consistent with simple rotation. Dynamical simulations indicate that the irregular velocity field and the stellar structure is consistent with the identification of this system as an ongoing interaction between two dwarf galaxies. The widespread, clumpy enhancements in the star formation in this system point to important differences in the effect of mergers on dwarf galaxies, compared to massive galaxies; rather than the funneling of gas to the nucleus and giving rise to a nuclear starburst, starbursts in low-mass galaxy mergers may be triggered by large-scale ISM compression, and thus may be more distributed.

  11. Crystal structure analysis of C-phycoerythrin from marine cyanobacterium Phormidium sp. A09DM.

    Science.gov (United States)

    Kumar, Vinay; Sonani, Ravi R; Sharma, Mahima; Gupta, Gagan D; Madamwar, Datta

    2016-07-01

    The role of unique sequence features of C-phycoerythrin, isolated from Phormidium sp. A09DM, has been investigated by crystallographic studies. Two conserved indels (i.e. inserts or deletions) are found in the β-subunit of Phormidium phycoerythrin that are distinctive characteristics of large number of cyanobacterial sequences. The identified signatures are a two-residue deletion from position 21 and a nine-residue insertion at position 146. Crystals of Phormidium phycoerythrin were obtained at pH values of 5 and 8.5, and structures have been resolved to high precision at 1.95 and 2.1 Å resolution, respectively. In both the structures, heterodimers of α- and β- subunits assemble as hexamers. The 7-residue insertion at position 146 significantly reduces solvent exposure of π-conjugated A-C rings of a phycoerythrobilin (PEB) chromophore, and can influence energy absorption and energy transfer characteristics. The structural analyses (with 12-fold redundancy) suggest that protein micro-environment alone dictates the conformation of bound chromophores. The low- and high-energy absorbing chromophores are identified based on A-B ring coplanarity. The spatial distribution of these is found to be similar to that observed in R-phycoerythrin, suggesting the direction of energy transfer from outer-surface of hexamer to inner-hollow cavity in the Phormidium protein. The crystal structures also reveal that a commonly observed Hydrogen-bonding network in phycobiliproteins, involving chromophore bound to α-subunit and amino acid at position 73 of β-subunit, may not be essential for structural and functional integrity of C-phycoerythrin orthologs. In solution, the protein displays slight red shift and decrease in fluorescence emission at acidic pH. The mechanism for which may be static and correlates with the proximity of +ve electric field of Arg148 to the C-ring of a PEB chromophore.

  12. Characterization and biocompatibility of glucan: a safe food additive from probiotic Lactobacillus plantarum DM5.

    Science.gov (United States)

    Das, Deeplina; Goyal, Arun

    2014-03-15

    Exopolysaccharide produced by lactic acid bacteria are the subject of an increasing number of studies for their potential applications in the food industry as stabilizing, bio-thickening and immunostimulating agents. In this regard, the authors isolated an exopolysaccharide producing probiotic lactic acid bacterium from fermented beverage Marcha of north eastern Himalayas. The isolate Lactobacillus plantarum DM5 showed extracellular glucansucrase activity of 0.48 U mg⁻¹ by synthesizing natural exopolysaccharide glucan (1.87 mg mL⁻¹) from sucrose. Zymogram analysis of purified enzyme confirms the presence of glucosyltransferase of approximately 148 kDa with optimal activity of 18.7 U mg⁻¹ at 30 °C and pH 5.4. The exopolysaccharide was purified by gel permeation chromatography and had an average molecular weight of 1.11 × 10⁶ Da. Acid hydrolysis and structural characterization of exopolysaccharide revealed that it was composed of d-glucose residues, containing 86.5% of α-(1→6) and 13.5% of α-(1→3) linkages. Rheological study exhibited a shear thinning effect of glucan appropriate for food additives. A cytotoxicity test of glucan on human embryonic kidney 293 (HEK 293) and human cervical cancer (HeLa) cell lines revealed its nontoxic biocompatible nature. This is the first report on the structure and biocompatibility of homopolysaccharide α-D-glucan (dextran) from probiotic Lactobacillus plantarum strain and its unique physical and rheological properties that facilitate its application in the food industry as viscosifying and gelling agent. © 2013 Society of Chemical Industry.

  13. Frequency of retinopathy in newly diagnosed patients of type 2 diabetes mellitus (dm)

    International Nuclear Information System (INIS)

    Khan, K.A.; Kamran, S.M.; Qureshi, M.N.

    2015-01-01

    This study was to determine the frequency of retinopathy in newly diagnosed type-II Diabetics. Study Design: Cross sectional descriptive study. Place and Duration of Study: It was conducted at Department of medicine, Military Hospital (MH), Rawalpindi from 1st Jan 2012 to 30 Jun 2012. Material and Methods: We included 200 patients of type-II DM from both genders diagnosed in last 03 months from both outdoor and indoor departments in the age range of 40 to 70 years by consecutive sampling. All patients having co morbidities affecting retina were excluded. Informed written consent was taken before enrollment. Formal approval of the study was taken from hospital ethical committee. Ocular Fundoscopy was performed with WelchAllyn Ophthalmoscope (REF 11470) as per standard protocols and both eyes were examined. The grade of DR (diabetic retinopathy) awarded as per highest changes in any of the two eyes. All tests were carried by a single person to avoid inter-observer variations. Findings of ocular fundoscopy were confirmed by ophthalmologist. All data was analyzed by using SPSS version 11. Results: Out of 200 subjects 63.5% were male and 36.5% were female. Age ranged from 40 to 70 years with mean age of 51.05+ 6.910 years. 29 (14.5%) subjects had Diabetic retinopathy. Out of 29 patients, 24 (82.8%) had preproliferative and 5 (17.2%) had proliferative diabetic retinopathy. Conclusion: A significant proportion of diabetic patients have retinopathy at the time of diagnosis of their disease which is more common in males and with increasing age. It is recommended to thoroughly screen the newly diagnosed diabetics for early detection of diabetic retinopathy and its management involving early referral to eye specialist. (author)

  14. Alcohol Consumption Is a Risk Factor for Lower Extremity Arterial Disease in Chinese Patients with T2DM

    Directory of Open Access Journals (Sweden)

    Shanshan Yang

    2017-01-01

    Full Text Available Objective. To investigate the relationship between alcohol consumption and diabetic lower extremity arterial disease (LEAD in hospitalized patients with type 2 diabetes mellitus (T2DM. Methods. We evaluated 138 hospitalized patients with T2DM who consumed alcohol and 833 who did not. We used propensity score matching to reduce the confounding bias between groups. Additionally, a logistic regression analysis was performed with the matched data to evaluate the LEAD risk. Results. In total, 119 pairs of patients who did and did not consume alcohol were matched. According to the logistic regression analysis, patients who consumed >8 U of alcohol/day had a higher risk of LEAD (odds ratio (OR: 6.35, 95% confidence interval (CI: 1.78–22.65 than patients who did not consume alcohol. Additionally, after adjusting for age, gender, region, occupation, smoking status, body mass index, weight change, and duration of diabetes, the OR of peripheral artery disease after >20 years of alcohol consumption was 3.48 (95% CI: 1.09–11.15. Furthermore, we observed a significant dose-response relationship between alcohol consumption and LEAD. Conclusions. Alcohol consumption may be a risk factor of LEAD in patients with T2DM. Patients with T2DM should be advised to stop drinking, to prevent the onset of LEAD.

  15. Association of TCF7L2 gene polymorphisms with T2DM in the population of Hyderabad, India.

    Directory of Open Access Journals (Sweden)

    Kommoju Uma Jyothi

    Full Text Available We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01. The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established.

  16. Prescription Pattern of Antihypertensive Agents in T2DM Patients Visiting Tertiary Care Centre in North India

    Directory of Open Access Journals (Sweden)

    Ethiraj Dhanaraj

    2012-01-01

    Full Text Available Background. Hypertension management is of a paramount importance in diabetic patients for cardiovascular risk reduction. Aim. To evaluate prescribing pattern of antihypertensive in T2DM (type 2 diabetes patients and compare with existing recent guidelines. Methods. A cross-sectional study involving evaluation of all T2DM patients referred to endocrinology unit at tertiary care centre for hypertension, comorbid complications, and recording prescription. Utilization of 5 different antihypertensive drug classes was compared for all patients receiving 1, 2, 3, 4, or more drugs. Logistical regression was used to assess likelihood of prescription of drugs and/or therapy for specific conditions mentioned in the guidelines. Results. Out of 1358, T2DM enrolled patients 1186 (87% had hypertension (males 52%, females 48%. The median duration (IQ of hypertension diabetics was 4 (1–10 years. A total of 25% patients had controlled BP and 75% with uncontrolled blood pressure (13% isolated systolic hypertension, 6% isolated diastolic hypertension, and 55% both elevated. Overall, ACE inhibitors (ACEIs were prescribed the highest (59% followed by angiotensin receptor blockers (ARBs (52%, calcium channel blockers (CCBs (29%, diuretics (27%, and beta-blockers (14%. Overall, 55% of T2DM patients were on polytherapy, 41% on monotherapy, and 4% had no antihypertensive treatment. Polytherapy was more predominant with age, duration of diabetes, duration of hypertension, and comorbid complications. Conclusion. Although prescribing pattern of antihypertensive showed adherence to existing evidence-based guidelines, higher proportion of uncontrolled hypertensive patients was found.

  17. Relationship between rumen protozoal growth, intake of DM, TDN, N, DOM and VFA production rate in buffalo calves

    International Nuclear Information System (INIS)

    Verma, D.N.; Singh, U.B.

    1981-01-01

    Relationships between in vivo rumen protozoal growth and intakes of dry matter (DM), nitrogen, digestible organic matter (DOM), total digestible nutrients (TDN) and volatile fatty acid (VFA) production have been studied. Isotope dilution technique and 14 C-labelled rumen protozoa were used in the studies. (author)

  18. Plasma amino acid and metabolite signatures tracking diabetes progression in the UCD-T2DM rat model

    Science.gov (United States)

    Elevations of plasma concentrations of branched-chain amino acids (BCAAs) are observed in human insulin resistance and type 2 diabetes mellitus (T2DM); however, there has been some controversy with respect to the passive or causative nature of the BCAA phenotype. Using untargeted metabolomics, plasm...

  19. Expansive hematoma in delayed cerebral radiation necrosis in patients treated with T-DM1: a report of two cases

    International Nuclear Information System (INIS)

    Mitsuya, Koichi; Watanabe, Junichiro; Nakasu, Yoko; Hayashi, Nakamasa; Harada, Hideyuki; Ito, Ichiro

    2016-01-01

    Multiple new targeted agents have been developed for patients with human epidermal growth factor receptor type 2 (HER2) – positive breast cancer. Patients with HER2– positive breast cancer will develop brain metastases with greater incidence than patients with non-HER2 cancers, and many of them will undergo stereotactic radiosurgery (SRS) or other CNS radiotherapy. The interaction between radiation effects and new targeted agents is not well understood. We report two cases suggesting a novel adverse effect of T-DM1 (trastuzumab emtansine) on symptomatic enlargement of radiation necrosis (RN) after SRS. Two patients with HER2-positive breast cancer had received SRS for single brain metastasis more than 5-years ago. They had been heavily treated for HER2-positive metastatic breast cancer (trastuzumab and pacritaxel, lapatinib and capecitabine). They initiated T-DM1 therapy for progressive systematic disease 5.5 years after stereotactic irradiation, when a small RN was recognized on brain MR images of each patient. The RN lesions increased in size and became symptomatic during 13 or 14 months of T-DM1 treatment. The patients underwent surgical resection of the lesion. Pathological examination revealed necrosis, hematoma, granulation tissue and telangiectasia without neoplastic cells. A potential enhancement of RN by T-DM1 in the brain may be one of important adverse events associated with the use of T-DM1 for patients after SRS. These cases highlight the need of careful follow-up when combining new systemic targeted therapies and SRS for brain metastases

  20. Study on the inter-relationship among the changes of serum levels of leptin, insulin and glucagon in patients with DM2 complicated with hypertension

    International Nuclear Information System (INIS)

    Zeng Zhiwei; Yan Songqin; Tan Wei

    2006-01-01

    Objective: To investigate the inter-relationship among the changes of serum leptin, insulin and glucagon levels in patients with type 2 diabetes mellitus (DM2) complicated with hypertension. Methods: Serum leptin, insulin and glucagon levels were, measured with RIA in 30 DM2 patients complicated with hypertension, 30 DM2 patients without hypertension and 30 controls. Results: Serum levels of leptin, insulin and glucagon in all the DM2 patients were significantly higher than those in controls (P<0.01). In addition, the serum levels in DM2 patients with hypertension were significantly higher than those in DM2 patients without hypertension (P<0.05). These levels were positively correlated with the severity of hypertension. Conclusion: The role played by leptin and glucagon in the pathogenesis of type 2 diabetes mellitns should be furthur studied. (authors)

  1. Runx transcription factors in neuronal development

    Directory of Open Access Journals (Sweden)

    Shiga Takashi

    2008-08-01

    Full Text Available Abstract Runt-related (Runx transcription factors control diverse aspects of embryonic development and are responsible for the pathogenesis of many human diseases. In recent years, the functions of this transcription factor family in the nervous system have just begun to be understood. In dorsal root ganglion neurons, Runx1 and Runx3 play pivotal roles in the development of nociceptive and proprioceptive sensory neurons, respectively. Runx appears to control the transcriptional regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As a consequence, Runx contributes to diverse aspects of the sensory system in higher vertebrates. In this review, we summarize recent progress in determining the role of Runx in neuronal development.

  2. Transcript structure and domain display: a customizable transcript visualization tool.

    Science.gov (United States)

    Watanabe, Kenneth A; Ma, Kaiwang; Homayouni, Arielle; Rushton, Paul J; Shen, Qingxi J

    2016-07-01

    Transcript Structure and Domain Display (TSDD) is a publicly available, web-based program that provides publication quality images of transcript structures and domains. TSDD is capable of producing transcript structures from GFF/GFF3 and BED files. Alternatively, the GFF files of several model organisms have been pre-loaded so that users only needs to enter the locus IDs of the transcripts to be displayed. Visualization of transcripts provides many benefits to researchers, ranging from evolutionary analysis of DNA-binding domains to predictive function modeling. TSDD is freely available for non-commercial users at http://shenlab.sols.unlv.edu/shenlab/software/TSD/transcript_display.html : jeffery.shen@unlv.nevada.edu. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Qing brick tea (QBT) aqueous extract protects monosodium glutamate-induced obese mice against metabolic syndrome and involves up-regulation Transcription Factor Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) antioxidant pathway.

    Science.gov (United States)

    Gao, Wenqi; Xiao, Changyi; Hu, Jun; Chen, Biaoxin; Wang, Chunyan; Cui, Bangping; Deng, Pengyi; Yang, Jian; Deng, Zhifang

    2018-04-18

    Qing brick tea (QBT), traditional and popular beverage for Chinese people, is an important post-fermentation dark tea. Our present study was performed to investigate the ameliorative effects of QBT aqueous extract on metabolic syndrome (Mets) in monosodium glutamate-induced obese mice and the potential mechanisms. Monosodium glutamate-induced obese mice were used to evaluate the anti-Mets effects of QBT. Content levels of malonaldehyde (MDA), reactive oxygen species (ROS) and protein carbonylation, antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione reductase (GR) in the skeletal muscle were assessed by commercial kits, respectively. Western blot and Q-PCR were used to detect the expressions of Transcription Factor Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2) signaling pathway and downstream antioxidant factors. In addition, activity of AKT signaling and expression of glucose transporter type 4 (GLUT4) in the skeletal muscle were investigated by western blot. QBT treatment limited gain of body weight, waistline and LEE index, improved insulin resistance and glucose intolerance, reduced lipid level in MSG mice. Content levels of MDA, ROS and protein carbonylation in skeletal muscle of QBT group were significantly improved compared to those of MSG mice. The antioxidant enzyme activities of SOD, GPx, CAT, and GR were increased in skeletal muscle of MSG mice intervened with QBT. After 20-week QBT treatment, Nrf2 signaling pathway and downstream antioxidant factors were both increased in the skeletal muscle. In addition, QBT treatment improved insulin signaling by preferentially augmenting AKT signaling, as well as increased the protein expression of GLUT4 in the skeletal muscle. Our results showed that QBT intake was effective in protecting monosodium glutamate-induced obese mice against metabolic syndrome and involved in the Nrf2 signaling pathway in the skeletal muscle. Copyright © 2018

  4. An in vivo analysis of Cr6+ induced biochemical, genotoxicological and transcriptional profiling of genes related to oxidative stress, DNA damage and apoptosis in liver of fish, Channa punctatus (Bloch, 1793).

