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Sample records for tp pz influencia

  1. Influencia de la soldadura sobre la rotura por tensiones en tubos de acero inoxidable austenitico del tipo 18-11NB(TP347

    Directory of Open Access Journals (Sweden)

    Gutiérrez de Saiz-Solabarria, S.

    2000-06-01

    Full Text Available This work has been undertaken to study the stress cracking failure in various 18Cr11Ni [TP347 (18-11Nb, TP 321 (18-11 Ti, TP304 (18-11 and TP316 (18-11-2] types austenitic stainless steel tubes. The material used was produced hot-rolling at 76,2 mm φ (3"φ x 2,54 mm (1/10" thickness. The study was carried out at 593ºC and applied stress of 50 Ton/in2.

    Se estudia el efecto de la soldadura sobre la rotura por tensiones en tubos de acero inoxidable austenítico estabilizado con Nb o Ti de los tipos 18-11Nb (TP 347 y 18-11Ti (TP 321 así como sin estabilizar del tipo 18-11 (TP 304 y con Mo del tipo 18-11-2 (TP 316. Los tubos, en todos los casos, son de dimensiones 76,2 mm (3” φ x 2,54 mm (1/10” de espesor y la tensión aplicada (σ de 10 Ton/in2, para una temperatura de servicio de 593ºC.

  2. Performance of an Ultraviolet Mutagenetic Polyphosphate-Accumulating Bacterium PZ2 and Its Application for Wastewater Treatment in a Newly Designed Constructed Wetland.

    Science.gov (United States)

    Tian, Jiang; Yu, Chenlei; Liu, Jiafeng; Ye, Chaoran; Zhou, Xiangjun; Chen, Lanzhou

    2017-02-01

    Total phosphorus (TP) removal performance and application for wastewater treatment of polyphosphate-accumulating bacteria (PAB) in constructed wetlands (CWs) were investigated. In this study, a novel isolated ultraviolet (UV) mutant PZ2 with phosphate-accumulating ability was screened from domestic wastewater and identified as Pseudomonas putida by 16S ribosomal DNA (rDNA) sequencing analysis. The TP removal performance of PZ2 in the synthetic wastewater reached the highest of 93.95 % within 45 h. Two vertical subsurface flow CWs planted with two aquatic macrophytes Canna indica and Acorus calamus were newly designed. After inoculating PZ2 into two CWs within 45 h, the average chemical oxygen demand (COD), TP, and ammonia-nitrogen (NH 3 -N) removal efficiencies reached 68.50, 60.22, and 66.81 %, respectively. Vegetation type and filter size significantly influenced the TP removal capability of PZ2 in CWs. Meanwhile, considerable qualitative differences were found in the pollutant removal efficiencies of PZ2 with and without CWs in synthetic wastewater. These results could also indicate potential applications of the UV mutagenesis in PAB isolation and the newly designed CWs in wastewater treatments.

  3. Model development and process simulation of postcombustion carbon capture technology with aqueous AMP/PZ solvent

    NARCIS (Netherlands)

    van der Spek, Mijndert; Arendsen, Richard; Ramirez, Andrea; Faaij, André

    2016-01-01

    This study presents the development, application, and uncertainty analysis of a process simulation model for postcombustion CO2 capture with an AMP/PZ solvent blend based on state of the art knowledge on AMP/PZ solvent technology. The development includes the improvement of the physical property

  4. TP Organics - maheuuringute tehnoloogiaplatvorm

    Index Scriptorium Estoniae

    2015-01-01

    TP Organics on 2008. a loodud Euroopa mahepõllumajanduse ja mahetoidu ning vähese sisendiga põllumajanduse tehnoloogiaplatvorm. Platvormi eesmärk on selgitada välja teadustöö ja uuenduste vajadused ning edastada see info poliitikutele

  5. Crystallization and preliminary X-ray crystallographic analysis of Pz peptidase B from Geobacillus collagenovorans MO-1.

    Science.gov (United States)

    Nakano, Hiroaki; Hosokawa, Allin; Tagawa, Ryuji; Inaka, Koji; Ohta, Kazunori; Nakatsu, Toru; Kato, Hiroaki; Watanabe, Kunihiko

    2012-07-01

    Pz peptidase B is an intracellular M3 metallopeptidase that is found together with Pz peptidase A in the thermophile Geobacillus collagenovorans MO-1 and recognizes collagen-specific tripeptide units (-Gly-Pro-X-). These peptidases have low homology in their primary structures; however, their cleavage patterns towards peptide substrates are similar. In this work, Pz peptidase B was crystallized using the counter-diffusion method. Data were collected to a resolution of 1.6 Å at 100 K from a crystal obtained in the Japanese Experiment Module (JEM; also known as `Kibo') at the International Space Station (ISS). The crystal belonged to the trigonal space group P3(1)21, with unit-cell parameters a = b = 87.64, c = 210.5 Å. A complete data set was also obtained from crystals of selenomethionine-substituted protein.

  6. Tp-e interval and Tp-e/QT ratio in patients with Human Immunodeficiency Virus.

    Science.gov (United States)

    Ünal, Sefa; Yayla, Çağrı; Açar, Burak; Ertem, Ahmet G; Akboğa, Mehmet K; Gökaslan, Serkan; Erdöl, Mehmet A; Sönmezer, Meliha Ç; Kaya Kiliç, Esra; Ataman Hatipoğlu, Çiğdem; Tulek, Necla; Erdinç, Fatma S; Aydoğdu, Sinan; Temizhan, Ahmet

    Human Immunodeficiency Virus (HIV) infection and AIDS are known to cause cardiovascular diseases such as premature coronary artery disease, cardiomyopathy, and arrhythmias. Recently, Tp-e interval and Tp-e/QT ratio has been shown as a novel marker of ventricular repolarization. We aimed to evaluate the ventricular repolarization using Tp-e interval and Tp-e/QT ratio in patients with Human Immunodeficiency Virus (HIV) infection. Totally 48 patients with HIV and 60 control subjects were enrolled to the study. Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were significantly higher in patients with HIV than control subjects (all pe interval and disease duration (r=0.298, p=0.048). and inverse correlation between Tp-e interval and CD4 count(r=-0.303, p=0.036). Our study showed that Tp-e interval, Tp-e/QT and Tp-e/QTc ratios were increased in patients with HIV than control subjects. Copyright © 2017. Published by Elsevier Ltd.

  7. Beroepsgroep diëtetiek: gegevensverzameling binnen vrijgevestigde praktijken voor diëtiek (Jaarboek LiPZ 2006 & 2007).

    NARCIS (Netherlands)

    Leemrijse, C.J.; Swinkels, I.C.S.; Veenhof, C.; Bakker, D. de

    2008-01-01

    De cliëntèle van de vrijgevestigde diëtist bestaat voor het grootste deel uit mensen met overgewicht, vaak in combinatie met een andere diagnose. Dit aandeel is sinds 1996 toegenomen, zo blijkt uit het Jaarboek LiPZ, beroepsgroep diëtetiek. Te dik Steeds meer mensen zijn te dik. Maar liefst 69%

  8. On the simultaneous Pell equations x 2 - (4m 2 - 1)y 2 = y 2 - pz 2 ...

    African Journals Online (AJOL)

    Let m be a positive integer, and let p be an odd prime. By using certain properties of Pell and quartic diophantine equations with some elementary number theory methods, we prove that the system of equations x2 - (4m2 - 1)y2 = 1 and y2 - pz2 = 1 has positive integer solutions (x, y, z) if and only if p ≡ 7(mod 8) and m = 1/4 ...

  9. TMACS Test Procedure TP011: Panalarm Interface

    International Nuclear Information System (INIS)

    Seghers, R.; Washburn, S.J.

    1994-01-01

    The TMACS Software Test Procedures translate the project's acceptance criteria into test steps. The TMACS Test Plan (WHC-SD-WM-TP-148) is fulfilled when all Test Cases are approved. This Test Procedure tests the TMACS Panalarm Interface functions

  10. SCPS-TP: A Satellite-Enhanced TCP

    Science.gov (United States)

    Scott, Keith; Torgerson, Leigh

    2004-01-01

    This viewgraph presentation reviews the Space Communications Protocol Standard Transport Protocol (SCPS-TP) which is a satellite enhanced Transport Control Protocol (TCP). The contents include: 1) Purpose; 2) Background; 3) Stressed Communication Environments; 4) SCPS-TP Features; 5) SCPS-TP Performance; 6) Performance Enhancing Proxies (PEPs); and 7) Ongoing and Future SCPS-TP Work.

  11. Tp-e interval and Tp-e/QT ratio in patients with celiac disease.

    Science.gov (United States)

    Demirtaş, K; Yayla, Ç; Yüksel, M; Açar, B; Ünal, S; Ertem, A G; Kaplan, M; Akpinar, M Y; Kiliç, Z M Y; Kayaçetin, E

    2017-11-01

    Celiac disease is a chronic immune-mediated disease of the small intestine. It has been known that dilated cardiomyopathy and ischemic coronary artery disease have become more frequent in patients with celiac disease. The aim of the study was to assess Tp-e interval and Tp-e/QT ratio in patients with celiac disease. This study was conducted at a single center in collaboration with gastroenterology and cardiology clinics. Between January 2014 and June 2015, a total of 76 consecutive patients were enrolled (38 patients with celiac disease and 38 control subjects). Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were measured from the 12-lead electrocardiogram. Tp-e interval (64.2±11.0 vs. 44.5±6.0; pceliac disease than control subjects. There was a significant positive correlation between Tp-e/QTc ratio and disease duration in patients with celiac disease (r=0.480, p=0.003) and also there was a significant positive correlation between Tp-e/QTc ratio and erythrocyte sedimentation rate (r=0.434, pceliac disease. Whether these changes increase the risk of ventricular arrhythmia deserve further studies. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  12. Overexpressed TP73 induces apoptosis in medulloblastoma

    International Nuclear Information System (INIS)

    Castellino, Robert C; De Bortoli, Massimiliano; Lin, Linda L; Skapura, Darlene G; Rajan, Jessen A; Adesina, Adekunle M; Perlaky, Laszlo; Irwin, Meredith S; Kim, John YH

    2007-01-01

    Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth. We analyzed medulloblastoma samples from thirty-four pediatric patients and the established medulloblastoma cell lines, Daoy and D283MED, for expression of TP73 RNA including the full-length transcript and the 5'-terminal variants that encode the ΔNp73 isoform, as well as TP53 RNA using quantitative real time-RTPCR. Protein expression of TAp73 and ΔNp73 was quantitated with immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 protein expression. To determine effects of overexpression or knock-down of TAp73 and ΔNp73 on cell cycle and apoptosis, we analyzed transiently transfected medulloblastoma cell lines with flow cytometric and TUNEL methods. Patient medulloblastoma samples and cell lines expressed full-length and 5'-terminal variant TP73 RNA species in 100-fold excess compared to non-neoplastic brain controls. Western immunoblot analysis confirmed their elevated levels of TAp73 and amino-terminal truncated ΔNp73 proteins. Kaplan-Meier analysis revealed trends toward favorable overall and progression-free survival of patients whose tumors display TAp73 RNA overexpression. Overexpression of TAp73 or ΔNp73 induced apoptosis under basal growth conditions in vitro and sensitized them to cell death in response to

  13. Overexpressed TP73 induces apoptosis in medulloblastoma

    Directory of Open Access Journals (Sweden)

    Perlaky Laszlo

    2007-07-01

    Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth. Methods We analyzed medulloblastoma samples from thirty-four pediatric patients and the established medulloblastoma cell lines, Daoy and D283MED, for expression of TP73 RNA including the full-length transcript and the 5'-terminal variants that encode the ΔNp73 isoform, as well as TP53 RNA using quantitative real time-RTPCR. Protein expression of TAp73 and ΔNp73 was quantitated with immunoblotting methods. Clinical outcome was analyzed based on TP73 RNA and p53 protein expression. To determine effects of overexpression or knock-down of TAp73 and ΔNp73 on cell cycle and apoptosis, we analyzed transiently transfected medulloblastoma cell lines with flow cytometric and TUNEL methods. Results Patient medulloblastoma samples and cell lines expressed full-length and 5'-terminal variant TP73 RNA species in 100-fold excess compared to non-neoplastic brain controls. Western immunoblot analysis confirmed their elevated levels of TAp73 and amino-terminal truncated ΔNp73 proteins. Kaplan-Meier analysis revealed trends toward favorable overall and progression-free survival of patients whose tumors display TAp73 RNA overexpression. Overexpression of TAp73 or ΔNp73 induced apoptosis under basal growth conditions in vitro and

  14. UARS Particle Environment Monitor (PEM) Level 3TP V004 (UARPE3TP) at GES DISC

    Data.gov (United States)

    National Aeronautics and Space Administration — The Particle Environment Monitor (PEM) Level 3TP data product consists of daily, 65.536 second and 2.048 interval time-ordered, vertical profiles of electron and...

  15. The Effect of Chronic Anabolic-Androgenic Steroid Use on Tp-E Interval, Tp-E/Qt Ratio, and Tp-E/Qtc Ratio in Male Bodybuilders.

    Science.gov (United States)

    Alizade, Elnur; Avcı, Anıl; Fidan, Serdar; Tabakçı, Mustafa; Bulut, Mustafa; Zehir, Regayip; Simsek, Zeki; Evlice, Mert; Arslantaş, Uğur; Çakır, Hakan; Emiroglu, Mehmet Yunus; Akçakoyun, Mustafa

    2015-11-01

    The chronic consumption of androgenic anabolic steroids has shown to cause atrial arrhythmias. Several studies have suggested that the interval from the peak to the end of the electrocardiographic T wave (Tp-e) may correspond to the transmural dispersion of repolarization and that increased Tp-e interval and Tp-e/QT ratio are associated with malignant ventricular arrhythmias. The aim of this study was to evaluate repolarization dispersion measured from the 12-lead surface electrocardiogram (including Tp-e interval, Tp-e/QT ratio, and Tp-e/cQT ratio) in bodybuilders who are using anabolic androgenic steroids (AAS). We selected a population of 33 competitive bodybuilders, including 15 actively using AAS for ≥ 2 years (users) and 18 who had never used AAS (nonusers), all men. QT, cQT, QTd, cQTd, JT, and cJT were significantly increased in AAS users bodybulders compared to the nonusers (all P < 0.001). Tp-e interval, Tp-e/QT ratio, and Tp-e/cQT ratio were also significantly higher in AAS user group compared to the nonuser group (all P < 0.001). QRS duration was not different between the groups. There were negative correlation between E(m) and Tp-e, Tp-e/QT ratio, Tp-e/cQT ration (r = -0.657, P < 0.01; r = -0.607, P = 0.02; r = -0.583, P = 0.02; respectively).There were also negative correlation between S(m) and Tp-e, Tp-e/QT ratio, Tp-e/cQT ration (r = -0.681, P < 0.01; r = -0.549, P = 0.03; r = -0.544, P = 0.023; respectively). In conclusion, we have presented a strong evidence suggesting that Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were increased in AAS users, which suggest that there might be a link between AAS use and ventricular arrthymias and sudden death. © 2015 Wiley Periodicals, Inc.

  16. Main - TP Atlas | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...me: tp_atlas_en.zip File URL: ftp://ftp.biosciencedbc.jp/archive/tp_atlas/LATEST/...d License Update History of This Database Site Policy | Contact Us Main - TP Atlas | LSDB Archive ...

  17. Analysis of Tp53 codon 72 polymorphisms, Tp53 mutations, and HPV infection in cutaneous squamous cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Keith R Loeb

    Full Text Available Non-melanoma skin cancers are one of the most common human malignancies accounting for 2-3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas.We studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism.We found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R.These studies suggest there are two separate pathways (HPV infection and Tp53 mutation leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly

  18. Comparative Environmental Life Cycle Assessment of Oxyfuel and Post-combustion Capture with MEA and AMP/PZ - Case Studies from the EDDiCCUT Project

    NARCIS (Netherlands)

    Oreggioni, Gabriel D.; Singh, Bhawna; Hung, Christine Roxanne; Van Der Spek, Mijndert W.; Skagestad, Ragnhild; Eldrup, Nils Henrik; Ramirez, Andrea; Strømman, Anders Hammer

    2017-01-01

    This work presents the results of a comparative life cycle assessment study for three CCS technologies applied to a coal-fired power plant: post-combustion capture with MEA, post combustion capture with AMP/PZ and cryogenic oxy-fuel. This study has been performed in the context of the EDDiCCUT

  19. CO2 Solubility in Electrolyte Solution of Potassium Carbonate with the Addition of Promotor Amines (MDEA-DEA/ PZ-DEA at Various Temperatures

    Directory of Open Access Journals (Sweden)

    Saidah Altway

    2016-12-01

    Full Text Available Carbon dioxide has a huge impact on the increase of greenhouse gas formation causing global warming and climate change. The most effective method to capture CO2 is chemical absorption using potassium carbonate (K2CO3 solution and amines as additive to enhance the absorption rate. CO2 solubilities in 30% of K2CO3 and 5% of the total composition of mixed methyldiethanolamine (MDEA–diethanolamine (DEA / piperazine (PZ-DEA solutions at various temperatures of 303.15-323.15 K and atmospheric pressure are reported. The solubility data were measured using an equilibrium cell apparatus with the N2O analogy method. The E-NRTL model was used to correlate the experimental data accurately. The binary interaction parameters of the model for the CO2-K2CO3-MDEA-DEA-H2O and CO2-K2CO3-PZ-DEA-H2O systems were obtained. The CO2 physical solubility in 30% of K2CO3, 5% of PZ, and 0% of DEA at 303.15 K had the highest value, while the Henry constant of CO2 in this solution had the lowest value. The CO2 loading increased with increasing partial pressure of CO2, while the CO2 solubility decreased with increasing temperature. Any increase in MDEA concentration from 0% to 5% enhanced the CO2 partial pressure, otherwise, an increase in PZ concentration from 0% to 5% decreased the CO2 partial pressure.

  20. Analysis list: TP53 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available TP53 Blood,Bone,Breast,Digestive tract,Epidermis,Others,Pluripotent stem cell + hg19 http:...//dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/TP53.1.tsv http://dbarchive.biosciencedbc.jp/kyushu...-u/hg19/target/TP53.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/target/TP53.10.tsv http://dbarchiv...e.biosciencedbc.jp/kyushu-u/hg19/colo/TP53.Blood.tsv,http://dbarchive.bioscienced...bc.jp/kyushu-u/hg19/colo/TP53.Bone.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/colo/TP53.Breast.tsv,http:

  1. TP53 gene status affects survival in advanced mycosis fungoides

    Directory of Open Access Journals (Sweden)

    Gitte Wooler

    2016-11-01

    Full Text Available TP53 is frequently mutated in different types of neoplasms including leukemia and lymphomas. Mutations of TP53 have also been reported in mycosis fungoides (MF, the most common type of cutaneous lymphoma. However, little is known about the frequency, spectrum of mutations and their prognostic significance in MF. In this study we have optimized the protocol for Sanger sequencing of TP53 using DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from patients with stage IIB MF or higher, 31% harboured mutations in TP53. Overall survival of the patients with mutated TP53 was significantly shorter than median survival in the age- and stage-matched patients treated in our Institution. Distribution of mutations was heterogenous in TP53 exons, however C>T transitions were common suggesting the causal role of ultraviolet radiation. We propose that TP53 mutation status would be useful for risk stratification of patients with advanced MF.

  2. New recombinant T. pallidum antigens Tp0453 and Tp0319 in the diagnostics of syphilis

    Directory of Open Access Journals (Sweden)

    A. V. Runina

    2014-01-01

    Full Text Available A new technology for obtaining a recombinant version of a new dedicated protein T. pallidum Tp0319 for the serological diagnostics of syphilis was gene engineered. As a result, a homogeneous (according to denaturating polyacrylamide gel electrophoresis recombinant version of T. pallidum Tp0319 protein was obtained. The molecular mass of recombinant T. pallidum Tp0319 protein according to electrophoretic mobility is about 37 kDa, which corresponds to the molecular mass of a fragment of Tp0319 protein without a signal peptide calculated based on the amino-acid sequence (37.3 kDa. According to the developed technology, purified recombinant T. pallidum Tp0319 and Tp0453 proteins were obtained. The proteins were used as antigens as a part of a solid-phase immunoadsorbent for detecting specific IgG to the study protein in the serum of patients suffering from different types of acquired syphilis. The use of the resulting recombinant protein enabled the authors to reveal T. pallidum antibodies in the blood serum in patients suffering from syphilis (primary, secondary, latent early and late stage syphilis. The examination of blood serum samples taken from healthy donors revealed no antibodies. Based on the study results, it is possible to make a conclusion about the possibility to use the resulting recombinant protein (Тр0319 as an extra antigen for diagnostics of syphilis. The introduction of the new antigen in the immunoadsorbent for test systems used for diagnosing syphilis (in the form of immune-enzyme assay, immunoblotting or immune chips expands the potential of serological diagnostics of this disease due to the expansion of the range of T. pallidum antibodies to be revealed.

  3. Alternative electrode placement in (automatic) sleep scoring (Fpz-Cz/Pz-Oz versus C4-A1).

    Science.gov (United States)

    van Sweden, B; Kemp, B; Kamphuisen, H A; Van der Velde, E A

    1990-06-01

    The purpose of this study is to investigate whether the international standard electrode placement (C4-A1) can be replaced by an alternative placement (Fpz-Cz/Pz-Oz) in an automatic sleep monitoring system without losing Rechtschaffen and Kales (R-K) balances. Single night-sleep polygraphic recordings of 10 patients, screened in a clinical sleep disorder setting, were recorded simultaneously with both placements, and visual sleep classification was performed separately by two independent observers. Interobserver and interplacement agreement were evaluated by way of average (dis)agreement matrices and kappa values computed for overall and individual stage scoring. Interobserver agreement for both the test and the standard electrode placements and interplacement agreement for both observers were assessed as fair to good or excellent. Scoring differences were evaluated by the rank sign test applied to clinical and theoretical difference scores. It appears that the interplacement differences are about equal to the interobserver differences, except for a slight tendency for sleep to be scored in a deeper stage with the proposed alternative placement. The data are presented and discussed in relation to current literature concepts.

  4. Charge transfer in collision of H+ with Li(1s22s,2pz) : TD-MADNESS approach.

    Science.gov (United States)

    Dominguez, F. Javier; Krstic, Predrag S.

    We study state-resolved charge transfer processes for H + collisions with atomic neutral lithium, in its ground and first excited state, in range from 1 to 25 keV/amu. We solve numerically the time-dependent Schrodinger equation (TDSE), using TD-MADNESS, Time-Dependent version of the Multiresolution Adaptive Numerical Environment for Scientific Simulation. An advantage of the MADNESS is that the desired local accuracy is input parameter to the calculation and the method adapts the multiresolution representation of the wavelets to obtain this accuracy. By working with the numerical mesh which adapts to the gradient of the potential, quite large numerical boxes can be used within realistic computing times. The large size numerical box in MADNESS enables accurate representations of the Rydberg states and continuum, usually a problem in other TDSE methods. The time evolution is modeled by the Chin-Chen representation of the evolution operator. The atomic Li target is modeled by frozen-core pseudo-potential while the ion projectile follows a straight line trajectory. We report new benchmark data for charge transfer cross section to n =2, and 3 states of H from 1s22s and 1s22pz of Li. Available theoretical and experimental data in the literature are in reasonable agreement with our results. Research supported by CONACyT postdoctoral scholarship.

  5. Prolonged Tp-e Interval, Tp-e/QT Ratio and Tp-e/QTc Ratio in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Alptug Tokatli

    2016-03-01

    Full Text Available BackgroundType 2 diabetes mellitus (T2DM is associated with increased risk of malignant ventricular arrhythmias. Cardiac electrical inhomogeneity may be the leading cause of the increased arrhythmic risk in patients with T2DM. The peak and the end of the T wave (Tp-e interval and associated Tp-e/QT ratio are promising measures of ventricular repolarization indicating transmural dispersion of repolarization. The aim of this study was to assess ventricular repolarization in patients with T2DM by using Tp-e interval, Tp-e/QT ratio and Tp-e/corrected QT interval (QTc ratio.MethodsForty-three patients with T2DM and 43 healthy control subjects, matched by gender and age, were studied. All participants underwent electrocardiography (ECG recording. PR, RR and QT intervals represents the ECG intervals. These are not abbreviations. In all literature these ECG intervals are written like in this text. Tp-e intervals were measured from 12-lead ECG. Rate QTc was calculated by using the Bazett's formula. Tp-e/QT ratio and Tp-e/QTc ratio were also calculated.ResultsMean Tp-e interval was significantly prolonged in patients with T2DM compared to controls (79.4±10.3, 66.4±8.1 ms, respectively; P<0.001. We also found significantly higher values of Tp-e/QT ratio and Tp-e/QTc ratio in patients with diabetes than controls (0.21±0.03, 0.17±0.02 and 0.19±0.02, 0.16±0.02, respectively; P<0.001. There was no difference in terms of the other ECG parameters between the groups.ConclusionTp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio were prolonged in patients with T2DM. We concluded that T2DM leads to augmentation of transmural dispersion of repolarization suggesting increased risk for ventricular arrhythmogenesis.

  6. Protein - TP Atlas | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available switchLanguage; BLAST Search Image Search Home About Archive Update History Data ...p_atlas_protein.zip File URL: ftp://ftp.biosciencedbc.jp/archive/tp_atlas/LATEST/...story of This Database Site Policy | Contact Us Protein - TP Atlas | LSDB Archive ...

  7. Bioinformatics and phylogenetic analysis of human Tp73 gene ...

    African Journals Online (AJOL)

    The Tp73 gene encoding p73 protein belongs to the Tp53 gene family and it functions in the initiation of cell-cycle arrest or apoptosis and also involves in regulating a series of pathways including breast cancer, neuroblastoma and cholorectal cancer. New discoveries about the control and function of p73 are still in progress ...

  8. Clear Plaque Mutants of Lactococcal Phage TP901-1

    DEFF Research Database (Denmark)

    Kot, Witold; Kilstrup, Mogens; Vogensen, Finn K.

    2016-01-01

    We report a method for obtaining turbid plaques of the lactococcal bacteriophage TP901-1 and its derivative TP901-BC1034. We have further used the method to isolate clear plaque mutants of this phage. Analysis of 8 such mutants that were unable to lysogenize the host included whole genome...... protein involved in the DNA binding. The conclusion is that cI is the only gene involved in clear plaque formation i.e. the CI protein is the determining factor for the lysogenic pathway and its maintenance in the lactococcal phage TP901-1....

  9. Biophysical and Bioinformatic Analyses Implicate the Treponema pallidum Tp34 Lipoprotein (Tp0971) in Transition Metal Homeostasis

    Science.gov (United States)

    Brautigam, Chad A.; Deka, Ranjit K.; Ouyang, Zhiming; Machius, Mischa; Knutsen, Gregory; Tomchick, Diana R.

    2012-01-01

    Metal ion homeostasis is a critical function of many integral and peripheral membrane proteins. The genome of the etiologic agent of syphilis, Treponema pallidum, is compact and devoid of many metabolic enzyme genes. Nevertheless, it harbors genes coding for homologs of several enzymes that typically require either iron or zinc. The product of the tp0971 gene of T. pallidum, designated Tp34, is a periplasmic lipoprotein that is thought to be tethered to the inner membrane of this organism. Previous work on a water-soluble (nonacylated) recombinant version of Tp34 established that this protein binds to Zn2+, which, like other transition metal ions, stabilizes the dimeric form of the protein. In this study, we employed analytical ultracentrifugation to establish that four transition metal ions (Ni2+, Co2+, Cu2+, and Zn2+) readily induce the dimerization of Tp34; Cu2+ (50% effective concentration [EC50] = 1.7 μM) and Zn2+ (EC50 = 6.2 μM) were the most efficacious of these ions. Mutations of the crystallographically identified metal-binding residues hindered the ability of Tp34 to dimerize. X-ray crystallography performed on crystals of Tp34 that had been incubated with metal ions indicated that the binding site could accommodate the metals examined. The findings presented herein, coupled with bioinformatic analyses of related proteins, point to Tp34's likely role in metal ion homeostasis in T. pallidum. PMID:23042995

  10. UARS Particle Environment Monitor (PEM) Level 3TP V001

    Data.gov (United States)

    National Aeronautics and Space Administration — The Particle Environment Monitor (PEM) Level 3TP data product consists of daily, 65.536 second and 2.048 interval time-ordered, vertical profiles of electron and...

  11. TP53 Modulates Oxidative Stress in Gata1+ Erythroid Cells

    Directory of Open Access Journals (Sweden)

    Ashley C. Kramer

    2017-02-01

    Full Text Available Metabolism of oxidative stress is necessary for cellular survival. We have previously utilized the zebrafish as a model of the oxidative stress response. In this study, we found that gata1-expressing erythroid cells contributed to a significant proportion of total-body oxidative stress when animals were exposed to a strong pro-oxidant. RNA-seq of zebrafish under oxidative stress revealed the induction of tp53. Zebrafish carrying tp53 with a mutation in its DNA-binding domain were acutely sensitive to pro-oxidant exposure and displayed significant reactive oxygen species (ROS and tp53-independent erythroid cell death resulting in an edematous phenotype. We found that a major contributing factor to ROS was increased basal mitochondrial respiratory rate without reserve. These data add to the concept that tp53, while classically a tumor suppressor and cell-cycle regulator, has additional roles in controlling cellular oxidative stress.

  12. License - TP Atlas | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available might be changed without notice. About This Database Database Description Download License Update History of This Database Site Policy | Contact Us License - TP Atlas | LSDB Archive ...

  13. TP53 Mutations in Nonsmall Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Akira Mogi

    2011-01-01

    Full Text Available The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC and nonsmall cell lung cancer (NSCLC. The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

  14. High pressure solubility of carbon dioxide (CO2) in aqueous solution of piperazine (PZ) activated N-methyldiethanolamine (MDEA) solvent for CO2 capture

    Science.gov (United States)

    Khan, Saleem Nawaz; Hailegiorgis, Sintayehu Mekuria; Man, Zakaria; Shariff, Azmi Mohd

    2017-10-01

    In this study, the solubility of carbon dioxide (CO2) in the aqueous solution of piperazine (PZ) activated N-methyldiethanolamine (MDEA) was investigated. In the aqueous solution the concentrations of the N-methyldiethanolamine (MDEA) and piperazine (PZ) were kept constant at 30 wt. % and 3 wt. %, respectively. The solubility experiments were carried out between the temperatures ranges of 303.15 to 333.15 K. The pressure range was selected as 2-50 bar for solubility of carbon dioxide in the aqueous solution. The solubility of the CO2 is reported in terms of CO2 loading capacity of the solvent. The loading capacity of the solvent is the ratio between the numbers of moles of CO2 absorbed to the numbers of moles of solvent used. The experimental data showed that the CO2 loading increased with increase in CO2 partial pressure, while it decreased with increase in system's temperature. It was also observed from the experimental data that the higher pressure favors the absorption process while the increased temperature hinders the absorption process of CO2 capture. The loading capacity of the investigated solvent was compared with the loading capacity of the solvents reported in the literature. The investigated solvent showed better solubility in terms of loading capacity.

  15. TP53 and Beta-catenin mutations in liver tumours

    Directory of Open Access Journals (Sweden)

    Pierre Hainaut

    2007-02-01

    Full Text Available

    HBV and HCV play key roles in the etiopathogenesis of Hepatocellular carcinoma (HCC . Studies mostly based on cases from Western countries suggest distinct genetic pathways of carcinogenesis involving either TP53 or CTTNB1 mutations. Inappropriate reactivation of Wnt pathway due to mutations in CTNNB1 (Beta-Catenin gene itself is also frequently reported. Mutant Beta-catenin escapes to ubiquitination and down regulation by GSK3-B, it accumulates and trans-activates variety of oncogenes involved in neoplasmic transformation mimicking Wnt pathway activation. Taking into consideration viral infection, chromosome instability and TP53 /Beta-catenin alterations, Laurent-Puig et al. described two distinct HCC profiles in a serie of 137 HCC cases , the first one associates HBV infection with frequent chromosomal alteration and distributes with TP53 mutations, the second would be observed in HBV negative large sized tumors and distributes with Beta-catenin mutations. We have investigated the status of HBV and HCV infections and of genetic alterations in TP53 and CTTNB1 in 26 patients with HCC from Thailand. In tumours, HBV DNA was found in 19 cases (73% and HCV RNA in 4 cases (15.4% cases, 3 of whom were co-infected. Among the 19 HBV positive cases, sequencing of S gene showed genotype C in 82% and genotype B in 18%. Furthermore, 5/19 cases were negative for HBsAg and were categorized as occult HBV infections. TP53 mutations were detected in 9 cases (34,6% including 7 mutations at codon 249 (AGG to AGT, arginine to serine, considered as ";fingerprint"; of mutagenesis by aflatoxin metabolites. All cases with 249ser mutation had overt HBV infection.

    CTNNB1 mutations were found in 6/26 cases (23%, 4 of whom also had TP53 mutation. There was no significant association between CTTNB1

  16. Number of rare germline CNVs and TP53 mutation types.

    Science.gov (United States)

    Silva, Amanda G; Achatz, Isabel Maria W; Krepischi, Ana Cv; Pearson, Peter L; Rosenberg, Carla

    2012-12-21

    The Li-Fraumeni syndrome (LFS), an inherited rare cancer predisposition syndrome characterized by a variety of early-onset tumors, is caused by different highly penetrant germline mutations in the TP53 gene; each separate mutation has dissimilar functional and phenotypic effects, which partially clarifies the reported heterogeneity between LFS families. Increases in copy number variation (CNV) have been reported in TP53 mutated individuals, and are also postulated to contribute to LFS phenotypic variability. The Brazilian p.R337H TP53 mutation has particular functional and regulatory properties that differ from most other common LFS TP53 mutations, by conferring a strikingly milder phenotype. We compared the CNV profiles of controls, and LFS individuals carrying either p.R337H or DNA binding domain (DBD) TP53 mutations by high resolution array-CGH. Although we did not find any significant difference in the frequency of CNVs between LFS patients and controls, our data indicated an increased proportion of rare CNVs per genome in patients carrying DBD mutations compared to both controls (p=0.0002***) and p.R337H (0.0156*) mutants. The larger accumulation of rare CNVs in DBD mutants may contribute to the reported anticipation and severity of the syndrome; likewise the fact that p.R337H individuals do not present the same magnitude of rare CNV accumulation may also explain the maintenance of this mutation at relatively high frequency in some populations.

  17. Number of rare germline CNVs and TP53 mutation types

    Directory of Open Access Journals (Sweden)

    Silva Amanda G

    2012-12-01

    Full Text Available Abstract Background The Li-Fraumeni syndrome (LFS, an inherited rare cancer predisposition syndrome characterized by a variety of early-onset tumors, is caused by different highly penetrant germline mutations in the TP53 gene; each separate mutation has dissimilar functional and phenotypic effects, which partially clarifies the reported heterogeneity between LFS families. Increases in copy number variation (CNV have been reported in TP53 mutated individuals, and are also postulated to contribute to LFS phenotypic variability. The Brazilian p.R337H TP53 mutation has particular functional and regulatory properties that differ from most other common LFS TP53 mutations, by conferring a strikingly milder phenotype. Methods We compared the CNV profiles of controls, and LFS individuals carrying either p.R337H or DNA binding domain (DBD TP53 mutations by high resolution array-CGH. Results Although we did not find any significant difference in the frequency of CNVs between LFS patients and controls, our data indicated an increased proportion of rare CNVs per genome in patients carrying DBD mutations compared to both controls (p=0.0002*** and p.R337H (0.0156* mutants. Conclusions The larger accumulation of rare CNVs in DBD mutants may contribute to the reported anticipation and severity of the syndrome; likewise the fact that p.R337H individuals do not present the same magnitude of rare CNV accumulation may also explain the maintenance of this mutation at relatively high frequency in some populations.

  18. ¿Efecto o influencia televisiva?

    Directory of Open Access Journals (Sweden)

    Marcia de la Flor Arbulú

    1986-06-01

    Full Text Available Deslindar los conceptos de Efecto e Influencia en el impacto de la observación de T.V., y adscribir cada término a las áreas de investigación sobre el tema, así como a un Modelo de Comunicación, es el objetivo del presente artículo.

  19. Los mecanismos de influencia en el liderazgo

    OpenAIRE

    Arango Cardona, Patricia

    2016-01-01

    Este trabajo tiene como objetivo fundamental identificar las tácticas de influencia que utiliza el señor Carlos Pérez, gerente y socio principal de G. & M., en su trato cotidiano con sus colaboradores, así como la reacción de estos últimos ante dichas tácticas.

  20. Analisis Jaringan VPN Menggunakan PPTP dan L2TP

    Directory of Open Access Journals (Sweden)

    Syariful Ikhwan

    2017-08-01

    Full Text Available VPN adalah teknologi yang membuat jaringan private (pribadi dengan menggunakan jaringan publik agar proses pertukaran data menjadi aman. Teknologi VPN biasanya diterapkan untuk koneksi antara kantor pusat dan kantor cabang. Dinhubkominfo Kabupaten Banyumas sebagai tempat penelitian memiliki beberapa kantor cabang (SKPD. Data yang dipertukarkan antar kantor cabang pada Dinhubkominfo terdiri dari beberapa jenis, namun pada penelitian ini hanya difokuskan pada pertukaran layanan FTP. Teknologi vpn yang saat ini digunakan pada jaringan Dinhubkominfo adalah PPTP. Akan tetapi, penggunaan teknologi tersebut belum tersebut masih belum diketahui tingkat performansi jaringan dibandingkan dengan penggunaan teknologi vpn yang lain. Pada penelitian ini akan dibandingkan penggunaan dua teknologi vpn yang berbeda yaitu antara PPTP dan L2TP, dimana parameter yang digunakan adalah throughput, delay, jitter, dan packet loss. Proses pengambilan data dilakukan dengan menambahkan beban trafik sebesar 512 kbps, 1024 kbps, dan 2048 kbps. Dari hasil penelitian diperoleh data bahwa, rata-rata nilai Delay pada L2TP lebih besar hingga 41% dibanding saat menggunakan PPTP, rata-rata Throughput PPTP naik hingga 34% dibandingkan L2TP, Rata-rata Jitter pada PPTP lebih besar hingga 44% dibandingkan L2TP, sedangkan packet loss yang terjadi pada masing-masing layanan vpn adalah 0

  1. TP53 codon 72 polymorphism in pigmentary phenotypes

    Indian Academy of Sciences (India)

    2012-01-20

    Jan 20, 2012 ... 85 validated polymorphisms described for the human TP53 gene that can directly or indirectly influence the ... pro-opiomelanocortin (POMC) gene in human keratinocytes. (Cui et al. 2007). http://www.ias.ac.in/ ..... development of human papilloma-virus-associated cancer. Nature 393 229–234. Sucheston L ...

  2. Phylogenetic analysis of human Tp53 gene using computational ...

    African Journals Online (AJOL)

    The TP53 gene encoding p53 protein is involved in regulating a series of pathways. New discoveries about the function and control of p53 are still in progress and it is hoped to develop better therapeutics and diagnostics by exploiting this system. Evolutionary studies are of prime importance in the field of biological ...

  3. Bioinformatics and phylogenetic analysis of human Tp73 gene

    African Journals Online (AJOL)

    Imtiaz

    2013-06-26

    Jun 26, 2013 ... 2Bioinformatics and Biotechnology, DES, FBAS International Islamic University, Islamabad, Pakistan. Accepted 26 April, 2013. The Tp73 ... New discoveries about the control and function of p73 are still in progress and it is ..... modern research for diagnostics and evolutionary history of p73. REFERENCES.

  4. Germline mutations of TP53 gene in breast cancer.

    Science.gov (United States)

    Damineni, Surekha; Rao, Vadlamudi Raghavendra; Kumar, Satish; Ravuri, Rajasekar Reddy; Kagitha, Sailaja; Dunna, Nageswara Rao; Digumarthi, Raghunadharao; Satti, Vishnupriya

    2014-09-01

    Germline alterations of the TP53 gene encoding the p53 protein have been observed in the majority of families with the Li-Fraumeni syndrome, a rare dominantly inherited disorder with breast cancer. Genomic DNA samples of 182 breast cancer cases and 186 controls were sequenced for TP53 mutations in the exon 5-9 and intervening introns 5, 7-9. Direct sequencing was done using Applied Biosystem 3730 DNA analyzer. In the present study, we observed nine mutations in the sequenced region, of which five were novel. Hardy-Weinberg equilibrium (HWE) was done for all the mutations; C14181T, T14201G, and G13203A have shown deviation from HWE. High linkage disequilibrium (LD) was observed between C14181T (rs129547788) and T14201G (rs12951053) (r (2) = 0.98.3; D' = 1.00), whereas other observed mutations do not show strong LD with any of the other mutations. None of the intronic mutations has shown significant association with the breast cancer, two exonic mutations G13203A (rs28934578) and A14572G are significantly (P = 0.04, P = 0.007) associated with breast cancer. Germline mutations observed in DNA-binding domain of the gene showed significant association with breast cancer. This study reports five novel germline mutations in the TP53 gene out of which one mutation may confer significant risk to the breast cancer. Mutations in DNA-binding domain of TP53 gene may play role in the early onset and prognosis of breast cancer. The population-based studies of germline mutations in DNA-binding domain of TP53 gene helps in identification of individuals and families who are at risk of developing cancers.

  5. Profile of TP53 gene mutations in sinonasal cancer

    DEFF Research Database (Denmark)

    Holmila, Reetta; Bornholdt, Jette; Suitiala, Tuula

    2010-01-01

    Genetic alterations underlying the development of the cancer of the nose and paranasal sinuses (sinonasal cancer, SNC), a rare cancer that can be included in the group of head and neck cancers, are still largely unknown. We recently reported that TP53 mutations are a common feature of SNC......, with an overall frequency of 77%, and they show association to adenocarcinoma and wood-dust exposure [15]. In this study, we report in detail the sequence change for 159 TP53 mutations identified by direct sequencing. More than half of the mutations (60%, 95/159) were missense mutations; there were also 28 (18......%) frameshift or nonsense mutations, and 36 (23%) intronic or silent mutations. In coding region, the most common base change detected was C-->T transition (43/125; 34% of base changes in the coding region). G-->T transversions occurred at a frequency of 10% (12/125), which is less than reported in mutation...

  6. Study of the Antimicrobial Activity of Tilapia Piscidin 3 (TP3) and TP4 and Their Effects on Immune Functions in Hybrid Tilapia (Oreochromis spp.)

    Science.gov (United States)

    Pan, Chieh-Yu; Tsai, Tsung-Yu; Su, Bor-Chyuan; Hui, Cho-Fat; Chen, Jyh-Yih

    2017-01-01

    To address the growing concern over antibiotic-resistant microbial infections in aquatic animals, we tested several promising alternative agents that have emerged as new drug candidates. Specifically, the tilapia piscidins are a group of peptides that possess antimicrobial, wound-healing, and antitumor functions. In this study, we focused on tilapia piscidin 3 (TP3) and TP4, which are peptides derived from Oreochromis niloticus, and investigated their inhibition of acute bacterial infections by infecting hybrid tilapia (Oreochromis spp.) with Vibrio vulnificus and evaluating the protective effects of pre-treating, co-treating, and post-treating fish with TP3 and TP4. In vivo experiments showed that co-treatment with V. vulnificus and TP3 (20 μg/fish) or TP4 (20 μg/fish) achieved 95.3% and 88.9% survival rates, respectively, after seven days. When we co-injected TP3 or TP4 and V. vulnificus into tilapia and then re-challenged the fish with V. vulnificus after 28 days, the tilapia exhibited survival rates of 35.6% and 42.2%, respectively. Pre-treatment with TP3 (30 μg/fish) or TP4 (20 μg/fish) for 30 minutes prior to V. vulnificus infection resulted in high survival rates of 28.9% and 37.8%, respectively, while post-treatment with TP3 (20 μg/fish or 30 μg/fish) or TP4 (20 μg/fish) 30 minutes after V. vulnificus infection yielded high survival rates of 33.3% and 48.9%. In summary, pre-treating, co-treating, and post-treating fish with TP3 or TP4 all effectively decreased the number of V. vulnificus bacteria and promoted significantly lower mortality rates in tilapia. The minimum inhibitory concentrations (MICs) of TP3 and TP4 that were effective for treating fish infected with V. vulnificus were 7.8 and 62.5 μg/ml, respectively, whereas the MICs of kanamycin and ampicillin were 31.2 and 3.91 μg/ml. The antimicrobial activity of these peptides was confirmed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM), both of which showed

  7. TP53 Gene Status Affects Survival in Advanced Mycosis Fungoides

    DEFF Research Database (Denmark)

    Wooler, Gitte; Melchior, Linea; Ralfkiaer, Elisabeth

    2016-01-01

    significance in MF. In this study, we have optimized the protocol for Sanger sequencing of TP53 using DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from patients with stage IIB MF or higher, 31% harbored mutations in TP53. Overall survival of the patients with mutated TP53...

  8. DIAGNOSTICO DE INFLUENCIA EN SISTEMAS ECONOMETRICOS COINTEGRADOS

    OpenAIRE

    TORRES TRUJILLO; MARCELO; TORRES TRUJILLO; MARCELO

    2011-01-01

    El presente trabajo desarrolla la técnica de diagnóstico de influencia local en modelos de corrección de errores (MCE) de sistemas econométricos cointegrados con el fin evaluar la sensibilidad de observaciones potencialmente influyentes sobre las estimaciones de verosimilitud máxima o inferencias hechas sobre el modelo: perturbando el parámetro de escala el cual conectamos con la técnica de diagnóstico de eliminación de casos y que nos permite evaluar analíticamente el supuesto de homoceda...

  9. Influencia de la Medicina Francesa en Colombia

    OpenAIRE

    Ernesto Andrade Valderrama

    1991-01-01

    Me da autoridad para hablar ante ustedes, quienes por segunda vez en nuestra Historia y ahora en una seria Asociación reviven los lazos de la Medicina Colombiana con la gran Escuela Francesa, el haber pertenecido a una de las últimas generaciones, formadas en la Universidad Nacional, que estudiaron toda la carrera en los textos provenientes de ese país y recibieron de maestros, casi todos formados bajo esa notable influencia, todos los principios y normas del ejercicio profesional. D...

  10. Simulation research on three-dimensional immune GA used to solve TP

    Science.gov (United States)

    Jin, Liang-Ping; Zhong, Jun-Hua

    2013-03-01

    Timetabling Problem (TP) in colleges and universities has become more important and complicated with the further reform in teaching and growing expansion of recruitment scale. In this paper, an optimized mathematical model of TP was established .The framework structure to solve TP was found. According to characteristics of TP, GA was introduced, a variety of improved schemes were designed, include: three-dimensional coding scheme, fitness function design scheme, immunization strategy. Simulation results show that the proposed GA can satisfy multiple constraint conditions and resolve TP more effectively.

  11. c-Myc inhibits TP53INP1 expression via promoter methylation in esophageal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Weng, Wenhao; Yang, Qinyuan [Department of Laboratory Medicine, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Huang, Miaolong [Department of Thoracic Surgery, Yuebei People' s Hospital, Shaoguan, Guangdong 512026 (China); Qiao, Yongxia [Department of Preventive Medicine, Tongji University, Shanghai City 200092 (China); Xie, Yuan; Yu, Yongchun [Department of Laboratory Medicine, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Jing, An, E-mail: Anjing77@gmail.com [Department of Thoracic Surgery, Yuebei People' s Hospital, Shaoguan, Guangdong 512026 (China); Institute of Cancer Research, Southern Medical University, Guangzhou 510515 (China); Li, Zhi, E-mail: lizhiweng2010@163.com [Department of Laboratory Medicine, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China)

    2011-02-11

    Research highlights: {yields} TP53INP1 expression is down-regulated in esophageal carcinoma and is associated with CGI-131 methylation. {yields} Inhibition of CGI-131 methylation upregulates TP53INP1 expression in ESCC cell lines. {yields} Ectopic expression of TP53INP1 inhibits growth of ESCC cells by inducing apoptosis and inhibiting cell cycle progression. {yields} c-Myc binds to the promoter of TP53INP1 in vivo and vitro and recruits DNMT3A to TP53INP1 promoter for CGI-131 methylation. -- Abstract: Tumor protein p53-induced nuclear protein 1 (TP53INP1) is a well known stress-induced protein that plays a role in both cell cycle arrest and p53-mediated apoptosis. Loss of TP53INP1 expression has been reported in human melanoma, breast carcinoma, and gastric cancer. However, TP53INP1 expression and its regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Our findings are in agreement with previous reports in that the expression of TP53INP1 was downregulated in 28% (10/36 cases) of ESCC lesions, and this was accompanied by significant promoter methylation. Overexpression of TP53INP1 induced G1 cell cycle arrest and increased apoptosis in ESCC cell lines (EC-1, EC-109, EC-9706). Furthermore, our study showed that the oncoprotein c-Myc bound to the core promoter of TP53INP1 and recruited DNA methyltransferase 3A to methylate the local promoter region, leading to the inhibition of TP53INP1 expression. Our findings revealed that TP53INP1 is a tumor suppressor in ESCC and that c-Myc-mediated DNA methylation-associated silencing of TP53INP1 contributed to the pathogenesis of human ESCC.

  12. Analytical and clinical comparison of Elecsys syphilis (Roche®) - Architect syphilis TP and reformulated Architect syphilis TP (Abbott®) assay.

    Science.gov (United States)

    De Keukeleire, Steven; Desmet, Stefanie; Lagrou, Katrien; Oosterlynck, Julie; Verhulst, Manon; Van Besien, Jessica; Saegeman, Veroniek; Reynders, Marijke

    2017-03-01

    The performance of Elecsys Syphilis was compared to Architect Syphilis TP and Reformulated Architect Syphilis TP. The overall sensitivity and specificity were 98.4% and 99.5%, 97.7% and 97.1%, and 99.2% and 99.7% respectively. The assays are comparable and considered adequate for syphilis screening. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Relaciones intergubernamentales, actores emergentes y mecanismos de influencia

    OpenAIRE

    Obdulia Vega; Raul Pacheco

    2004-01-01

    Las ONG ejercen influencia sobre los gobiernos, misma que ha sido estudiada con poca sistematicidad. En este trabajo, se examina el elusivo concepto de influencia y se establece un recorte teórico y analítico para el estudio de la influencia de las ONG ambientalistas sobre las relaciones entre diferentes niveles de gobierno en México. Se analiza el caso de la construcción de un confinamiento de residuos peligrosos en Guadalcázar (cerca de la ciudad de San Luis Potosí). En dicho caso, las r...

  14. TP-model transformation-based-control design frameworks

    CERN Document Server

    Baranyi, Péter

    2016-01-01

    This book covers new aspects and frameworks of control, design, and optimization based on the TP model transformation and its various extensions. The author outlines the three main steps of polytopic and LMI based control design: 1) development of the qLPV state-space model, 2) generation of the polytopic model; and 3) application of LMI to derive controller and observer. He goes on to describe why literature has extensively studied LMI design, but has not focused much on the second step, in part because the generation and manipulation of the polytopic form was not tractable in many cases. The author then shows how the TP model transformation facilitates this second step and hence reveals new directions, leading to powerful design procedures and the formulation of new questions. The chapters of this book, and the complex dynamical control tasks which they cover, are organized so as to present and analyze the beneficial aspect of the family of approaches (control, design, and optimization). Additionally, the b...

  15. TP53inp1 Gene Is Implicated in Early Radiation Response in Human Fibroblast Cells

    Directory of Open Access Journals (Sweden)

    Nikolett Sándor

    2015-10-01

    Full Text Available Tumor protein 53-induced nuclear protein-1 (TP53inp1 is expressed by activation via p53 and p73. The purpose of our study was to investigate the role of TP53inp1 in response of fibroblasts to ionizing radiation. γ-Ray radiation dose-dependently induces the expression of TP53inp1 in human immortalized fibroblast (F11hT cells. Stable silencing of TP53inp1 was done via lentiviral transfection of shRNA in F11hT cells. After irradiation the clonogenic survival of TP53inp1 knockdown (F11hT-shTP cells was compared to cells transfected with non-targeting (NT shRNA. Radiation-induced senescence was measured by SA-β-Gal staining and autophagy was detected by Acridine Orange dye and microtubule-associated protein-1 light chain 3 (LC3B immunostaining. The expression of TP53inp1, GDF-15, and CDKN1A and alterations in radiation induced mitochondrial DNA deletions were evaluated by qPCR. TP53inp1 was required for radiation (IR induced maximal elevation of CDKN1A and GDF-15 expressions. Mitochondrial DNA deletions were increased and autophagy was deregulated following irradiation in the absence of TP53inp1. Finally, we showed that silencing of TP53inp1 enhances the radiation sensitivity of fibroblast cells. These data suggest functional roles for TP53inp1 in radiation-induced autophagy and survival. Taken together, we suppose that silencing of TP53inp1 leads radiation induced autophagy impairment and induces accumulation of damaged mitochondria in primary human fibroblasts.