    Science.gov (United States)

    Awasthi, Yashika; Ratn, Arun; Prasad, Rajesh; Kumar, Manoj; Trivedi, Sunil P

    2018-07-01

    Present study was designed to assess the hexavalent chromium (Cr 6+ ) mediated oxidative stress that induces DNA damage and apoptosis in adult fish, Channa punctatus (35 ± 3.0 g; 14.5 ± 1.0 cm; Actinopterygii). Fishes were maintained in three groups for 15, 30 and 45 d of exposure periods. They were treated with 5% (Group T1) and 10% (Group T2) of 96 h-LC 50 of chromium trioxide (Cr 6+ ). Controls were run for the similar duration. A significant (p < 0.05) increment in the activities of antioxidant enzymes, SOD and CAT in liver tissues of the exposed fish evinces the persistence of oxidative stress. A significant (p < 0.05) increase in induction of micronuclei (MN) coupled with transcriptional responses of target genes related to antioxidant enzymes, DNA damage and apoptosis (sod, cat, gsr, nox-1, p53, bax, bcl-2, apaf-1 and casp3a) establishes the impact of oxidative stress due to in vivo, Cr 6+ accumulation in liver as compared to control (0 mg/L), in a dose and exposure-dependent manner. Initially, the increased level of reactive oxygen species (ROS) in liver coincided with that of enhanced mRNA expression of antioxidant enzymes, sod, cat, gsr and nox-1 but, later, the overproduction of ROS, after 45 d of exposure of Cr 6+ , resulted in a significant (p < 0.05) up-regulation of p53. Our findings also unveil that the up-regulation of bax, apaf-1 and casp3a and down-regulation of bcl-2 are associated with Cr 6+ -induced oxidative stress mediated-apoptosis in liver of test fish. Aforesaid molecular markers can, thus, be efficiently utilized for bio-monitoring of aquatic regimes and conservation of fish biodiversity. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Source-Related Effects of Wastewater on Transcription Factor (AhR, CAR and PXR-Mediated Induction of Gene Expression in Cultured Rat Hepatocytes and Their Association with the Prevalence of Antimicrobial-Resistant Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Keerthi S Guruge

    Full Text Available Extracts of wastewater collected from 4 sewage treatment plants (STPs receiving effluents from different sources in South India were investigated for their levels of transcription factor-mediated gene induction in primary cultured rat hepatocytes. In addition, the relation between gene induction levels and the prevalence of antimicrobial-resistant Escherichia coli (E. coli in wastewater was examined. STP-3, which treats only hospital wastewater, exhibited significantly greater induction potency of all 6 drug metabolizing cytochrome P450 (CYP genes examined, CYP1A1, 1A2, 1B1, 2B15, 3A1, and 3A2, whereas the wastewater at STP-1, which exclusively receives domestic sewage, showed significantly diminished levels of induction of 3 CYP genes when compared to the levels of CYP induction at STP-2, which receives mixed wastewater. Samples collected during the monsoon season showed a significantly altered gene induction capacity compared to that of samples from the pre-monsoon period. The data suggest that the toxicity of wastewater in STPs was not significantly diminished during the treatment process. The chemical-gene interaction data predicted that a vast number of chemicals present in the wastewater would stimulate the genes studied in the rat hepatocytes. The multivariable logistic regression analysis demonstrated that the prevalence of isolates resistant to cefotaxime, imipenem and streptomycin was significantly correlated with the levels of induction of at least three CYP-isozymes in STP wastewater. In addition, the resistance of isolates in treatment plants was not altered by the treatment steps, whereas the sampling season did have an impact on the resistance to specific antimicrobials. The identification of receptor-mediated gene regulation capacities offers important data not limited to the (synergistic physiological role of chemicals in biological systems but may provide new insight into the link between the effects of known/unknown drugs and

  6. Nucleocytoplasmic shuttling of transcription factors

    DEFF Research Database (Denmark)

    Cartwright, P; Helin, K

    2000-01-01

    To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... of the transcriptional response is essential for cells to progress through the cell cycle in a normal manner. The involvement of cytoplasmic and nuclear accessory molecules, and the general nuclear membrane transport components, are essential for this process. Although nuclear import and export for different...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...

  7. Transcriptional Silencing of Retroviral Vectors

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M.; Pedersen, F.S.

    1996-01-01

    . Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral...... transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the t......RNA primer for reverse transcription may have a major influence on transcriptional silencing. Alterations of these elements of the vector backbone as well as the use of internal promoter elements from housekeeping genes may contribute to reduce transcriptional silencing. The use of cell culture and animal...

  8. DNA topology and transcription

    Science.gov (United States)

    Kouzine, Fedor; Levens, David; Baranello, Laura

    2014-01-01

    Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions. PMID:24755522

  9. Dose-dependent and gender-related radiation-induced transcription alterations of Gadd45a and Ier5 in human lymphocytes exposed to gamma ray emitted by 60Co

    International Nuclear Information System (INIS)

    Tavakoli, H.; Manoochehri, M.; Mosalla, S. M. M.; Ghafori, M.; Karimi, A. A.

    2013-01-01

    Growth arrest DNA damage-inducible 45a gene (Gadd45a) and immediate early response gene 5 (Ier5) have been emphasised as ideal radiation bio-markers in several reports. However, some aspects of radiation-induced transcriptional alterations of these genes are unknown. In this study, gender-dependency and dose-dependency as two factors that may affect radiation induced transcription of Gadd45a and Ier5 genes were investigated. Human lymphocyte cells from six healthy voluntary blood donors (three women and three men) were irradiated in vitro with doses of 0.5-4.0 Gy from a 60 Co source and RNA isolated 4 h later using the High Pure RNA Isolation Kit. Dose and gender dependency of radiation-induced transcriptional alterations of Gadd45a and Ier5 genes were studied by quantitative real-time polymerase chain reaction. The results showed that as a whole, Gadd45a and Ier5 gave responses to gamma rays, while the responses were independent of radiation doses. Therefore, regardless of radiation dose, Gadd45a and Ier5 can be considered potential radiation bio-markers. Besides, although radiation-induced transcriptional alterations of Gadd45a in female and male lymphocyte samples were insignificant at 0.5 Gy, at other doses, their quantities in female samples were at a significantly higher level than in male samples. Radiation induced transcription of Ier5 of females samples had a reduction in comparison with male samples at 1 and 2 Gy, but at doses of 0.5 and 4 Gy, females were significantly more susceptible to radiation-induced transcriptional alteration of Ier5. (authors)

  10. Transcriptional and post-transcriptional regulation of nucleotide excision repair genes in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefkofsky, Hailey B. [Translational Oncology Program, University of Michigan Medical School, Ann Arbor, MI (United States); Veloso, Artur [Translational Oncology Program, University of Michigan Medical School, Ann Arbor, MI (United States); Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI (United States); Bioinformatics Program, Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI (United States); Ljungman, Mats, E-mail: ljungman@umich.edu [Translational Oncology Program, University of Michigan Medical School, Ann Arbor, MI (United States); Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI (United States); Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI (United States)

    2015-06-15

    Nucleotide excision repair (NER) removes DNA helix-distorting lesions induced by UV light and various chemotherapeutic agents such as cisplatin. These lesions efficiently block the elongation of transcription and need to be rapidly removed by transcription-coupled NER (TC-NER) to avoid the induction of apoptosis. Twenty-nine genes have been classified to code for proteins participating in nucleotide excision repair (NER) in human cells. Here we explored the transcriptional and post-transcriptional regulation of these NER genes across 13 human cell lines using Bru-seq and BruChase-seq, respectively. Many NER genes are relatively large in size and therefore will be easily inactivated by UV-induced transcription-blocking lesions. Furthermore, many of these genes produce transcripts that are rather unstable. Thus, these genes are expected to rapidly lose expression leading to a diminished function of NER. One such gene is ERCC6 that codes for the CSB protein critical for TC-NER. Due to its large gene size and high RNA turnover rate, the ERCC6 gene may act as dosimeter of DNA damage so that at high levels of damage, ERCC6 RNA levels would be diminished leading to the loss of CSB expression, inhibition of TC-NER and the promotion of cell death.

  11. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

    Science.gov (United States)

    Le Billan, Florian; Amazit, Larbi; Bleakley, Kevin; Xue, Qiong-Yao; Pussard, Eric; Lhadj, Christophe; Kolkhof, Peter; Viengchareun, Say; Fagart, Jérôme; Lombès, Marc

    2018-05-07

    Mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) are two closely related hormone-activated transcription factors that regulate major pathophysiologic functions. High homology between these receptors accounts for the crossbinding of their corresponding ligands, MR being activated by both aldosterone and cortisol and GR essentially activated by cortisol. Their coexpression and ability to bind similar DNA motifs highlight the need to investigate their respective contributions to overall corticosteroid signaling. Here, we decipher the transcriptional regulatory mechanisms that underlie selective effects of MRs and GRs on shared genomic targets in a human renal cellular model. Kinetic, serial, and sequential chromatin immunoprecipitation approaches were performed on the period circadian protein 1 ( PER1) target gene, providing evidence that both receptors dynamically and cyclically interact at the same target promoter in a specific and distinct transcriptional signature. During this process, both receptors regulate PER1 gene by binding as homo- or heterodimers to the same promoter region. Our results suggest a novel level of MR-GR target gene regulation, which should be considered for a better and integrated understanding of corticosteroid-related pathophysiology.-Le Billan, F., Amazit, L., Bleakley, K., Xue, Q.-Y., Pussard, E., Lhadj, C., Kolkhof, P., Viengchareun, S., Fagart, J., Lombès, M. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

  12. Living with a Red Dwarf: A Chandra Archival Study of dM Star Activity and Habitability

    Science.gov (United States)

    Engle, Scott

    2017-09-01

    We propose to analyze 6 archival Chandra visits, not pointed at, but serendipitously including 3 dM stars of known age. GJ 669 AB are a common proper motion pair, each are resolved and detected in 3 exposures, and LHS 373 is a much older dM star also detected on 3 exposures. Photometry (by us) of GJ 669 AB began 5 years ago, is ongoing, and has precisely determined rotation rates for both stars and evidence of frequent flaring from GJ 669 B. We will analyze the multiple exposures, derive an accurate mean level of X-ray activity from the targets, and also separate out and individually analyze and model any observed X-ray flares. This proposal will provide highly accurate coronal properties for the targets, but also very useful data for stellar evolution and planetary habitability studies.

  13. Characterization of human mesothelin transcripts in ovarian and pancreatic cancer

    International Nuclear Information System (INIS)

    Muminova, Zhanat E; Strong, Theresa V; Shaw, Denise R

    2004-01-01

    Mesothelin is an attractive target for cancer immunotherapy due to its restricted expression in normal tissues and high level expression in several tumor types including ovarian and pancreatic adenocarcinomas. Three mesothelin transcript variants have been reported, but their relative expression in normal tissues and tumors has been poorly characterized. The goal of the present study was to clarify which mesothelin transcript variants are commonly expressed in human tumors. Human genomic and EST nucleotide sequences in the public databases were used to evaluate sequences reported for the three mesothelin transcript variants in silico. Subsequently, RNA samples from normal ovary, ovarian and pancreatic carcinoma cell lines, and primary ovarian tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing to directly identify expressed transcripts. In silico comparisons of genomic DNA sequences with available EST sequences supported expression of mesothelin transcript variants 1 and 3, but there were no sequence matches for transcript variant 2. Newly-derived nucleotide sequences of RT-PCR products from tissues and cell lines corresponded to mesothelin transcript variant 1. Mesothelin transcript variant 2 was not detected. Transcript variant 3 was observed as a small percentage of total mesothelin amplification products from all studied cell lines and tissues. Fractionation of nuclear and cytoplasmic RNA indicated that variant 3 was present primarily in the nuclear fraction. Thus, mesothelin transcript variant 3 may represent incompletely processed hnRNA. Mesothelin transcript variant 1 represents the predominant mature mRNA species expressed by both normal and tumor cells. This conclusion should be important for future development of cancer immunotherapies, diagnostic tests, and gene microarray studies targeting mesothelin

  14. DM2 results on e+e- annihilation into multihadrons in the 1350-2400 MeV energy range

    International Nuclear Information System (INIS)

    Bisello, D.; Busetto, G.; Castro, A.; Nigro, M.; Pescara, L.; Sartori, P.; Stanco, L.; Antonelli, A.; Baldini, R.; Biagini, M.E.; Calcaterra, A.; Schioppa, M.; Augustin, J.E.; Cosme, G.; Couchot, F.; Fulda, F.; Grosdidier, G.; Jean-Marie, B.; Lepeltier, V.; Szklarz, G.

    1990-06-01

    We present preliminary results on the study of e + e - annihilation into π + π - π + π - , π + π - π 0 π 0 , π + π - π 0 , π + π - π + π - π 0 , K + K - π + π - and K s 0 K ± π -+ in the 1350-2400 MeV energy range. Data have been collected with the DM2 detector at DCI, the Orsay colliding ring, and refer to about 2 pb -1 integrated luminosity

  15. P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients

    International Nuclear Information System (INIS)

    Tang, Ruoping; Legrand, Ollivier; Marie, Jean-Pierre; Cohen, Simy; Perrot, Jean-Yves; Faussat, Anne-Marie; Zuany-Amorim, Claudia; Marjanovic, Zora; Morjani, Hamid; Fava, Fanny; Corre, Elise

    2009-01-01

    AVE9633 is a new immunoconjugate comprising a humanized monoclonal antibody, anti-CD33 antigen, linked through a disulfide bond to the maytansine derivative DM4, a cytotoxic agent and potent tubulin inhibitor. It is undergoing a phase I clinical trial. Chemoresistance to anti-mitotic agents has been shown to be related, in part, to overexpression of ABC proteins. The aim of the present study was to investigate the potential roles of P-gp, MRP1 and BCRP in cytotoxicity in AVE9633-induced acute myeloid leukaemia (AML). This study used AML cell lines expressing different levels of P-gp, MRP1 or BCRP proteins and twenty-five samples from AML patients. Expression and functionality of the transporter protein were analyzed by flow cytometry. The cytotoxicity of the drug was evaluated by MTT and apoptosis assays. P-gp activity, but not MRP1 and BCRP, attenuated AVE9633 and DM4 cytotoxicity in myeloid cell lines. Zosuquidar, a potent specific P-gp inhibitor, restored the sensitivity of cells expressing P-gp to both AVE9633 and DM4. However, the data from AML patients show that 10/25 samples of AML cells (40%) were resistant to AVE9633 or DM4 (IC 50 > 500 nM), and this was not related to P-gp activity (p-Value: 0.7). Zosuquidar also failed to re-establish drug sensitivity. Furthermore, this resistance was not correlated with CD33 expression (p-Value: 0.6) in those cells. P-gp activity is not a crucial mechanism of chemoresistance to AVE9633. For patients whose resistance to conventional anthracycline AML regimens is related to ABC protein expression, a combination with AVE9633 could be beneficial. Other mechanisms such as microtubule alteration could play an important role in chemoresistance to AVE9633

  16. Proteomic characterization of the acid tolerance response in Lactobacillus delbrueckii subsp. bulgaricus CAUH1 and functional identification of a novel acid stress-related transcriptional regulator Ldb0677.

    Science.gov (United States)

    Zhai, Zhengyuan; Douillard, François P; An, Haoran; Wang, Guohong; Guo, Xinghua; Luo, Yunbo; Hao, Yanling

    2014-06-01

    To overcome the deleterious effects of acid stress, Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) elicits an adaptive response to acid stress. In this study, proteomics approach complemented by transcriptional analysis revealed some cellular changes in L. bulgaricus CAUH1 during acid adaptation. We observed an increase of glycolysis-associated proteins, promoting an optimal utilization of carbohydrates. Also, rerouting of the pyruvate metabolism to fatty acid biosynthesis was observed, indicating a possible modification of the cell membrane rigidity and impermeability. In addition, expression of ribosomal protein S1 (RpsA) was repressed; however, the expression of EF-Tu, EF-G and TypA was up-regulated at both protein and transcript levels. This suggests a reduction of protein synthesis in response to acid stress along with possible enhancement of the translational accuracy and protein folding. It is noteworthy that the putative transcriptional regulator Ldb0677 was 1.84-fold up-regulated. Heterologous expression of Ldb0677 was shown to significantly enhance acid resistance in host strain Lactococcus lactis. To clarify its role in transcriptional regulation network, the DNA-binding specificity of Ldb0677 was determined using bacterial one-hybrid and electrophoretic mobility shift assay. The identification of a binding motif (SSTAGACR) present in the promoter regions of 22 genes indicates that it might function as a major regulator in acid stress response in L. bulgaricus. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  17. An SGS3-like protein functions in RNA-directed DNA methylation and transcriptional gene silencing in Arabidopsis

    KAUST Repository

    Zheng, Zhimin

    2010-01-06

    RNA-directed DNA methylation (RdDM) is an important epigenetic mechanism for silencing transgenes and endogenous repetitive sequences such as transposons. The RD29A promoter-driven LUCIFERASE transgene and its corresponding endogenous RD29A gene are hypermethylated and silenced in the Arabidopsis DNA demethylase mutant ros1. By screening for second-site suppressors of ros1, we identified the RDM12 locus. The rdm12 mutation releases the silencing of the RD29A-LUC transgene and the endogenous RD29A gene by reducing the promoter DNA methylation. The rdm12 mutation also reduces DNA methylation at endogenous RdDM target loci, including transposons and other repetitive sequences. In addition, the rdm12 mutation affects the levels of small interfering RNAs (siRNAs) from some of the RdDM target loci. RDM12 encodes a protein with XS and coiled-coil domains, and is similar to SGS3, which is a partner protein of RDR6 and can bind to double-stranded RNAs with a 5′ overhang, and is required for several post-transcriptional gene silencing pathways. Our results show that RDM12 is a component of the RdDM pathway, and suggest that RdDM may involve double-stranded RNAs with a 5′ overhang and the partnering between RDM12 and RDR2. © 2010 Blackwell Publishing Ltd.