  16. Are There Low-Penetrance TP53 Alleles? Evidence from Childhood Adrenocortical Tumors

    OpenAIRE

    Varley, Jennifer M.; McGown, Gail; Thorncroft, Mary; James, Louise A.; Margison, Geoffrey P.; Forster, Gill; Evans, D. Gareth R.; Harris, Martin; Kelsey, Anna M.; Birch, Jillian M.

    1999-01-01

    We have analyzed a panel of 14 cases of childhood adrenocortical tumors unselected for family history and have identified germline TP53 mutations in >80%, making this the highest known incidence of a germline mutation in a tumor-suppressor gene in any cancer. The spectrum of germline TP53 mutations detected is remarkably limited. Analysis of tumor tissue for loss of constitutional heterozygosity, with respect to the germline mutant allele and the occurrence of other somatic TP53 mutations, in...

  17. Tp53 gene mediates distinct dopaminergic neuronal damage in different dopaminergic neurotoxicant models

    Directory of Open Access Journals (Sweden)

    Tao Lu

    2017-01-01

    Full Text Available Tp53, a stress response gene, is involved in diverse cell death pathways and its activation is implicated in the pathogenesis of Parkinson's disease. However, whether the neuronal Tp53 protein plays a direct role in regulating dopaminergic (DA neuronal cell death or neuronal terminal damage in different neurotoxicant models is unknown. In our recent studies, in contrast to the global inhibition of Tp53 function by pharmacological inhibitors and in traditional Tp53 knock-out mice, we examined the effects of DA-specific Tp53 gene deletion after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and methamphetamine exposure. Our data suggests that the Tp53 gene might be involved in both neuronal apoptosis and neuronal terminal damage caused by different neurotoxicants. Additional results from other studies also suggest that as a master regulator of many pathways that regulate apoptosis and synaptic terminal damage, it is possible that Tp53 may function as a signaling hub to integrate different signaling pathways to mediate distinctive target pathways. Tp53 protein as a signaling hub might be able to evaluate the microenvironment of neurons, assess the forms and severities of injury incurred, and determine whether apoptotic cell death or neuronal terminal degeneration occurs. Identification of the precise mechanisms activated in distinct neuronal damage caused by different forms and severities of injuries might allow for development of specific Tp53 inhibitors or ways to modulate distinct downstream target pathways involved.

  18. TP53 mutation spectrum in smokers and never smoking lung cancer patients

    Directory of Open Access Journals (Sweden)

    Ann Rita Halvorsen

    2016-05-01

    Full Text Available AbstractBackground: TP53 mutations are among the most common mutations found in lung cancers, identified as an independent prognostic factor in many types of cancers. The purpose of this study was to investigate the frequency and prognostic impact of TP53 mutations in never-smokers and in different histological subtypes of lung cancer.Methods: We analysed tumour tissue from 394 non-small cell carcinomas including adenocarcinomas (n=229, squamous cell carcinomas (n=112, large cell carcinomas (n=30 and others (n=23 for mutations in TP53 by the use of Sanger sequencing (n=394 and next generation sequencing (n=100. Results: TP53 mutations were identified in 47.2% of the samples, with the highest frequency (65% of mutations among squamous cell carcinomas. Among never-smokers, 36% carried a TP53 mutation, identified as a significant independent negative prognostic factor in this subgroup. For large cell carcinomas, a significantly prolonged progression free survival was found for those carrying a TP53 mutation. In addition, the frequency of frameshift mutations was doubled in squamous cell carcinomas (20.3% compared to adenocarcinomas (9.1%.Conclusion: TP53 mutation patterns differ between the histological subgroups of lung cancers, as also influenced by smoking history. This indicates that the histological subtypes in lung cancer are genetically different, and that smoking-induced TP53 mutations may have a different biological impact than TP53 mutations occurring in never-smokers.

  19. Prevalence of germline TP53 mutations in HER2+ breast cancer patients.

    Science.gov (United States)

    Rath, Michelle G; Masciari, Serena; Gelman, Rebecca; Miron, Alexander; Miron, Penelope; Foley, Kathleen; Richardson, Andrea L; Krop, Ian E; Verselis, Sigitas J; Dillon, Deborah A; Garber, Judy E

    2013-05-01

    Breast cancer is the most frequent tumor in Li-Fraumeni syndrome (LFS), a rare inherited cancer syndrome associated with germline mutations in the TP53 gene. Recent data show that breast cancer in germline TP53 mutation carriers is commonly HER2+ (63-83 %). We assessed the prevalence of germline TP53 mutations in a cohort of women with HER2+ breast cancer diagnosed age ≤50 years. We identified blood specimens from 213 women with primary invasive HER2+ breast cancer age ≤50 years from a single center. Exon grouping analysis sequencing and multiplex ligation-dependent probe amplification techniques were used to screen for germline TP53 mutations. Among 213 women with HER2+ breast cancer age ≤50 years, 3 (ages at diagnosis 23, 32, 44 years) were found to carry a TP53 mutation (1.4 %, 95 % CI 0.3-4.1 %). ER/PR status was not uniform. Two TP53 carriers met Chompret criteria for LFS; none met classic LFS criteria. Although two-thirds of breast cancers in women with TP53 mutations are HER2+, we observed a low prevalence of germline TP53 mutations among unselected young women with HER2+ breast cancer. Given the potential clinical impact, consideration of germline TP53 testing should be given to young women with HER2+ breast cancer, especially if family cancer history is notable.

  20. Prevalence of germline TP53 mutations in HER2-positive Breast Cancer Patients

    Science.gov (United States)

    Rath, Michelle G.; Masciari, Serena; Gelman, Rebecca; Miron, Alexander; Miron, Penelope; Foley, Kathleen; Richardson, Andrea L.; Krop, Ian E.; Verselis, Sigitas J.; Dillon, Deborah A.; Garber, Judy E.

    2014-01-01

    Background Breast cancer is the most frequent tumor in Li-Fraumeni syndrome (LFS), a rare inherited cancer syndrome associated with germline mutations in the TP53 gene. Recent data show that breast cancer in germline TP53 mutation carriers is commonly HER2-positive (63–83%). We assessed the prevalence of germline TP53 mutations in a cohort of women with HER2+ breast cancer diagnosed age ≤ 50 years. Material & Methods We identified blood specimens from 213 women with primary invasive HER2+ breast cancer age ≤ 50 years from a single center. EGAN sequencing and MLPA techniques were used to screen for germline TP53 mutations. Results Among 213 women with HER2+ breast cancer age ≤ 50 years, 3 (ages at diagnosis 23, 32, 44 years) were found to carry a TP53 mutation (1.4%, 95%CI 0.3%–4.1%). ER/PR status was not uniform. Two TP53-carriers met Chompret criteria for LFS; none met classic LFS criteria. Conclusion Although two-thirds of breast cancers in women with TP53 mutations are HER2+, we observed a low prevalence of germline TP53 mutations among unselected young women with HER2+ breast cancer. Given the potential clinical impact, consideration of germline TP53 testing should be given to young women with HER2+ breast cancer, especially if family cancer history is notable. PMID:23580068

  1. Low Prevalence of TP53 Mutations and MDM2 Amplifications in Pediatric Rhabdomyosarcoma

    Directory of Open Access Journals (Sweden)

    Simona Ognjanovic

    2012-01-01

    Full Text Available The tumor suppressor gene TP53 is the most commonly mutated gene in human cancer. The reported prevalence of mutations in rhabdomyosarcoma (RMS varies widely, with recent larger studies suggesting that TP53 mutations in pediatric RMS may be extremely rare. Overexpression of MDM2 also attenuates p53 function. We have performed TP53 mutation/MDM2 amplification analyses in the largest series analyzed thus far, including DNA isolated from 37 alveolar and 38 embryonal RMS tumor samples obtained from the Cooperative Human Tissue Network (CHTN. Available samples were frozen tumor tissues (N=48 and histopathology slides. TP53 mutations in exons 4–9 were analyzed by direct sequencing in all samples, and MDM2 amplification analysis was performed by differential PCR on a subset of 22 samples. We found only one sample (1/75, 1.3% carrying a TP53 mutation at codon 259 (p.D259Y and no MDM2 amplification. Two SNPs in the TP53 pathway, associated with accelerated tumor onset in germline TP53 mutation carriers, (TP53 SNP72 (rs no. 1042522 and MDM2 SNP309 (rs no. 2279744, were not found to confer earlier tumor onset. In conclusion, we confirm the extremely low prevalence of TP53 mutations/MDM2 amplifications in pediatric RMS (1.33% and 0%, respectively. The possible inactivation of p53 function by other mechanisms thus remains to be elucidated.

  2. Field Investigation of Steamside Oxidation for TP347H

    DEFF Research Database (Denmark)

    Montgomery, Melanie; Larsen, Ole Hede; Jensen, Søren Aakjær

    2004-01-01

    The steamside oxide formed on two TP347H superheater tubes was compared. The two specimens investigated were exposed in situ in power plants in Denmark, one specimen was coarse-grained and the other was fine-grained. Parts of both the coarse-grained and the fine-grained specimens were turned...... (machined on the inner side) to give a constant metal thickness so more precise wall thickness measurements could be undertaken. Machined and non-machined areas were investigated using light optical microscopy, and scanning electron microscopy with EDS analysis. The oxide on the fine-grained specimen...... was also investigated with grazing incidence X-ray diffraction. Results from coarse-grained and fine-grained specimens (machined and non-machined) show that grain size influenced oxide thickness and morphology. The oxides from non-machined specimens has an outer iron rich oxide and an inner iron chromium...

  3. Bioinformatic dissecting of TP53 regulation pathway underlying butyrate-induced histone modification in epigenetic regulation

    Science.gov (United States)

    Butyrate affects cell proliferation, differentiation and motility. Butyrate inhibits histone deacetylase (HDAC) activities and induces cell cycle arrest and apoptosis. TP53 is one of the most active upstream regulators discovered by IPA in our RNA sequencing data set. The TP53 signaling pathway pl...

  4. Cloning and characterization of a gene encoding trehalose phosphorylase (TP) from Pleurotus sajor-caju.

    Science.gov (United States)

    Han, Sang-Eun; Kwon, Hawk-Bin; Lee, Seung-Bum; Yi, Bu-Young; Murayama, Ikuo; Kitamoto, Yutaka; Byun, Myung-Ok

    2003-08-01

    Complementary DNA for a gene encoding trehalose phosphorylase (TP) that reversibly catalyzes trehalose synthesis and degradation from alpha-glucose-1-phosphate (alpha-Glc-1-P) and glucose was cloned from Pleurotus sajor-caju. The cDNA of P. sajor-caju TP (designated PsTP, GenBank Accession No. AF149777) encodes a polypeptide of 751 amino acids with a deduced molecular mass of 83.7 kDa. The PsTP gene is expressed in mycelia, pilei, and stipes of fruiting bodies. Trehalose phosphorylase PsTP was purified from PsTP-transformed Escherichia coli. The enzyme catalyzes both the phosphorolysis of trehalose to produce alpha-Glc-1-P and glucose, and the synthesis of trehalose. The apparent K(m) values for trehalose and Pi in phosphorolytic reaction at pH 7.0 were 74.8 and 5.4 mM, respectively. The PsTP gene complemented Saccharomyces cerevisiae Deltatps1, Deltatps2 double-mutant cells, allowing their growth on glucose medium. Furthermore, yeast transformed with PsTP produced 2-2.5-fold more trehalose than non-transformants or cells transformed with empty vector only.

  5. Network File - TP Atlas | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available List Contact us TP Atlas Network File Data detail Data name Network File DOI 10.18908/lsdba.nbdc01161-003 De...scription of data contents Network diagrams (in CSML format) for each project. One project has one pathway f... Update History of This Database Site Policy | Contact Us Network File - TP Atlas | LSDB Archive ...

  6. Influence of Martensite Volume Fraction on Impact Properties of Triple Phase (TP) Steels

    Science.gov (United States)

    Zare, Ahmad; Ekrami, A.

    2013-03-01

    Ferrite-bainite-martensite triple phase (TP) microstructures with different volume fractions of martensite were obtained by changing heat treatment time during austempering at 300 °C. Room temperature impact properties of TP steels with different martensite volume fractions ( V M) were determined by means of Charpy impact testing. The effects of test temperature on impact properties were also investigated for two selected microstructures containing 0 (the DP steel) and 8.5 vol.% martensite. Test results showed reduction in toughness with increasing V M in TP steels. Fracture toughness values for the DP and TP steels with 8.5 vol.% martensite were obtained from correlation between fracture toughness and the Charpy impact energy. Fractography of Charpy specimens confirmed decrease in TP steels' toughness with increasing V M by considering and comparing radial marks and crack initiation regions at the fracture surfaces of the studied steels.

  7. DNA Damage Is a Potential Marker for TP53 Mutation in Colorectal Carcinogenesis.

    Science.gov (United States)

    Scalise, José Ricardo; Poças, Regina Caeli Guerra; Caneloi, Thamy Pelatieri; Lopes, Camila Oliveira; Kanno, Danilo Toshio; Marques, Mayara Gonçalves; Valdivia, Júlio Cesar Martins; Maximo, Felipe Rodrigues; Pereira, José Aires; Ribeiro, Marcelo Lima; Priolli, Denise Gonçalves

    2016-12-01

    The ability to measure oxidative DNA damage in a tissue allows establishment of the relationship between DNA damage and mutations in normal and neoplastic cells. It is well known that TP53 is a key inhibitor of tumor development and preserves the genome integrity in each cell. The aim of the present study was to investigate the relationship between DNA damage and TP53 mutation in colorectal adenoma and adenocarcinoma, and the value of DNA damage as potential marker of TP53 mutation in non-tumor tissues adjacent to colon malignant lesions. Tissue samples were obtained by colonoscopy from patients with adenoma and/or adenocarcinoma and from healthy volunteers. Diagnosis was defined by histopathology. Immunohistochemistry with computer-assisted image analysis was performed to quantify TP53 mutation. Oxidative DNA damage was determined by comet assay. Statistical analyses were performed with 5 % of significance level. The TP53 level was higher in non-tumor tissues from tumor patients than in normal tissues from healthy volunteers (p = 0.01). Likewise, higher TP53 levels were observed in tumor tissues compared with the non-tumor tissues (p = 0.00). Oxidative DNA damage levels were higher in tumor tissues than in non-tumor tissues (p = 0.00). The amount of TP53 (p = 0.00) and oxidative DNA damage (p = 0.00) in normal and tumor tissue was related. The relationship between oxidative DNA damage and TP53 mutation was demonstrated in all samples (p = 0.00). Oxidative DNA damage is an intervening variable for TP53 mutation in colorectal adenoma-carcinoma. Our data suggests that oxidative DNA damage is a potential marker of TP53 mutation in colorectal carcinogenesis.

  8. Main achievements of the european research project NERIS-TP

    International Nuclear Information System (INIS)

    Duranova, T.; Bohunova, J.; Raskop, W.; Schneider, T.; Liland, A.; Andronopoulos, S.; Mustonen, R.

    2014-01-01

    Activities of the NERIS-TP association are described. The NERIS ICRP Workshop, held in Bratislava, Slovak Republic in February 6-8, 2012, was organized by VUJE in cooperation with ICRP aiming to provide a forum for discussion and sharing of experiences on the implementation of the ICRP Recommendations. International, European and national perspectives were presented. 88 specialists from 51 organizations from 26 countries participated in the workshop. The final Dissemination Workshop 'Strengthening the Preparedness at National and Territorial Level Using New Tools and Methods - Stakeholders Experiences', was conducted in Oslo from 22 to 24 January 2014. International organisations such as HERCA, EC DG Research, IAEA, OECD/NEA, and NGOs such as NTW (Nuclear Transparency Watch) and GMF (Group of European Municipalities with Nuclear Facilities) as well as representatives of the OPERRA project participated in the workshop and particular panels. 82 experts and stakeholders participated in the workshop, representing twenty countries. Notably, participants from Japanese organisations provided first feedback from the management of the consequences of the Fukushima accident. (authors)

  9. Insights into the potential function and membrane organization of the TP0435 (Tp17) lipoprotein from Treponema pallidum derived from structural and biophysical analyses.

    Science.gov (United States)

    Brautigam, Chad A; Deka, Ranjit K; Liu, Wei Z; Norgard, Michael V

    2015-01-01

    The sexually transmitted disease syphilis is caused by the bacterial spirochete Treponema pallidum. This microorganism is genetically intractable, accounting for the large number of putative and undercharacterized members of the pathogen's proteome. In an effort to ascribe a function(s) to the TP0435 (Tp17) lipoprotein, we engineered a soluble variant of the protein (rTP0435) and determined its crystal structure at a resolution of 2.42 Å. The structure is characterized by an eight-stranded β-barrel protein with a shallow "basin" at one end of the barrel and an α-helix stacked on the opposite end. Furthermore, there is a disulfide-linked dimer of the protein in the asymmetric unit of the crystals. Solution hydrodynamic experiments established that purified rTP0435 is monomeric, but specifically forms the disulfide-stabilized dimer observed in the crystal structure. The data herein, when considered with previous work on TP0435, imply plausible roles for the protein in either ligand binding, treponemal membrane architecture, and/or pathogenesis. © 2014 The Protein Society.

  10. Influencia de la identidad grupal en la cohesion estudio piloto

    OpenAIRE

    Bohórquez, M. Rocío; Lorenzo, Macarena

    2012-01-01

    La cohesión grupal es uno de los procesos dinámicos más estudiados en los equipos deportivos, su relación con procesos como el clima grupal o la eficacia colectiva ha sido ampliamente abordada. Sin embargo, el estudio de la influencia que la identidad grupal pudiera tener sobre la cohesión está aún por emprender. Así, el objetivo de este estudio fue determinar la influencia que la identidad grupal pudiera tener sobre la cohesión de los equipos deportivos. En el experimento p...

  11. Tumor protein 53-induced nuclear protein 1 (TP53INP1 enhances p53 function and represses tumorigenesis

    Directory of Open Access Journals (Sweden)

    Jeyran eShahbazi

    2013-05-01

    Full Text Available Tumor protein 53-induced nuclear protein 1 (TP53INP1 is a stress-induced p53 target gene whose expression is modulated by transcription factors such as p53, p73 and E2F1. TP53INP1 gene encodes two isoforms of TP53INP1 proteins, TP53INP1α and TP53INP1β, both of which appear to be key elements in p53 function. When associated with homeodomain-interacting protein kinase-2 (HIPK2, TP53INP1 phosphorylates p53 protein at Serine 46, enhances p53 protein stability and its transcriptional activity, leading to transcriptional activation of p53 target genes such as p21, PIG-3 and MDM2, cell growth arrest and apoptosis upon DNA damage stress. The anti-proliferative and pro-apoptotic activities of TP53INP1 indicate that TP53INP1 has an important role in cellular homeostasis and DNA damage response. Deficiency in TP53INP1 expression results in increased tumorigenesis; while TP53INP1 expression is repressed during early stages of cancer by factors such as miR-155. This review aims to summarize the roles of TP53INP1 in blocking tumor progression through p53-dependant and p53-independent pathways, as well as the elements which repress TP53INP1 expression, hence highlighting its potential as a therapeutic target in cancer treatment.

  12. An activator of transcription regulates phage TP901-1 late gene expression

    DEFF Research Database (Denmark)

    Brøndsted, Lone; Pedersen, Margit; Hammer, Karin

    2001-01-01

    bp contains both the promoter and the region necessary for activation by ORF29. The transcriptional start site of the promoter was identified by primer extension to position 13073 on the TP901-1 genome, thus located 87 bp downstream of orf29 in a 580-bp intergenic region between orf29 and orf30......A promoter active in the late phase of the lytic cycle of lactococcal bacteriophage TP901-1 has been identified. The promoter is tightly regulated and requires the product of the phage TP901-1 orf29 for activity. A deletion analysis of the late promoter region showed that a fragment as small as 99...

  13. Clinical Impact of TP53 Gene Mutations in Diffuse Large B-Cell Lymphoma (DLBCL)

    DEFF Research Database (Denmark)

    Young, Ken H; Patten, Nancy; Truong, Sim

    2009-01-01

    Mutations of the TP53 tumor suppressor gene are associated with a poor clinical outcome in DLBCL patients treated with CHOP. The impact of TP53 mutations on clinical outcome of DLBCL patients treated with Rituxan-CHOP has not been comprehensively analyzed. The purpose of this study was to analyze......, compared to 77% for those with wt-TP53. However, the clinical outcome and treatment response to the Rituxan-CHOP varied in patients with mutations in different regions of the DNA-binding domains. Patients with mutations in the DNA minor binding groove motif (Loop L3, 17% of all mutations) had significantly...

  14. Germline TP53 mutational spectrum in French Canadians with breast cancer.

    Science.gov (United States)

    Arcand, Suzanna L; Akbari, Mohammed R; Mes-Masson, Anne-Marie; Provencher, Diane; Foulkes, William D; Narod, Steven A; Tonin, Patricia N

    2015-04-12

    Specific germline mutations in the hereditary breast-ovarian cancer susceptibility (HBC/HBOC) genes, BRCA1, BRCA2 and PALB2, have been shown to recur in French Canadians of Quebec, Canada, and this has been attributed to common ancestors. Germline TP53 mutation carriers are known to segregate in Li-Fraumeni syndrome families, which feature young age of onset breast cancer. We have reported rare TP53 mutation carriers in French Canadian HBC families, though none recurred possibly due to the limited number of cancer families investigated. Here we describe TP53 germline mutations found in French Canadian cancer families provided from hereditary cancer clinics; investigate 37 new BRCA1 and BRCA2 mutation-negative HBC/HBOC families for the TP53 mutations; and assess the frequency of TP53 mutations in a 1235 French Canadian breast cancer cases not selected for family history of cancer. TP53 mutation-positive pedigrees from French Canadian cancer families were provided from local hereditary cancer clinics. Bidirectional Sanger sequencing of all protein encoding exons of TP53 was performed using peripheral blood lymphocyte DNA from breast/ovarian cancer probands from 37 HBC/HBOC families of French Canadian descent. Targeted bidirectional Sanger sequencing assay of regions containing the identified TP53 mutations was performed on 1235 French Canadian breast cancer cases not selected for family history cancer. Five new TP53 mutations were identified in six pedigrees from hereditary cancer clinics. No deleterious mutations were identified in cancer probands from 37 HBC/HBOC families. A targeted mutation screen of the 1235 breast cancer cases identified a c.844C>T [p.Arg282Trp] mutation carrier. This mutation was also found among the six mutation-positive cancer families provided by the local hereditary cancer clinics. The targeted screen also uncovered a new TP53 mutation, c.685T>C [p.Cys229Arg] that was found in two breast cancer cases. All TP53 mutation carriers were among

  15. Use of the integration elements encoded by the temperate lactococcal bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Brøndsted, Lone; Hammer, Karin

    1999-01-01

    Previously we showed that only one phage-expressed protein (Orf1), a 425-bp region upstream of the orf1 gene (presumably encoding a promoter), and the attP region are necessary and also sufficient for integration of the bacteriophage TP901-1 genome into the chromosome of Lactococcus lactis subsp......P region seem to be necessary for site-specific integration of the temperate bacteriophage TP901-1. By use of the integrative elements (attP and orf1) expressed by the temperate lactococcal bacteriophage TP901-1, a system for obtaining stable chromosomal single-copy transcriptional fusions in L. lactis...

  16. Mutational profile of TP53 in esophageal squamous cell carcinoma associated with chagasic megaesophagus.

    Science.gov (United States)

    Lacerda, C F; Cruvinel-Carloni, A; de Oliveira, A T Torres; Scapulatempo-Neto, C; López, R V M; Crema, E; Adad, S J; Rodrigues, M A M; Henry, M A C A; Guimarães, D P; Reis, R M

    2017-04-01

    Chaga's disease is an important communicable neglected disease that is gaining wider attention due to its increasing incidence worldwide. Achalasia due to chagasic megaesophagus (CM), a complication of this disease, is a known-yet, poorly understood-etiological factor for esophageal squamous cell carcinoma (ESCC) development. In this study, we aimed to perform the analysis of TP53 mutations in a series of Brazilian patients with ESCC that developed in the context CM (ESCC/CM), and to compare with the TP53 mutation profile of patients with benign CM and patients with nonchagasic ESCC. Additionally, we intended to correlate the TP53 mutation results with patient's clinical pathological features. By polymerase chain reaction (PCR) followed by direct sequencing of the hotspot regions of TP53 (exon 5 to 8), we found that TP53 mutations were present in 40.6% (13/32) of the ESCC/CM group, 45% (18/40) of the nonchagasic ESCC group, and in only 3% (1/33) of the benign CM group. Missense mutations were the most common in the three groups, yet, the type and mutated exon mutation varied significantly among the groups. Clinically, the groups exhibited distinct features, with both cancer groups (ESCC and ESCC/CM) been significantly associated higher consumption of alcohol and tobacco, older age, worse Karnofsky performance status, poor outcome than the patients with benign CM. No significant association was found between TP53 mutation profile and clinical-pathological features in any of the three groups. We describe first the time the analysis of TP53 mutations in ESCC that developed in the context of CM, and the observed high frequency of mutations, suggest that TP53 also plays an important role in the tumorigenic process of this unexplored etiological condition. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Somatic and GermlineTP53Alterations in Second Malignant Neoplasms from Pediatric Cancer Survivors.

    Science.gov (United States)

    Sherborne, Amy L; Lavergne, Vincent; Yu, Katharine; Lee, Leah; Davidson, Philip R; Mazor, Tali; Smirnoff, Ivan V; Horvai, Andrew E; Loh, Mignon; DuBois, Steven G; Goldsby, Robert E; Neglia, Joseph P; Hammond, Sue; Robison, Leslie L; Wustrack, Rosanna; Costello, Joseph F; Nakamura, Alice O; Shannon, Kevin M; Bhatia, Smita; Nakamura, Jean L

    2017-04-01

    Purpose: Second malignant neoplasms (SMNs) are severe late complications that occur in pediatric cancer survivors exposed to radiotherapy and other genotoxic treatments. To characterize the mutational landscape of treatment-induced sarcomas and to identify candidate SMN-predisposing variants, we analyzed germline and SMN samples from pediatric cancer survivors. Experimental Design: We performed whole-exome sequencing (WES) and RNA sequencing on radiation-induced sarcomas arising from two pediatric cancer survivors. To assess the frequency of germline TP53 variants in SMNs, Sanger sequencing was performed to analyze germline TP53 in 37 pediatric cancer survivors from the Childhood Cancer Survivor Study (CCSS) without any history of a familial cancer predisposition syndrome but known to have developed SMNs. Results: WES revealed TP53 mutations involving p53's DNA-binding domain in both index cases, one of which was also present in the germline. The germline and somatic TP53- mutant variants were enriched in the transcriptomes for both sarcomas. Analysis of TP53- coding exons in germline specimens from the CCSS survivor cohort identified a G215C variant encoding an R72P amino acid substitution in 6 patients and a synonymous SNP A639G in 4 others, resulting in 10 of 37 evaluable patients (27%) harboring a germline TP53 variant. Conclusions: Currently, germline TP53 is not routinely assessed in patients with pediatric cancer. These data support the concept that identifying germline TP53 variants at the time a primary cancer is diagnosed may identify patients at high risk for SMN development, who could benefit from modified therapeutic strategies and/or intensive posttreatment monitoring. Clin Cancer Res; 23(7); 1852-61. ©2016 AACR . ©2016 American Association for Cancer Research.

  18. Mutations and polymorphisms in TP53 gene--an overview on the role in colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Naccarati, Alessio; Poláková, Veronika; Pardini, Barbara; Vodičková, Ludmila; Hemminki, K.; Kumar, R.; Vodička, Pavel (ed.)

    2012-01-01

    Roč. 27, č. 2 (2012), s. 211-218 ISSN 0267-8357 R&D Projects: GA ČR GP305/09/P194; GA ČR GAP304/10/1286 Grant - others:GA UK(CZ) GA96908/B/2008 Institutional research plan: CEZ:AV0Z50390512 Keywords : TP53 mutations * TP53 polymorphisms * cancer risk Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012

  19. High resolution melting for mutation scanning of TP53 exons 5–8

    International Nuclear Information System (INIS)

    Krypuy, Michael; Dobrovic, Alexander; Ahmed, Ahmed Ashour; Etemadmoghadam, Dariush; Hyland, Sarah J; Australian Ovarian Cancer Study Group; Fazio, Anna de; Fox, Stephen B; Brenton, James D; Bowtell, David D

    2007-01-01

    p53 is commonly inactivated by mutations in the DNA-binding domain in a wide range of cancers. As mutant p53 often influences response to therapy, effective and rapid methods to scan for mutations in TP53 are likely to be of clinical value. We therefore evaluated the use of high resolution melting (HRM) as a rapid mutation scanning tool for TP53 in tumour samples. We designed PCR amplicons for HRM mutation scanning of TP53 exons 5 to 8 and tested them with DNA from cell lines hemizygous or homozygous for known mutations. We assessed the sensitivity of each PCR amplicon using dilutions of cell line DNA in normal wild-type DNA. We then performed a blinded assessment on ovarian tumour DNA samples that had been previously sequenced for mutations in TP53 to assess the sensitivity and positive predictive value of the HRM technique. We also performed HRM analysis on breast tumour DNA samples with unknown TP53 mutation status. One cell line mutation was not readily observed when exon 5 was amplified. As exon 5 contained multiple melting domains, we divided the exon into two amplicons for further screening. Sequence changes were also introduced into some of the primers to improve the melting characteristics of the amplicon. Aberrant HRM curves indicative of TP53 mutations were observed for each of the samples in the ovarian tumour DNA panel. Comparison of the HRM results with the sequencing results revealed that each mutation was detected by HRM in the correct exon. For the breast tumour panel, we detected seven aberrant melt profiles by HRM and subsequent sequencing confirmed the presence of these and no other mutations in the predicted exons. HRM is an effective technique for simple and rapid scanning of TP53 mutations that can markedly reduce the amount of sequencing required in mutational studies of TP53

  20. IDH1/IDH2 but Not TP53 Mutations Predict Prognosis in Bulgarian Glioblastoma Patients

    Directory of Open Access Journals (Sweden)

    Gergana Stancheva

    2014-01-01

    Full Text Available Mutations in genes encoding isocitrate dehydrogenase isoforms 1 (IDH1 and 2 (IDH2 have been associated with good prognosis for patients with brain neoplasias and have been commonly found together with mutated TP53 gene. To determine the prevalence of IDH1, IDH2, and TP53 mutations and their impact on overall survival 106 glioblastoma patients were analysed. IDH1 mutations were detected in 13 and IDH2 mutation in one patient. Two homozygous samples with R132H mutation in IDH1 gene and a novel aberration K129R in IDH2 gene were found. Sixty-four percent of IDH1/IDH2 mutated tumours harboured also a mutation in TP53 gene. Genetic aberrations in TP53 were present in 37 patients. Statistical analysis of the impact of the studied factors on the overall survival showed that the mutations in IDH1/IDH2, but not the ones in TP53, were associated with longer survival. Also, the impact of age on prognosis was confirmed. This is the first comprehensive study on glioblastomas in Bulgaria. Our results suggest that IDH1/IDH2 but not TP53 mutations together with other prognostic factors such as age might be applied in clinical practice for prediction of outcome in patients with glioblastomas.

  1. A novel HER2-positive breast cancer phenotype arising from germline TP53 mutations.

    Science.gov (United States)

    Wilson, J R F; Bateman, A C; Hanson, H; An, Q; Evans, G; Rahman, N; Jones, J L; Eccles, D M

    2010-11-01

    The Li-Fraumeni Syndrome is caused by a germline TP53 mutation and is associated with a high risk of breast cancer at young ages. Basal (triple negative) breast cancers are now well recognised to be a typical sub-type of breast cancer developing in a large proportion of BRCA1 gene carriers. We considered whether a similar narrow sub-type of breast cancer was found in TP53 gene mutation carriers. A hypothesis generating study to investigate whether there are specific breast tumour characteristics associated with germline TP53 mutations. Pathological characteristics in 12 breast cancers arising in nine patients carrying pathogenic TP53 mutations were compared to a reference panel of 231 young onset breast tumours included in the POSH study. Patients carrying a TP53 mutation showed a significantly higher likelihood of developing a breast cancer with Human Epidermal growth factor Receptor (HER2) amplification (83%) when compared to the cohort of young onset breast cancer cases (16%); ER and PR status were equivalent between groups. These findings suggest that breast cancer developing on a background of an inherited TP53 mutation is highly likely to present with amplification of HER2.

  2. Childhood adrenocortical carcinoma as a sentinel cancer for detecting families with germline TP53 mutations.

    Science.gov (United States)

    Choong, S S; Latiff, Z A; Mohamed, M; Lim, L L W; Chen, K S; Vengidasan, L; Razali, H; Abdul Rahman, E J; Ariffin, H

    2012-12-01

    Li-Fraumeni syndrome (LFS) is a highly penetrant, autosomal dominant disorder where affected individuals carry a 50% risk of developing cancer before 30 years of age. It is most commonly associated with mutations in the tumour suppressor gene, TP53. Adrenocortical carcinoma (ACC) is a very rare paediatric cancer, and up to 80% of affected children are found to carry germline TP53 mutations. Hence, we propose using childhood ACC incidence as selection criteria for referral for TP53 mutation testing, independent of familial cancer history. Under the auspices of the Malaysian Society of Paediatric Haematology-Oncology, four eligible children diagnosed with ACC over a 30-month study period were referred for mutation testing. Three had a germline TP53 mutation. Subsequent TP53 testing in relatives showed two inherited mutations and one de novo mutation. These findings strongly support paediatric ACC as a useful sentinel cancer for initiating a germline TP53/LFS detection programme, particularly in countries where the lack of structured oncogenetic practice precludes the identification of families with LFS features. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  3. Routine TP53 testing for breast cancer under age 30: ready for prime time?

    Science.gov (United States)

    McCuaig, Jeanna M; Armel, Susan R; Novokmet, Ana; Ginsburg, Ophira M; Demsky, Rochelle; Narod, Steven A; Malkin, David

    2012-12-01

    It is well known that early-onset breast cancer may be due to an inherited predisposition. When evaluating women diagnosed with breast cancer under age 30, two important syndromes are typically considered: Hereditary Breast and Ovarian Cancer Syndrome and Li-Fraumeni syndrome. Many women are offered genetic testing for mutations in the BRCA1 and BRCA2 genes; however, few are offered genetic testing for mutations in the TP53 gene. There is a concern that overly restrictive testing of TP53 may fail to recognize families with Li-Fraumeni syndrome. We reviewed the genetic test results and family histories of all women with early-onset breast cancer who had genetic testing of the TP53 gene at the Toronto Hospital for Sick Children. Of the 28 women tested, six (33.3 %) had a mutation in the TP53 gene; a mutation was found in 7.7 % of women who did not meet current criteria for Li-Fraumeni syndrome. By reviewing similar data published between 2000 and 2011, we estimate that 5-8 % of women diagnosed with early-onset breast cancer, and who have a negative family history, may have a mutation in the TP53 gene. Given the potential benefits versus harms of this testing, we discuss the option of simultaneous testing of all three genes (BRCA1, BRCA2, and TP53) for women diagnosed with breast cancer before age 30.

  4. Optimized p53 immunohistochemistry is an accurate predictor of TP53 mutation in ovarian carcinoma.

    Science.gov (United States)

    Köbel, Martin; Piskorz, Anna M; Lee, Sandra; Lui, Shuhong; LePage, Cecile; Marass, Francesco; Rosenfeld, Nitzan; Mes Masson, Anne-Marie; Brenton, James D

    2016-10-01

    TP53 mutations are ubiquitous in high-grade serous ovarian carcinomas (HGSOC), and the presence of TP53 mutation discriminates between high and low-grade serous carcinomas and is now an important biomarker for clinical trials targeting mutant p53. p53 immunohistochemistry (IHC) is widely used as a surrogate for TP53 mutation but its accuracy has not been established. The objective of this study was to test whether improved methods for p53 IHC could reliably predict TP53 mutations independently identified by next generation sequencing (NGS). Four clinical p53 IHC assays and tagged-amplicon NGS for TP53 were performed on 171 HGSOC and 80 endometrioid carcinomas (EC). p53 expression was scored as overexpression (OE), complete absence (CA), cytoplasmic (CY) or wild type (WT). p53 IHC was evaluated as a binary classifier where any abnormal staining predicted deleterious TP53 mutation and as a ternary classifier where OE, CA or WT staining predicted gain-of-function (GOF or nonsynonymous), loss-of-function (LOF including stopgain, indel, splicing) or no detectable TP53 mutations (NDM), respectively. Deleterious TP53 mutations were detected in 169/171 (99%) HGSOC and 7/80 (8.8%) EC. The overall accuracy for the best performing IHC assay for binary and ternary prediction was 0.94 and 0.91 respectively, which improved to 0.97 (sensitivity 0.96, specificity 1.00) and 0.95 after secondary analysis of discordant cases. The sensitivity for predicting LOF mutations was lower at 0.76 because p53 IHC detected mutant p53 protein in 13 HGSOC with LOF mutations. CY staining associated with LOF was seen in 4 (2.3%) of HGSOC. Optimized p53 IHC can approach 100% specificity for the presence of TP53 mutation and its high negative predictive value is clinically useful as it can exclude the possibility of a low-grade serous tumour. 4.1% of HGSOC cases have detectable WT staining while harboring a TP53 LOF mutation, which limits sensitivity for binary prediction of mutation to 96%.

  5. Evaluation of the recombinant protein TpF1 of Treponema pallidum for serodiagnosis of syphilis.

    Science.gov (United States)

    Jiang, Chuanhao; Zhao, Feijun; Xiao, Jinhong; Zeng, Tiebing; Yu, Jian; Ma, Xiaohua; Wu, Haiying; Wu, Yimou

    2013-10-01

    Syphilis is a chronic infection caused by Treponema pallidum subsp. pallidum, and diagnosis with sensitive and specific methods is a challenging process that is important for its prevention and treatment. In the present study, we established a recombinant protein TpF1-based indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and a Western blot assay for human and rabbit sera. The 20-kDa recombinant protein TpF1 was detected by Western blotting performed with sera from rabbits immunized with recombinant TpF1 and infected with the T. pallidum Nichols strain and T. pallidum clinical isolates but was not detected by Western blotting with sera from uninfected rabbits. The sensitivity of the recombinant protein was determined by screening sera from individuals with primary, secondary, latent, and congenital syphilis (n = 82). The specificity of the recombinant protein was determined by screening sera from uninfected controls (n = 30) and individuals with potentially cross-reactive infections, including Lyme disease (n = 30) and leptospirosis (n = 5). The sensitivities of TpF1-based ELISAs were 93.3%, 100%, 100%, and 100% for primary, secondary, latent, and congenital syphilis, respectively, and the specificities were all 100% for sera from uninfected controls and individuals with potentially cross-reactive infections. In Western blot assays, the sensitivities and specificities of TpF1 for human sera were all 100%. The reactivities of TpF1 with syphilitic sera were proportional to the titers of the T. pallidum particle agglutination (TPPA) assay. These data indicate that the recombinant protein TpF1 is a highly immunogenic protein in human and rabbit infections and a promising marker for the screening of syphilis.

  6. Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma.

    Science.gov (United States)

    Shaul, Eliana; Roth, Michael; Lo, Yungtai; Geller, David S; Hoang, Bang; Yang, Rui; Malkin, David; Gorlick, Richard; Gill, Jonathan

    2018-03-15

    Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7% carry exonic variants of unknown significance in TP53. Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4% vs 12.4%; P offer TP53 testing once they were provided with the new data (25.4% vs 12.4%; P = .0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4% vs 10.2%; P = .0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018;124:1242-50. © 2018 American Cancer Society. © 2018 American Cancer Society.

  7. Evaluation of the Recombinant Protein TpF1 of Treponema pallidum for Serodiagnosis of Syphilis

    Science.gov (United States)

    Jiang, Chuanhao; Zhao, Feijun; Xiao, Jinhong; Zeng, Tiebing; Yu, Jian; Ma, Xiaohua; Wu, Haiying

    2013-01-01

    Syphilis is a chronic infection caused by Treponema pallidum subsp. pallidum, and diagnosis with sensitive and specific methods is a challenging process that is important for its prevention and treatment. In the present study, we established a recombinant protein TpF1-based indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and a Western blot assay for human and rabbit sera. The 20-kDa recombinant protein TpF1 was detected by Western blotting performed with sera from rabbits immunized with recombinant TpF1 and infected with the T. pallidum Nichols strain and T. pallidum clinical isolates but was not detected by Western blotting with sera from uninfected rabbits. The sensitivity of the recombinant protein was determined by screening sera from individuals with primary, secondary, latent, and congenital syphilis (n = 82). The specificity of the recombinant protein was determined by screening sera from uninfected controls (n = 30) and individuals with potentially cross-reactive infections, including Lyme disease (n = 30) and leptospirosis (n = 5). The sensitivities of TpF1-based ELISAs were 93.3%, 100%, 100%, and 100% for primary, secondary, latent, and congenital syphilis, respectively, and the specificities were all 100% for sera from uninfected controls and individuals with potentially cross-reactive infections. In Western blot assays, the sensitivities and specificities of TpF1 for human sera were all 100%. The reactivities of TpF1 with syphilitic sera were proportional to the titers of the T. pallidum particle agglutination (TPPA) assay. These data indicate that the recombinant protein TpF1 is a highly immunogenic protein in human and rabbit infections and a promising marker for the screening of syphilis. PMID:23945159

  8. Glucagon-Secreting Alpha Cell Selective Two-Photon Fluorescent Probe TP-α: For Live Pancreatic Islet Imaging.

    Science.gov (United States)

    Agrawalla, Bikram Keshari; Chandran, Yogeswari; Phue, Wut-Hmone; Lee, Sung-Chan; Jeong, Yun-Mi; Wan, Si Yan Diana; Kang, Nam-Young; Chang, Young-Tae

    2015-04-29

    Two-photon (TP) microscopy has an advantage for live tissue imaging which allows a deeper tissue penetration up to 1 mm comparing to one-photon (OP) microscopy. While there are several OP fluorescence probes in use for pancreatic islet imaging, TP imaging of selective cells in live islet still remains a challenge. Herein, we report the discovery of first TP live pancreatic islet imaging probe; TP-α (Two Photon-alpha) which can selectively stain glucagon secreting alpha cells. Through fluorescent image based screening using three pancreatic cell lines, we discovered TP-α from a TP fluorescent dye library TPG (TP-Green). In vitro fluorescence test showed that TP-α have direct interaction and appear glucagon with a significant fluorescence increase, but not with insulin or other hormones/analytes. Finally, TP-α was successfully applied for 3D imaging of live islets by staining alpha cell directly. The newly developed TP-α can be a practical tool to evaluate and identify live alpha cells in terms of localization, distribution and availability in the intact islets.

  9. Phase I study of TP300 in patients with advanced solid tumors with pharmacokinetic, pharmacogenetic and pharmacodynamic analyses

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    Anthoney D

    2012-11-01

    Full Text Available Abstract Background A Phase I dose escalation first in man study assessed maximum tolerated dose (MTD, dose-limiting toxicity (DLT and recommended Phase II dose of TP300, a water soluble prodrug of the Topo-1 inhibitor TP3076, and active metabolite, TP3011. Methods Eligible patients with refractory advanced solid tumors, adequate performance status, haematologic, renal, and hepatic function. TP300 was given as a 1-hour i.v. infusion 3-weekly and pharmacokinetic (PK profiles of TP300, TP3076 and TP3011 were analysed. Polymorphisms in CYP2D6, AOX1 and UGT1A1 were studied and DNA strand-breaks measured in peripheral blood mononuclear cells (PBMCs. Results 32 patients received TP300 at 1, 2, 4, 6, 8, 10, 12 mg/m2. MTD was 10 mg/m2; DLTs at 12 (2/4 patients and 10 mg/m2 (3/12 included thrombocytopenia and febrile neutropenia; diarrhoea was uncommon. Six patients (five had received irinotecan, had stable disease for 1.5-5 months. TP3076 showed dose proportionality in AUC and Cmax from 1–10 mg/m2. Genetic polymorphisms had no apparent influence on exposure. DNA strand-breaks were detected after TP300 infusion. Conclusions TP300 had predictable hematologic toxicity, and diarrhoea was uncommon. AUC at MTD is substantially greater than for SN38. TP3076 and TP3011 are equi-potent with SN38, suggesting a PK advantage. Trial registration EU-CTR2006-001345-33

  10. Influencia de la Medicina Francesa en Colombia

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    Ernesto Andrade Valderrama

    1991-12-01

    Full Text Available

    Me da autoridad para hablar ante ustedes, quienes por segunda vez en nuestra Historia y ahora en una seria Asociación reviven los lazos de la Medicina Colombiana con la gran Escuela Francesa, el haber pertenecido a una de las últimas generaciones, formadas en la Universidad Nacional, que estudiaron toda la carrera en los textos provenientes de ese país y recibieron de maestros, casi todos formados bajo esa notable influencia, todos los principios y normas del ejercicio profesional. Disminuída casi al mínimo, tras la ruptura de comunicación y situación originada por la Segunda Guerra Mundial y tras los cambios, que en el orden social y tecnológico han ocurrido en estos últimos cincuenta años, hoy buscan todas las entidades que tienen a su cargo la Educación Médica, revivir la imagen de un médico general, familiar o comunitario, que pueda restituir la perdida relación Médico-Paciente, base de la antigua Escuela Francesa y que correctamente orientado y utilizando la esplendorosa tecnología de este final de siglo, pueda ser la salvación para el cuidado integral del paciente del próximo milenio que se avecina.

    A través de la Historia, se ha visto cómo el cetro de la Medicina ha rotado por diversas culturas y países. España, por razones políticas, alejada de Francia, recibió, en el campo médico el influjo de Alemania e Inglaterra. A sus colonias de América, fué muy poco lo que de ellas llegó. Sólo hasta finales del siglo XVIII, vino un hombre genial, naturalista y médico, quien pasara a la Historia Universal con la célebre Expedición Botánica y que fué el padre de la medicina colombiana: José Celestino Mutis. El puso en marcha la primera Escuela de Medicina, en 1802 y allí estudiaron los primeros médicos que pasada la Guerra de la Independencia, encabezados por José Félix Merizalde, habrían de recibir la primera Misión Francesa, en 1823.

    Médicos franceses conocidos antes en el país fueron

  11. TP53 and lacZ mutagenesis induced by 3-nitrobenzanthrone in Xpa-deficient human TP53 knock-in mouse embryo fibroblasts.

    Science.gov (United States)

    Kucab, Jill E; Zwart, Edwin P; van Steeg, Harry; Luijten, Mirjam; Schmeiser, Heinz H; Phillips, David H; Arlt, Volker M

    2016-03-01

    3-Nitrobenzanthrone (3-NBA) is a highly mutagenic compound and possible human carcinogen found in diesel exhaust. 3-NBA forms bulky DNA adducts following metabolic activation and induces predominantly G:CT:A transversions in a variety of experimental systems. Here we investigated the influence of nucleotide excision repair (NER) on 3-NBA-induced mutagenesis of the human tumour suppressor gene TP53 and the reporter gene lacZ. To this end we utilised Xpa -knockout (Xpa-Null) human TP53 knock-in (Hupki) embryo fibroblasts (HUFs). As Xpa is essential for NER of bulky DNA adducts, we hypothesized that DNA adducts induced by 3-NBA would persist in the genomes of Xpa-Null cells and lead to an increased frequency of mutation. The HUF immortalisation assay was used to select for cells harbouring TP53 mutations following mutagen exposure. We found that Xpa-Null Hupki mice and HUFs were more sensitive to 3-NBA treatment than their wild-type (Xpa-WT) counterparts. However, following 3-NBA treatment and immortalisation, a similar frequency of TP53-mutant clones arose from Xpa-WT and Xpa-Null HUF cultures. In cells from both Xpa genotypes G:CT:A transversion was the predominant TP53 mutation type and mutations exhibited bias towards the non-transcribed strand. Thirty-two percent of 3-NBA-induced TP53 mutations occurred at CpG sites, all of which are hotspots for mutation in smokers' lung cancer (codons 157, 158, 175, 245, 248, 273, 282). We also examined 3-NBA-induced mutagenesis of an integrated lacZ reporter gene in HUFs, where we again observed a similar mutant frequency in Xpa-WT and Xpa-Null cells. Our findings suggest that 3-NBA-DNA adducts may evade removal by global genomic NER; the persistence of 3-NBA adducts in DNA may be an important factor in its mutagenicity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Las influencias orientales en el pensamiento occidental: de la ilustración al idealismo postkantiano

    OpenAIRE

    Terol, Gabriel

    2011-01-01

    Repasamos las influencias orientalistas del pensamiento occidental en el período comprendido entre los siglos XVII y XVIII, subrayando estas influencias en tres representantes de la Ilustración (Leibniz, Wolff y Hume), un representante de la reacción al racionalismo ilustrado (Herder) y dos representantes del idealismo poskantiano posterior (Schelling y Hegel), para constatar la relevancia de estas influencias. Proponemos exponer la trayectoria del pensamiento occidental de modo que alcancemo...

  13. Specific mutation screening of TP53 gene by low-density DNA microarray

    Science.gov (United States)

    Rangel-López, Angélica; Méndez-Tenorio, Alfonso; Beattie, Kenneth L; Maldonado, Rogelio; Mendoza, Patricia; Vázquez, Guelaguetza; Pérez-Plasencia, Carlos; Sánchez, Martha; Navarro, Guillermo; Salcedo, Mauricio

    2009-01-01

    TP53 is the most commonly mutated gene in human cancers. Approximately 90% of mutations in this gene are localized between domains encoding exons 5 to 8. The aim of this investigation was to examine the ability of the low density DNA microarray with the assistance of double tandem hybridization platform to characterize TP53 mutational hotspots in exons 5, 7, and 8 of the TP53. Nineteen capture probes specific to each potential mutation site were designed to hybridize to specific site. Virtual hybridization was used to predict the stability of hybridization of each capture probe with the target. Thirty-three DNA samples from different sources were analyzed for mutants in these exons. A total of 32 codon substitutions were found by DNA sequencing. 24 of them a showed a perfect correlation with the hybridization pattern system and DNA sequencing analysis of the regions scanned. Although in this work we directed our attention to some of the most representative mutations of the TP53 gene, the results suggest that this microarray system proved to be a rapid, reliable, and effective method for screening all the mutations in TP53 gene. PMID:24198462

  14. Are there low-penetrance TP53 Alleles? evidence from childhood adrenocortical tumors.

    Science.gov (United States)

    Varley, J M; McGown, G; Thorncroft, M; James, L A; Margison, G P; Forster, G; Evans, D G; Harris, M; Kelsey, A M; Birch, J M

    1999-10-01

    We have analyzed a panel of 14 cases of childhood adrenocortical tumors unselected for family history and have identified germline TP53 mutations in >80%, making this the highest known incidence of a germline mutation in a tumor-suppressor gene in any cancer. The spectrum of germline TP53 mutations detected is remarkably limited. Analysis of tumor tissue for loss of constitutional heterozygosity, with respect to the germline mutant allele and the occurrence of other somatic TP53 mutations, indicates complex sequences of genetic events in a number of tumors. None of the families had cancer histories that conformed to the criteria for Li-Fraumeni syndrome, but, in some families, we were able to demonstrate that the mutation had been inherited. In these families there were gene carriers unaffected in their 40s and 50s, and there were others with relatively late-onset cancers. These data provide evidence that certain TP53 alleles confer relatively low penetrance for predisposition to the development of cancer, and they imply that deleterious TP53 mutations may be more frequent in the population than has been estimated previously. Our findings have considerable implications for the clinical management of children with andrenocortical tumors and their parents, in terms of both genetic testing and the early detection and treatment of tumors.

  15. Alterations of the TP53 Gene in Gastric and Esophageal Carcinogenesis

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    Marilanda Ferreira Bellini

    2012-01-01

    Full Text Available TP53 genes is one of more important tumor suppressor gene, which acts as a potent transcription factor with fundamental role in the maintenance of genetic stability. The development of esophageal and gastric cancers is a multistep process resulting in successive accumulation of genetic alterations that culminates in the malignant transformation. Thus, this study highlights the participation of the main genetic alterations of the TP53 gene in esophageal and gastric carcinogenesis. Among these changes, high frequency of TP53 mutations, loss of heterozygosity (LOH, overexpression of the p53 protein, and consequently loss of p53 function, which would be early events in esophageal and gastric cancers, as well as an important biomarker of the prognosis and treatment response. Furthermore, Single Nucleotide Polymorphisms (SNPs of TP53 have been implicated in the development and prognosis of several cancers, mainly TP53 codon 72 polymorphism whose role has been extensively studied in relation to susceptibility for esophageal and gastric cancer development.