  18. Relationship between serum leptin levels, ATPase activity of erythrocyte membrance and development of diabetic nephropathy in patients with DM2

    International Nuclear Information System (INIS)

    Wang Yuming

    2009-01-01

    Objective: To study the possible mechanism of development of nephrosis affected by changes of serum leptin levels and alteration of activities of Na + K + -ATPase and Ca 2+ Mg 2+ -ATPase of erythrocyte membrane in patients with type 2 diabetes(DM2). Methods: Serum leptin levels (with RIA) and erythrocyte membrane Na + K + -ATPase and Ca 2+ Mg 2+ -ATPase activitities (with Reinila method) were determined in 40 DM2 patients without nephropathy, 32 DM2 patients with nephropathy and 35 controls. Results Serum leptin levels were significantly higher in the diabetics as a whole than those in controls (P + K + -ATPase and Ca 2+ Mg 2+ -ATPase activities were significantly lower (P<0.01). Among the diabetic patients, the serum leptin levels in patients without nephrosis (P<0.05), but the RBC membrance ATPase activities were significantly lower(P<0.05). Conclusion: Development of type 2 diabetes nephrosis might be correlated with the high serum leptin level and decreased ATPase activities of erythrocite membrane. (authors)

  19. Mitigation of Membrane Biofouling in MBR Using a Cellulolytic Bacterium, Undibacterium sp. DM-1, Isolated from Activated Sludge.

    Science.gov (United States)

    Nahm, Chang Hyun; Lee, Seonki; Lee, Sang Hyun; Lee, Kibaek; Lee, Jaewoo; Kwon, Hyeokpil; Choo, Kwang-Ho; Lee, Jung-Kee; Jang, Jae Young; Lee, Chung-Hak; Park, Pyung-Kyu

    2017-03-28

    Biofilm formation on the membrane surface results in the loss of permeability in membrane bioreactors (MBRs) for wastewater treatment. Studies have revealed that cellulose is not only produced by a number of bacterial species but also plays a key role during formation of their biofilm. Hence, in this study, cellulase was introduced to a MBR as a cellulose-induced biofilm control strategy. For practical application of cellulase to MBR, a cellulolytic ( i.e ., cellulase-producing) bacterium, Undibacterium sp. DM-1, was isolated from a lab-scale MBR for wastewater treatment. Prior to its application to MBR, it was confirmed that the cell-free supernatant of DM-1 was capable of inhibiting biofilm formation and of detaching the mature biofilm of activated sludge and cellulose-producing bacteria. This suggested that cellulase could be an effective anti-biofouling agent for MBRs used in wastewater treatment. Undibacterium sp. DM-1-entrapping beads ( i.e ., cellulolytic-beads) were applied to a continuous MBR to mitigate membrane biofouling 2.2-fold, compared with an MBR with vacant-beads as a control. Subsequent analysis of the cellulose content in the biofilm formed on the membrane surface revealed that this mitigation was associated with an approximately 30% reduction in cellulose by cellulolytic-beads in MBR.

  20. Uncontrolled Hypertension and Its Determinants in Patients with Concomitant Type 2 Diabetes Mellitus (T2DM in Rural South Africa.

    Directory of Open Access Journals (Sweden)

    Oladele Vincent Adeniyi

    Full Text Available Paucity of data on the prevalence, treatment and control of hypertension in individuals living with type 2 diabetes mellitus (T2DM in the rural communities of South Africa may undermine efforts to reduce the morbidity and mortality associated with cardiovascular diseases. This study examines the socio-demographic and clinical determinants of uncontrolled hypertension among individuals living with T2DM in the rural communities of Mthatha, South Africa.This cross-sectional study involved a serially selected sample of 265 individuals living with T2DM and hypertension at Mthatha General Hospital, Mthatha. Uncontrolled hypertension was defined as systolic blood pressure greater than or equal to 140 mmHg and diastolic blood pressure greater than or equal to 90mmHg in accordance with the Eight Joint National Committee Report (JNC 8 (2014. We performed univariate and multivariate logistic regression analyses to identify the significant determinants of uncontrolled hypertension.Of the total participants (n = 265, the prevalence of uncontrolled hypertension was 75.5% (n = 200. In univariate analysis of all participants, male gender (p = 0.029, age≥65 years (p = 0.016, unemployed status (p<0.0001, excessive alcohol intake (p = 0.005 and consumption of western-type diet (p<0.0001 were positively associated with uncontrolled hypertension. In multivariate logistic regression (LR method analysis, unemployed status (p<0.0001, excessive alcohol intake (p = 0.007 and consumption of western-type diet (p<0.0001 were independently and significantly associated with uncontrolled hypertension. There is significant association between increasing number and classes of anti-hypertensive drugs and uncontrolled hypertension (p = 0.05 and 0.02, respectively.Prevalence of uncontrolled hypertension was high in individuals with concomitant hypertension and T2DM in the study population. Male sex, aging, clinic inertia, unemployed status and nutritional transitions are the most

  1. Laser Boost of a Small Interstellar Ram Jet to Obtain Operational Velocity. Implications for the DM Rocket/Ram Jet Model

    Science.gov (United States)

    Walcott Beckwith, Andrew

    2010-05-01

    In other conference research papers, Beckwith obtained a maximum DM mass/energy value of up to 5 TeV, as opposed to 400 GeV for DM, which may mean more convertible power for a dark matter ram jet. The consequences are from assuming that axions are CDM, and KK gravitons are for WDM, then ρWarm-Dark-Matter would dominate not only structure formation in early universe formation, but would also influence the viability of the DM ram jet applications for interstellar travel. The increase in convertible DM mass makes the ram jet a conceivable option. This paper in addition to describing the scientific issues leading to that 5 TeV mass for DM also what are necessary and sufficient laser boost systems which would permit a ram net to become operational.

  2. Reconstructing transcriptional regulatory networks through genomics data

    OpenAIRE

    Sun, Ning; Zhao, Hongyu

    2009-01-01

    One central problem in biology is to understand how gene expression is regulated under different conditions. Microarray gene expression data and other high throughput data have made it possible to dissect transcriptional regulatory networks at the genomics level. Owing to the very large number of genes that need to be studied, the relatively small number of data sets available, the noise in the data and the different natures of the distinct data types, network inference presents great challen...

  3. [Development of a multimedia learning DM diet education program using standardized patients and analysis of its effects on clinical competency and learning satisfaction for nursing students].

    Science.gov (United States)

    Hyun, Kyung Sun; Kang, Hyun Sook; Kim, Won Ock; Park, Sunhee; Lee, Jia; Sok, Sohyune

    2009-04-01

    The purpose of this study was to develop a multimedia learning program for patients with diabetes mellitus (DM) diet education using standardized patients and to examine the effects of the program on educational skills, communication skills, DM diet knowledge and learning satisfaction. The study employed a randomized control posttest non-synchronized design. The participants were 108 third year nursing students (52 experimental group, 56 control group) at K university in Seoul, Korea. The experimental group had regular lectures and the multimedia learning program for DM diet education using standardized patients while the control group had regular lectures only. The DM educational skills were measured by trained research assistants. The students who received the multimedia learning program scored higher for DM diet educational skills, communication skills and DM diet knowledge compared to the control group. Learning satisfaction of the experimental group was higher than the control group, but statistically insignificant. Clinical competency was improved for students receiving the multimedia learning program for DM diet education using standardized patients, but there was no statistically significant effect on learning satisfaction. In the nursing education system there is a need to develop and apply more multimedia materials for education and to use standardized patients effectively.

  4. ANAEMIA AS A RISK FACTOR FOR MICROVASCULAR COMPLICATIONS IN TYPE 2 DM- A CROSS-SECTIONAL STUDY

    Directory of Open Access Journals (Sweden)

    Kamanuru Ethirajulu Govindarajulu

    2016-11-01

    Full Text Available BACKGROUND It is well known that diabetes adversely affects the kidneys finally leading to anaemia by various mechanisms. Several studies had postulated that anaemia developing before renal complications has an independent association with microvascular complication in type 2 diabetic patients. The aim of the study is to estimate the prevalence of anaemia in persons with type 2 diabetes mellitus and its role as a risk factor for the presence and the severity of microvascular complication in a populationbased study. MATERIALS AND METHODS This is a cross-sectional study conducted in patients coming to OPD of the Department of General Medicine in Government Vellore Medical College for a duration of 3 months from June 01, 2016, to August 31, 2016. Type 2 DM patients between the age group 20-60 years attending our diabetic clinic of both sex were included in our study. RESULTS From a total of 100 patients, 41% had anaemia including 34% with normochromic normocytic, 65.85% with hyperchromic microcytic anaemia and none of the patient had macrocytic anaemia. Patients who are anaemic had more frequent microvascular complications. There was no significant difference between males and females. The average duration of diabetes has a positive correlation with anaemia. All the microvascular complications like neuropathy, nephropathy and retinopathy had significant association with the presence of anaemia in type 2 patients. Nephropathy had a significant higher frequency compared to others as a complication in type 2 DM. CONCLUSION Our study shows that there is increased prevalence of anaemia in type 2 DM patients and the prevalence of microvascular complications is significantly higher among the diabetic patients with anaemia.

  5. The Nile Rat (Arvicanthis niloticus as a Superior Carbohydrate-Sensitive Model for Type 2 Diabetes Mellitus (T2DM

    Directory of Open Access Journals (Sweden)

    Avinaash Subramaniam

    2018-02-01

    Full Text Available Type II diabetes mellitus (T2DM is a multifactorial disease involving complex genetic and environmental interactions. No single animal model has so far mirrored all the characteristics or complications of diabetes in humans. Since this disease represents a chronic nutritional insult based on a diet bearing a high glycemic load, the ideal model should recapitulate the underlying dietary issues. Most rodent models have three shortcomings: (1 they are genetically or chemically modified to produce diabetes; (2 unlike humans, most require high-fat feeding; (3 and they take too long to develop diabetes. By contrast, Nile rats develop diabetes rapidly (8–10 weeks with high-carbohydrate (hiCHO diets, similar to humans, and are protected by high fat (with low glycemic load intake. This review describes diabetes progression in the Nile rat, including various aspects of breeding, feeding, and handling for best experimental outcomes. The diabetes is characterized by a striking genetic permissiveness influencing hyperphagia and hyperinsulinemia; random blood glucose is the best index of disease progression; and kidney failure with chronic morbidity and death are outcomes, all of which mimic uncontrolled T2DM in humans. Non-alcoholic fatty liver disease (NAFLD, also described in diabetic humans, results from hepatic triglyceride and cholesterol accumulation associated with rising blood glucose. Protection is afforded by low glycemic load diets rich in certain fibers or polyphenols. Accordingly, the Nile rat provides a unique opportunity to identify the nutritional factors and underlying genetic and molecular mechanisms that characterize human T2DM.

  6. The nuclear factor-erythroid 2-related factor/heme oxygenase-1 axis is critical for the inflammatory features of type 2 diabetes-associated osteoarthritis.

    Science.gov (United States)

    Vaamonde-Garcia, Carlos; Courties, Alice; Pigenet, Audrey; Laiguillon, Marie-Charlotte; Sautet, Alain; Houard, Xavier; Kerdine-Römer, Saadia; Meijide, Rosa; Berenbaum, Francis; Sellam, Jérémie

    2017-09-01

    Epidemiological findings support the hypothesis that type 2 diabetes mellitus (T2DM) is a risk factor for osteoarthritis (OA). Moreover, OA cartilage from patients with T2DM exhibits a greater response to inflammatory stress, but the molecular mechanism is unclear. To investigate whether the antioxidant defense system participates in this response, we examined here the expression of nuclear factor-erythroid 2-related factor (Nrf-2), a master antioxidant transcription factor, and of heme oxygenase-1 (HO-1), one of its main target genes, in OA cartilage from T2DM and non-T2DM patients as well as in murine chondrocytes exposed to high glucose (HG). Ex vivo experiments indicated that Nrf-2 and HO-1 expression is reduced in T2DM versus non-T2DM OA cartilage (0.57-fold Nrf-2 and 0.34-fold HO-1), and prostaglandin E 2 (PGE 2 ) release was increased in samples with low HO-1 expression. HG-exposed, IL-1β-stimulated chondrocytes had lower Nrf-2 levels in vitro , particularly in the nuclear fraction, than chondrocytes exposed to normal glucose (NG). Accordingly, HO-1 levels were also decreased (0.49-fold) in these cells. The HO-1 inducer cobalt protoporphyrin IX more efficiently attenuated PGE 2 and IL-6 release in HG+IL-1β-treated cells than in NG+IL-1β-treated cells. Greater reductions in HO-1 expression and increase in PGE 2 /IL-6 production were observed in HG+IL-1β-stimulated chondrocytes from Nrf-2 -/- mice than in chondrocytes from wild-type mice. We conclude that the Nrf-2/HO-1 axis is a critical pathway in the hyperglucidic-mediated dysregulation of chondrocytes. Impairments in this antioxidant system may explain the greater inflammatory responsiveness of OA cartilage from T2DM patients and may inform treatments of such patients. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Cmin - herramienta case basada en crisp-dm para el soporte de proyectos de minería de datos

    OpenAIRE

    Cobos, Carlos; Zuñiga, Jhon; Guarin, Juan; León, Elizabeth; Mendoza, Martha

    2010-01-01

    En este artículo se presenta la CMIN, una herramienta CASE (Computer Aided Software Engineering) integrada (que soporta todas las fases de un proceso) basada en CRISP-DM 1.0 (Cross – Industry Standard Process for Data Mining) para soportar el desarrollo de proyectos de minería de datos.Primero se expone la funcionalidad general de CMIN, lo que incluye la gestión de procesos, plantillas y proyectos, y se destaca la capacidad de CMIN para realizar el seguimiento de los proyectos de una forma fá...

  8. Prostaglandin E (dmPGE{sub 2}) action in vitro on the activity of rat liver Golgi apparatus galactosyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Kordowiak, A.M.; Tomecki, J.; Procyk, K.; Kapusta, P. [Uniwersytet Jagiellonski, Cracow (Poland)

    1993-12-31

    In vitro addition of 16,16`-dimethyl prostaglandin E{sub 2} to Golgi-rich membrane fraction in final concentration of 0.1 {mu}g/1 mg of protein increased generally the activity of galactosyltransferase in comparison with control. The percentage of phospholipids in the whole fraction was similar in both investigated groups, only the sum of phosphatidylenoamine + phosphatidic acid was significantly lower after addition of dmPGE{sub 2} than in the control (0.001 < P < 0.01). (author). 25 refs, 2 figs, 1 tab.

  9. Propuesta para el cálculo del Índice Dm para la validez de los ítemes

    OpenAIRE

    Dominguez Lara, Sergio

    2013-01-01

    Se presenta un programa en formato MS Excel para calcular el índice Dm para la validez de los ítemes. La validez es un proceso de acumulación de pruebas para apoyar la interpretación y el uso de las puntuaciones de los tests psicológicos, siendo las relaciones de los puntajes con otras variables externas una importante fuente de validación. Una variante es la llamada validez relacionada al criterio, en la cual se espera una correlación significativa con aquellos criterios externos que son teó...

  10. Perspectives on Peripheral Neuropathy as a Consequence of Metformin-Induced Vitamin B12 Deficiency in T2DM

    Directory of Open Access Journals (Sweden)

    Marwan A. Ahmed

    2017-01-01

    Full Text Available Peripheral neuropathy (PN is a primary complication of type 2 diabetes mellitus (T2DM and a direct manifestation of vitamin B12 deficiency. Examining the effects of metformin use on PN status became imperative following clinical studies that showed the vitamin B12-lowering effect of the medication. The complexity of the topic and the inconsistency of the results warrant consideration of topic-specific perspectives for better understanding of the available evidence and more appropriate design of future studies.

  11. Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM.

    Science.gov (United States)

    Stagi, Stefano; Lapi, Elisabetta; Seminara, Salvatore; Pelosi, Paola; Del Greco, Paolo; Capirchio, Laura; Strano, Massimo; Giglio, Sabrina; Chiarelli, Francesco; de Martino, Maurizio

    2015-02-15

    Treatments for childhood obesity are critically needed because of the risk of developing co-morbidities, although the interventions are frequently time-consuming, frustrating, difficult, and expensive. We conducted a longitudinal, randomised, clinical study, based on a per protocol analysis, on 133 obese children and adolescents (n = 69 males and 64 females; median age, 11.3 years) with family history of obesity and type 2 diabetes mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53 patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard, only a LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic and disposition indexes were calculated at T0 and after 1 year (T1). At T1, the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p 1) in Arm A and from 2.23 to 1.99 (p 13.2% to 5.6%; p 1) and B (p 1) and B (p obese children and adolescents with family history of obesity and T2DM.

  12. RNA-guided transcriptional regulation

    Science.gov (United States)

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

    2016-02-23

    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  13. Transcriptional control of megakaryocyte development.

    Science.gov (United States)

    Goldfarb, A N

    2007-10-15

    Megakaryocytes are highly specialized cells that arise from a bipotent megakaryocytic-erythroid progenitor (MEP). This developmental leap requires coordinated activation of megakaryocyte-specific genes, radical changes in cell cycle properties, and active prevention of erythroid differentiation. These programs result from upregulation of megakaryocyte-selective transcription factors, downregulation of erythroid-selective transcription factors and ongoing mediation of common erythro-megakaryocytic transcription factors. Unlike most developmental programs, no single lineage-unique family of master regulators exerts executive control over the megakaryocytic plan. Rather, an assemblage of non-unique factors and signals converge to determine lineage and differentiation. In human megakaryopoiesis, hereditary disorders of platelet production have confirmed contributions from three distinct transcription factor families. Murine models have extended this repertoire to include multiple additional factors. At a mechanistic level, the means by which these non-unique factors collaborate in the establishment of a perfectly unique cell type remains a central question.