  16. Gaining insights into the codon usage patterns of TP53 gene across eight mammalian species.

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    Tarikul Huda Mazumder

    Full Text Available TP53 gene is known as the "guardian of the genome" as it plays a vital role in regulating cell cycle, cell proliferation, DNA damage repair, initiation of programmed cell death and suppressing tumor growth. Non uniform usage of synonymous codons for a specific amino acid during translation of protein known as codon usage bias (CUB is a unique property of the genome and shows species specific deviation. Analysis of codon usage bias with compositional dynamics of coding sequences has contributed to the better understanding of the molecular mechanism and the evolution of a particular gene. In this study, the complete nucleotide coding sequences of TP53 gene from eight different mammalian species were used for CUB analysis. Our results showed that the codon usage patterns in TP53 gene across different mammalian species has been influenced by GC bias particularly GC3 and a moderate bias exists in the codon usage of TP53 gene. Moreover, we observed that nature has highly favored the most over represented codon CTG for leucine amino acid but selected against the ATA codon for isoleucine in TP53 gene across all mammalian species during the course of evolution.

  17. Relaciones intergubernamentales, actores emergentes y mecanismos de influencia

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    Obdulia Vega

    2004-01-01

    Full Text Available Las ONG ejercen influencia sobre los gobiernos, misma que ha sido estudiada con poca sistematicidad. En este trabajo, se examina el elusivo concepto de influencia y se establece un recorte teórico y analítico para el estudio de la influencia de las ONG ambientalistas sobre las relaciones entre diferentes niveles de gobierno en México. Se analiza el caso de la construcción de un confinamiento de residuos peligrosos en Guadalcázar (cerca de la ciudad de San Luis Potosí. En dicho caso, las relaciones entre gobierno federal, gobierno estatal y gobierno municipal en México se vieron afectadas por la presión externa del gobierno de los Estados Unidos de Norteamérica. Más aún, la influencia de la sociedad civil potosina, a través de ONGA cuya esfera de atención se concentraba en el área geográfica de San Luis Potosí, ejerció un impacto decisivo sobre la forma en la cual se desarrollaron los eventos que culminaron en una disputa formal en los tribunales a la luz del Tratado de Libre Comercio de América del Norte (TLCAN En este trabajo examinamos el caso de Metalclad a la luz de un marco teórico interdisciplinario, y definimos hasta qué punto las ONGA lograron influir sobre las relaciones intergubernamentales entre gobiernos federal, estatal y municipal.

  18. Two TP53 germline mutations in a classical Li-Fraumeni syndrome family.

    Science.gov (United States)

    van Hest, Liselotte P; Ruijs, Mariëlle W G; Wagner, Anja; van der Meer, Conny A; Verhoef, Senno; van't Veer, Laura J; Meijers-Heijboer, Hanne

    2007-01-01

    Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited cancer predisposition syndrome characterized by a combination of tumors including sarcoma, breast cancer, brain tumors, adrenocortical carcinoma and leukemia. Germline mutations in the tumor suppressor gene TP53 are associated with LFS. We present a family with LFS in which initially a novel germline TP53 intron 5 splice site mutation was found. A second germline TP53 mutation, the exon 7 Asn235Ser (704A-->G) mutation, was detected in this family through pre-symptomatic DNA testing. This latter mutation has been reported repeatedly in the literature as a pathogenic mutation involved in LFS. We provide evidence for pathogenicity of the novel intron 5 splice site mutation, whereas this evidence is lacking for the exon 7 Asn235Ser (704A-->G) mutation. Our findings emphasize the importance of performing additional tests in case of germline sequence variants with uncertain functional effects.

  19. Evaluation of the Lumipulse G TP-N Chemiluminescent Immunoassay as a Syphilis Screening Test.

    Science.gov (United States)

    Ortiz, Daniel A; Loeffelholz, Michael J

    2017-11-01

    A syphilis diagnosis is often aided by the detection of treponemal and nontreponemal antibodies. Automated treponemal antibody detection systems enable high-volume clinical laboratories to perform syphilis screening at a faster pace with lower labor costs. The Lumipulse G TP-N chemiluminescent immunoassay is an automated system that qualitatively detects IgG and IgM antibodies against Treponema pallidum antigens in human serum and plasma. To assess performance characteristics and workflow efficiency, the Lumipulse G TP-N assay was compared to the Bioplex 2200 Syphilis IgG multiplex flow immunoassay. Among the 4,134 routine and HIV samples tested by the two automated assays, the percentage of agreement was excellent at 99.0% (95% confidence interval [CI], 98.6% to 99.2%; κ, 0.89), with the Lumipulse G TP-N having a shorter time to first and subsequent results. All specimens with reactive syphilis screening results were further tested by rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TP·PA) testing ( n = 231). The results from the RPR-reactive samples ( n = 82) showed complete concordance with the two automated assays, while the TP·PA assay displayed some discrepancies. The positive percent agreement (PPA) and negative percent agreement (NPA) between the TP·PA test and the Lumipulse G TP-N test were 98.9% and 77.3%, respectively. The Bioplex 2200 Syphilis IgG immunoassay displayed a similar PPA (100%) but a substantially lower NPA (15.9%). Patient chart reviews of discrepant results suggested that the Lumipulse G TP-N assay produced 27 fewer falsely reactive results and can reduce the amount of additional confirmatory RPR and TP·PA testing needed. The analogous performance characteristics of the two automated systems indicate that the Lumipulse G TP-N assay is suitable for high-throughput syphilis screening. Copyright © 2017 American Society for Microbiology.

  20. Pemetaan Pusat Pelayanan Terpadu Pemberdayaan Perempuan dan Anak (P2TP2A Provinsi Sumatera Bar

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    Hallen Abu Bakar

    2017-09-01

    Full Text Available The Center of Integrated Service for Women and Children Empowerment (P2TP2A is established by the government based community in order to eliminate the violence towards women and children. It also aims to empower the position of women and children. The purpose of the study is to describe comprehensively the existance of P2TP2A in sub-district, district, city, and province in West Sumatra. Descriptive qualitative research was used where the data taken from questionnaire and in-deepthinterview. The study found that the Center of Integrated Service for Women and Children Empowerment was established by following certain procedure, legality and personnel structure. It also found that the majority of P2TP2A in West Sumatra has insufficient infrastructures. Meanwhile, it is only P2TP2A Limpapeh Rumah Nan Gadang of West Sumatera, and P2TP2A Luhak Nan Tuo Batusangkar has sufficient infrastructures. Many of them were located at the corner of Community Empowerment and Women and Family Planning office (BPMPKB. Every P2TP2A in those district and city have made their programs, but they faced some difficulties in realize them doe to financial problems. The human resources were recruited from SKPD, academician, professional, society figures, LSM who concern on gender meanstreaming. They play the role more on providing the service than giving information and empowerment. The last finding of the study showed that the involvement of local government, Health offices, social services, police, ministry of religion, prosecutors and social services have been effective.

  1. Knockdown of HSPA9 induces TP53-dependent apoptosis in human hematopoietic progenitor cells.

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    Tuoen Liu

    Full Text Available Myelodysplastic syndromes (MDS are the most common adult myeloid blood cancers in the US. Patients have increased apoptosis in their bone marrow cells leading to low peripheral blood counts. The full complement of gene mutations that contribute to increased apoptosis in MDS remains unknown. Up to 25% of MDS patients harbor and acquired interstitial deletion on the long arm of chromosome 5 [del(5q], creating haploinsufficiency for a large set of genes including HSPA9. Knockdown of HSPA9 in primary human CD34+ hematopoietic progenitor cells significantly inhibits growth and increases apoptosis. We show here that HSPA9 knockdown is associated with increased TP53 expression and activity, resulting in increased expression of target genes BAX and p21. HSPA9 protein interacts with TP53 in CD34+ cells and knockdown of HSPA9 increases nuclear TP53 levels, providing a possible mechanism for regulation of TP53 by HSPA9 haploinsufficiency in hematopoietic cells. Concurrent knockdown of TP53 and HSPA9 rescued the increased apoptosis observed in CD34+ cells following knockdown of HSPA9. Reduction of HSPA9 below 50% results in severe inhibition of cell growth, suggesting that del(5q cells may be preferentially sensitive to further reductions of HSPA9 below 50%, thus providing a genetic vulnerability to del(5q cells. Treatment of bone marrow cells with MKT-077, an HSPA9 inhibitor, induced apoptosis in a higher percentage of cells from MDS patients with del(5q compared to non-del(5q MDS patients and normal donor cells. Collectively, these findings indicate that reduced levels of HSPA9 may contribute to TP53 activation and increased apoptosis observed in del(5q-associated MDS.

  2. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes.

    Science.gov (United States)

    Petitjean, A; Achatz, M I W; Borresen-Dale, A L; Hainaut, P; Olivier, M

    2007-04-02

    A large amount of data is available on the functional impact of missense mutations in TP53 and on mutation patterns in many different cancers. New data on mutant p53 protein function, cancer phenotype and prognosis have recently been integrated in the International Agency for Research on Cancer TP53 database (http://www-p53.iarc.fr/). Based on these data, we summarize here current knowledge on the respective roles of mutagenesis and biological selection of mutations with specific functional characteristic in shaping the patterns and phenotypes of mutations observed in human cancers. The main conclusion is that intrinsic mutagenicity rates, loss of transactivation activities, and to a lesser extent, dominant-negative activities are the main driving forces that determine TP53 mutation patterns and influence tumor phenotype. In contrast, current experimental data on the acquisition of oncogenic activities (gain of function) by p53 mutants are too scarce and heterogenous to assess whether this property has an impact on tumor development and outcome. In the case of inherited TP53 mutations causing Li-Fraumeni and related syndromes, the age at onset of some tumor types is in direct relation with the degree of loss of transactivation capacity of missense mutations. Finally, studies on large case series demonstrate that TP53 mutations are independent markers of bad prognosis in breast and several other cancers, and that the exact type and position of the mutation influences disease outcome. Further studies are needed to determine how TP53 haplotypes or loss of alleles interact with mutations to modulate their impact on cancer development and prognosis.

  3. Intronic TP53 Germline Sequence Variants Modify the Risk in German Breast/Ovarian Cancer Families

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    Liu Xuan

    2004-07-01

    Full Text Available Abstract To establish the contribution of TP53 germline mutations to familial breast/ovarian cancer in Germany we screened the complete coding region of the TP53 gene in a series of German breast/ovarian cancer families negative for mutations in the BRCA1 and BRCA2 genes. Two different intronic TP53 sequence variants were identified in 6/48 (12.5% breast/ovarian cancer families. A novel A to T nucleotide change at position 17708 in intron 10 segregating with the disease was detected in three breast cancer families (6.2%. One 17708 A>T-associated breast tumour showed loss of the wild-type allele. This variant was also found in 5/112 (4.5% healthy controls indicating that it is a polymorphism. A second sequence variant changing a G to C at position 13964 in intron 6 not segregating with the disease was found in two breast cancer families and one breast-ovarian cancer family (6.2%. This variant has previously been shown to occur at an elevated frequency in hereditary breast cancer patients from North America and to be of functional importance leading to inhibition of apoptosis and prolongation of cell survival after DNA-damage. Screening of 185 consecutive unselected German breast cancer patients revealed the 13964 G>C variant in four patients (2.2%. Immunohistochemical analysis of the TP53 protein showed negative immunoreactivity in normal and tumour tissues of one 17708 A>T and six 13964 G>C carriers. TP53 overexpression was detected in the tumour tissue of one sporadic breast cancer patient carrying the 13964 G>C variant. Our results show that intronic changes of the TP53 gene may act as or be associated with risk modifiers in familial breast cancer.

  4. TP0326, a Treponema pallidum β-Barrel Assembly Machinery A (BamA) Ortholog and Rare Outer Membrane Protein

    Science.gov (United States)

    Desrosiers, Daniel C.; Anand, Arvind; Luthra, Amit; Dunham-Ems, Star M; LeDoyt, Morgan; Cummings, Michael A. D.; Eshghi, Azad; Cameron, Caroline E.; Cruz, Adriana R.; Salazar, Juan C.; Caimano, Melissa J.; Radolf, Justin D.

    2011-01-01

    SUMMARY Definitive identification of Treponema pallidum (Tp) rare outer membrane proteins (OMPs) has long eluded researchers. TP0326, the sole protein in Tp with sequence homology to a Gram-negative OMP, belongs to the BamA family of proteins essential for OM biogenesis. Structural modeling predicted that five polypeptide transport-associated (POTRA) domains comprise the N-terminus of TP0326, while the C-terminus forms an 18-stranded amphipathic β-barrel. Circular dichroism, heat-modifiability by SDS-PAGE, Triton X-114 phase partitioning and liposome incorporation supported these topological predictions and confirmed that the β-barrel is responsible for the native protein's amphiphilicity. Expression analyses revealed that native TP0326 is expressed at low abundance, while a protease-surface accessibility assay confirmed surface exposure. Size-exclusion chromatography and blue native polyacrylamide gel electrophoresis revealed a modular Bam complex in Tp considerably larger than that of E. coli. Non-orthologous ancillary factors and self-association of TP0326 via its β-barrel may both contribute to the Bam complex. Tp-infected rabbits mount a vigorous antibody response to both POTRA and β-barrel portions of TP0326, whereas humans with secondary syphilis respond predominantly to POTRA. The syphilis spirochete appears to have devised a stratagem for harnessing the Bam pathway while satisfying its need to limit surface antigenicity. PMID:21488980

  5. TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development

    Science.gov (United States)

    Volodko, Natalia; Salla, Mohamed; Eksteen, Bertus; Fedorak, Richard N; Huynh, Hien Q; Baksh, Shairaz

    2015-01-01

    AIM: To investigate the association between tumor protein 53 (TP53) codon 72 polymorphisms and the risk for inflammatory bowel disease (IBD) development. METHODS: Numerous genetic and epigenetic drivers have been identified for IBD including the TP53 gene. Pathogenic mutations in TP53 gene have only been reported in 50% of colorectal cancer (CRC) patients. A single nucleotide polymorphism (SNP) in the TP53 gene resulting in the presence of either arginine (Arg) or proline (Pro) or both at codon 72 was shown to alter TP53 tumor-suppressor properties. This SNP has been investigated as a risk factor for numerous cancers, including CRC. In this study we analyzed TP53 codon 72 polymorphism distribution in 461 IBD, 181 primary sclerosing cholangitis patients and 62 healthy controls. Genotyping of TP53 was performed by sequencing and restriction fragment length polymorphism analysis of genomic DNA extracted from peripheral blood. RESULTS: The most frequent TP53 genotype in IBD patients was Arg/Arg occurring in 54%-64% of cases (and in only 32% of controls). Arg/Pro was the most prevalent genotype in controls (53%) and less common in patients (31%-40%). Pro/Pro frequency was not significantly different between controls and IBD patients. CONCLUSION: The data suggests that the TP53 codon 72 Arg/Arg genotype is associated with increased risk for IBD development. PMID:26420962

  6. Lack of mutations in the TP53 tumor suppressor gene exons 5 to 8 in Fanconi's anemia.

    Science.gov (United States)

    Jonveaux, P; Le Coniat, M; Grausz, D; Berger, R

    1991-01-01

    The TP53 gene is considered to be a negative regulator of cell growth whose inactivation is an important step in the development or progression of malignancies. Recently, germ line TP53 mutations have been detected in a familial cancer syndrome, the dominantly inherited Li-Fraumeni syndrome. Using single strand conformation polymorphism analysis of PCR products, we looked for TP53 mutations in DNA of patients with Fanconi anemia, an autosomal recessive disease characterized by increased predisposition to neoplasia. We did not find any TP53 mutation in 13 patients, suggesting that this tumor suppressor gene is not directly involved in the cancer susceptibility observed in Fanconi's anemia.

  7. Profile of anti-Tp47 antibodies in patients with positive serology for syphilis analized by Western Blot.

    Science.gov (United States)

    Miranda, Ana Paula Félix de; Sato, Neuza Satomi

    2008-04-01

    In Brazil, syphilis is still a great problem of public health. Serological test is essential for syphilis diagnosis and the current trend is the use of recombinant antigen in the treponemal tests, due to its confirmed higher sensibility and specificity. The purpose of the present study was to analyze the profile of anti-Tp47 antibodies in patients with positive serology for syphilis. One hundred positive sera samples were analyzed by Western Blot (WB) technique, using the recombinant antigen (rTp47). Ten of them did not present antibodies against the fraction rTp47, the results were confirmed by WB using native T. pallidum antigen. All ten samples had antibodies against the fractions Tp17 and Tp15 and presented low reactivity in VDRL, negative results or title below than 1:4. Considering that VDRL is used for therapeutic monitoring due to seroreversion of nontreponemal antibodies in response to the treatment, and that some studies reported loss of treponemal antibodies after treatment, we could speculate if these ten samples are cases of serological memory from patients previously treated for syphilis. In addition, although several features state the Tp47 fraction as one of the major antigenic components, based on our results we point out to the importance of including other antigenic proteins such as Tp17 and Tp15 in addition to Tp47 in tests for serological screening of syphilis.

  8. Stimulation of antibody formation through polypeptide thymic fraction (TP) in irradiated animals. [X radiation, rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Milcu, S.M.; Potop, I.; Boeru, V.; Olinici, N.

    1975-02-28

    Total sublethal irradiation with x-rays of the rabbits immunized with the Salmonella TH 901 antigen induces a decrease in the serum antibody level as compared with nonirradiated controls. Administration of the polypeptide thymic (TP) extract to rabbits immunized with antigen and x-rayed in similar conditions produces a stimulation of antibody formation in these animals as compared to the nontreated controls. The level of antibodies is altered in the animals irradiated, and treatment with the TP extract shows that it has a protective effect on the organism.

  9. Long term steam oxidation of TP 347H FG in power plants

    DEFF Research Database (Denmark)

    Hansson, Anette Nørgaard; Korcakova, Leona; Hald, John

    2005-01-01

    The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in test superheater loops in a Danish coal-fired power plant. The steamside oxide layer was investigated with scanning electron microscopy and energy dispersive Xray diffract......The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in test superheater loops in a Danish coal-fired power plant. The steamside oxide layer was investigated with scanning electron microscopy and energy dispersive Xray...

  10. Development and translational imaging of a TP53 porcine tumorigenesis model.

    Science.gov (United States)

    Sieren, Jessica C; Meyerholz, David K; Wang, Xiao-Jun; Davis, Bryan T; Newell, John D; Hammond, Emily; Rohret, Judy A; Rohret, Frank A; Struzynski, Jason T; Goeken, J Adam; Naumann, Paul W; Leidinger, Mariah R; Taghiyev, Agshin; Van Rheeden, Richard; Hagen, Jussara; Darbro, Benjamin W; Quelle, Dawn E; Rogers, Christopher S

    2014-09-01

    Cancer is the second deadliest disease in the United States, necessitating improvements in tumor diagnosis and treatment. Current model systems of cancer are informative, but translating promising imaging approaches and therapies to clinical practice has been challenging. In particular, the lack of a large-animal model that accurately mimics human cancer has been a major barrier to the development of effective diagnostic tools along with surgical and therapeutic interventions. Here, we developed a genetically modified porcine model of cancer in which animals express a mutation in TP53 (which encodes p53) that is orthologous to one commonly found in humans (R175H in people, R167H in pigs). TP53(R167H/R167H) mutant pigs primarily developed lymphomas and osteogenic tumors, recapitulating the tumor types observed in mice and humans expressing orthologous TP53 mutant alleles. CT and MRI imaging data effectively detected developing tumors, which were validated by histopathological evaluation after necropsy. Molecular genetic analyses confirmed that these animals expressed the R167H mutant p53, and evaluation of tumors revealed characteristic chromosomal instability. Together, these results demonstrated that TP53(R167H/R167H) pigs represent a large-animal tumor model that replicates the human condition. Our data further suggest that this model will be uniquely suited for developing clinically relevant, noninvasive imaging approaches to facilitate earlier detection, diagnosis, and treatment of human cancers.

  11. Development and translational imaging of a TP53 porcine tumorigenesis model

    Science.gov (United States)

    Sieren, Jessica C.; Meyerholz, David K.; Wang, Xiao-Jun; Davis, Bryan T.; Newell, John D.; Hammond, Emily; Rohret, Judy A.; Rohret, Frank A.; Struzynski, Jason T.; Goeken, J. Adam; Naumann, Paul W.; Leidinger, Mariah R.; Taghiyev, Agshin; Van Rheeden, Richard; Hagen, Jussara; Darbro, Benjamin W.; Quelle, Dawn E.; Rogers, Christopher S.

    2014-01-01

    Cancer is the second deadliest disease in the United States, necessitating improvements in tumor diagnosis and treatment. Current model systems of cancer are informative, but translating promising imaging approaches and therapies to clinical practice has been challenging. In particular, the lack of a large-animal model that accurately mimics human cancer has been a major barrier to the development of effective diagnostic tools along with surgical and therapeutic interventions. Here, we developed a genetically modified porcine model of cancer in which animals express a mutation in TP53 (which encodes p53) that is orthologous to one commonly found in humans (R175H in people, R167H in pigs). TP53R167H/R167H mutant pigs primarily developed lymphomas and osteogenic tumors, recapitulating the tumor types observed in mice and humans expressing orthologous TP53 mutant alleles. CT and MRI imaging data effectively detected developing tumors, which were validated by histopathological evaluation after necropsy. Molecular genetic analyses confirmed that these animals expressed the R167H mutant p53, and evaluation of tumors revealed characteristic chromosomal instability. Together, these results demonstrated that TP53R167H/R167H pigs represent a large-animal tumor model that replicates the human condition. Our data further suggest that this model will be uniquely suited for developing clinically relevant, noninvasive imaging approaches to facilitate earlier detection, diagnosis, and treatment of human cancers. PMID:25105366

  12. Resolvase-like recombination performed by the TP901-1 integrase

    DEFF Research Database (Denmark)

    Breüner, A.; Brøndsted, Lone; Hammer, Karin

    2001-01-01

    are consistent with the hypothesis that the TC dinucleotide constitutes the TP901-1 overlap region. A 2 bp overlap region has been observed in recombination reactions catalysed by all other members of the resolvase/invertase family tested so far. By selecting for attB sites with a decreased ability...

  13. Microstructure and properties of TP2 copper tube with La microalloying by horizontal continuous casting

    Directory of Open Access Journals (Sweden)

    Jin-hu Wu

    2018-01-01

    Full Text Available The TP2 copper tube was prepared with La microalloying by horizontal continuous casting (HCC. The absorptivity of La and its effects on microstructure, tensile and corrosion properties of HCC TP2 copper tube were studied by means of the inductively coupled plasma optical emission spectrometer (ICP-OES, optical microscope (OM, scanning electron microscope (SEM and potentiodynamic polarization measurements. The results show that the absorptivity of La in the HCC TP2 copper tube is about 15% under antivacuum conditions due to the good chemical activities of La. The impurity elements in copper tube such as O, S, Pb and Si can be significantly reduced, and the average columnar dendrite spacing of the copper tube can also be reduced from 2.21 mm to 0.93 mm by adding La. The ultimate tensile strength and the elongation with and without La addition are almost unchanged. However, the annual corrosion rate of the HCC TP2 copper tube is reduced from 10.18 mm•a-1 to 9.37 mm•a-1 by the purification effect of trace La.

  14. Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer

    DEFF Research Database (Denmark)

    Holmila, Reetta; Bornholdt, Jette; Heikkilä, Pirjo

    2010-01-01

    to wood dust, using capillary electrophoresis single-strand conformation polymorphism analysis and direct sequencing. A significant association between wood-dust exposure and adenocarcinoma histology was observed [adjusted odds ratio (OR) 12.6, 95% confidence interval (CI), 5.0-31.6]. TP53 mutations...

  15. Neural network predicts sequence of TP53 gene based on DNA chip

    DEFF Research Database (Denmark)

    Spicker, J.S.; Wikman, F.; Lu, M.L.

    2002-01-01

    We have trained an artificial neural network to predict the sequence of the human TP53 tumor suppressor gene based on a p53 GeneChip. The trained neural network uses as input the fluorescence intensities of DNA hybridized to oligonucleotides on the surface of the chip and makes between zero...

  16. New recurrent deletions in the PPARgamma and TP53 genes are associated with childhood myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Silveira, Cássia G T; Oliveira, Fábio M; Valera, Elvis T

    2009-01-01

    observed in 17 and 18 cases, respectively. Using quantitative RT-PCR, it was detected PPARgamma transcript downexpression in a subset of these cases. G-banding analysis revealed 17p deletions in a small number of these cases. One MDS therapy-related patient had neither a loss of PPARgamma nor TP53...

  17. A genomic region of lactococcal temperate bacteriophage TP901-1 encoding major virion proteins

    DEFF Research Database (Denmark)

    Johnsen, Mads G.; Appel, Karen Fuglede; Madsen, Hans Peter Lynge

    1996-01-01

    Two major structural proteins, MHP (major head protein) and MTP (major tail protein), from the lactococcal temperate phage TP901-1 were sequenced at their amino acid termini, and derived degenerate oligonucleotides were used to locate the corresponding genes in the phage genome. This genomic regi...

  18. Two TP53 germline mutations in a classical Li-Fraumeni syndrome family

    NARCIS (Netherlands)

    van Hest, Liselotte P.; Ruijs, Mariëlle W. G.; Wagner, Anja; van der Meer, Conny A.; Verhoef, Senno; van 't Veer, Laura J.; Meijers-Heijboer, Hanne

    2007-01-01

    Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited cancer predisposition syndrome characterized by a combination of tumors including sarcoma, breast cancer, brain tumors, adrenocortical carcinoma and leukemia. Germline mutations in the tumor suppressor gene TP53 are associated with LFS.

  19. The Relationship between TP53 Gene Status and Carboxylesterase 2 Expression in Human Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Momoko Ishimine

    2018-01-01

    Full Text Available Irinotecan (CPT-11 is an anticancer prodrug that is activated by the carboxylesterase CES2 and has been approved for the treatment of many types of solid tumors, including colorectal cancer. Recent studies with cell lines show that CES2 expression is regulated by the tumor suppressor protein p53. However, clinical evidence for this regulatory mechanism in cancer is lacking. In this study, we examined the relationship between TP53 gene status and CES2 expression in human colorectal cancer. Most colorectal cancer specimens (70%; 26 of 37 showed lower CES2 mRNA levels (≥1.5-fold lower than the adjacent normal tissue, and only 30% (12 of 37 showed similar (<1.5-fold lower or higher CES2 mRNA levels. However, TP53 gene sequencing revealed no relationship between CES2 downregulation and TP53 mutational status. Moreover, while colorectal cancer cells expressing wild-type p53 exhibited p53-dependent upregulation of CES2, PRIMA-1MET, a drug that restores the transcriptional activity of mutant p53, failed to upregulate CES2 expression in cells with TP53 missense mutations. These results, taken together, suggest that CES2 mRNA expression is decreased in human colorectal cancer independently of p53.

  20. Field test results for steam oxidation of TP347H FG - growth of inner oxide

    DEFF Research Database (Denmark)

    Montgomery, Melanie; Jianmin, Jia; Larsen, OH

    2005-01-01

    A series of field tests have been conducted with TP347H FG in test superheater loops in coal-fired and biomass fired boilers of steam pressure 256 and 91 bar respectively. The exposure times are from 3,500 to 30,000 hours and the temperature range is from 450-630¢XC. The morphology, composition...

  1. Analysis of the collar-whisker structure of temperate lactococcal bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Vegge, Christina Skovgaard; Neve, Horst; Brøndsted, Lone

    2006-01-01

    Proteins homologous to the protein NPS (neck passage structure) are widespread among lactococcal phages. We investigated the hypothesis that NPS is involved in the infection of phage TP901-1 by analysis of an NPS mutant. NPS was determined to form a collar-whisker complex but was shown to be none...

  2. Key Players in the Genetic Switch of Bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Alsing, Anne; Pedersen, Margit; Sneppen, Kim

    2011-01-01

    the bistable genetic switch of bacteriophage TP901-1 through experiments and statistical mechanical modeling. We examine the activity of the lysogenic promoter Pr at different concentrations of the phage repressor, CI, and compare the effect of CI on Pr in the presence or absence of the phage-encoded MOR...

  3. TP53 mutations in clinically normal mucosa adjacent to oral carcinomas

    DEFF Research Database (Denmark)

    Thode, C; Bilde, A; Von Buchwald, C

    2010-01-01

    products were separated by denatured gradient gel electrophoresis. Fragments with a deviant DGEE pattern were sequenced. RESULTS: TP53 mutations were found in six of 18 tumours. Fourteen specimens contained histologically normal mucosa adjacent to the tumour; 13 of these showed small clusters of p53...

  4. TP53 Codon 72 Polymorphism and P53 Protein Expression in Colorectal Cancer Specimens in Isfahan

    Directory of Open Access Journals (Sweden)

    Mehdi Nikbahkt Dastjerdi

    2011-02-01

    Full Text Available The TP53 tumor suppressor gene plays important roles in genomic stability. A common polymorphism at codon 72 of TP53 gene has been associated with increased risk for many human cancers. The p53 protein is expressed in colorectal cancer, but the reported prevalence of its expression varies widely. In the present study, the p53 protein expression in different genotypes of its codon 72 , was investigated. We undertook a case-control study on 250 controls and 250 paraffin block specimens of sporadic colorectal adenocarcinomas from the city of Isfahan. PCR amplification of TP53 codon 72 polymorphism: TP53 codon 72 genotypes were detected by PCR using specific primer pairs for amplifying the proline or the arginine Alleles. The PCR reaction was done separately for each of the two polymorphic variants. The amplified products were subjected to electrophoresis on 1% agarose gel in 1× TBE buffer and visualized on a transilluminator using ethidium bromide. Immunohistochemical Staining: We evaluated the expression patterns of p53 protein, as potential prognostic marker in colorectal cancer specimens by immunohistochemical staining. Statistical analyses: The χ2-test was used to assess the significance of any difference in the prevalence of TP53 codon 72 polymorphism between colorectal cancer patients and controls. The odds ratio and 95% CI (confidence intervals was used as a measure of the strength of the association. Statistical significance level was set to P≤0.05. In control samples, the genotype distribution for TP53 polymorphism showed 30.4%, 45.2% and 24.4% for the arginine/arginine, arginine/proline and proline/proline genotypes, respectively. Allelic frequencies corresponded to 0.663 for the arginine allele and 0.338 for the proline allele. In the cancer group 38.8% of the cases were arginine/arginine, 40.4% were arginine/proline and 20.8% were proline/proline. The corresponding frequencies were 0.590 for the arginine allele and 0.410 for the

  5. Heterologous expression of the Treponema pallidum laminin-binding adhesin Tp0751 in the culturable spirochete Treponema phagedenis.

    Science.gov (United States)

    Cameron, Caroline E; Kuroiwa, Janelle M Y; Yamada, Mitsunori; Francescutti, Teresa; Chi, Bo; Kuramitsu, Howard K

    2008-04-01

    Treponema pallidum subsp. pallidum, the causative agent of syphilis, is an unculturable, genetically intractable bacterium. Here we report the use of the shuttle vector pKMR4PEMCS for the expression of a previously identified T. pallidum laminin-binding adhesin, Tp0751, in the nonadherent, culturable spirochete Treponema phagedenis. Heterologous expression of Tp0751 in T. phagedenis was confirmed via reverse transcriptase PCR analysis with tp0751 gene-specific primers and immunofluorescence analysis with Tp0751-specific antibodies; the latter assay verified the expression of the laminin-binding adhesin on the treponemal surface. Expression of Tp0751 within T. phagedenis was functionally confirmed via laminin attachment assays, in which heterologous Tp0751 expression conferred upon T. phagedenis the capacity to attach to laminin. Further, specific inhibition of the attachment of T. phagedenis heterologously expressing Tp0751 to laminin was achieved by using purified antibodies raised against recombinant T. pallidum Tp0751. This is the first report of heterologous expression of a gene from an unculturable treponeme in T. phagedenis. This novel methodology will significantly advance the field of syphilis research by allowing targeted investigations of T. pallidum proteins purported to play a role in pathogenesis, and specifically host cell attachment, in the nonadherent spirochete T. phagedenis.

  6. Tilapia Piscidin 4 (TP4 Stimulates Cell Proliferation and Wound Closure in MRSA-Infected Wounds in Mice

    Directory of Open Access Journals (Sweden)

    Hang-Ning Huang

    2015-05-01

    Full Text Available Antimicrobial peptides (AMPs are endogenous antibiotics that directly affect microorganisms, and also have a variety of receptor-mediated functions. One such AMP, Tilapia piscidin 4 (TP4, was isolated from Nile tilapia (Oreochromis niloticus; TP4 has antibacterial effects and regulates the innate immune system. The aim of the present study was to characterize the role of TP4 in the regulation of wound closure in mice and proliferation of a keratinocyte cell line (HaCaT and fibroblast cell line (Hs-68. In vitro, TP4 stimulated cell proliferation and activated collagen I, collagen III, and keratinocyte growth factor (KGF gene expression in Hs-68 cells, which induces keratin production by HaCaT cells. This effect was detectable at TP4 concentrations of 6.25 µg/mL in both cell lines. In vivo, TP4 was found to be highly effective at combating peritonitis and wound infection caused by MRSA in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. Taken together, our results indicate that TP4 enhances the survival rate of mice infected with the bacterial pathogen MRSA through both antimicrobial and wound closure activities mediated by epidermal growth factor (EGF, transforming growth factor (TGF, and vascular endothelial growth factor (VEGF. The peptide is likely involved in antibacterial processes and regulation of tissue homeostasis in infected wounds in mice. Overall, these results suggest that TP4 may be suitable for development as a novel topical agent for wound dressing.

  7. MGMT promoter hypermethylation is a frequent, early, and consistent event in astrocytoma progression, and not correlated with TP53 mutation

    NARCIS (Netherlands)

    F.H. Groenendijk (Floris); W. Taal (Walter); H.J. Dubbink (Erik Jan); C.R. Haarloo (Cathleen); M.C.M. Kouwenhoven (Mathilde); M.J. van den Bent (Martin); J.M. Kros (Johan); W.N.M. Dinjens (Winand)

    2011-01-01

    textabstractHypermethylation of the MGMT gene promoter and mutation of the TP53 tumor-suppressor gene are frequently present in diffuse astrocytomas. However, there is only anecdotal information about MGMT methylation status and TP53 mutations during progression of low-grade diffuse astrocytoma

  8. Human papillomavirus type 16 and TP53 mutation in oral cancer: matched analysis of the IARC multicenter study.

    NARCIS (Netherlands)

    Dai, M; Clifford, GM; Calvez, F le; Castellsague, X; Snijders, P.J.F.; Pawlita, M; Herrero, R; Hainaut, P; Franceschi, S

    2004-01-01

    TP53 mutations were analyzed in 35 human papillomavirus (HPV) type 16 DNA-positive cancers of the oral cavity and oropharynx and in 35 HPV DNA-negative cancers matched by subsite, country, sex, age, and tobacco and alcohol consumption. Wild-type TP53 was found more frequently in cancer specimens

  9. Recombinant Treponema pallidum protein Tp0965 activates endothelial cells and increases the permeability of endothelial cell monolayer.

    Directory of Open Access Journals (Sweden)

    Rui-Li Zhang

    Full Text Available The recombinant Treponema pallidum protein Tp0965 (rTp0965, one of the many proteins derived from the genome of T. pallidum subsp. pallidum, shows strong immunogenicity and immunoreactivity. In this study, we investigated the effects of rTp0965 on the endothelial barrier. Treatment of human umbilical vein endothelial cells (HUVECs with rTp0965 resulted in increased levels of ICAM-1, E-selectin, and MCP-1 mRNA and protein expression. These increases contributed to the adhesion and chemataxis of monocytes (THP-1 cells to HUVECs preincubated with rTp0965. In addition, rTp0965 induced reorganization of F-actin and decreased expression of claudin-1 in HUVECs. Interestingly, inhibition of the RhoA/ROCK signal pathway protected against rTp0965-induced higher endothelial permeability as well as transendothelial migration of monocytes. These data indicate that Tp0965 protein may play an important role in the immunopathogenesis of syphilis.

  10. TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients

    NARCIS (Netherlands)

    Braakhuis, B.J.M.; Rietbergen, M.M.; Buijze, M.; Snijders, P.J.F.; Bloemena, E.; Brakenhoff, R.H.; Leemans, C.R.

    2014-01-01

    Objective Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. Methods TP53 mutations

  11. Mutational analysis of the activator of late transcription, Alt , in the lactococcal bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Pedersen, Margit; Hammer, Karin

    2007-01-01

    An activator protein, Alt, synthesized during the early state of lytic infection is required for transcription of the late operon in the lactococcal phage TP901-1. In order to identify amino acid residues in the Alt protein required for activation of the TP901-1 late promoter, Plate, hydroxylamin...

  12. TP53 codon 72 polymorphism as a risk factor for cardiovascular disease in a Brazilian population

    Directory of Open Access Journals (Sweden)

    M.A.C. Smith

    2007-11-01

    Full Text Available TP53, a tumor suppressor gene, has a critical role in cell cycle, apoptosis and cell senescence and participates in many crucial physiological and pathological processes. Identification of TP53 polymorphism in older people and age-related diseases may provide an understanding of its physiology and pathophysiological role as well as risk factors for complex diseases. TP53 codon 72 (TP53:72 polymorphism was investigated in 383 individuals aged 66 to 97 years in a cohort from a Brazilian Elderly Longitudinal Study. We investigated allele frequency, genotype distribution and allele association with morbidities such as cardiovascular disease, type II diabetes, obesity, neoplasia, low cognitive level (dementia, and depression. We also determined the association of this polymorphism with serum lipid fractions and urea, creatinine, albumin, fasting glucose, and glycated hemoglobin levels. DNA was isolated from blood cells, amplified by PCR using sense 5'-TTGCCGTCCCAAGCAATGGATGA-3' and antisense 5'-TCTGGGAAGGGACAGAAGATGAC-3' primers and digested with the BstUI enzyme. This polymorphism is within exon 4 at nucleotide residue 347. Descriptive statistics, logistic regression analysis and Student t-test using the multiple comparison test were used. Allele frequencies, R (Arg = 0.69 and P (Pro = 0.31, were similar to other populations. Genotype distributions were within Hardy-Weinberg equilibrium. This polymorphism did not show significant association with any age-related disease or serum variables. However, R allele carriers showed lower HDL levels and a higher frequency of cardiovascular disease than P allele subjects. These findings may help to elucidate the physiopathological role of TP53:72 polymorphism in Brazilian elderly people.

  13. Evidence that TP_0144 of Treponema pallidum is a thiamine-binding protein.

    Science.gov (United States)

    Bian, Jiang; Tu, Youbin; Wang, Song-Mei; Wang, Xuan-Yi; Li, Chunhao

    2015-04-01

    Thiamine pyrophosphate (TPP), the biologically active form of thiamine (also known as vitamin B1), is an essential cofactor for several important enzymes involved in carbohydrate metabolism, and therefore, it is required for all living organisms. We recently found that a thiamine-binding protein (TDE_0143) is essential for the survival of Treponema denticola, an important bacterial pathogen that is associated with human periodontitis. In this report, we provide experimental evidence showing that TP_0144, a homolog of TDE_0143 from the syphilis spirochete Treponema pallidum, is a thiamine-binding protein that has biochemical features and functions that are similar to those of TDE_0143. First, structural modeling analysis reveal that both TDE_0143 and TP_0144 contain a conserved TPP-binding site and share similar structures to the thiamine-binding protein of Escherichia coli. Second, biochemical analysis shows that these two proteins bind to TPP with similar dissociation constant (Kd) values (TDE_0143, Kd of 36.50 nM; TP_0144, Kd of 32.62 nM). Finally, heterologous expression of TP_0144 in a ΔTDE_0143 strain, a previously constructed TDE_0143 mutant of T. denticola, fully restores its growth and TPP uptake when exogenous thiamine is limited. Collectively, these results indicate that TP_0144 is a thiamine-binding protein that is indispensable for T. pallidum to acquire exogenous thiamine, a key nutrient for bacterial survival. In addition, the studies shown in this report further underscore the feasibility of using T. denticola as a platform to study the biology and pathogenicity of T. pallidum and probably other uncultivable treponemal species as well. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Extremely high Tp53 mutation load in esophageal squamous cell carcinoma in Golestan Province, Iran.

    Directory of Open Access Journals (Sweden)

    Behnoush Abedi-Ardekani

    Full Text Available BACKGROUND: Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC. METHODOLOGY/PRINCIPAL FINDINGS: Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9%, including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 "hotspots" but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40% at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs. Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence. CONCLUSION/SIGNIFICANCE: ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis.

  15. EstimatingTP53Mutation Carrier Probability in Families with Li-Fraumeni Syndrome Using LFSPRO.

    Science.gov (United States)

    Peng, Gang; Bojadzieva, Jasmina; Ballinger, Mandy L; Li, Jialu; Blackford, Amanda L; Mai, Phuong L; Savage, Sharon A; Thomas, David M; Strong, Louise C; Wang, Wenyi

    2017-06-01

    Background: Li-Fraumeni syndrome (LFS) is associated with germline TP53 mutations and a very high lifetime cancer risk. Algorithms that assess a patient's risk of inherited cancer predisposition are often used in clinical counseling. The existing LFS criteria have limitations, suggesting the need for an advanced prediction tool to support clinical decision making for TP53 mutation testing and LFS management. Methods: Based on a Mendelian model, LFSPRO estimates TP53 mutation probability through the Elston-Stewart algorithm and consequently estimates future risk of cancer. With independent datasets of 1,353 tested individuals from 867 families, we evaluated the prediction performance of LFSPRO. Results: LFSPRO accurately predicted TP53 mutation carriers in a pediatric sarcoma cohort from MD Anderson Cancer Center in the United States, the observed to expected ratio (OE) = 1.35 (95% confidence interval, 0.99-1.80); area under the receiver operating characteristic curve (AUC) = 0.85 (0.75-0.93); a population-based sarcoma cohort from the International Sarcoma Kindred Study in Australia, OE = 1.62 (1.03-2.55); AUC = 0.67 (0.54-0.79); and the NCI LFS study cohort, OE = 1.28 (1.17-1.39); AUC = 0.82 (0.78-0.86). LFSPRO also showed higher sensitivity and specificity than the classic LFS and Chompret criteria. LFSPRO is freely available through the R packages LFSPRO and BayesMendel. Conclusions: LFSPRO shows good performance in predicting TP53 mutations in individuals and families in varied situations. Impact: LFSPRO is more broadly applicable than the current clinical criteria and may improve clinical management for individuals and families with LFS. Cancer Epidemiol Biomarkers Prev; 26(6); 837-44. ©2017 AACR . ©2017 American Association for Cancer Research.

  16. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression.

    Science.gov (United States)

    Jädersten, Martin; Saft, Leonie; Smith, Alexander; Kulasekararaj, Austin; Pomplun, Sabine; Göhring, Gudrun; Hedlund, Anette; Hast, Robert; Schlegelberger, Brigitte; Porwit, Anna; Hellström-Lindberg, Eva; Mufti, Ghulam J

    2011-05-20

    To determine the frequency of TP53 mutations and the level of p53 protein expression by immunohistochemistry (IHC) in low-risk myelodysplastic syndromes (MDS) with del(5q) and to assess their impact on disease progression. Pre- and postprogression bone marrow (BM) samples from 55 consecutive patients with International Prognostic Scoring System low risk (n = 32) or intermediate-1 risk (n = 23) were studied by next-generation sequencing of TP53. IHC for p53 was performed on 148 sequential BM samples. TP53 mutations with a median clone size of 11% (range, 1% to 54%) were detected in 10 patients (18%) already at an early phase of the disease. Mutations were equally common in low-risk and intermediate-1-risk patients and were associated with evolution to acute myeloid leukemia (5 of 10 v 7 of 45; P = .045). Nine of 10 patients carrying mutations showed more than 2% BM progenitors with strong p53 staining. The probability of a complete cytogenetic response to lenalidomide was lower in mutated patients (0 of 7 v 12 of 24; P = .024). By using sensitive deep-sequencing technology, we demonstrated that TP53 mutated populations may occur at an early disease stage in almost a fifth of low-risk MDS patients with del(5q). Importantly, mutations were present years before disease progression and were associated with an increased risk of leukemic evolution. TP53 mutations could not be predicted by common clinical features but were associated with p53 overexpression. Our findings indicate a previously unrecognized heterogeneity of the disease which may significantly affect clinical decision making.

  17. Influencia de las regiones de estabilidad del biorreactor

    OpenAIRE

    Paz Astudillo, Isabel Cristina; Cardona Alzate, Carlos Ariel

    2011-01-01

    Influence of bioreactor stability regions in the efficient production of fuel ethanol Título corto: Influencia de las regiones de estabilidad en la producción de alcohol carburanteResumen Colombia ha desarrollado un proyecto ambicioso en la producción de alcohol carburante, y actualmente es uno de los países líderes de América Latina en la producción de biocombustibles. No obstante, algunas de sus plantas industriales productoras de etanol presentan problemas durante el arranque y la operació...

  18. Influencias de Miguel de Unamuno en Ernesto Sábato

    OpenAIRE

    Hermosilla Sánchez, Alejandro

    2007-01-01

    [ES] El artículo tiene como objetivo estudiar las influencias que el pensamiento de Unamuno ha ejercido sobre la obra de Ernesto Sábato y otros autores argentinos. Para conseguir este objetivo, el artículo analiza la particular interpretación de Unamuno del mito de Caín y Abel y observa cómo la misma ha sido fundamental para delimitar los parámetros a través de los que la literatura argentina y, concretamente, la obra de Sábato trabaja. [EN] The article has like as objective to study the i...

  19. LOH rather than genotypes of TP53 codon 72 is associated with disease-free survival in primary breast cancer

    DEFF Research Database (Denmark)

    Kyndi, Marianne; Alsner, Jan; Hansen, Lise Lotte

    2006-01-01

    Mutations in the TP53 gene are a well-documented strong prognostic factor in breast cancer. A prognostic value of the Arg72Pro polymorphism of the TP53 gene is more contradictory. We assessed TP53 mutations and genotypes of the Arg72Pro polymorphism in a study including 204 Danish women. Patients......-free survival was found for patients with LOH and retention of the Pro allele as compared to patients with LOH and retention of the Arg allele and patients with no LOH (p = 0.05). In conclusion, we find a highly significant prognostic value of TP53 mutations but find a possible prognostic value of the Arg72Pro...... with mutations in the TP53 gene had a significant reduction in disease-free survival of breast cancer (p mutations nor with disease-free survival (p = 0.4). Among heterozygous patients a reduction in disease...

  20. TP53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk: a case control study in a Chinese population

    International Nuclear Information System (INIS)

    Li, Yanli; Su, Jia; Cai, Lin; Yu, Shunzhang; Zhang, Zuo-Feng; Mu, Lina; Chang, Shen-Chih; Niu, Rungui; Liu, Li; Crabtree-Ide, Christina R; Zhao, Baoxing; Shi, Jianping; Han, Xiaoyou; Li, Jiawei

    2013-01-01

    A pathway-based genotyping analysis suggested rs2078486 was a novel TP53 SNP, but very few studies replicate this association. TP53 rs1042522 is the most commonly studied SNP, but very few studies examined its potential interaction with environmental factors in relation to lung cancer risk. This study aims to examine associations between two TP53 single-nucleotide polymorphisms (SNPs) (rs2078486, rs1042522), their potential interaction with environmental factors and risk of lung cancer. A case–control study was conducted in Taiyuan, China. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Multiplicative and additive interactions between TP53 SNPs and lifestyle factors were evaluated. Variant TP53 rs2078486 SNP was significantly associated with elevated lung cancer risk among smokers (OR: 1.70, 95% CI: 1.08 - 2.67) and individuals with high indoor air pollution exposure (OR: 1.51, 95% CI: 1.00-2.30). Significant or borderline significant multiplicative and additive interactions were found between TP53 rs2078486 polymorphism with smoking and indoor air pollution exposure. The variant genotype of TP53 SNP rs1042522 significantly increased lung cancer risk in the total population (OR: 1.57, 95% CI: 1.11-2.21), but there was no evidence of heterogeneity among individuals with different lifestyle factors. This study confirmed that TP53 rs2078486 SNP is potentially a novel TP53 SNP that may affect lung cancer risk. Our study also suggested potential synergetic effects of TP53 rs2078486 SNP with smoking and indoor air pollution exposure on lung cancer risk

  1. Specific mutation screening of TP53 gene by low-density DNA microarray

    Directory of Open Access Journals (Sweden)

    Angélica Rangel-López

    2009-01-01

    Full Text Available Angélica Rangel-López1–3, Alfonso Méndez-Tenorio3, Kenneth L Beattie4, Rogelio Maldonado3, Patricia Mendoza1, Guelaguetza Vázquez1, Carlos Pérez-Plasencia5, Martha Sánchez2, Guillermo Navarro6, Mauricio Salcedo11Laboratorio de Oncología Genómica, Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología, CMN Siglo XXI-IMSS, Mexico City, Mexico; 2Unidad de Investigación Médica en Enfermedades Nefrológicas, Hospital de Especialidades, CMN Siglo XXI-IMSS, Mexico City; Mexico; 3Laboratorio de Biotecnología y Bioinformática Genómica, Escuela Nacional de Ciencias Biológicas, IPN Mexico City, Mexico; 4Amerigenics, Inc., Crossville, TN, USA; 5Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México UNAM, Instituto Nacional de Cancerología INCAN, Mexico City, Mexico; 6Laboratorio de Organometálicos UNAM, Mexico City, MexicoAbstract: TP53 is the most commonly mutated gene in human cancers. Approximately 90% of mutations in this gene are localized between domains encoding exons 5 to 8. The aim of this investigation was to examine the ability of the low density DNA microarray with the assistance of double tandem hybridization platform to characterize TP53 mutational hotspots in exons 5, 7, and 8 of the TP53. Nineteen capture probes specific to each potential mutation site were designed to hybridize to specific site. Virtual hybridization was used to predict the stability of hybridization of each capture probe with the target. Thirty-three DNA samples from different sources were analyzed for mutants in these exons. A total of 32 codon substitutions were found by DNA sequencing. 24 of them a showed a perfect correlation with the hybridization pattern system and DNA sequencing analysis of the regions scanned. Although in this work we directed our attention to some of the most representative mutations of the TP503 gene, the results suggest

  2. FOXP1 and TP63 involvement in the progression of myelodysplastic syndrome with 5q- and additional cytogenetic abnormalities

    International Nuclear Information System (INIS)

    L’Abbate, Alberto; Tagliafico, Enrico; Minoia, Carla; De Tullio, Giacoma; Guarini, Attilio; Testoni, Nicoletta; Agostinelli, Claudio; Storlazzi, Clelia Tiziana; Lo Cunsolo, Crocifissa; Macrì, Ettore; Iuzzolino, Paolo; Mecucci, Cristina; Doglioni, Claudio; Coco, Michelina; Muscarella, Lucia Anna; Salati, Simona

    2014-01-01

    The progression of low-risk del(5q) myelodysplastic syndrome to acute myeloid leukemia is increased when associated with mutations of TP53, or with additional chromosomal abnormalities. However, to date the prognostic impact and molecular consequences of these rearrangements were poorly investigated. Single additional alterations to del(5q) by balanced chromosome rearrangements were rarely found in myelodysplasia. In particular, balanced alterations involving TP63 and FOXP1 genes were never reported in the literature. Here we report on a 79-year woman with an aggressive form of myelodysplastic syndrome with del(5q), no TP53 mutation, and a novel complex rearrangement of chromosome 3 in bone marrow cells. Our results revealed that the FOXP1 and TP63 genes were both relocated along chromosome 3. Strikingly, immunohistochemistry analysis showed altered protein levels, disclosing that this rearrangement triggered the expression of FOXP1 and TP63 genes. FOXP1 was also found activated in other patients with myelodysplasia and acute myeloid leukemia, showing that it is an important, recurrent event. We document an apparent role of FOXP1 and TP63, up to now poorly documented, in the progression of MDS in our patient who is lacking mutations in the TP53 tumor suppressor gene normally associated with poor outcome in myelodysplastic syndrome with 5q-. Finally, our results may suggest a possible broader role of FOXP1 in the pathogenesis and progression of myelodysplasia and acute myeloid leukemia

  3. Use of tilapia piscidin 3 (TP3) to protect against MRSA infection in mice with skin injuries.

    Science.gov (United States)

    Huang, Han-Ning; Chan, Yi-Lin; Hui, Cho-Fat; Wu, Jen-Leih; Wu, Chang-Jer; Chen, Jyh-Yih

    2015-05-30

    Antimicrobial peptides (AMPs), represent promising agents for new therapeutic approaches of infected wound treatment, on account of their antimicrobial and wound closure activities, and low potential for inducing resistance. However, therapeutic applications of these AMPs are limited by their toxicity and low stability in vivo. Previously, we reported that the 23 amino-acid designer peptide TP3 possessed antimicrobial activities. Here, we analyzed the wound closure activities of TP3 both and in vivo. TP3 at doses of up to 40 μg/ml did not affect the viability of baby hamster kidney cells. Furthermore, TP3 was found to be highly effective at combating peritonitis and wound infection caused by MRSA in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. TP3 treatment increased survival by 100% at 8 days after infection, and accelerated the progression of proliferation, remodeling, and maturation of infected wounds. Taken together, our results indicate that TP3 enhances the rate of survival of mice infected with the bacterial pathogen MRSA through both antimicrobial and immunomodulatory effects. Overall, these results suggest that TP3 may be suitable for development as a novel topical agent for treatment of infected wounds.