  14. Enzymatic Hydrolysis of biomasses having a high dry matter (DM) content

    DEFF Research Database (Denmark)

    2010-01-01

    that the biomasses are subjected to mechanical forces, primarily shear and tear forces. Furthermore, the present invention relates to the further utilization of such processed biomasses, e.g. for subsequent fermentation into bio-ethanol, bio-gas, specialty carbohydrates for food and fees as well as carbon feedstock...... for processing into plastics and chemicals....

  15. National Capital Planning Commission Meeting Transcripts

    Data.gov (United States)

    National Capital Planning Commission — Transcripts of the monthly (with the exception of August) National Capital Planning Commission meeting transcripts are provided for research to confirm actions taken...

  16. Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

    Directory of Open Access Journals (Sweden)

    Amanda Malvessi Cattani

    Full Text Available Transcriptional regulation, a multiple-step process, is still poorly understood in the important pig pathogen Mycoplasma hyopneumoniae. Basic motifs like promoters and terminators have already been described, but no other cis-regulatory elements have been found. DNA repeat sequences have been shown to be an interesting potential source of cis-regulatory elements. In this work, a genome-wide search for tandem and palindromic repetitive elements was performed in the intergenic regions of all coding sequences from M. hyopneumoniae strain 7448. Computational analysis demonstrated the presence of 144 tandem repeats and 1,171 palindromic elements. The DNA repeat sequences were distributed within the 5' upstream regions of 86% of transcriptional units of M. hyopneumoniae strain 7448. Comparative analysis between distinct repetitive sequences found in related mycoplasma genomes demonstrated different percentages of conservation among pathogenic and nonpathogenic strains. qPCR assays revealed differential expression among genes showing variable numbers of repetitive elements. In addition, repeats found in 206 genes already described to be differentially regulated under different culture conditions of M. hyopneumoniae strain 232 showed almost 80% conservation in relation to M. hyopneumoniae strain 7448 repeats. Altogether, these findings suggest a potential regulatory role of tandem and palindromic DNA repeats in the M. hyopneumoniae transcriptional profile.

  17. Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

    Science.gov (United States)

    Cattani, Amanda Malvessi; Siqueira, Franciele Maboni; Guedes, Rafael Lucas Muniz; Schrank, Irene Silveira

    2016-01-01

    Transcriptional regulation, a multiple-step process, is still poorly understood in the important pig pathogen Mycoplasma hyopneumoniae. Basic motifs like promoters and terminators have already been described, but no other cis-regulatory elements have been found. DNA repeat sequences have been shown to be an interesting potential source of cis-regulatory elements. In this work, a genome-wide search for tandem and palindromic repetitive elements was performed in the intergenic regions of all coding sequences from M. hyopneumoniae strain 7448. Computational analysis demonstrated the presence of 144 tandem repeats and 1,171 palindromic elements. The DNA repeat sequences were distributed within the 5' upstream regions of 86% of transcriptional units of M. hyopneumoniae strain 7448. Comparative analysis between distinct repetitive sequences found in related mycoplasma genomes demonstrated different percentages of conservation among pathogenic and nonpathogenic strains. qPCR assays revealed differential expression among genes showing variable numbers of repetitive elements. In addition, repeats found in 206 genes already described to be differentially regulated under different culture conditions of M. hyopneumoniae strain 232 showed almost 80% conservation in relation to M. hyopneumoniae strain 7448 repeats. Altogether, these findings suggest a potential regulatory role of tandem and palindromic DNA repeats in the M. hyopneumoniae transcriptional profile.

  18. A code for transcription initiation in mammalian genomes

    DEFF Research Database (Denmark)

    Frith, Martin C.; Valen, Eivind Dale; Krogh, Anders

    2007-01-01

    that initiation events are clustered on the chromosomes at multiple scales - clusters within clusters - indicating multiple regulatory processes. Within the smallest of such clusters, which can be interpreted as core promoters, the local DNA sequence predicts the relative transcription start usage of each...... of large- and small-scale effects: the selection of transcription start sites is largely governed by the local DNA sequence, whereas the transcriptional activity of a locus is regulated at a different level; it is affected by distal features or events such as enhancers and chromatin remodeling....

  19. CMIN - herramienta case basada en CRISP-DM para el soporte de proyectos de minería de datos

    Directory of Open Access Journals (Sweden)

    Carlos Cobos

    2010-09-01

    Full Text Available En este artículo se presenta la CMIN, una herramienta CASE (Computer Aided Software Engineering integrada (que soporta todas las fases de un proceso basada en CRISP-DM 1.0 (Cross – Industry Standard Process for Data Mining para soportar el desarrollo de proyectos de minería de datos.Primero se expone la funcionalidad general de CMIN, lo que incluye la gestión de procesos, plantillas y proyectos, y se destaca la capacidad de CMIN para realizar el seguimiento de los proyectos de una forma fácil e intuitiva y la manera como CMIN posibilita que el usuario incremente su conocimiento en el uso de CRISP-DM o de cualquier otro proceso que se defina en la herramienta a través de las ayudas e información que se ofrece en cada paso del proceso. Después, se detalla cómo CMIN permite enlazar en tiempo de ejecución (sin necesidad de volver a compilar la herramienta nuevos algoritmos de minería de datos que apoyen la labor de modelado (basada en un flujo de trabajo o workflow en un proyecto de minería de datos. Finalmente, se ofrecen los resultados de dos evaluaciones de la herramienta, las conclusiones y el trabajo futuro.

  20. Relativity

    CERN Document Server

    Einstein, Albert

    2013-01-01

    Time magazine's ""Man of the Century"", Albert Einstein is the founder of modern physics and his theory of relativity is the most important scientific idea of the modern era. In this short book, Einstein explains, using the minimum of mathematical terms, the basic ideas and principles of the theory that has shaped the world we live in today. Unsurpassed by any subsequent books on relativity, this remains the most popular and useful exposition of Einstein's immense contribution to human knowledge.With a new foreword by Derek Raine.

  1. Pengendalian status gizi, kadar glukosa darah, dan tekanan darah melalui terapi gizi medis pada pasien diabetes mellitus (DM tipe 2 rawat jalan di RSU Mataram NTB

    Directory of Open Access Journals (Sweden)

    Suhaema Suhaema

    2010-11-01

    Conclusion: Intake of nutrient, nutrition status, blood glucose level and blood pressure of type 2 DM patients that got MNT was more controllable than of those that got conventional nutrition counseling.

  2. The Stop Transmission of Polio Data Management (STOP DM) assignment and its role in polio eradication and immunization data improvement in Africa.

    Science.gov (United States)

    Benke, Amalia; Williams, Alford Joseph; MacNeil, Adam

    2017-01-01

    The availability and use of high quality immunization and surveillance data are crucial for monitoring all components of the Global Polio Eradication Program (GPEI). The Stop Transmission of Polio (STOP) program was initiated in 1999 to train and mobilize human resources to provide technical support to polio endemic and at-risk countries and in 2002 the STOP data management (STOP DM) deployment was created to provide capacity development in the area of data management for immunization and surveillance data for these countries. Since 2002, Africa has received the majority of support from the STOP DM program, with almost 80% of assignments being placed in African countries. The STOP DM program has played a valuable role in improving the quality and use of data for the GPEI and has increasingly supported other immunization program data needs. In this report we provide an overview of the history, current status, and future of the STOP DM program, with a specific focus on the African continent.

  3. Decreased Muscle Strength and Quality in Diabetes-Related Dementia

    Directory of Open Access Journals (Sweden)

    Akito Tsugawa

    2017-12-01

    Full Text Available Background/Aims: Diabetes-related dementia (DrD, a dementia subgroup associated with specific diabetes mellitus (DM-related metabolic abnormalities, is clinically and pathophysiologically different from Alzheimer disease (AD and vascular dementia. We determined whether skeletal muscle strength, quality, and mass decrease in individuals with DrD. Methods: We evaluated grip and knee extension strength, muscle mass, and gait speed in 106 patients with probable AD and without type 2 DM (AD[–DM] group, 74 patients with probable AD and with DM (AD[+DM] group, and 36 patients with DrD (DrD group. Muscle quality was defined as the ratio of muscle strength to muscle mass. Results: Both female and male subjects with DrD showed significantly decreased muscle strength and quality in the upper extremities compared with the subjects with AD[–DM] or AD[+DM]. Female subjects with DrD showed significantly decreased muscle quality in the lower extremities compared with the subjects with AD[–DM]. Both female and male subjects with DrD had a significantly lower gait speed compared with the subjects with AD[–DM]. However, there were no significant differences in muscle mass and the prevalence of sarcopenia between the groups. Conclusion: Subjects with DrD showed decreased muscle strength and quality, but not muscle mass, and had a low gait speed.

  4. Final Report Integrated DM1200 Melter Testing Using AZ-102 And C-106/AY-102 HLW Simulants: HLW Simulant Verification VSL-05R5800-1, Rev. 0, 6/27/05

    International Nuclear Information System (INIS)

    Kruger, A.A.; Matlack, K.S.; Gong, W.; Bardakci, T.; D'Angelo, N.A.; Brandys, M.; Kot, W.K.; Pegg, I.L.

    2011-01-01

    The principal objectives of the DM1200 melter tests were to determine the effects of feed rheology, feed solid content, and bubbler configuration on glass production rate and off-gas system performance while processing the HLW AZ-101 and C-106/AY-102 feed compositions; characterize melter off-gas emissions; characterize the performance of the prototypical off-gas system components, as well as their integrated performance; characterize the feed, glass product, and off-gas effluents; and perform pre- and post test inspections of system components. The specific objectives (including test success criteria) of this testing, along with how each objective was met, are outlined in a table. The data provided in this Final Report address the impacts of HLW melter feed rheology on melter throughput and validation of the simulated HLW melter feeds. The primary purpose of this testing is to further validate/verify the HLW melter simulants that have been used for previous melter testing and to support their continued use in developing melter and off-gas related processing information for the Project. The primary simulant property in question is rheology. Simulants and melter feeds used in all previous melter tests were produced by direct addition of chemicals; these feed tend to be less viscous than rheological the upper-bound feeds made from actual wastes. Data provided here compare melter processing for the melter feed used in all previous DM100 and DM1200 tests (nominal melter feed) with feed adjusted by the feed vendor (NOAH Technologies) to be more viscous, thereby simulating more closely the upperbounding feed produced from actual waste. This report provides results of tests that are described in the Test Plan for this work. The Test Plan is responsive to one of several test objectives covered in the WTP Test Specification for this work; consequently, only part of the scope described in the Test Specification was addressed in this particular Test Plan. For the purpose of

  5. FINAL REPORT INTEGRATED DM1200 MELTER TESTING USING AZ 102 AND C 106/AY-102 HLW SIMULANTS: HLW SIMULANT VERIFICATION VSL-05R5800-1 REV 0 6/27/05

    Energy Technology Data Exchange (ETDEWEB)

    KRUGER AA; MATLACK KS; GONG W; BARDAKCI T; D' ANGELO NA; BRANDYS M; KOT WK; PEGG IL

    2011-12-29

    The principal objectives of the DM1200 melter tests were to determine the effects of feed rheology, feed solid content, and bubbler configuration on glass production rate and off-gas system performance while processing the HLW AZ-101 and C-106/AY-102 feed compositions; characterize melter off-gas emissions; characterize the performance of the prototypical off-gas system components, as well as their integrated performance; characterize the feed, glass product, and off-gas effluents; and perform pre- and post test inspections of system components. The specific objectives (including test success criteria) of this testing, along with how each objective was met, are outlined in a table. The data provided in this Final Report address the impacts of HLW melter feed rheology on melter throughput and validation of the simulated HLW melter feeds. The primary purpose of this testing is to further validate/verify the HLW melter simulants that have been used for previous melter testing and to support their continued use in developing melter and off-gas related processing information for the Project. The primary simulant property in question is rheology. Simulants and melter feeds used in all previous melter tests were produced by direct addition of chemicals; these feed tend to be less viscous than rheological the upper-bound feeds made from actual wastes. Data provided here compare melter processing for the melter feed used in all previous DM100 and DM1200 tests (nominal melter feed) with feed adjusted by the feed vendor (NOAH Technologies) to be more viscous, thereby simulating more closely the upperbounding feed produced from actual waste. This report provides results of tests that are described in the Test Plan for this work. The Test Plan is responsive to one of several test objectives covered in the WTP Test Specification for this work; consequently, only part of the scope described in the Test Specification was addressed in this particular Test Plan. For the purpose of

  6. The Dionaea muscipula ammonium channel DmAMT1 provides NH₄⁺ uptake associated with Venus flytrap's prey digestion.

    Science.gov (United States)

    Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; Kruse, Jörg; Karl, Franziska; von Rüden, Martin; Escalante-Perez, Maria; Müller, Thomas; Rennenberg, Heinz; Al-Rasheid, Khaled A S; Neher, Erwin; Hedrich, Rainer

    2013-09-09

    Ammonium transporter (AMT/MEP/Rh) superfamily members mediate ammonium uptake and retrieval. This pivotal transport system is conserved among all living organisms. For plants, nitrogen represents a macronutrient available in the soil as ammonium, nitrate, and organic nitrogen compounds. Plants living on extremely nutrient-poor soils have developed a number of adaptation mechanisms, including a carnivorous lifestyle. This study addresses the molecular nature, function, and regulation of prey-derived ammonium uptake in the Venus flytrap, Dionaea muscipula, one of the fastest active carnivores. The Dionaea muscipula ammonium transporter DmAMT1 was localized in gland complexes where its expression was upregulated upon secretion. These clusters of cells decorating the inner trap surface are engaged in (1) secretion of an acidic digestive enzyme cocktail and (2) uptake of prey-derived nutrients. Voltage clamp of Xenopus oocytes expressing DmAMT1 and membrane potential recordings with DmAMT1-expressing Dionaea glands were used to monitor and compare electrophysiological properties of DmAMT1 in vitro and in planta. DmAMT1 exhibited the hallmark biophysical properties of a NH4(+)-selective channel. At depolarized membrane potentials (Vm = 0), the Km (3.2 ± 0.3 mM) indicated a low affinity of DmAMT1 for ammonium that increased systematically with negative going voltages. Upon hyperpolarization to, e.g., -200 mV, a Km of 0.14 ± 0.015 mM documents the voltage-dependent shift of DmAMT1 into a NH4(+) transport system of high affinity. We suggest that regulation of glandular DmAMT1 and membrane potential readjustments of the endocrine cells provide for effective adaptation to varying, prey-derived ammonium sources. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. T-DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo

    International Nuclear Information System (INIS)

    English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

    2014-01-01

    Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody–drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy

  8. Extension of a Computer Assisted Decision Support (CADS) Study to Improve Outcomes in Patients with Type 2 DM Treated by Primary Cary Providers (short title, CADS-X)

    Science.gov (United States)

    2012-10-01

    National Health and Nutrition Examination Survey (NHANES) data demonstrated that 42.3% of patients with DM have A1Cs over 7% (22). The military healthcare...system (MHS) - where there is no cost to the patient for care and testing supplies - has similar results with hemoglobin A1C’s over 7% in 42% of...Endocrinologists and Certified Diabetes Educators in both military and civilian health care settings (23), the vast majority of patients with DM are

  9. Extension of a Computer Assisted Decision Support (CADS) Study to Improve Outcomes in Patients with Type 2 DM Treated Primary Cary Providers

    Science.gov (United States)

    2013-10-01

    latest (2004) National Health and Nutrition Examination Survey (NHANES) data demonstrated that 42.3% of patients with DM have A1Cs over 7% (22). The...military healthcare system (MHS) - where there is no cost to the patient for care and testing supplies - has similar results with hemoglobin A1C’s... Educators in both military and civilian health care settings (23), the vast majority of patients with DM are managed by primary care providers (PCPs

  10. Presence of elevated non-HDL among patients with T2DM with CV events despite of optimal LDL-C – A report from South India

    Directory of Open Access Journals (Sweden)

    Satyavani Kumpatla

    2016-05-01

    Full Text Available Elevated non-high density lipoprotein cholesterol (non-HDL-C was the commonest lipid abnormality among T2DM patients with cardiovascular events (CV events. Prevalence of elevated non-HDL-C was 21.6% among patients who were on statin therapy and with optimal low density lipoprotein-cholesterol (LDL-C levels. Despite an optimal LDL-C level, 47% of the T2DM patients with CV events had elevated non-HDL-C.

  11. Arsenic exposure and calpain-10 polymorphisms impair the function of pancreatic beta-cells in humans: a pilot study of risk factors for T2DM.

    Directory of Open Access Journals (Sweden)

    Andrea Díaz-Villaseñor

    Full Text Available The incidence of type 2 diabetes mellitus (T2DM is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs in the calpain-10 gene (CAPN-10, which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2 in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function.

  12. Evidences of +896 A/G TLR4 Polymorphism as an Indicative of Prevalence of Complications in T2DM Patients

    Directory of Open Access Journals (Sweden)

    Carmela Rita Balistreri

    2014-01-01

    Full Text Available T2DM is today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DM complications, including 367 T2DM patients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication’s prevalence. In particular, AG carriers had higher risk prevalence for neuropathy (P=0.026, lower limb arteriopathy (P=0.013, and the major cardiovascular pathologies (P=0.017. Their cumulative risk was significant (P=0.01, with a threefold risk to develop neuropathy, lower limb arteriopathy, and major cardiovascular events in AG cases compared to AA cases. The adjusted OR for the confounding variables was 3.788 (95% CI: 1.642–8.741. Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients.