  4. Laboratory and telescope demonstration of the TP3-WFS for the adaptive optics segment of AOLI

    Science.gov (United States)

    Colodro-Conde, C.; Velasco, S.; Fernández-Valdivia, J. J.; López, R.; Oscoz, A.; Rebolo, R.; Femenía, B.; King, D. L.; Labadie, L.; Mackay, C.; Muthusubramanian, B.; Pérez Garrido, A.; Puga, M.; Rodríguez-Coira, G.; Rodríguez-Ramos, L. F.; Rodríguez-Ramos, J. M.; Toledo-Moreo, R.; Villó-Pérez, I.

    2017-05-01

    Adaptive Optics Lucky Imager (AOLI) is a state-of-the-art instrument that combines adaptive optics (AO) and lucky imaging (LI) with the objective of obtaining diffraction-limited images in visible wavelength at mid- and big-size ground-based telescopes. The key innovation of AOLI is the development and use of the new Two Pupil Plane Positions Wavefront Sensor (TP3-WFS). The TP3-WFS, working in visible band, represents an advance over classical wavefront sensors such as the Shack-Hartmann WFS because it can theoretically use fainter natural reference stars, which would ultimately provide better sky coverages to AO instruments using this newer sensor. This paper describes the software, algorithms and procedures that enabled AOLI to become the first astronomical instrument performing real-time AO corrections in a telescope with this new type of WFS, including the first control-related results at the William Herschel Telescope.

  5. Clinical characteristics and registry-validated extended pedigrees of germline TP53 mutation carriers in Denmark

    DEFF Research Database (Denmark)

    Stoltze, Ulrik; Skytte, Anne-Bine; Roed, Henriette

    2018-01-01

    INTRODUCTION: TP53 mutation carrier (Li-Fraumeni Syndrome, LFS) cohort studies often suffer from lack of extensive pedigree exploration. METHODS: We performed a nation-wide exploration of TP53 mutation carrier families identified through all clinical genetics departments in Denmark. Pedigrees were...... expanded and verified using unique national person identification, cancer, cause of death, pathology, and church registries. RESULTS: We identified 30 confirmed, six obligate and 14 assumed carriers in 15 families harboring 14 different mutations, including five novel and three de novo germline mutations....... All but two (96%) developed cancer by age 54 years [mean debut age; 29.1 y., median 33.0 y., n = 26 (17F, 9M), range 1-54 y

  6. Rhabdomyosarcoma-associated renal cell carcinoma: a link with constitutional Tp53 mutation.

    LENUS (Irish Health Repository)

    Curry, Sarah

    2012-02-01

    The 2004 World Health Organization classification includes the new entity "neuroblastoma-associated renal cell carcinoma." The pathogenetic link between these entities is unknown as yet. The patient reported herein developed renal cell carcinoma after anaplastic embryonal rhabdomyosarcoma, a previously unknown association. The 2nd malignancy developed very soon after the 1st one, prompting concern for inherent cancer predisposition rather than a therapy-induced 2nd malignancy. A variety of features raised suspicion for Tp53 mutation, and indeed a pathogenic germline Tp53 mutation was identified in this child, despite a negative family history for Li-Fraumeni syndrome. Consideration of underlying predisposition is advocated in the context of rapid evolution of 2nd childhood malignancy.

  7. Fischer-344 Tp53-knockout rats exhibit a high rate of bone and brain neoplasia with frequent metastasis

    Directory of Open Access Journals (Sweden)

    Sarah A. Hansen

    2016-10-01

    Full Text Available Somatic mutations in the Tp53 tumor suppressor gene are the most commonly seen genetic alterations in cancer, and germline mutations in Tp53 predispose individuals to a variety of early-onset cancers. Development of appropriate translational animal models that carry mutations in Tp53 and recapitulate human disease are important for drug discovery, biomarker development and disease modeling. Current Tp53 mouse and rat models have significant phenotypic and genetic limitations, and often do not recapitulate certain aspects of human disease. We used a marker-assisted speed congenic approach to transfer a well-characterized Tp53-mutant allele from an outbred rat to the genetically inbred Fischer-344 (F344 rat to create the F344-Tp53tm1(EGFP-PacQly/Rrrc (F344-Tp53 strain. On the F344 genetic background, the tumor spectrum shifted, with the primary tumor types being osteosarcomas and meningeal sarcomas, compared to the hepatic hemangiosarcoma and lymphoma identified in the original outbred stock model. The Fischer model is more consistent with the early onset of bone and central nervous system sarcomas found in humans with germline Tp53 mutations. The frequency of osteosarcomas in F344-Tp53 homozygous and heterozygous animals was 57% and 36%, respectively. Tumors were highly representative of human disease radiographically and histologically, with tumors found primarily on long bones with frequent pulmonary metastases. Importantly, the rapid onset of osteosarcomas in this promising new model fills a current void in animal models that recapitulate human pediatric osteosarcomas and could facilitate studies to identify therapeutic targets.

  8. LncRNA-TP53TG1 Participated in the Stress Response Under Glucose Deprivation in Glioma.

    Science.gov (United States)

    Chen, Xin; Gao, Yang; Li, Deheng; Cao, Yiqun; Hao, Bin

    2017-12-01

    Gliomas are the most common brain tumors of the center nervous system. And long non-coding RNAs (lncRNAs) are non-protein coding transcripts, which have been considered as one type of gene expression regulator for cancer development. In this study, we investigated the role of lncRNA-TP53TG1 in response to glucose deprivation in human gliomas. The expression levels of TP53TG1 in glioma tissues and cells were analyzed by qRT-PCR. In addition, the influence of TP53TG1 on glucose metabolism related genes at the mRNA level during both high and low glucose treatment was detected by qRT-PCR. MTT, clonogenicity assays, and flow cytometry were performed to detect the cell proliferation and cell apoptosis. Furthermore, the migration of glioma cells was examined by Transwell assays. The expression of TP53TG1 was significantly higher in human glioma tissues or cell lines compared with normal brain tissue or NHA. Moreover, TP53TG1 and some tumor glucose metabolism related genes, such as GRP78, LDHA, and IDH1 were up-regulated significantly in U87 and LN18 cells under glucose deprivation. In addition, knockdown of TP53TG1 decreased cell proliferation and migration and down-regulated GRP78 and IDH1 expression levels and up-regulated PKM2 levels in U87 cells under glucose deprivation. However, over-expression of TP53TG1 showed the opposite tendency. Moreover, the effects of TP53TG1 were more remarkable in low glucose than that in high glucose. Our data showed that TP53TG1 under glucose deprivation may promote cell proliferation and migration by influencing the expression of glucose metabolism related genes in glioma. J. Cell. Biochem. 118: 4897-4904, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Increased Oxidative Damage in Carriers of the Germline TP53 p.R337H Mutation

    Science.gov (United States)

    Macedo, Gabriel S.; Lisbôa da Motta, Leonardo; Giacomazzi, Juliana; Netto, Cristina B. O.; Manfredini, Vanusa; S.Vanzin, Camila; Vargas, Carmen Regla; Hainaut, Pierre; Klamt, Fábio; Ashton-Prolla, Patricia

    2012-01-01

    Germline mutations in TP53 are the underlying defect of Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome, autosomal dominant disorders characterized by predisposition to multiple early onset cancers. In Brazil, a variant form of LFS/LFL is commonly detected because of the high prevalence of a founder mutation at codon 337 in TP53 (p.R337H). The p53 protein exerts multiple roles in the regulation of oxidative metabolism and cellular anti-oxidant defense systems. Herein, we analyzed the redox parameters in blood samples from p.R337H mutation carriers (C, n = 17) and non-carriers (NC, n = 17). We identified a significant increase in erythrocyte GPx activity and in plasma carbonyl content,an indicator of protein oxidative damage, in mutation carriers compared to non-carriers (P = 0.048 and P = 0.035, respectively). Mutation carriers also showed a four-fold increase in plasma malondialdehyde levels, indicating increased lipid peroxidation (NC = 40.20±0.71, C = 160.5±0.88, P<0.0001). Finally, carriers showed increased total antioxidant status but a decrease in plasma ascorbic acid content. The observed imbalance could be associated with deregulated cell bioenergetics and/or with increased inflammatory stress, two effects that may result from loss of wild-type p53 function. These findings provide the first evidence that oxidative damage occurs in carriers of a germline TP53 mutation, and these may have important implications regarding our understanding of the mechanisms responsible for germline TP53 p.R337H mutation-associated carcinogenesis. PMID:23056559

  10. Radiosensitivity and TP 53, EGFR amplification and LOH10 analysis of primary glioma cell cultures

    International Nuclear Information System (INIS)

    Gerlach, B.; Harder, A.H.; Slotman, B.J.; Sminia, P.; Hulsebos, T.J.M.; Leenstra, S.; Peter Vandertop, W.; Hartmann, K.A.

    2002-01-01

    Aim: Determination of in-vitro radiosensitivity and genetic alterations of cell cultures derived from human glioma biopsy tissue and established glioma cell lines. Material and Methods: Fresh brain tumor specimens of six patients were processed to early passage cell cultures. In addition the cell lines D 384 and Gli 6 were used. Cell cultures were irradiated with doses from 2 to 10 Gy. Following irradiation, cell survival was determined by clonogenic assay and survival curves were generated. The surviving fractions after 2 Gy (SF2) and 4 Gy (SF4) were used as radiosensitivity parameters. Genetic analysis included determination of the mutational and loss of heterozygosity (LOH) status of TP 53 (exons 5-8), the LOH 10- and epidermal growth factor receptor gene (EGFR) amplification status. Results: The SF2 and SF4 values ranged from 0.54 to 0.88 (mean: 0.70) and from 0.13 to 0.52 (mean: 0.32), respectively. Genetic alterations were found in the Gli 6 cell line and in two primary cell cultures. The genetic profile of Gli 6 showed LOH but no TP 53 mutation, complete LOH 10 and no EGFR amplification. The VU 15 cell culture showed TP 53 mutation but no LOH 10 or EGFR amplification, while VU 24 showed incomplete LOH 10, EGFR amplification and no TP 53 mutation. In the other four cell cultures and D 384 cell line no genetic alterations were diagnosed. Histopathological classification of glioblastoma multiforme and/or genetic alterations resulted in lower radiosensitivity. Conclusion: In this small series of early passage glioma cell cultures low radiosensitivity and alterations in cell regulatory genes were seen. Further testing of biological behavior in larger series of patient-derived material is ongoing. (orig.)

  11. A NEW GENERATION OF PARSEC-COLIBRI STELLAR ISOCHRONES INCLUDING THE TP-AGB PHASE

    Energy Technology Data Exchange (ETDEWEB)

    Marigo, Paola; Aringer, Bernhard; Chen, Yang; Dussin, Marco; Nanni, Ambra; Pastorelli, Giada; Rodrigues, Thaíse S.; Trabucchi, Michele; Bladh, Sara; Montalbán, Josefina [Dipartimento di Fisica e Astronomia Galileo Galilei, Università di Padova, Vicolo dell’Osservatorio 3, I-35122 Padova (Italy); Girardi, Léo [Osservatorio Astronomico di Padova—INAF, Vicolo dell’Osservatorio 5, I-35122 Padova (Italy); Bressan, Alessandro [SISSA, via Bonomea 365, I-34136 Trieste (Italy); Rosenfield, Philip [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Dalcanton, Julianne [Department of Astronomy, University of Washington, Box 351580, Seattle, WA 98195 (United States); Groenewegen, Martin A. T. [Koninklijke Sterrenwacht van België, Ringlaan 3, B-1180 Brussels (Belgium); Wood, Peter R. [Research School of Astronomy and Astrophysics, Australian National University, Cotter Road, Weston Creek, ACT 2611 (Australia)

    2017-01-20

    We introduce a new generation of PARSEC–COLIBRI stellar isochrones that includes a detailed treatment of the thermally pulsing asymptotic giant branch (TP-AGB) phase, covering a wide range of initial metallicities (0.0001 < Z {sub i} < 0.06). Compared to previous releases, the main novelties and improvements are use of new TP-AGB tracks and related atmosphere models and spectra for M and C-type stars; inclusion of the surface H+He+CNO abundances in the isochrone tables, accounting for the effects of diffusion, dredge-up episodes and hot-bottom burning; inclusion of complete thermal pulse cycles, with a complete description of the in-cycle changes in the stellar parameters; new pulsation models to describe the long-period variability in the fundamental and first-overtone modes; and new dust models that follow the growth of the grains during the AGB evolution, in combination with radiative transfer calculations for the reprocessing of the photospheric emission. Overall, these improvements are expected to lead to a more consistent and detailed description of properties of TP-AGB stars expected in resolved stellar populations, especially in regard to their mean photometric properties from optical to mid-infrared wavelengths. We illustrate the expected numbers of TP-AGB stars of different types in stellar populations covering a wide range of ages and initial metallicities, providing further details on the “C-star island” that appears at intermediate values of age and metallicity, and about the AGB-boosting effect that occurs at ages close to 1.6-Gyr for populations of all metallicities. The isochrones are available through a new dedicated web server.

  12. Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation.

    Science.gov (United States)

    Figueiredo, B C; Sandrini, R; Zambetti, G P; Pereira, R M; Cheng, C; Liu, W; Lacerda, L; Pianovski, M A; Michalkiewicz, E; Jenkins, J; Rodriguez-Galindo, C; Mastellaro, M J; Vianna, S; Watanabe, F; Sandrini, F; Arram, S B I; Boffetta, P; Ribeiro, R C

    2006-01-01

    An inherited germline P53 mutation has been identified in cases of childhood adrenocortical carcinoma (ACT), a neoplasm with a high incidence in southern Brazil. The penetrance of ACT in carriers of the point mutation, which encodes an arginine-to-histidine substitution at codon 337 of TP53 (R337H), has not been determined. To investigate the penetrance of childhood ACT in carriers of the R337H TP53 mutation. The family histories of 30 kindreds of 41 southern Brazilian children with ACT were obtained. A PCR based assay was used to detect this P53 mutation in a large number of relatives of children with ACT. In all, 927 individuals were tested for the mutation, 232 from the non-carrier and 695 (including the 40 probands) from the carrier parental lines. 40 children with ACT carried the TP53 R337H mutation; the remaining child with ACT was not tested. There was no evidence of Li-Fraumeni syndrome in any of the kindreds; however, seven met the criteria for Li-Fraumeni-like syndrome. The carrier parental line was identified in each kindred. Of the 695 individuals tested in the carrier parental line, 240 (34.5%) were positive for the mutation, while none of the 232 individuals in the other parental line carried the mutation. The penetrance of ACT was 9.9% (95% confidence interval, 8.7% to 11.1%). The TP53 R337H mutation dramatically increases predisposition to childhood ACT but not to other cancers, and explains the increased frequency of ACT observed in this geographic region.

  13. Lack of the host membrane protease FtsH hinders release of the Lactococcus lactis bacteriophage TP712.

    Science.gov (United States)

    Roces, Clara; Wegmann, Udo; Campelo, Ana B; García, Pilar; Rodríguez, Ana; Martínez, Beatriz

    2013-12-01

    The temperate bacteriophage TP712 was unable to plaque on Lactococcus lactis ΔftsH lacking the membrane protease FtsH and complementation in trans restored the WT phenotype. Absence of ftsH did not hinder phage adsorption, phage DNA delivery or activation of the lytic cycle. Thin sections revealed that TP712 virions appeared to be correctly assembled inside the ΔftsH host, but were not released. These virions were infective, demonstrating that a functional host FtsH is required by TP712 to proceed effectively with lysis of the host.

  14. Molecular Characterization of TP53 Gene in Human Populations Exposed to Low-Dose Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Igor Brasil-Costa

    2013-01-01

    Full Text Available Ionizing radiation, such as that emitted by uranium, may cause mutations and consequently lead to neoplasia in human cells. The TP53 gene acts to maintain genomic integrity and constitutes an important biomarker of susceptibility. The present study investigated the main alterations observed in exons 4, 5, 6, 7, and 8 of the TP53 gene and adjacent introns in Amazonian populations exposed to radioactivity. Samples were collected from 163 individuals. Occurrence of the following alterations was observed: (i a missense exchange in exon 4 (Arg72Pro; (ii 2 synonymous exchanges, 1 in exon 5 (His179His, and another in exon 6 (Arg213Arg; (iii 4 intronic exchanges, 3 in intron 7 (C → T at position 13.436; C → T at position 13.491; T → G at position 13.511 and 1 in intron 8 (T → G at position 13.958. Alteration of codon 72 was found to be an important risk factor for cancer development (P=0.024; OR=6.48; CI: 1.29–32.64 when adjusted for age and smoking. Thus, TP53 gene may be an important biomarker for carcinogenesis susceptibility in human populations exposed to ionizing radiation.

  15. A New Generation of PARSEC-COLIBRI Stellar Isochrones Including the TP-AGB Phase

    Science.gov (United States)

    Marigo, Paola; Girardi, Léo; Bressan, Alessandro; Rosenfield, Philip; Aringer, Bernhard; Chen, Yang; Dussin, Marco; Nanni, Ambra; Pastorelli, Giada; Rodrigues, Thaíse S.; Trabucchi, Michele; Bladh, Sara; Dalcanton, Julianne; Groenewegen, Martin A. T.; Montalbán, Josefina; Wood, Peter R.

    2017-01-01

    We introduce a new generation of PARSEC-COLIBRI stellar isochrones that includes a detailed treatment of the thermally pulsing asymptotic giant branch (TP-AGB) phase, covering a wide range of initial metallicities (0.0001 burning; inclusion of complete thermal pulse cycles, with a complete description of the in-cycle changes in the stellar parameters; new pulsation models to describe the long-period variability in the fundamental and first-overtone modes; and new dust models that follow the growth of the grains during the AGB evolution, in combination with radiative transfer calculations for the reprocessing of the photospheric emission. Overall, these improvements are expected to lead to a more consistent and detailed description of properties of TP-AGB stars expected in resolved stellar populations, especially in regard to their mean photometric properties from optical to mid-infrared wavelengths. We illustrate the expected numbers of TP-AGB stars of different types in stellar populations covering a wide range of ages and initial metallicities, providing further details on the “C-star island” that appears at intermediate values of age and metallicity, and about the AGB-boosting effect that occurs at ages close to 1.6-Gyr for populations of all metallicities. The isochrones are available through a new dedicated web server.

  16. TransportTP: A two-phase classification approach for membrane transporter prediction and characterization

    Directory of Open Access Journals (Sweden)

    Udvardi Michael K

    2009-12-01

    Full Text Available Abstract Background Membrane transporters play crucial roles in living cells. Experimental characterization of transporters is costly and time-consuming. Current computational methods for transporter characterization still require extensive curation efforts, especially for eukaryotic organisms. We developed a novel genome-scale transporter prediction and characterization system called TransportTP that combined homology-based and machine learning methods in a two-phase classification approach. First, traditional homology methods were employed to predict novel transporters based on sequence similarity to known classified proteins in the Transporter Classification Database (TCDB. Second, machine learning methods were used to integrate a variety of features to refine the initial predictions. A set of rules based on transporter features was developed by machine learning using well-curated proteomes as guides. Results In a cross-validation using the yeast proteome for training and the proteomes of ten other organisms for testing, TransportTP achieved an equivalent recall and precision of 81.8%, based on TransportDB, a manually annotated transporter database. In an independent test using the Arabidopsis proteome for training and four recently sequenced plant proteomes for testing, it achieved a recall of 74.6% and a precision of 73.4%, according to our manual curation. Conclusions TransportTP is the most effective tool for eukaryotic transporter characterization up to date.

  17. ESTADO DEL ARTE MPLS-TP CONMUTACIÓN MULTIPROTOCOLO MEDIANTE ETIQUETAS - PERFIL DE TRANSPORTE

    Directory of Open Access Journals (Sweden)

    Lois Albert Espinel García

    2013-09-01

    Full Text Available La creciente demanda en servicios de telecomunicaciones genera la necesidad de desarrollar diferentes modelos de red. En el año 2008, la UIT-T une sinergias con la IETF para desarrollar un protocolo llamado MPLS-TP cuya arquitectura representa el resultado la agregación de la eficiencia en el transporte de paquetes de IP/MPLS con la fiabilidad en el transporte de SONET/SDH. Este trabajo presenta un estado del arte de MPLS-TP donde se plasman los estudios actuales y avances relacionados con ésta tecnología: modelos de arquitectura óptica, modelos de protección en OAM. Además se presenta la estructura, funcionamiento y características que hacen de MPLS-TP una opción para las redes de transporte de siguiente generación. El material de apoyo para el desarrollo de este artículo ha sido obtenido de la base documental de recursos electrónicos con contenido científico de apoyo a la investigación de la Universidad Distrital Francisco José de Caldas.

  18. Influence of filled d pi-manifold and L/L' ligands on the structure, basicity, and bond rotations of the octahedral and d(6) amido complexes TpRu(L)(L')(NHPh) (Tp = hydridotris(pyrazolyl)borate; L = L' = PMe(3) or P(OMe)(3), or L = CO and L' = PPh(3)): solid-state structures of [TpRu(PMe(3))(2)(NH(2)Ph)][OTf], [TpRu[P(OMe)(3)](2)(NH(2)Ph)][OTf], and TpRu[P(OMe)(3)](2)(NHPh).

    Science.gov (United States)

    Conner, David; Jayaprakash, K N; Gunnoe, T Brent; Boyle, Paul D

    2002-06-03

    It has been suggested that the reactivity of pi-donating ligands bound to late-transition-metal complexes is heightened due to high d-electron counts. Herein, the synthesis and characterization of the Ru(II) amine and Ru(II) amido complexes [TpRuL(2)(NH(2)Ph)][OTf] (OTf = trifluoromethanesulfonate) and TpRuL(2)(NHPh) (L = PMe(3) or P(OMe)(3)) are presented, including solid-state X-ray diffraction studies of [TpRu(PMe(3))(2)(NH(2)Ph)][OTf], [TpRu[P(OMe)(3)](2)(NH(2)Ph)][OTf], and TpRu[P(OMe)(3)](2)(NHPh). The pK(a)'s of the Ru(II) amine complexes and the previously reported [TpRu(CO)(PPh(3))(NH(2)Ph)](+) have been estimated to be comparable to that of malononitrile in methylene chloride. In addition, the impact of the filled dpi-manifold (i.e., Ru(II) and d(6) octahedral systems) on barriers to rotation of the Ru-NHPh moieties has been studied. For TpRu(PMe(3))(2)(NHPh) and TpRu[P(OMe)(3)](2)(NHPh), evidence for hindered rotation about the amido nitrogen and phenyl ipso carbon has been observed, and the relative N-C and Ru-N bond rotational barriers for the series of three amido complexes are discussed in terms of the pi-conflict.

  19. Technique analysis of T-MPLS OAM and MPLS-TP OAM

    Science.gov (United States)

    Yun, Xiang; Wang, Zhong

    2009-08-01

    OAM plays an important role in PTN technology. The main function of OAM is check defect before abnormal event. The bit errors which could be corrected or time deviation could be isolated within a certain range. It dose not disturb network operation. And therefore, it ensure carrier to fulfill QoS commitment and reach SLA subscription.T-MPLS is connection-oriented packet transport technology. Connection-oriented means it can provide carrier-level service and must have equal OAM (Operation, Administration and Maintenance) function of traditional transport network. OAM mechanism becomes key technology of T-MPLS. OAM function is very important to telecom network. It's especially import to network which has QoS. OAM could simplify network operation, check network performance and reduce operation cost. Firstly, the functional requirements of T-MPLS OAM and MPLS-TP OAM are analyzed. The similarity of T-MPLS OAM and MPLS-TP OAM is founded. By deep analysis the mechanism of T-MPLS OAM, it shows that the OAM is import for PTN. Then OAM technique of T-MPLS and MPLS-TP is analyzed in detail. At last, analysis of commonality is carried out on function types. Domain reference model and nesting-technique shows the consistency of both OAM functions. Both of T-MPLS and MPLS-TP introduce OAM nesting. Eight MEG Levels (from 0 to 7) are available to accommodate different network deployment scenarios. In order to distinguish OAM packets of nested MEGs, each MEP tunnels incoming OAM packets by incrementing the MEL in the source direction and decrementing it in the sink direction. Each MEP/MIP generates and processes OAM packets at the MEL=0, while other OAM packets are forwarded with traffic. It's very simple and high efficiency method. By comparing the functions of T-MPLS OAM and MPLS-TP OAM, even there are few differences on PTN implementation detail; the OAM mechanism and framework are basically same. Both of them meet the requirements of carrier-grade OAM. They has important role in

  20. Influencia de los cambios posturales en el electrocardiograma

    Directory of Open Access Journals (Sweden)

    Giuseppe Lanza

    2014-04-01

    Full Text Available Diferentes posiciones del cuerpo tienen influencia demostrada en los cambios de trazo de un electrocardiograma: alteración de la respiración, cambios en el vectocardiograma, posiciones de los brazos y segmento ST, posición del cuerpo y el síndrome de QT largo, alteración del voltaje de R, onda Q y eje eléctrico, colocación inadecuada de electrodos, entre otros aspectos. En este artículo se realiza una revisión global a fin de llamar la atención en aquellos cambios del trazo del electrocardiograma que pudieran interpretarse de manera inadecuada o atribuirse a patología inexistente.

  1. Influencia de los cambios posturales en el electrocardiograma

    Directory of Open Access Journals (Sweden)

    Giuseppe Lanza

    2014-03-01

    Full Text Available Diferentes posiciones del cuerpo tienen influencia demostrada en los cambios de trazo de un electrocardiograma: alteración de la respiración, cambios en el vectocardiograma, posiciones de los brazos y segmento ST, posición del cuerpo y el síndrome de QT largo, alteración del voltaje de R, onda Q y eje eléctrico, colocación inadecuada de electrodos, entre otros aspectos. En este artículo se realiza una revisión global a fin de llamar la atención en aquellos cambios del trazo del electrocardiograma que pudieran interpretarse de manera inadecuada o atribuirse a patología inexistente.

  2. Study of the TP53 codon 72 polymorphism in oral cancer and oral potentially malignant disorders in Argentine patients.