  13. Oligomerization and chaperone-like activity of Drosophila melanogaster small heat shock protein DmHsp27 and three arginine mutants in the alpha-crystallin domain.

    Science.gov (United States)

    Moutaoufik, Mohamed Taha; Morrow, Geneviève; Maaroufi, Halim; Férard, Céline; Finet, Stéphanie; Tanguay, Robert M

    2017-07-01

    The small Hsp DmHsp27 from Drosophila melanogaster is one of the few small heat shock proteins (sHsps) found within the nucleus. We report that its dimerization is independent of disulfide bond formation and seems to rely on salt bridges. Unlike metazoan sHsps, DmHsp27 forms two populations of oligomers not in equilibrium. Mutations at highly conserved arginine residues in mammalian sHsps have been reported to be associated with protein conformational defects and intracellular aggregation. Independent mutation of three highly conserved arginines (R122, R131, and R135) to glycine in DmHsp27 results in only one population of higher molecular weight form. In vitro, the chaperone-like activity of wild-type DmHsp27 was comparable with that of its two isolated populations and to the single population of the R122G, R131G, and R135G using luciferase as substrate. However, using insulin, the chaperone-like activity of wild-type DmHsp27 was lower than that of R122G and R131G mutants. Altogether, the results characterize wild-type DmHsp27 and its alpha-crystallin domain (ACD) arginine mutants and may give insight into protection mechanism of sHsps.

  14. Nurbayev D.M. Public and dispositive segments of abuse of the subjective right: interdisciplinary look.

    Directory of Open Access Journals (Sweden)

    Vladimir Azarov

    2017-01-01

    Full Text Available УДК 343.12The subject. The article is devoted to the analysis of a phenomenon "abuse of the right" from a position of the public and dispositive beginnings of his manifestation.The purpose of this article is to consider public and dispositive principles of abuse of the right in the scope of legal theory to qualify this phenomenon in criminal proceedings properly.Methodology. The author use methods of theoretical analysis and interdisciplinary approach as well as legal methods, including formal legal method and comparative law.Results, scope of it’s application. The authors note that the use of the advantages offered by abuse of the right is initially inherent only for the defending party in criminal proceedings.Abuse of the right in the procedural segment of disposition appears in the implementation of the right to protection in the criminal procedure as well as in the implementation of almost any rights in the civil proceedings.The main resource of publicity is realized exclusively by the courts in the civil procedure as well as by all government entities and officials in the criminal process. That’s why abuse of the right is interdicted by the activity of the court in civil procedure.The imperative method of legal regulation of public relations, that is the basis of publicity, is in fact one of the ways of prevention and suppression of abuse of rights. The disposition method, that is the basis of competition in legal relations, is a catalyst for the creation of situations of possible abuse of rights.Abuse of rights is manifested first and foremost in terms of the disposition, moreover – the higher the level of disposition in the particular branch of law provokes the greater likelihood of abuse of the right. Publicity limits disposition and, therefore, the possibility of abuse of the right.Conclusions. Legal institute of abuse of right requires early normative entrenchment in the criminal process. It should contain specific grounds for

  15. Modulation of transcription factors by curcumin.

    Science.gov (United States)

    Shishodia, Shishir; Singh, Tulika; Chaturvedi, Madan M

    2007-01-01

    Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.

  16. Assessing Concordance of Drug-Induced Transcriptional Response in Rodent Liver and Cultured Hepatocytes.

    Directory of Open Access Journals (Sweden)

    Jeffrey J Sutherland

    2016-03-01

    Full Text Available The effect of drugs, disease and other perturbations on mRNA levels are studied using gene expression microarrays or RNA-seq, with the goal of understanding molecular effects arising from the perturbation. Previous comparisons of reproducibility across laboratories have been limited in scale and focused on a single model. The use of model systems, such as cultured primary cells or cancer cell lines, assumes that mechanistic insights derived from the models would have been observed via in vivo studies. We examined the concordance of compound-induced transcriptional changes using data from several sources: rat liver and rat primary hepatocytes (RPH from Drug Matrix (DM and open TG-GATEs (TG, human primary hepatocytes (HPH from TG, and mouse liver/HepG2 results from the Gene Expression Omnibus (GEO repository. Gene expression changes for treatments were normalized to controls and analyzed with three methods: 1 gene level for 9071 high expression genes in rat liver, 2 gene set analysis (GSA using canonical pathways and gene ontology sets, 3 weighted gene co-expression network analysis (WGCNA. Co-expression networks performed better than genes or GSA when comparing treatment effects within rat liver and rat vs. mouse liver. Genes and modules performed similarly at Connectivity Map-style analyses, where success at identifying similar treatments among a collection of reference profiles is the goal. Comparisons between rat liver and RPH, and those between RPH, HPH and HepG2 cells reveal lower concordance for all methods. We observe that the baseline state of untreated cultured cells relative to untreated rat liver shows striking similarity with toxicant-exposed cells in vivo, indicating that gross systems level perturbation in the underlying networks in culture may contribute to the low concordance.

  17. Realization and optimization of AES algorithm on the TMS320DM6446 based on DaVinci technology

    Science.gov (United States)

    Jia, Wen-bin; Xiao, Fu-hai

    2013-03-01

    The application of AES algorithm in the digital cinema system avoids video data to be illegal theft or malicious tampering, and solves its security problems. At the same time, in order to meet the requirements of the real-time, scene and transparent encryption of high-speed data streams of audio and video in the information security field, through the in-depth analysis of AES algorithm principle, based on the hardware platform of TMS320DM6446, with the software framework structure of DaVinci, this paper proposes the specific realization methods of AES algorithm in digital video system and its optimization solutions. The test results show digital movies encrypted by AES128 can not play normally, which ensures the security of digital movies. Through the comparison of the performance of AES128 algorithm before optimization and after, the correctness and validity of improved algorithm is verified.

  18. Piperazines as nootropic agents: New derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents.

    Science.gov (United States)

    Martino, Maria Vittoria; Guandalini, Luca; Di Cesare Mannelli, Lorenzo; Menicatti, Marta; Bartolucci, Gianluca; Dei, Silvia; Manetti, Dina; Teodori, Elisabetta; Ghelardini, Carla; Romanelli, Maria Novella

    2017-03-15

    The piperazine ring of the potent nootropic drug DM235 has been decorated with H-bond donor and acceptor groups (CH 2 OH, CH 2 OMe, CH 2 OCOMe, COOEt); the aim was to insert new functional groups, suitable for further chemical manipulation. The influence of these modifications on nootropic activity was assessed by means of the mouse passive avoidance test; some of the newly synthesized molecules (alcohol 7b, acetate 8b and ester 10d) showed interesting in vivo potency. This makes it possible to use these functional groups for adding other residues, in order to increase molecular diversity, or for anchoring a biotin group, to obtain compounds useful to capture the biological target. Moreover, the new compounds will improve our knowledge of structure activity relationships of this family of drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. GPR119 agonists: a promising approach for T2DM treatment? A SWOT analysis of GPR119.

    Science.gov (United States)

    Kang, Sang-Uk

    2013-12-01

    Ever since its advent as a promising therapeutic target for type 2 diabetes mellitus (T2DM), G-protein-coupled receptor 119 (GPR119) has received much interest from the pharmaceutical industry. This interest peaked in June 2010, when Sanofi-Aventis agreed to pay Metabolex (Cymabay Therapeutics) US$375 million for MBX-2982, which was a representative orally active GPR119 agonist. However, Sanofi-Aventis opted to terminate the deal in May 2011 and another leading GPR119 agonist, GSK1292263, had a loss of efficacy during its clinical trial. In this review, I discuss the pros and cons of GPR119 through a strengths, weaknesses, opportunities, and threats (SWOT) analysis and propose development strategies for the eventual success of a GPR119 agonist development program. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Multipole induced splitting of metal-cage vibrations in crystalline endohedral D2d-M2@C84 dimetallofullerenes.

    Science.gov (United States)

    Krause, M; Popov, V N; Inakuma, M; Tagmatarchis, N; Shinohara, H; Georgi, P; Dunsch, L; Kuzmany, H

    2004-01-22

    Metal-carbon cage vibrations of crystalline endohedral D2d-M2@C84 (M=Sc,Y,Dy) dimetallofullerenes were analyzed by temperature dependent Raman scattering and a dynamical force field model. Three groups of metal-carbon cage modes were found at energies of 35-200 cm(-1) and assigned to metal-cage stretching and deformation vibrations. They exhibit a textbook example for the splitting of molecular vibrations in a crystal field. Induced dipole-dipole and quadrupole-quadrupole interactions account quantitatively for the observed mode splitting. Based on the metal-cage vibrational structure it is demonstrated that D2d-Y2@C84 dimetallofullerene retains a monoclinic crystal structure up to 550 K and undergoes a transition from a disordered to an ordered orientational state at a temperature of approximately 150 K.

  1. EpCAM aptamer-functionalized polydopamine-coated mesoporous silica nanoparticles loaded with DM1 for targeted therapy in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Li Y

    2017-08-01

    Full Text Available Yang Li,1,* Yanhong Duo,2,3,* Shiyun Bao,1 Lisheng He,4 Kai Ling,5 Jinfeng Luo,4 Yue Zhang,1 Hao Huang,2 Han Zhang,2 Xiaofang Yu1 1Department of Hepatobiliary and Pancreas Surgery, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, 2Shenzhen Engineering Laboratory of Phosphorene and Optoelectronics, Collaborative Innovation Center for Optoelectronic Science and Technology, Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 3Key Laboratory of Plant Cell Activities and Stress Adaptation, Ministry of Education, School of Life Sciences, Lanzhou University, Lanzhou, 4Department of Pathology, 5Institute of Respiratory Diseases, Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, China *These authors contributed equally to this work Abstract: DM1, a maytansine derivative, is a highly potential cytotoxic agent but with severe side effects; therefore, its application in clinical cancer therapy is limited. Here, in order to mitigate this intrinsic drawback of DM1, we developed mesoporous silica nanoparticles (MSNs loaded with DM1 and surface-decorated with hydrochloride dopamine (PDA, polyethylene glycol (PEG, and epithelial cell adhesion molecule (EpCAM aptamer (APt for the targeted treatment of colorectal cancer (CRC. In this system, the PDA coating could be used as pH-sensitive gatekeepers to control the release of DM1 from MSNs in response to the pH stimulus and EpCAM APt-guided active targeting enables the increased delivery of DM1 to CRC as well as a reduction in toxicity and side effects by minimizing the exposure of normal tissues to DM1. Results demonstrated that DM1 inhibited the formation of microtubules and induced apoptosis in tumor cells via caspase signaling. In comparison with the control groups, the MSNs-DM1@PDA-PEG-APt bioconjugates exhibited

  2. The fine structure of Gowdy spacetimes[04.20.-q Classical general relativity; 04.25.Dm Numerical relativity; 04.20.Dw Singularities and cosmic censorship;

    Energy Technology Data Exchange (ETDEWEB)

    Garfinkle, David [Department of Physics, University of Guelph, Guelph, Ontario, N1G 2W1 (Canada)

    2004-02-07

    The approach to the singularity in Gowdy spacetimes consists of velocity term dominated behaviour, except at a set of isolated points. At and near these points, spiky features grow. This paper reviews what is known about these spikes.

  3. DeepBound: accurate identification of transcript boundaries via deep convolutional neural fields

    KAUST Repository

    Shao, Mingfu; Ma, Jianzhu; Wang, Sheng

    2017-01-01

    Motivation: Reconstructing the full- length expressed transcripts (a. k. a. the transcript assembly problem) from the short sequencing reads produced by RNA-seq protocol plays a central role in identifying novel genes and transcripts as well as in studying gene expressions and gene functions. A crucial step in transcript assembly is to accurately determine the splicing junctions and boundaries of the expressed transcripts from the reads alignment. In contrast to the splicing junctions that can be efficiently detected from spliced reads, the problem of identifying boundaries remains open and challenging, due to the fact that the signal related to boundaries is noisy and weak.

  4. DeepBound: accurate identification of transcript boundaries via deep convolutional neural fields

    KAUST Repository

    Shao, Mingfu

    2017-04-20

    Motivation: Reconstructing the full- length expressed transcripts (a. k. a. the transcript assembly problem) from the short sequencing reads produced by RNA-seq protocol plays a central role in identifying novel genes and transcripts as well as in studying gene expressions and gene functions. A crucial step in transcript assembly is to accurately determine the splicing junctions and boundaries of the expressed transcripts from the reads alignment. In contrast to the splicing junctions that can be efficiently detected from spliced reads, the problem of identifying boundaries remains open and challenging, due to the fact that the signal related to boundaries is noisy and weak.

  5. Relationship between perception with the quality of life of T2DM patients in Dok II Jayapura Hospital

    Science.gov (United States)

    Perwitasari, D. A.; Faridah, I. N.; Kulle, Y.; Yulistika, M.

    2017-11-01

    Diabetes mellitus disease is one of the chronic diseases which can cause a fatal risk if its management is not appropriate. The purpose of this study was to determine the relationship between perception and quality of life in Dok II Jayapura hospital. This study used an observational research design with cross sectional approach with prospective sampling in diabetic patients in internal disease policemen who were underwent outpatient treatment at Dok II Jayapura hospital. Research instruments used EQ-5D (European Quality-5 Dimension) and B-IPQ (Brief Illness Perception Quetionare). Data analysis used was univariate analysis by using percentage or mean value, bivariate using T-test or Mann-Whitney test, and multivariate using multiple linear regression. There were 80 T2DM patients who met the inclusion criteria. Based on patient demographic data, there were 29 people (36.6%) male patients and 51 people (63.8%) female patients, with mean age of patient (55.79±10.52) year. Perception has correlation with quality of life influenced by index value on treatment control (6.73±1.475) and emotional response (3.11±2.199) and by visual analog scale on understanding (5.99±1.587), duration (6.50±2.968), and personal controls (6.20±1.641). Based on the results obtained to improve the quality of life of T2DM patients that is on the index value on the control of treatment and emotional response and on visual analog scale on the understanding, duration and personal control should be changed so that the quality of life of patients increases. The family history, social status and type of treatment factors also affect the quality of life.

  6. Assessing soil hydrological variability at the cm- to dm-scale using air permeameter measurements

    Science.gov (United States)

    Beerten, K.; Vandersmissen, N.; Rogiers, B.; Mallants, D.

    2012-04-01

    , regardless the transfer function used, are within 10% (logKs) from perfect correlation. However, it is not clear yet which transfer function would best fit to the data: both show a slight systematic offset of ca. 5% (logKs) from the line of perfect agreement. Reasons for the observed discrepancies can be differences in measurement scale (5-10 times smaller for the air permeameter compared to constant head core samples) and possibly effects of the soil's saturation degree. Despite the small but systematic offset, we conclude that field based air permeametry is a relatively cheap, quick and reliable method to map the spatial variability of saturated hydraulic conductivity in heterogeneous soil profiles.

  7. The economic impact of insulin-related hypoglycemia in Denmark

    DEFF Research Database (Denmark)

    Hoskins, Nicki; Tikkanen, Christian Klyver; Pedersen-Bjergaard, Ulrik

    2017-01-01

    AIMS: To estimate the direct cost of hypoglycemia in insulin-treated adults with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in Denmark. MATERIALS AND METHODS: The Local Impact of Hypoglycemia Tool (LIHT) was used to estimate the costs associated with insulin-related hypoglycemia. Average...

  8. Dynamic usage of transcription start sites within core promoters

    DEFF Research Database (Denmark)

    Kawaji, Hideya; Frith, Martin C; Katayama, Shintaro

    2006-01-01

    BACKGROUND: Mammalian promoters do not initiate transcription at single, well defined base pairs, but rather at multiple, alternative start sites spread across a region. We previously characterized the static structures of transcription start site usage within promoters at the base pair level......, based on large-scale sequencing of transcript 5' ends. RESULTS: In the present study we begin to explore the internal dynamics of mammalian promoters, and demonstrate that start site selection within many mouse core promoters varies among tissues. We also show that this dynamic usage of start sites...... is associated with CpG islands, broad and multimodal promoter structures, and imprinting. CONCLUSION: Our results reveal a new level of biologic complexity within promoters--fine-scale regulation of transcription starting events at the base pair level. These events are likely to be related to epigenetic...

  9. In vitro transcription of a torsionally constrained template

    DEFF Research Database (Denmark)

    Bentin, Thomas; Nielsen, Peter E

    2002-01-01

    RNA polymerase (RNAP) and the DNA template must rotate relative to each other during transcription elongation. In the cell, however, the components of the transcription apparatus may be subject to rotary constraints. For instance, the DNA is divided into topological domains that are delineated...... of torsionally constrained DNA by free RNAP. We asked whether or not a newly synthesized RNA chain would limit transcription elongation. For this purpose we developed a method to immobilize covalently closed circular DNA to streptavidin-coated beads via a peptide nucleic acid (PNA)-biotin conjugate in principle...... constrained. We conclude that transcription of a natural bacterial gene may proceed with high efficiency despite the fact that newly synthesized RNA is entangled around the template in the narrow confines of torsionally constrained supercoiled DNA....

  10. Detecting Differential Transcription Factor Activity from ATAC-Seq Data

    Directory of Open Access Journals (Sweden)

    Ignacio J. Tripodi

    2018-05-01

    Full Text Available Transcription factors are managers of the cellular factory, and key components to many diseases. Many non-coding single nucleotide polymorphisms affect transcription factors, either by directly altering the protein or its functional activity at individual binding sites. Here we first briefly summarize high-throughput approaches to studying transcription factor activity. We then demonstrate, using published chromatin accessibility data (specifically ATAC-seq, that the genome-wide profile of TF recognition motifs relative to regions of open chromatin can determine the key transcription factor altered by a perturbation. Our method of determining which TFs are altered by a perturbation is simple, is quick to implement, and can be used when biological samples are limited. In the future, we envision that this method could be applied to determine which TFs show altered activity in response to a wide variety of drugs and diseases.

  11. Is gene transcription involved in seed dry after-ripening?

    Directory of Open Access Journals (Sweden)

    Patrice Meimoun

    Full Text Available Orthodox seeds are living organisms that survive anhydrobiosis and may display dormancy, an inability to germinate at harvest. Seed germination potential can be acquired during a prolonged period of dry storage called after-ripening. The aim of this work was to determine if gene transcription is an underlying regulatory mechanism for dormancy alleviation during after-ripening. To identify changes in gene transcription strictly associated with the acquisition of germination potential but not with storage, we used seed storage at low relative humidity that maintains dormancy as control. Transcriptome profiling was performed using DNA microarray to compare change in gene transcript abundance between dormant (D, after-ripened non-dormant (ND and after-ripened dormant seeds (control, C. Quantitative real-time polymerase chain reaction (qPCR was used to confirm gene expression. Comparison between D and ND showed the differential expression of 115 probesets at cut-off values of two-fold change (p<0.05. Comparisons between both D and C with ND in transcript abundance showed that only 13 transcripts, among 115, could be specific to dormancy alleviation. qPCR confirms the expression pattern of these transcripts but without significant variation between conditions. Here we show that sunflower seed dormancy alleviation in the dry state is not related to regulated changes in gene expression.

  12. Data supporting characterization of CLIC1, CLIC4, CLIC5 and DmCLIC antibodies and localization of CLICs in endoplasmic reticulum of cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Devasena Ponnalagu

    2016-06-01

    Full Text Available Chloride intracellular channel (CLICs proteins show 60–70% sequence identity to each other, and exclusively localize to the intracellular organelle membranes and cytosol. In support of our recent publication, “Molecular identity of cardiac mitochondrial chloride intracellular channel proteins” (Ponnalagu et al., 2016 [1], it was important to characterize the specificity of different CLIC paralogs/ortholog (CLIC1, CLIC4, CLIC5 and DmCLIC antibodies used to decipher their localization in cardiac cells. In addition, localization of CLICs in the other organelles such as endoplasmic reticulum (ER of cardiomyocytes was established. This article also provides data on the different primers used to show the relative abundance of CLIC paralogs in cardiac tissue and the specificity of the various CLIC antibodies used. We demonstrate that the predominant CLICs in the heart, namely CLIC1, CLIC4 and CLIC5, show differential distribution in endoplasmic reticulum. CLIC1 and CLIC4 both show co-localization to the endoplasmic reticulum whereas CLIC5 does not.

  13. The Expression of Activating Receptor Gene of Natural Killer Cells (KLRC3 in Patients with Type 1 Diabetes Mellitus (T1DM

    Directory of Open Access Journals (Sweden)

    Dalia Shalaby

    2017-07-01

    Full Text Available Objectives: To identify the possible role of natural killer (NK cells in the pathogenesis of type 1 diabetes mellitus (T1DM through studying the expression of the KLRC3 gene, which encodes the NK cell activating receptor (NKG2E. Methods: This study was conducted at Alexandria University Children’s Hospital from April to October 2015. The study was conducted with 30 newly diagnosed T1DM patients (15 males and 15 females, aged 7–13 years (10.6±1.8 years and 20 non-diabetic subjects served as age- and sex-matched controls. The patients were further sub-divided into two groups; group I included patients who first presented with classical symptoms of DM (polyuria, polydipsia, and polyphagia without diabetes ketoacidosis (DKA and group II included patients who first presented with DKA. The expression of the KLRC3 gene was measured in each group using the real-time polymerase chain reaction. Results: KLRC3 gene expression was significantly downregulated in T1DM cases compared to healthy controls (p = 0.001. Expression was more downregulated in group I patients (p = 0.008. Moreover, there was higher mean value of glycated heamoglobin and lower C-peptide levels in group I than group II. Serum pancreatic amylase showed no significant difference between the two groups. Conclusions: KLRC3 gene expression was downregulated in patients with T1DM compared to healthy controls. Downregulation of expression was greater in DKA patients compared to those who presented with classical symptoms. Expression of KLRC3 in T1DM might play a role in the pathogenesis of T1DM and could be a predictor of its severity.

  14. The Expression of Activating Receptor Gene of Natural Killer Cells (KLRC3) in Patients with 
Type 1 Diabetes Mellitus (T1DM)

    Science.gov (United States)

    Shalaby, Dalia; Saied, Marwa; Khater, Doaa; Abou Zeid, Abla

    2017-01-01

    Objectives To identify the possible role of natural killer (NK) cells in the pathogenesis of type 1 diabetes mellitus (T1DM) through studying the expression of the KLRC3 gene, which encodes the NK cell activating receptor (NKG2E). Methods This study was conducted at Alexandria University Children’s Hospital from April to October 2015. The study was conducted with 30 newly diagnosed T1DM patients (15 males and 15 females), aged 7–13 years (10.6±1.8 years) and 20 non-diabetic subjects served as age- and sex-matched controls. The patients were further sub-divided into two groups; group I included patients who first presented with classical symptoms of DM (polyuria, polydipsia, and polyphagia) without diabetes ketoacidosis (DKA) and group II included patients who first presented with DKA. The expression of the KLRC3 gene was measured in each group using the real-time polymerase chain reaction. Results KLRC3 gene expression was significantly downregulated in T1DM cases compared to healthy controls (p = 0.001). Expression was more downregulated in group I patients (p = 0.008). Moreover, there was higher mean value of glycated heamoglobin and lower C-peptide levels in group I than group II. Serum pancreatic amylase showed no significant difference between the two groups. Conclusions KLRC3 gene expression was downregulated in patients with T1DM compared to healthy controls. Downregulation of expression was greater in DKA patients compared to those who presented with classical symptoms. Expression of KLRC3 in T1DM might play a role in the pathogenesis of T1DM and could be a predictor of its severity. PMID:28804584

  15. Transcriptional regulation of hepatic lipogenesis.

    Science.gov (United States)

    Wang, Yuhui; Viscarra, Jose; Kim, Sun-Joong; Sul, Hei Sook

    2015-11-01

    Fatty acid and fat synthesis in the liver is a highly regulated metabolic pathway that is important for very low-density lipoprotein (VLDL) production and thus energy distribution to other tissues. Having common features at their promoter regions, lipogenic genes are coordinately regulated at the transcriptional level. Transcription factors, such as upstream stimulatory factors (USFs), sterol regulatory element-binding protein 1C (SREBP1C), liver X receptors (LXRs) and carbohydrate-responsive element-binding protein (ChREBP) have crucial roles in this process. Recently, insights have been gained into the signalling pathways that regulate these transcription factors. After feeding, high blood glucose and insulin levels activate lipogenic genes through several pathways, including the DNA-dependent protein kinase (DNA-PK), atypical protein kinase C (aPKC) and AKT-mTOR pathways. These pathways control the post-translational modifications of transcription factors and co-regulators, such as phosphorylation, acetylation or ubiquitylation, that affect their function, stability and/or localization. Dysregulation of lipogenesis can contribute to hepatosteatosis, which is associated with obesity and insulin resistance.

  16. Structural insights into transcription complexes

    NARCIS (Netherlands)

    Berger, I.; Blanco, A.G.; Boelens, R.; Cavarelli, J.; Coll, M.; Folkers, G.E.; Nie, Y.; Pogenberg, V.; Schultz, P.; Wilmanns, M.; Moras, D.; Poterszman, A.

    2011-01-01

    Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of

  17. Transcription factor-based biosensor

    Science.gov (United States)

    Dietrich, Jeffrey A; Keasling, Jay D

    2013-10-08

    The present invention provides for a system comprising a BmoR transcription factor, a .sigma..sup.54-RNA polymerase, and a pBMO promoter operatively linked to a reporter gene, wherein the pBMO promoter is capable of expression of the reporter gene with an activated form of the BmoR and the .sigma..sup.54-RNA polymerase.

  18. Aproveitamento de subproduto industrial de óleos vegetais para produção de riboflavina por Candida guilliermondii DM 644 Utilization industrial waste from vegetal oils riboflavine production by candida guilliermondii DM 644

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes Andrade Pessoa

    2003-12-01

    Full Text Available A produção e consumo de alimentos industrializados têm aumentado a preocupação com suplementação e enriquecimento de alimentos com vitaminas e sais minerais, visando repor as possíveis perdas durante os processos de fabricação, principalmente das vitaminas hidrossolúveis, mais especificamente da vitamina B2 ou riboflavina. Assim sendo, a proposta deste trabalho foi utilizar como componente principal do meio, para produção da riboflavina, um subproduto do refino de óleos vegetais e o microrganismo Candida guillermondii DM 644. A produção da vitamina B2 foi realizada por fermentação em batelada utilizando Erlenmeyer. As condições empregadas foram agitação orbital, ausência de luz, 30°C, e 24h de incubação. A otimização da produção de riboflavina foi realizada através de Delineamento Fatorial Fracionário, para avaliar os efeitos da concentração de matéria graxa, fonte de nitrogênio, pH, velocidade de agitação, fonte de fósforo e extrato de levedura e as possíveis interações. A concentração máxima de riboflavina foi 19,12mg/mL. Os fatores mais importantes para produção de riboflavina foram a concentração de matéria graxa e a fonte de nitrogênio, enquanto que a fonte de fósforo e o extrato de leveduras não estimularam sua biossíntese. A máxima produção foi obtida com matéria graxa a 10g/L, uréia a 2,5g/L e pH 5,0. A velocidade de agitação (200 e 400rpm não interferiu no processo biotecnológico.The ever growing production and consumption of industrialized foods have increased the concern about supplementation and enrichment of food with vitamins and minerals, attempting the replenishment of the possible losses during their production processes, mainly the hydrosoluble vitamins, more specifically B2 vitamin or riboflavin. A subproduct of vegetal oil refining and the microorganism Candida guilliermondii DM 644 were used as the main substrate. The vitamin B2 was produced by the batch

  19. Omeprazole induces NAD(P)H quinone oxidoreductase 1 via aryl hydrocarbon receptor-independent mechanisms: Role of the transcription factor nuclear factor erythroid 2–related factor 2

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shaojie; Patel, Ananddeep; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2015-11-13

    Activation of the aryl hydrocarbon receptor (AhR) transcriptionally induces phase I (cytochrome P450 (CYP) 1A1) and phase II (NAD(P)H quinone oxidoreductase 1 (NQO1) detoxifying enzymes. The effects of the classical and nonclassical AhR ligands on phase I and II enzymes are well studied in human hepatocytes. Additionally, we observed that the proton pump inhibitor, omeprazole (OM), transcriptionally induces CYP1A1 in the human adenocarcinoma cell line, H441 cells via AhR. Whether OM activates AhR and induces the phase II enzyme, NAD(P)H quinone oxidoreductase 1 (NQO1), in fetal primary human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce NQO1 in HPMEC via the AhR. The concentrations of OM used in our experiments did not result in cytotoxicity. OM activated AhR as evident by increased CYP1A1 mRNA expression. However, contrary to our hypothesis, OM increased NQO1 mRNA and protein via an AhR-independent mechanism as AhR knockdown failed to abrogate OM-mediated increase in NQO1 expression. Interestingly, OM activated Nrf2 as evident by increased phosphoNrf2 (S40) expression in OM-treated compared to vehicle-treated cells. Furthermore, Nrf2 knockdown abrogated OM-mediated increase in NQO1 expression. In conclusion, we provide evidence that OM induces NQO1 via AhR-independent, but Nrf2-dependent mechanisms. - Highlights: • We investigated whether omeprazole induces NQO1 in human fetal lung cells. • Omeprazole induces the phase II enzyme, NQO1, in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of NQO1. • Omeprazole increases phosphoNrf2 (S40) protein expression in human fetal lung cells. • Nrf2 knockdown abrogates the induction of NQO1 by omeprazole in human lung cells.

  20. The Constellation of Macrovascular Risk Factors in Early Onset T2DM: A Cross-Sectional Study in Xinjiang Province, China

    Directory of Open Access Journals (Sweden)

    Mingchen Zhang

    2018-01-01

    Full Text Available Background. Despite a rapid popular of early onset type 2 diabetes (defined as diagnosis at <40 years old recently, there is a lack of studies on this population in economically undeveloped area. We aimed to investigate the risk factors of macrovascular complications in the early onset T2DM patients in Xinjiang, China. Methods. A cross-sectional survey of 1736 consecutive patients with T2DM was conducted. Macrovascular complications and risk factors were documented. Another nondiabetic population matched with age and sex was as a control group. Logistic regression analysis was performed to obtain odds ratios (OR for macrovascular complications in early and late onset T2DM, respectively. Results. The final analysis consisted of 1036 late onset and 219 early onset T2DM patients. The mean HbA1c in the early onset group was higher than that in the late onset group (9.1 ± 2.4% versus 8.3 ± 2.2%, P=0.039 despite a higher proportion of patients in the early onset group receiving insulin treatment (73.1% versus 58.7%, P<0.001. Compared to the control, early onset patients had higher blood pressure and worse lipid profiles (all P<0.01. More than half of the early onset T2DM patients already had macro- and microvascular complications, despite of their young age (39.5 ± 10.8 and short DM duration (6.6 ± 8.0. In the early onset group, women had a ~3-fold hazard of atherosclerotic plaques compared with men (OR 3.22, 95% CI 1.53–6.78. Conclusions. Patients with early onset T2DM have worse glycemic control and higher burden of atherogenic risk factors. The prevalence of macro- and microvascular complications is astonishingly high in these young adults with T2DM. Moreover, young women with T2DM are more susceptible to cardiovascular complications than their male counterpart.

  1. 22 CFR 1500.9 - Transcripts, recording of closed meetings.

    Science.gov (United States)

    2010-04-01

    ..., closed to the public. (b) The Foundation, after review by the General Counsel, shall make promptly... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Transcripts, recording of closed meetings. 1500.9 Section 1500.9 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION SUNSHINE REGULATIONS § 1500.9...

  2. Ranges of control in the transcriptional regulation of Escherichia coli.

    Science.gov (United States)

    Sonnenschein, Nikolaus; Hütt, Marc-Thorsten; Stoyan, Helga; Stoyan, Dietrich

    2009-12-24

    The positioning of genes in the genome is an important evolutionary degree of freedom for organizing gene regulation. Statistical properties of these distributions have been studied particularly in relation to the transcriptional regulatory network. The systematics of gene-gene distances then become important sources of information on the control, which different biological mechanisms exert on gene expression. Here we study a set of categories, which has to our knowledge not been analyzed before. We distinguish between genes that do not participate in the transcriptional regulatory network (i.e. that are according to current knowledge not producing transcription factors and do not possess binding sites for transcription factors in their regulatory region), and genes that via transcription factors either are regulated by or regulate other genes. We find that the two types of genes ("isolated" and "regulatory" genes) show a clear statistical repulsion and have different ranges of correlations. In particular we find that isolated genes have a preference for shorter intergenic distances. These findings support previous evidence from gene expression patterns for two distinct logical types of control, namely digital control (i.e. network-based control mediated by dedicated transcription factors) and analog control (i.e. control based on genome structure and mediated by neighborhood on the genome).

  3. Transcriptional network systems in cartilage development and disease.

    Science.gov (United States)

    Nishimura, Riko; Hata, Kenji; Nakamura, Eriko; Murakami, Tomohiko; Takahata, Yoshifumi

    2018-04-01

    Transcription factors play important roles in the regulation of cartilage development by controlling the expression of chondrogenic genes. Genetic studies have revealed that Sox9/Sox5/Sox6, Runx2/Runx3 and Osterix in particular are essential for the sequential steps of cartilage development. Importantly, these transcription factors form network systems that are also required for appropriate cartilage development. Molecular cloning approaches have largely contributed to the identification of several transcriptional partners for Sox9 and Runx2 during cartilage development. Although the importance of a negative-feedback loop between Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP) in chondrocyte hypertrophy has been well established, recent studies indicate that several transcription factors interact with the Ihh-PTHrP loop and demonstrated that Ihh has multiple functions in the regulation of cartilage development. The most common cartilage disorder, osteoarthritis, has been reported to result from the pathological action of several transcription factors, including Runx2, C/EBPβ and HIF-2α. On the other hand, NFAT family members appear to play roles in the protection of cartilage from osteoarthritis. It is also becoming important to understand the homeostasis and regulation of articular chondrocytes, because they have different cellular and molecular features from chondrocytes of the growth plate. This review summarizes the regulation and roles of transcriptional network systems in cartilage development and their pathological roles in osteoarthritis.

  4. Metagenomic screening for aromatic compound-responsive transcriptional regulators.

    Directory of Open Access Journals (Sweden)

    Taku Uchiyama

    Full Text Available We applied a metagenomics approach to screen for transcriptional regulators that sense aromatic compounds. The library was constructed by cloning environmental DNA fragments into a promoter-less vector containing green fluorescence protein. Fluorescence-based screening was then performed in the presence of various aromatic compounds. A total of 12 clones were isolated that fluoresced in response to salicylate, 3-methyl catechol, 4-chlorocatechol and chlorohydroquinone. Sequence analysis revealed at least 1 putative transcriptional regulator, excluding 1 clone (CHLO8F. Deletion analysis identified compound-specific transcriptional regulators; namely, 8 LysR-types, 2 two-component-types and 1 AraC-type. Of these, 9 representative clones were selected and their reaction specificities to 18 aromatic compounds were investigated. Overall, our transcriptional regulators were functionally diverse in terms of both specificity and induction rates. LysR- and AraC- type regulators had relatively narrow specificities with high induction rates (5-50 fold, whereas two-component-types had wide specificities with low induction rates (3 fold. Numerous transcriptional regulators have been deposited in sequence databases, but their functions remain largely unknown. Thus, our results add valuable information regarding the sequence-function relationship of transcriptional regulators.

  5. Isolated guitar transcription using a deep belief network

    Directory of Open Access Journals (Sweden)

    Gregory Burlet

    2017-03-01

    Full Text Available Music transcription involves the transformation of an audio recording to common music notation, colloquially referred to as sheet music. Manually transcribing audio recordings is a difficult and time-consuming process, even for experienced musicians. In response, several algorithms have been proposed to automatically analyze and transcribe the notes sounding in an audio recording; however, these algorithms are often general-purpose, attempting to process any number of instruments producing any number of notes sounding simultaneously. This paper presents a polyphonic transcription algorithm that is constrained to processing the audio output of a single instrument, specifically an acoustic guitar. The transcription system consists of a novel note pitch estimation algorithm that uses a deep belief network and multi-label learning techniques to generate multiple pitch estimates for each analysis frame of the input audio signal. Using a compiled dataset of synthesized guitar recordings for evaluation, the algorithm described in this work results in an 11% increase in the f-measure of note transcriptions relative to Zhou et al.’s (2009 transcription algorithm in the literature. This paper demonstrates the effectiveness of deep, multi-label learning for the task of polyphonic transcription.

  6. Evaluation of new alternatives in wastewater treatment plants based on dynamic modelling and life cycle assessment (DM-LCA).

    Science.gov (United States)

    Bisinella de Faria, A B; Spérandio, M; Ahmadi, A; Tiruta-Barna, L

    2015-11-01

    With a view to quantifying the energy and environmental advantages of Urine Source-Separation (USS) combined with different treatment processes, five wastewater treatment plant (WWTP) scenarios were compared to a reference scenario using Dynamic Modelling (DM) and Life Cycle Assessment (LCA), and an integrated DM-LCA framework was thus developed. Dynamic simulations were carried out in BioWin(®) in order to obtain a realistic evaluation of the dynamic behaviour and performance of plants under perturbation. LCA calculations were performed within Umberto(®) using the Ecoinvent database. A Python™ interface was used to integrate and convert simulation data and to introduce them into Umberto(®) to achieve a complete LCA evaluation comprising foreground and background processes. Comparisons between steady-state and dynamic simulations revealed the importance of considering dynamic aspects such as nutrient and flow peaks. The results of the evaluation highlighted the potential of the USS scenario for nutrient recovery whereas the Enhanced Primary Clarification (EPC) scenario gave increased biogas production and also notably decreased aeration consumption, leading to a positive energy balance. Both USS and EPC scenarios also showed increased stability of plant operation, with smaller daily averages of total nitrogen and phosphorus. In this context, USS and EPC results demonstrated that the coupled USS + EPC scenario and its combinations with agricultural spreading of N-rich effluent and nitritation/anaerobic deammonification could present an energy-positive balance with respectively 27% and 33% lower energy requirements and an increase in biogas production of 23%, compared to the reference scenario. The coupled scenarios also presented lesser environmental impacts (reduction of 31% and 39% in total endpoint impacts) along with effluent quality well within the specified limits. The marked environmental performance (reduction of global warming) when nitrogen is used

  7. Resveratrol Ameliorates Dysregulation of Th1, Th2, Th17, and T Regulatory Cell-Related Transcription Factor Signaling in a BTBR T + tf/J Mouse Model of Autism.

    Science.gov (United States)

    Bakheet, Saleh A; Alzahrani, Mohammad Zeed; Ansari, Mushtaq Ahmad; Nadeem, Ahmed; Zoheir, Khairy M A; Attia, Sabry M; Al-Ayadhi, Laila Yousef; Ahmad, Sheikh Fayaz

    2017-09-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder. It is characterized by impaired social communication, abnormal social interactions, and repetitive behaviors and/or restricted interests. BTBR T + tf/J (BTBR) inbred mice are commonly used as a model for ASD. Resveratrol is used widely as a beneficial therapeutic in the treatment of an extensive array of pathologies, including neurodegenerative diseases. In the present study, the effect of resveratrol administration (20 and 40 mg/kg) was evaluated in both BTBR and C57BL/6 (B6) mice. Behavioral (self-grooming), Foxp3, T-bet, GATA-3, RORγt, and IL-17A in CD4 + T cells were assessed. Our study showed that BTBR control mice exhibited a distinct immune profile from that of the B6 control mice. BTBR mice were characterized by lower levels of Foxp3 + and higher levels of RORγt + , T-bet + , and GATA-3 + production in CD4 + T cells when compared with B6 control. Resveratrol (20 and 40 mg/kg) treatment to B6 and BTBR mice showed substantial induction of Foxp3 + and reduction of T-bet + , GATA-3 + , and IL-17A + expression in CD4 + cells when compared with the respective control groups. Moreover, resveratrol treatment resulted in upregulated expression of Foxp3 mRNA and decreased expression levels of T-bet, GATA-3, RORγt, and IL-17A in the spleen and brain tissues. Western blot analysis confirmed that resveratrol treatment decreased the protein expression of T-bet, GATA-3, RORγ, and IL-17 and that it increased Foxp3 in B6 and BTBR mice. Our results suggest that autism is associated with dysregulation of transcription factor signaling that can be corrected by resveratrol treatment.

  8. Alternative staffing services. Contract transcription.

    Science.gov (United States)

    Tessier, C

    1992-03-01

    Contract medical transcription services can be of great assistance in meeting the demands for transcription, without jeopardizing patient, physician, or institutional confidentiality. You simply must require the contract service to provide at least the same degree of protection and preservation of confidentiality that you should require inhouse. To achieve this you must make these requirements explicit, comprehensive, comprehensible, believable, and enforceable. Discuss the requirements with prospective contractors. Review them at least annually with existing contractors and when contracts are due for renewal. Be sure to specify the consequence of breaching confidentiality, and if there are breaches, enforce the terms of the contract. Consult your institution's legal counsel both in developing the contract and in enforcing its provisions. Take into consideration your department's and institution's policies, AHIMA's statement on confidentiality, as well as local, state, and federal laws. Above all, never lose sight of the patient. Ultimately, it is not patient information that you are obligated to protect. It is the patient.

  9. First search for a dark matter annual modulation signal with NaI(Tl) in the Southern Hemisphere by DM-Ice17

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa de Souza, E.; Cherwinka, J.; Cole, A.; Ezeribe, A. C.; Grant, D.; Halzen, F.; Heeger, K. M.; Hsu, L.; Hubbard, A. J. F.; Jo, J. H.; Karle, A.; Kauer, M.; Kudryavtsev, V. A.; Lim, K. E.; Macdonald, C.; Maruyama, R. H.; Mouton, F.; Paling, S. M.; Pettus, W.; Pierpoint, Z. P.; Reilly, B. N.; Robinson, M.; Rogers, F. R.; Sandstrom, P.; Scarff, A.; Spooner, N. J. C.; Telfer, S.; Yang, L.

    2017-02-28

    The first search for a dark matter annual modulation signal with NaI(Tl) target material in the Southern Hemisphere conducted with the DM-Ice17 experiment is presented. DM-Ice17 consists of 17 kg of NaI(Tl) scintillating crystal under 2200 m.w.e. overburden of Antarctic glacial ice. The analysis presented here utilizes a 60.8 kg yr exposure. While unable to exclude the signal reported by DAMA/LIBRA, the DM-Ice17 data are consistent with no modulation in the energy range of 4-20 keV, providing the strongest limits on WIMP candidates from a direct detection experiment located in the Southern Hemisphere. Additionally, the successful deployment and stable operation of 17 kg of NaI(Tl) crystal over 3.5 years establishes the South Pole ice as a viable location for future underground, low-background experiments.

  10. The post-transcriptional operon

    DEFF Research Database (Denmark)

    Tenenbaum, Scott A.; Christiansen, Jan; Nielsen, Henrik

    2011-01-01

    model (PTO) is used to describe data from an assortment of methods (e.g. RIP-Chip, CLIP-Chip, miRNA profiling, ribosome profiling) that globally address the functionality of mRNA. Several examples of post-transcriptional operons have been documented in the literature and demonstrate the usefulness...... of the model in identifying new participants in cellular pathways as well as in deepening our understanding of cellular responses....

  11. Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

    Science.gov (United States)

    Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran

    2017-02-01

    Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  12. RNA sequence analyses of r-Moj-DM treated cells: TXNIP is required to induce apoptosis of SK-Mel-28.

    Science.gov (United States)

    McBride, Terri D; Andrew, U; Ly, Nicko; Soto, Julio G

    2016-10-01

    RNA sequencing of untreated and r-Moj-DM treated SK-Mel-28 cells was performed after 6 h, to begin unraveling the apoptotic pathway induced by r-Moj-DM. Bioinformatic analyses of RNA sequencing data yielded 40 genes that were differentially expressed. Nine genes were upregulated and 31 were downregulated. qRT-PCR was used to validate differential expression of 13 genes with known survival or apoptotic-inducing activities. Expression of BNiP3, IGFBP3, PTPSF, Prune 2, TGF-ß, and TXNIP were compared from cells treated with r-Moj-DN (a strong apoptotic inducer) or r-Moj-DA (a non-apoptotic inducer) for 1 h, 2 h, 4 h, and 6 h after treatment. Our results demonstrate that significant differences in expression are only detected after 4 h of treatment. In addition, expression of TXNIP (an apoptotic inducer) remains elevated at 4 h and 6 h only in r-Moj-DN treated cells. Based on the consistency of elevated TXNIP expression, we further studied TXNIP as a novel target of disintegrin activation. Confocal microscopy of anti-TXNIP stained SK-Mel-28 cells suggests nuclear localization of TXNIP after r-Moj-DM treatment. A stable TXNIP knockdown SK-Mel-28 cell line was produced to test TXNIP' role in the apoptotic induction by r-Moj-DM. High cell viability (74.3% ±9.1) was obtained after r-Moj-DM treatment of TXNIP knocked down SK-Mel-28 cells, compared to 34% ±0.187 for untransduced cells. These results suggest that TXNIP is required early in the apoptotic-inducing pathway resulting from r-Moj-DM binding to the αv integrin subunit. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Efficient calculation of open quantum system dynamics and time-resolved spectroscopy with distributed memory HEOM (DM-HEOM).

    Science.gov (United States)

    Kramer, Tobias; Noack, Matthias; Reinefeld, Alexander; Rodríguez, Mirta; Zelinskyy, Yaroslav

    2018-06-11

    Time- and frequency-resolved optical signals provide insights into the properties of light-harvesting molecular complexes, including excitation energies, dipole strengths and orientations, as well as in the exciton energy flow through the complex. The hierarchical equations of motion (HEOM) provide a unifying theory, which allows one to study the combined effects of system-environment dissipation and non-Markovian memory without making restrictive assumptions about weak or strong couplings or separability of vibrational and electronic degrees of freedom. With increasing system size the exact solution of the open quantum system dynamics requires memory and compute resources beyond a single compute node. To overcome this barrier, we developed a scalable variant of HEOM. Our distributed memory HEOM, DM-HEOM, is a universal tool for open quantum system dynamics. It is used to accurately compute all experimentally accessible time- and frequency-resolved processes in light-harvesting molecular complexes with arbitrary system-environment couplings for a wide range of temperatures and complex sizes. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  14. TREX-DM: a low-background Micromegas-based TPC for low-mass WIMP detection

    Energy Technology Data Exchange (ETDEWEB)

    Iguaz, F.J.; Garza, J.G.; Castel, J.F.; Cebrian, S.; Dafni, T.; Garcia, J.A.; Irastorza, I.G.; Lagraba, A.; Luzon, G.; Peiro, A. [Universidad de Zaragoza, Grupo de Fisica Nuclear y Astroparticulas, Zaragoza (Spain); Aznar, F. [Universidad de Zaragoza, Grupo de Fisica Nuclear y Astroparticulas, Zaragoza (Spain); Universidad de Zaragoza, Centro Universitario de la Defensa, Zaragoza (Spain)

    2016-10-15

    If Dark Matter is made of Weakly Interacting Massive Particles (WIMPs) with masses below ∝20 GeV, the corresponding nuclear recoils in mainstream WIMP experiments are of energies too close, or below, the experimental threshold. Gas Time Projection Chambers (TPCs) can be operated with a variety of target elements, offer good tracking capabilities and, on account of the amplification in gas, very low thresholds are achievable. Recent advances in electronics and in novel radiopure TPC readouts, especially micro-mesh gas structure (Micromegas), are improving the scalability and low-background prospects of gaseous TPCs. Here we present TREX-DM, a prototype to test the concept of a Micromegas-based TPC to search for low-mass WIMPs. The detector is designed to host an active mass of ∝0.300 kg of Ar at 10 bar, or alternatively ∝0.160 kg of Ne at 10 bar, with an energy threshold below 0.4 keVee, and is fully built with radiopure materials. We will describe the detector in detail, the results from the commissioning phase on surface, as well as a preliminary background model. The anticipated sensitivity of this technique may go beyond current experimental limits for WIMPs of masses of 2-8 GeV. (orig.)

  15. INTEGRATED DM 1200 MELTER TESTING OF HLW C-106/AY-102 COMPOSITION USING BUBBLERS VSL-03R3800-1 REV 0 9/15/03

    Energy Technology Data Exchange (ETDEWEB)

    KRUGER AA; MATLACK KS; GONG W; BARDAKCI T; D' ANGELO NA; KOT WK; PEGG IL

    2011-12-29

    This report documents melter and off-gas performance results obtained on the DM1200 HLW Pilot Melter during processing of simulated HLW C-106/AY-102 feed. The principal objectives of the DM1200 melter testing were to determine the achievable glass production rates for simulated HLW C-106/AY-102 feed; determine the effect of bubbling rate on production rate; characterize melter off-gas emissions; characterize the performance of the prototypical off-gas system components as well as their integrated performance; characterize the feed, glass product, and off-gas effluents; and to perform pre- and post test inspections of system components.

  16. Integrated DM 1200 Melter Testing Of HLW C-106/AY-102 Composition Using Bubblers VSL-03R3800-1, Rev. 0, 9/15/03

    International Nuclear Information System (INIS)

    Kruger, A.A.; Matlack, K.S.; Kot, W.K.; Bardakci, T.; Gong, W.; D'Angelo, N.A.; Pegg, I.L.

    2011-01-01

    This report documents melter and off-gas performance results obtained on the DM1200 HLW Pilot Melter during processing of simulated HLW C-106/AY-102 feed. The principal objectives of the DM1200 melter testing were to determine the achievable glass production rates for simulated HLW C-106/AY-102 feed; determine the effect of bubbling rate on production rate; characterize melter off-gas emissions; characterize the performance of the prototypical off-gas system components as well as their integrated performance; characterize the feed, glass product, and off-gas effluents; and to perform pre- and post test inspections of system components.

  17. Mutual interdependence of splicing and transcription elongation.

    Science.gov (United States)

    Brzyżek, Grzegorz; Świeżewski, Szymon

    2015-01-01

    Transcription and splicing are intrinsically linked, as splicing needs a pre-mRNA substrate to commence. The more nuanced view is that the rate of transcription contributes to splicing regulation. On the other hand there is accumulating evidence that splicing has an active role in controlling transcription elongation by DNA-dependent RNA polymerase II (RNAP II). We briefly review those mechanisms and propose a unifying model where splicing controls transcription elongation to provide an optimal timing for successive rounds of splicing.

  18. Interplay between DNA supercoiling and transcription elongation.

    Science.gov (United States)

    Ma, Jie; Wang, Michelle

    2014-01-01

    Transcription-coupled DNA supercoiling has been shown to be an important regulator of transcription that is broadly present in the cell. Here we review experimental work which shows that RNA polymerase is a powerful torsional motor that can alter DNA topology and structure, and DNA supercoiling in turn directly affects transcription elongation.

  19. Type 1 Diabetes Mellitus Case Decisions: Health-Related Service Considerations for School Psychologists

    Science.gov (United States)

    Schmitt, Ara J.; Wodrich, David L.; Lazar, Susan

    2010-01-01

    Type 1 diabetes mellitus (T1DM) is a chronic illness that can impact learning and often requires medical management in the school setting. School psychologists must therefore be knowledgeable of special service eligibility criteria associated with T1DM, the health-related services often required of such students, and what health-related services…

  20. Directing traffic on DNA-How transcription factors relieve or induce transcriptional interference.

    Science.gov (United States)

    Hao, Nan; Palmer, Adam C; Dodd, Ian B; Shearwin, Keith E

    2017-03-15

    Transcriptional interference (TI) is increasingly recognized as a widespread mechanism of gene control, particularly given the pervasive nature of transcription, both sense and antisense, across all kingdoms of life. Here, we discuss how transcription factor binding kinetics strongly influence the ability of a transcription factor to relieve or induce TI.

  1. Emergence of the mass discrepancy-acceleration relation from dark matter-baryon interactions

    Science.gov (United States)

    Famaey, Benoit; Khoury, Justin; Penco, Riccardo

    2018-03-01

    The observed tightness of the mass discrepancy-acceleration relation (MDAR) poses a fine-tuning challenge to current models of galaxy formation. We propose that this relation could arise from collisional interactions between baryons and dark matter (DM) particles, without the need for modification of gravity or ad hoc feedback processes. We assume that these interactions satisfy the following three conditions: (i) the relaxation time of DM particles is comparable to the dynamical time in disk galaxies; (ii) DM exchanges energy with baryons due to elastic collisions; (iii) the product between the baryon-DM cross section and the typical energy exchanged in a collision is inversely proportional to the DM number density. As a proof of principle, we present an example of a particle physics model that gives a DM-baryon cross section with the desired density and velocity dependence. For consistency with direct detection constraints, our DM particles must be either very light (m ll mb) or very heavy (mgg mb), corresponding respectively to heating and cooling of DM by baryons. In both cases, our mechanism applies and an equilibrium configuration can in principle be reached. In this exploratory paper, we focus on the heavy DM/cooling case because it is technically simpler, since the average energy exchanged turns out to be approximately constant throughout galaxies. Under these assumptions, we find that rotationally-supported disk galaxies could naturally settle to equilibrium configurations satisfying a MDAR at all radii without invoking finely tuned feedback processes. We also discuss issues related to the small scale clumpiness of baryons, as well as predictions for pressure-supported systems. We argue in particular that galaxy clusters do not follow the MDAR despite being DM-dominated because they have not reached their equilibrium configuration. Finally, we revisit existing phenomenological, astrophysical and cosmological constraints on baryon-DM interactions in light

  2. Inferring Molecular Processes Heterogeneity from Transcriptional Data.

    Science.gov (United States)

    Gogolewski, Krzysztof; Wronowska, Weronika; Lech, Agnieszka; Lesyng, Bogdan; Gambin, Anna

    2017-01-01

    RNA microarrays and RNA-seq are nowadays standard technologies to study the transcriptional activity of cells. Most studies focus on tracking transcriptional changes caused by specific experimental conditions. Information referring to genes up- and downregulation is evaluated analyzing the behaviour of relatively large population of cells by averaging its properties. However, even assuming perfect sample homogeneity, different subpopulations of cells can exhibit diverse transcriptomic profiles, as they may follow different regulatory/signaling pathways. The purpose of this study is to provide a novel methodological scheme to account for possible internal, functional heterogeneity in homogeneous cell lines, including cancer ones. We propose a novel computational method to infer the proportion between subpopulations of cells that manifest various functional behaviour in a given sample. Our method was validated using two datasets from RNA microarray experiments. Both experiments aimed to examine cell viability in specific experimental conditions. The presented methodology can be easily extended to RNA-seq data as well as other molecular processes. Moreover, it complements standard tools to indicate most important networks from transcriptomic data and in particular could be useful in the analysis of cancer cell lines affected by biologically active compounds or drugs.

  3. Influence of CSN1S2 protein from Caprine milk Etawah Breed (EB) on histology of microglial cells in rat (Rattus norvegicus) Type-2 diabetes mellitus (T2DM)

    Science.gov (United States)

    Rika, Margareth; Fatchiyah

    2017-11-01

    Type-2 diabetes mellitus (T2DM) is a degenerative disease that causes an imbalance in the metabolism. The aim of this research is to determine the influences of CSN1S2 on the structure of microglial cells in T2DM. Rats (Rattus norvegicus) were divided into eight groups of treatment with looping three times each between treatment groups (CM) Control. The control is given a milk treatment with doses of 375 mg/kg (CM375), 750 mg/kg (CM750), and 1500 mg/kg (CM1500), T2DM (DMK), and T2DM with CSN1S2 375 mg/kg dose (DM375), 750mg/kg (DM750), and 1500 mg/kg (DM1500). The animal model T2DM was induced by a high-fat diet in the form of feed followed by injection of STZ (dose of 25 mg/kg of animal treatment) and treatment of CSN1S2 for 28 days. Brain organs were taken and analysed in histopathology stained by Hematoxylin-eosin (HE) and observed using Olympus BX53. Based on the results, it was concluded that CSN1S2 protein is influential for induction of microglial cell proliferation in animal models of T2DM, as immunity responds to the inflammatory condition in T2DM.

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

    Science.gov (United States)

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

    2016-01-01

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

  5. Optimizing the calculation of DM,CO and VC via the single breath single oxygen tension DLCO/NO method.

    Science.gov (United States)

    Coffman, Kirsten E; Taylor, Bryan J; Carlson, Alex R; Wentz, Robert J; Johnson, Bruce D

    2016-01-15

    Alveolar-capillary membrane conductance (D(M,CO)) and pulmonary-capillary blood volume (V(C)) are calculated via lung diffusing capacity for carbon monoxide (DL(CO)) and nitric oxide (DL(NO)) using the single breath, single oxygen tension (single-FiO2) method. However, two calculation parameters, the reaction rate of carbon monoxide with blood (θ(CO)) and the D(M,NO)/D(M,CO) ratio (α-ratio), are controversial. This study systematically determined optimal θ(CO) and α-ratio values to be used in the single-FiO2 method that yielded the most similar D(M,CO) and V(C) values compared to the 'gold-standard' multiple-FiO2 method. Eleven healthy subjects performed single breath DL(CO)/DL(NO) maneuvers at rest and during exercise. D(M,CO) and V(C) were calculated via the single-FiO2 and multiple-FiO2 methods by implementing seven θ(CO) equations and a range of previously reported α-ratios. The RP θ(CO) equation (Reeves, R.B., Park, H.K., 1992. Respiration Physiology 88 1-21) and an α-ratio of 4.0-4.4 yielded DM,CO and VC values that were most similar between methods. The RP θ(CO) equation and an experimental α-ratio should be used in future studies. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Reducing Glucose Variability Due to Meals and Postprandial Exercise in T1DM Using Switched LPV Control: In Silico Studies.

    Science.gov (United States)

    Colmegna, Patricio H; Sánchez-Peña, Ricardo S; Gondhalekar, Ravi; Dassau, Eyal; Doyle, Francis J

    2016-05-01

    Time-varying dynamics is one of the main issues for achieving safe blood glucose control in type 1 diabetes mellitus (T1DM) patients. In addition, the typical disturbances considered for controller design are meals, which increase the glucose level, and physical activity (PA), which increases the subject's sensitivity to insulin. In previous works the authors have applied a linear parameter-varying (LPV) control technique to manage unannounced meals. A switched LPV controller that switches between 3 LPV controllers, each with a different level of aggressiveness, is designed to further cope with both unannounced meals and postprandial PA. Thus, the proposed control strategy has a "standard" mode, an "aggressive" mode, and a "conservative" mode. The "standard" mode is designed to be applied most of the time, while the "aggressive" mode is designed to deal only with hyperglycemia situations. On the other hand, the "conservative" mode is focused on postprandial PA control. An ad hoc simulator has been developed to test the proposed controller. This simulator is based on the distribution version of the UVA/Padova model and includes the effect of PA based on Schiavon.(1) The test results obtained when using this simulator indicate that the proposed control law substantially reduces the risk of hypoglycemia with the conservative strategy, while the risk of hyperglycemia is scarcely affected. It is demonstrated that the announcement, or anticipation, of exercise is indispensable for letting a mono-hormonal artificial pancreas deal with the consequences of postprandial PA. In view of this the proposed controller allows switching into a conservative mode when notified of PA by the user. © 2016 Diabetes Technology Society.

  7. The Journey of a Transcription Factor

    DEFF Research Database (Denmark)

    Pireyre, Marie

    Plants have developed astonishing networks regulating their metabolism to adapt to their environment. The complexity of these networks is illustrated by the expansion of families of regulators such as transcription factors in the plant kingdom. Transcription factors specifically impact...... transcriptional networks by integrating exogenous and endogenous stimuli and regulating gene expression accordingly. Regulation of transcription factors and their activation is thus highly important to modulate the transcriptional programs and increase fitness of the plant in a given environment. Plant metabolism....... The biosynthetic machinery of GLS is governed by interplay of six MYB and three bHLH transcription factors. MYB28, MYB29 and MYB76 regulate methionine-derived GLS, and MYB51, MYB34 and MYB122 regulate tryptophan-derived GLS. The three bHLH transcription factors MYC2, MYC3 and MYC4 physically interact with all six...

  8. Effect of combined Jiqi hypoglycemic tablet conventional western medicine treatment on plasma ET-1 and sICAM-1 levels in patients with DM2

    International Nuclear Information System (INIS)

    Xu Jun; Qi Falian; Wang Bing; Ke Bingshen; Chen Yingjian; Yin Qiuxia

    2006-01-01

    Objective: To investigate the clinical beneficial effect of Jiqi hypoglycemic tablet on lowering the plasma ET-1 and soluble intercellular adhesion molecule-1 (sICAM-1) levels in patients with DM2. Methods: Plasma ET-1 and sICAM-1 levels were determined with ELISA in 30 patients with DM2 randomly selected to be treated with conventional western only medicine and 30 other DM2 patients selected to be treated with additional Jiqi hypoglycemic tablet both before and after 3 months' treatment. The blood sugar level, HbAlc percentage and lipid test (cholesterol, triglyceride, HDL, LDL) were also examined. Results: Blood sugar levels decreased significantly after 3 months' treatment in both groups. However, favorable changes of levels of other parameters (HbAlc, TC, TG, HDL, LDL, ET-1, sICAM-1) were demonstrated only in the patients treated with combined Jiqi hypoglycemic tablet and conventional western medicine (P<0.05 or P<0.01). Conclusion: Additional Jiqi hypoglycemic tablet might be desirable for the treatment of DM2 patients, especially due to the possible protection on vascular endothelium through lowering of the plasma ET-1 and sICAM-1 levels. (authors)

  9. Impact of faecal DM excretion on faecal calcium losses in dogs eating complete moist and dry pet foods - food digestibility is a major determinant of calcium requirements.

    Science.gov (United States)

    Kienzle, Ellen; Brenten, Thomas; Dobenecker, Britta

    2017-01-01

    The recommendations for the Ca supply for maintenance of dogs have been reduced by about 75 % in the last decades. An important factor for Ca requirements is faecal Ca losses. In previous studies with experimental diets faecal Ca losses depended on Ca intake and on faecal DM excretion. A predictive equation for faecal Ca losses in mg/kg body weight (BW) developed in a fibre model is: faecal losses = -33·8 + (13·6 faecal DM excretion (g/kg BW)) + (0·78 Ca intake (mg/kg BW)). The present study aimed at testing this equation in pet food with material from trials carried out for other purposes. Digestion trials with twenty-five dry and fifteen moist foods (326 observations in total) were evaluated retrospectively. Faecal DM excretion and faecal Ca losses were significantly correlated ( r 2  0·86; P  losses in a practical feeding situation. In conclusion, Ca requirements for maintenance may vary with food DM intake and digestibility.

  10. Repression of Meiotic Genes by Antisense Transcription and by Fkh2 Transcription Factor in Schizosaccharomyces pombe

    OpenAIRE

    Chen, Huei-Mei; Rosebrock, Adam P.; Khan, Sohail R.; Futcher, Bruce; Leatherwood, Janet K.

    2012-01-01

    In S. pombe, about 5% of genes are meiosis-specific and accumulate little or no mRNA during vegetative growth. Here we use Affymetrix tiling arrays to characterize transcripts in vegetative and meiotic cells. In vegetative cells, many meiotic genes, especially those induced in mid-meiosis, have abundant antisense transcripts. Disruption of the antisense transcription of three of these mid-meiotic genes allowed vegetative sense transcription. These results suggest that antisense transcription ...

  11. Navigating the transcriptional roadmap regulating plant secondary cell wall deposition

    Directory of Open Access Journals (Sweden)

    Steven Grant Hussey

    2013-08-01

    Full Text Available The current status of lignocellulosic biomass as an invaluable resource in industry, agriculture and health has spurred increased interest in understanding the transcriptional regulation of secondary cell wall (SCW biosynthesis. The last decade of research has revealed an extensive network of NAC, MYB and other families of transcription factors regulating Arabidopsis SCW biosynthesis, and numerous studies have explored SCW-related transcription factors in other dicots and monocots. Whilst the general structure of the Arabidopsis network has been a topic of several reviews, they have not comprehensively represented the detailed protein-DNA and protein-protein interactions described in the literature, and an understanding of network dynamics and functionality has not yet been achieved for SCW formation. Furthermore the methodologies employed in studies of SCW transcriptional regulation have not received much attention, especially in the case of non-model organisms. In this review, we have reconstructed the most exhaustive literature-based network representations to date of SCW transcriptional regulation in Arabidopsis. We include a manipulable Cytoscape representation of the Arabidopsis SCW transcriptional network to aid in future studies, along with a list of supporting literature for each documented interaction. Amongst other topics, we discuss the various components of the network, its evolutionary conservation in plants, putative modules and dynamic mechanisms that may influence network function, and the approaches that have been employed in network inference. Future research should aim to better understand network function and its response to dynamic perturbations, whilst the development and application of genome-wide approaches such as ChIP-seq and systems genetics are in progress for the study of SCW transcriptional regulation in non-model organisms.

  12. Rationally designed, heterologous S. cerevisiae transcripts expose novel expression determinants

    Science.gov (United States)

    Ben-Yehezkel, Tuval; Atar, Shimshi; Zur, Hadas; Diament, Alon; Goz, Eli; Marx, Tzipy; Cohen, Rafael; Dana, Alexandra; Feldman, Anna; Shapiro, Ehud; Tuller, Tamir

    2015-01-01

    Deducing generic causal relations between RNA transcript features and protein expression profiles from endogenous gene expression data remains a major unsolved problem in biology. The analysis of gene expression from heterologous genes contributes significantly to solving this problem, but has been heavily biased toward the study of the effect of 5′ transcript regions and to prokaryotes. Here, we employ a synthetic biology driven approach that systematically differentiates the effect of different regions of the transcript on gene expression up to 240 nucleotides into the ORF. This enabled us to discover new causal effects between features in previously unexplored regions of transcripts, and gene expression in natural regimes. We rationally designed, constructed, and analyzed 383 gene variants of the viral HRSVgp04 gene ORF, with multiple synonymous mutations at key positions along the transcript in the eukaryote S. cerevisiae. Our results show that a few silent mutations at the 5′UTR can have a dramatic effect of up to 15 fold change on protein levels, and that even synonymous mutations in positions more than 120 nucleotides downstream from the ORF 5′end can modulate protein levels up to 160%–300%. We demonstrate that the correlation between protein levels and folding energy increases with the significance of the level of selection of the latter in endogenous genes, reinforcing the notion that selection for folding strength in different parts of the ORF is related to translation regulation. Our measured protein abundance correlates notably(correlation up to r = 0.62 (p=0.0013)) with mean relative codon decoding times, based on ribosomal densities (Ribo-Seq) in endogenous genes, supporting the conjecture that translation elongation and adaptation to the tRNA pool can modify protein levels in a causal/direct manner. This report provides an improved understanding of transcript evolution, design principles of gene expression regulation, and suggests simple

  13. Health-related behaviors in women with lifestyle-related diseases.

    Science.gov (United States)

    Kozica, Samantha L; Deeks, Amanda A; Gibson-Helm, Melanie E; Teede, Helena J; Moran, Lisa J

    2012-01-01

    Lifestyle related diseases associated with physical inactivity and poor diet quality, represent a major health burden. This study assessed negative and positive health habits and health care utilization in healthy women (n = 50) and women with lifestyle related diseases such as polycystic ovary syndrome (PCOS) (n = 50), gestational diabetes mellitus (GDM) (n = 44) and type 2 diabetes (DM2) (n = 43). A significant difference existed across groups for negative health habits (P = .012) with a trend for positive health habits (P = .06) elevated in women with PCOS. Women with DM2 had the highest amount of health care utilization including doctors office visits (P women with DM2 but there were no differences in positive health habits across sub-groups. Encouraging lifestyle modification in women with precursor diseases such as GDM and PCOS is vital in order to prevent progression to DM2.

  14. Control of cellulose biosynthesis by overexpression of a transcription factor

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kyung-Hwan; Ko, Jae-Heung; Kim, Won-Chan; Kim; , Joo-Yeol

    2017-05-16

    The invention relates to the over-expression of a transcription factor selected from the group consisting of MYB46, HAM1, HAM2, MYB112, WRKY11, ERF6, and any combination thereof in a plant, which can modulate and thereby modulating the cellulose content of the plant.

  15. Incorporating evolution of transcription factor binding sites into ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    Identifying transcription factor binding sites (TFBSs) is essential to elucidate ... alignments with parts annotated as gap lessly aligned TFBSs (pair-profile hits) are generated. Moreover, the pair- profile related parameters are derived in a sound statistical framework. ... Much research has gone into the study of the evolution of.

  16. E6-associated transcription patterns in human papilloma virus 16-positive cervical tissues.

    Science.gov (United States)

    Lin, Kezhi; Lu, Xulian; Chen, Jun; Zou, Ruanmin; Zhang, Lifang; Xue, Xiangyang

    2015-01-01

    The change in transcription pattern induced by post-transcriptional RNA splicing is an important mechanism in the regulation of the early gene expression of human papilloma virus (HPV). The present study was conducted to establish a method to specifically amplify HPV-16 E6-associated transcripts. The E6-related transcripts from 63 HPV-16-positive cervical tumor tissue samples were amplified, consisting of eight cases of low-risk intraepithelial lesions, 38 cases of high-risk intraepithelial les