    Science.gov (United States)

    Zarate, Ana Maria; Don, Julieta; Secchi, Dante; Carrica, Andres; Galindez Costa, Fernanda; Panico, Rene; Brusa, Martin; Barra, José Luis; Brunotto, Mabel

    2017-05-01

    The aim of this work was to evaluate the prevalence of TP53Arg72Pro mutations and their possible relationship with oral carcinoma and oral potentially malignant disorders in Argentine patients. A cross-sectional study was performed on 111 exfoliated cytologies from patients with oral cancer (OC), oral potentially malignant disorders (OPMD) and controls. The TP53Arg72Pro mutations were determined using conventional PCR. We evaluated univariate and multivariate study variables, setting p oral leukoplakia (OL) diagnosis; (b) multivariate association among the TP53CC genotype and females over 45 years with no tobacco nor alcohol habits with oral lichen planus pathology; (c) multivariate association between the TP53GC genotype and males with alcohol and tobacco habits and OC and OL pathologies. Our results showed that the wild-type Arg72variant was related to control patients and Pro72variant was related to OC and OPMD, in Argentine patients.

  3. The Resistance of Vibrio cholerae O1 El Tor Strains to the Typing Phage 919TP, a Member of K139 Phage Family

    OpenAIRE

    Shen, Xiaona; Zhang, Jingyun; Xu, Jialiang; Du, Pengcheng; Pang, Bo; Li, Jie; Kan, Biao

    2016-01-01

    Bacteriophage 919TP is a temperate phage of Vibrio cholerae serogroup O1 El Tor and is used as a subtyping phage in the phage-biotyping scheme in cholera surveillance in China. In this study, sequencing of the 919TP genome showed that it belonged to the Vibrio phage K139 family. The mechanisms conferring resistance to 919TP infection of El Tor strains were explored to help understand the subtyping basis of phage 919TP and mutations related to 919TP resistance. Among the test strains resistant...

  4. Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients

    DEFF Research Database (Denmark)

    Dufour, Annika; Palermo, Giuseppe; Zellmeier, Evelyn

    2013-01-01

    In chronic lymphocytic leukemia (CLL) patients, disruptions of the TP53 tumor suppressor pathway by 17p13 deletion (del17p), somatic TP53 mutations, or downregulation of microRNA-34a have been associated with a poor prognosis. So far, the impact of the various TP53 defects has not been evaluated...... in a large cohort of previously treated and relapsed CLL patients. Here, we present the results of TP53 gene sequencing and fluorescence in situ hybridization for del17p in a phase 3 clinical trial (REACH [Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia]). Of the 457 patients, 52 had TP53...

  5. Clinicopathological features and clinical outcomes associated with TP53 and BRAFNon-V600mutations in cutaneous melanoma patients.

    Science.gov (United States)

    Kim, Dae Won; Haydu, Lauren E; Joon, Aron Y; Bassett, Roland L; Siroy, Alan E; Tetzlaff, Michael T; Routbort, Mark J; Amaria, Rodabe N; Wargo, Jennifer A; McQuade, Jennifer L; Kemnade, Jan; Hwu, Patrick; Woodman, Scott E; Roszik, Jason; Kim, Kevin B; Gershenwald, Jeffrey E; Lazar, Alexander J; Davies, Michael A

    2017-04-15

    BRAF V600 , NRAS, TP53, and BRAF Non-V600 are among the most common mutations detected in non-acral cutaneous melanoma patients. Although several studies have identified clinical and pathological features associated with BRAF V600 and NRAS mutations, limited data are available regarding the correlates and significance of TP53 and BRAF Non-V600 mutations. This study analyzed the patient demographics, primary tumor features, and clinical outcomes of a large cohort of non-acral cutaneous melanoma patients who had undergone clinically indicated molecular testing (n = 926). The prevalence of BRAF V600 , NRAS, TP53, and BRAF Non-V600 mutations was 43%, 21%, 19%, and 7%, respectively. The presence of a TP53 mutation was associated with older age (P = .019), a head and neck primary tumor site (P = .0001), and longer overall survival (OS) from the diagnosis of stage IV disease in univariate (P = .039) and multivariate analyses (P = .015). BRAF Non-V600 mutations were associated with older age (P = .005) but not with primary tumor features or OS from stage IV. Neither TP53 nor BRAF Non-V600 mutations correlated significantly with OS with frontline ipilimumab treatment, and the TP53 status was not significantly associated with outcomes with frontline BRAF inhibitor therapy. Eleven patients with BRAF Non-V600 mutations were treated with a BRAF inhibitor. Three patients were not evaluable for a response because of treatment cessation for toxicities; the remaining patients had disease progression as the best response to therapy. These results add to the understanding of the clinical features associated with TP53 and BRAF Non-V600 mutations in advanced cutaneous melanoma patients, and they support the rationale for evaluating the prognostic significance of TP53 in other cohorts of melanoma patients. Cancer 2017;123:1372-1381. © 2016 American Cancer Society. © 2016 American Cancer Society.

  6. The Resistance of Vibrio cholerae O1 El Tor Strains to the Typing Phage 919TP, a Member of K139 Phage Family.

    Science.gov (United States)

    Shen, Xiaona; Zhang, Jingyun; Xu, Jialiang; Du, Pengcheng; Pang, Bo; Li, Jie; Kan, Biao

    2016-01-01

    Bacteriophage 919TP is a temperate phage of Vibrio cholerae serogroup O1 El Tor and is used as a subtyping phage in the phage-biotyping scheme in cholera surveillance in China. In this study, sequencing of the 919TP genome showed that it belonged to the Vibrio phage K139 family. The mechanisms conferring resistance to 919TP infection of El Tor strains were explored to help understand the subtyping basis of phage 919TP and mutations related to 919TP resistance. Among the test strains resistant to phage 919TP, most contained the temperate 919TP phage genome, which facilitated superinfection exclusion to 919TP. Our data suggested that this immunity to Vibrio phage 919TP occurred after absorption of the phage onto the bacteria. Other strains contained LPS receptor synthesis gene mutations that disable adsorption of phage 919TP. Several strains resistant to 919TP infection possessed unknown resistance mechanisms, since they did not contain LPS receptor mutations or temperate K139 phage genome. Further research is required to elucidate the phage infection steps involved in the resistance of these strains to phage infection.

  7. Structural profiles of TP53 gene mutations predict clinical outcome in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Young, Ken H; Leroy, Karen; Møller, Michael Boe

    2008-01-01

    The purpose of this study is to correlate the presence of TP53 gene mutations with the clinical outcome of a cohort of patients with diffuse large B-cell lymphoma (DLBCL) assembled from 12 medical centers. TP53 mutations were identified in 102 of 477 patients and the overall survival (OS......) of patients with TP53 mutations was significantly worse than those with wild-type TP53 (p=0.0006). However, subsets of TP53 mutations were found to have different effects on OS. Mutations in the TP53 DNA binding domains were the strongest predictors of poor OS (p=0.0003). Mutations in the Loop......-Sheet-Helix and Loop-L3 were associated with significantly decreased OS (p=0.002), but OS was not significantly affected by mutations in Loop-L2. A subset of missense mutations (His(158), His(175), Ser(245), Gln(248), His(273), Arg(280) and Arg(282)) in the DNA binding domains had the worst prognosis. Multivariate...

  8. Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population

    International Nuclear Information System (INIS)

    Xiao, Mang; Zhang, Lei; Zhu, Xinhua; Huang, Jun; Jiang, Huifen; Hu, Sunhong; Liu, Yuehui

    2010-01-01

    The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored. In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP. We found an increased NPC risk associated with the MDM2 GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58). The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC

  9. The TP73 gene polymorphism (rs4648551, A>G is associated with diminished ovarian reserve.

    Directory of Open Access Journals (Sweden)

    Laura Diniz Vagnini

    Full Text Available It's known that the members of the TP53 family are involved in the regulation of female reproduction. Studies in mice showed that the TP73 gene (member of this family plays a role in the size of follicular pool, ovulation rate and maintenance of genomic stability. In the present study we analyzed data from 605 patients with ≤ 37 years attending their first intracytoplasmic sperm injection (ICSI. The association between the TP73 polymorphism (rs4648551, A>G and the following parameters related to ovarian reserve, like age, antral follicular count (AFC, anti-Mullerian hormone levels (AMH and ovarian response prediction index (ORPI was evaluated. Our results showed an association of the AA genotype with diminished ovarian reserve (AMH <1, AFC ≤9. Women presenting the AA genotype had a 2.0-fold increased risk for having AMH <1 and AFC ≤9 (OR 2.0, 95% CI 1.23-3.31, P = 0.005. Patients presenting AA genotype had the lowest levels of AMH (P = 0.02, the lowest number of antral follicles (P = 0.01 and the lowest ORPI (P = 0.007. Analyzing the alleles, we can see an enrichment of the A allele in the group of diminished ovarian reserve (OR 1.4, 95%CI 1.02-1.83, P = 0.04. To the best of our knowledge, the present study is the first to analyze this polymorphism in humans for assessing the numbers of ovarian follicles and AMH levels and, therefore, the ovarian reserve. Our findings can contribute to the use of this polymorphism as a potential marker of diminished ovarian reserve.

  10. Initiation of prostate cancer in mice by Tp53R270H: evidence for an alternative molecular progression

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    Ruth L. Vinall

    2012-11-01

    Tp53 mutations are common in human prostate cancer (CaP, occurring with a frequency of ∼30% and ∼70% in localized and metastatic disease, respectively. In vitro studies have determined several common mutations of Tp53 that have specific gain-of-function properties in addition to loss of function, including the ability to promote castration-resistant (CR growth of CaP cells in some contexts. To date, a lack of suitable mouse models has prohibited investigation of the role played by Tp53 mutations in mediating CaP progression in vivo. Here, we describe the effects of conditional expression of a mutant Tp53 (Tp53R270H; equivalent to the human hotspot mutant R273H in the prostate epithelium of mice. Heterozygous “Tp53LSL-R270H/+” [129S4(Trp53tm3Tyj] and “Nkx3.1-Cre” [129S(Nkx3-1tm3(creMms] mice with prostate-specific expression of the Tp53R270H mutation (p53R270H/+ Nkx3.1-Cre mice were bred onto an FVB/N background via speed congenesis to produce strain FVB.129S4(Trp53tm3Tyj/wt; FVB.129S(Nkx3-1tm3(creMms/wt and littermate genotype negative control mice. These mutant mice had significantly increased incidences of prostatic intraepithelial neoplasia (PIN lesions, and these appeared earlier, compared with the Nkx3.1 haploinsufficient (Nkx3.1-Cre het littermate mice, which did not express the Tp53 mutation. PIN lesions in these mice showed consistent progression and some developed into invasive adenocarcinoma with a high grade, sarcomatoid or epithelial-mesenchymal transition (EMT phenotype. PIN lesions were similar to those seen in PTEN conditional knockout mice, with evidence of AKT activation concomitant with neoplastic proliferation. However, the invasive tumor phenotype is rarely seen in previously described mouse models of prostatic neoplasia. These data indicate that the Tp53R270H mutation plays a role in CaP initiation. This finding has not previously been reported. Further characterization of this model, particularly in a setting of androgen

  11. Contribution of germline TP53 variants and assessment of HER-2 status among young breast cancer patients in Malaysia

    Directory of Open Access Journals (Sweden)

    Shao Yan Lau

    2017-12-01

    Full Text Available Background: Li-Fraumeni Syndrome (LFS is caused by a mutation in the TP53 tumour suppressor gene. This rare hereditary condition predisposes individuals to an increased risk of cancers including breast cancer in women at a relatively young age, which accounts for nearly 25%–30% of all LFS‑associated cancers. Studies have shown that breast tumours in women with a germline TP53 deleterious variants are associated with a human epidermal growth factor receptor 2 (HER2-positive phenotype. Taken together, this study aimed to investigate the contribution of germline TP53 variants and its association with tumour HER-2 status in a cohort of young women with breast cancer. Methods: From 2002 to 2017, 4048 women with breast cancer treated at University Malaya Medical Centre or Sime Darby Medical Centre participated in the Malaysian Breast Cancer Genetics Study. Of which, 87 patients were diagnosed before 30 years of age. All patients were analysed for germline TP53 single nucleotide variants, small insertions or deletions by amplicon‑based targeted sequencing and validated by Sanger sequencing. DNA from patients who tested negative for sequencing were subsequently evaluated for the presence of TP53 exon deletions or duplications by multiplex ligation‑dependent probe amplification. HER-2 status of breast tumours was defined by immunohistochemistry, fluorescence in situ hybridisation and/or silver in situ hybridisation. Results: 5 distinct TP53 variants were detected in 5 individuals. 3 out of 5 TP53 variants were classified as frameshift mutations, one nonsense mutation and one in-frame duplication. Variants in other genes were detected in 17 individuals. No large genomic rearrangements were detected in the remaining 65 sequencing-negative patients. The assessment of HER-2 status will be presented. Conclusions: Our results suggest that alterations in TP53 gene were identified in approximately 5.7% (5/87 of this cohort of young women with breast

  12. Identification of TP53 as an Acute Lymphocytic Leukemia Susceptibility Gene Through Exome Sequencing

    Science.gov (United States)

    Powell, Bradford C.; Jiang, Lichun; Muzny, Donna M.; Treviño, Lisa R.; Dreyer, ZoAnn E.; Strong, Louise C.; Wheeler, David A.; Gibbs, Richard A.; Plon, Sharon E.

    2014-01-01

    Although acute lymphocytic leukemia (ALL) is the most common childhood cancer, genetic predisposition to ALL remains poorly understood. Whole-exome sequencing was performed in an extended kindred in which five individuals had been diagnosed with leukemia. Analysis revealed a nonsense variant of TP53 which has been previously reported in families with sarcomas and other typical Li Fraumeni syndrome-associated cancers but never in a familial leukemia kindred. This unexpected finding enabled identification of an appropriate sibling bone marrow donor and illustrates that exome sequencing will reveal atypical clinical presentations of even well-studied genes. PMID:23255406

  13. CT Image Reconstruction from Sparse Projections Using Adaptive TpV Regularization

    Directory of Open Access Journals (Sweden)

    Hongliang Qi

    2015-01-01

    Full Text Available Radiation dose reduction without losing CT image quality has been an increasing concern. Reducing the number of X-ray projections to reconstruct CT images, which is also called sparse-projection reconstruction, can potentially avoid excessive dose delivered to patients in CT examination. To overcome the disadvantages of total variation (TV minimization method, in this work we introduce a novel adaptive TpV regularization into sparse-projection image reconstruction and use FISTA technique to accelerate iterative convergence. The numerical experiments demonstrate that the proposed method suppresses noise and artifacts more efficiently, and preserves structure information better than other existing reconstruction methods.

  14. Fetal colon cell line FHC exhibits tumorigenic phenotype, complex karyotype, and TP53 gene mutation

    Czech Academy of Sciences Publication Activity Database

    Souček, Karel; Jirsová, Pavla; Brázdová, Marie; Hýžďalová, Martina; Kočí, Lenka; Vydra, D.; Trojanec, R.; Pernicová, Zuzana; Lentvorská, L.; Hajdúch, M.; Hofmanová, Jiřina; Kozubík, Alois

    2010-01-01

    Roč. 197, č. 2 (2010), s. 107-116 ISSN 0165-4608 R&D Projects: GA MŠk ME 919; GA ČR(CZ) GA204/07/0834; GA ČR(CZ) GA204/08/1560; GA AV ČR(CZ) 1QS500040507; GA MZd NS9600 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : colon epithelial cells * TP53 * MYC Subject RIV: BO - Biophysics Impact factor: 1.551, year: 2010

  15. Mutation screening of the TP53 gene by temporal temperature gradient gel electrophoresis.

    Science.gov (United States)

    Sørlie, Therese; Johnsen, Hilde; Vu, Phuong; Lind, Guro Elisabeth; Lothe, Ragnhild; Børresen-Dale, Anne-Lise

    2005-01-01

    A protocol for detection of mutations in the TP53 gene using temporal temperature gradient gel electrophoresis (TTGE) is described. TTGE is a mutation detection technique that separates DNA fragments differing by single base pairs according to their melting properties in a denaturing gel. It is based on constant denaturing conditions in the gel combined with a temperature gradient during the electrophoretic run. This method combines some of the advantages of the related techniques denaturing gradient gel electrophoresis (DGGE) and constant denaturant gel electrophoresis (CDGE) and eliminates some of the problems. The result is a rapid and sensitive screening technique that is robust and easily set up in smaller laboratory environments.

  16. Mutation screening of the TP53 gene by temporal temperature gel electrophoresis (TTGE).

    Science.gov (United States)

    Sørlie, Therese; Johnsen, Hilde; Vu, Phuong; Lind, Guro Elisabeth; Lothe, Ragnhild; Børresen-Dale, Anne-Lise

    2014-01-01

    A protocol for detection of mutations in the TP53 gene using temporal temperature gradient electrophoresis (TTGE) is described. TTGE is a mutation detection technique that separates DNA fragments differing by single base pairs according to their melting properties in a denaturing gel. It is based on constant denaturing conditions in the gel combined with a temperature gradient during the electrophoretic run. This method combines some of the advantages of the related techniques, denaturing gradient gel electrophoresis and constant denaturant gel electrophoresis, and eliminates some of the problems. The result is a rapid and sensitive screening technique which is robust and easily set up in smaller laboratory environments.

  17. High pemetrexed sensitivity of docetaxel-resistant A549 cells is mediated by TP53 status and downregulated thymidylate synthase.

    Science.gov (United States)

    Kuo, Wei-Ting; Tu, Dom-Gene; Chiu, Ling-Yen; Sheu, Gwo-Tarng; Wu, Ming-Fang

    2017-11-01

    The chemoresistance of non-small cell lung cancer (NSCLC) that occurs in docetaxel (DOC) chemotherapy substantially decreases the survival of patients. To overcome DOC-induced chemoresistance, we established DOC-selected A549 lung cancer sublines (A549/D16 and A549/D32) and revealed that both sublines were cross-resistant to vincristine (VCR) and doxorubicin (DXR). Notably, both sublines were more sensitive to pemetrexed (PEM) than parental cells according to MTT and clonogenic assays. The expression levels of thymidylate synthase (TS) and γ-glutamyl hydrolase (GGH) were downregulated in DOC-resistant sublines. When exogenous TS was overexpressed in A549/D16 cells, PEM sensitivity was significantly decreased, however it was not decreased by overexpression of exogenous GGH. PEM treatment induced more apoptotic sub-G1 cells in both DOC-resistant sublines and in the in vivo PEM sensitivities of A549/D16 cells. These findings were further confirmed by a xenografted tumor model. To unmask the mediator of TS downregulation, we investigated human lung cancer cell lines that have various TP53 statuses using DOC treatment. The level of TS protein was significantly decreased in wild-type TP53-containing cells with DOC treatment; TS expression levels were not affected in mutant-TP53 and TP53‑null cells under the same conditions. Furthermore, when the expression of TP53 was inhibited in A549 cells, the expression level of TS was increased. Our data indicated that DOC activated wild-type TP53 and suppressed TS expression under continuous DOC exposure. Therefore, the expression of TS remained at low levels in DOC-resistant A549 cancer cells. Our data revealed that for lung cancer with DOC resistance and wild‑type TP53 status, the administration of PEM as a second-line agent to overcome DOC-resistance may benefit patients.

  18. High prevalence of TP53 mutations is associated with poor survival and an EMT signature in gliosarcoma patients.

    Science.gov (United States)

    Cho, Sung-Yup; Park, Changho; Na, Deukchae; Han, Jee Yun; Lee, Jieun; Park, Ok-Kyoung; Zhang, Chengsheng; Sung, Chang Ohk; Moon, Hyo Eun; Kim, Yona; Kim, Jeong Hoon; Kim, Jong Jae; Khang, Shin Kwang; Nam, Do-Hyun; Choi, Jung Won; Suh, Yeon-Lim; Kim, Dong Gyu; Park, Sung Hye; Youn, Hyewon; Yun, Kyuson; Kim, Jong-Il; Lee, Charles; Paek, Sun Ha; Park, Hansoo

    2017-04-14

    Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87-199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial-mesenchymal transition (EMT) process of sarcomatous components of GS. We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.

  19. Overexpression of RBBP6, alone or combined with mutant TP53, is predictive of poor prognosis in colon cancer.

    Directory of Open Access Journals (Sweden)

    Jian Chen

    Full Text Available Retinoblastoma binding protein 6 (RBBP6 plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of RBBP6 expression in colon cancer is unknown; in particular, the prognostic value of RBBP6 combined with TP53 expression has not been explored. Therefore, quantitative real-time PCR and western blot analyses were performed to detect RBBP6 expression in colon cancer tissues. RBBP6 and TP53 expression were assessed by immunohistochemistry in a tissue microarray format, in which the primary colon cancer tissue was paired with noncancerous tissue. Tissue specimens were obtained from 203 patients. We found that RBBP6 was overexpressed in colon tumorous tissues and was significantly associated with clinical stage, depth of tumor invasion, lymph node metastasis (LNM, distant metastasis, and histologic grade. Further studies revealed that a corresponding correlation between RBBP6 overexpression and mutant TP53 was evident in colon cancer (r = 0.450; P<0.001. RBBP6 expression was an independent prognostic factor for overall survival (OS and disease free survival (DFS. Interestingly, patients with tumors that had both RBBP6 overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P<0.001. Multivariate analysis showed that patients with LNM and patients with both RBBP6- and TP53-positive tumors had extremely poor OS (HR 6.75; 95% CI 2.63-17.35; P<0.001 and DFS (HR 8.08; 95% CI 2.80-23.30; P<0.001. These clinical findings indicate that the assessment of both RBBP6 and mutant TP53 expression will be helpful in predicting colon cancer prognosis.

  20. A novel TP53 germline inframe deletion identified in a Spanish series of Li-fraumeni syndrome suspected families.

    Science.gov (United States)

    Llovet, Patricia; Illana, Francisco J; Martín-Morales, Lorena; de la Hoya, Miguel; Garre, Pilar; Ibañez-Royo, M Dolores; Pérez-Segura, Pedro; Caldés, Trinidad; García-Barberán, Vanesa

    2017-10-01

    Li-Fraumeni syndrome (LFS) is an autosomal dominant, inherited tumor predisposition syndrome associated with heterozygous germline mutations in the TP53 gene. The molecular diagnosis of LFS is important to develop strategies for early detection and access to the genetic counseling. Our study evaluated germline TP53 mutations in Spanish families with a history suggestive of LFS. Germline TP53 alterations in 22 families with a history suggestive of LFS were evaluated by Sanger sequencing and multiplex ligation-dependent probe amplification. Loss of heterozygosity analysis and immunohistochemistry of the protein in the tumor were performed in order to evaluate the pathogenicity of a novel alteration detected. A total of seven TP53 mutations were detected, six point mutations (4 missense and 2 nonsense) and a novel inframe deletion. 93% of mutation carriers developed at least one malignancy (mainly breast cancer and sarcomas), with a mean age at diagnosis of the first tumor of 30.2 years. Two missense mutations acted as dominant-negative. The novel inframe mutation c.437_445del was located in the DNA-binding domain. This mutation segregated with cancer in the family, and both high expression of the protein and loss of the wild-type TP53 allele were detected in the tumor of the carrier. We have found a novel inframe deletion in TP53 that likely results in the loss of p53 function and acts in a non-dominant negative way, although further studies are necessary to clarify this issue. The identification of novel TP53 alterations is crucial for a personalized cancer-risk management of the Li-Fraumeni syndrome.

  1. Hepatitis B and Hepatitis C Infection Biomarkers and TP53 Mutations in Hepatocellular Carcinomas from Colombia

    Directory of Open Access Journals (Sweden)

    Maria-Cristina Navas

    2011-01-01

    Full Text Available Hepatocellular Carcinoma (HCC is a leading cause of cancer-related death worldwide. Globally, the most important HCC risk factors are Hepatitis B Virus (HBV and/or Hepatitis C Virus (HCV, chronic alcoholism, and dietary exposure to aflatoxins. We have described the epidemiological pattern of 202 HCC samples obtained from Colombian patients. Additionally we investigated HBV/HCV infections and TP53 mutations in 49 of these HCC cases. HBV biomarkers were detected in 58.1% of the cases; HBV genotypes F and D were characterized in three of the samples. The HCV biomarker was detected in 37% of the samples while HBV/HCV coinfection was found in 19.2%. Among TP53 mutations, 10.5% occur at the common aflatoxin mutation hotspot, codon 249. No data regarding chronic alcoholism was available from the cases. In conclusion, in this first study of HCC and biomarkers in a Colombian population, the main HCC risk factor was HBV infection.

  2. Investigation of steam oxidation behaviour of TP347H FG Part 2: Exposure at 91 bar

    DEFF Research Database (Denmark)

    Jianmin, J; Montgomery, Melanie; Larsen, OH

    2005-01-01

    Tube specimens of TP347FG were exposed in a test superheater loop in a biomass plant in Denmark. The specimens were exposed to surface metal temperatures in the range of 455-568C, steam pressure of 91 bar and exposure duration of 3500 and 8700 hours. The oxide thickness and morphology was investi......Tube specimens of TP347FG were exposed in a test superheater loop in a biomass plant in Denmark. The specimens were exposed to surface metal temperatures in the range of 455-568C, steam pressure of 91 bar and exposure duration of 3500 and 8700 hours. The oxide thickness and morphology...... was investigated using light optical and scanning electron microscopy. The oxide present on the specimens is a duplex oxide with an inner chromium rich oxide and an outer iron rich oxide. The inner oxide consisted of a primary iron chromium nickel oxide in the original alloy grain and a chromium rich oxide......, "healing layer", at the grain boundaries. This gave the appearance of uneven inner oxide and it was clear that the varying subsurface grain size effected inner oxide thickness, especially after longer exposure times. Longer exposure times from 3500 to 8700 hours resulted in increased pit thickness...

  3. TP-Space RRT – Kinematic Path Planning of Non-Holonomic Any-Shape Vehicles

    Directory of Open Access Journals (Sweden)

    Jose Luis Blanco

    2015-05-01

    Full Text Available The autonomous navigation of vehicles typically combines two kinds of methods: a path is first planned, and then the robot is driven by a local obstacle-avoidance controller. The present work, which focuses on path planning, proposes an extension to the well-known rapidly-exploring random tree (RRT algorithm to allow its integration with a trajectory parameter-space (TP-space as an efficient method to detect collision-free, kinematically-feasible paths for arbitrarily-shaped vehicles. In contrast to original RRT, this proposal generates navigation trees, with poses as nodes, whose edges are all kinematically-feasible paths, suitable to being accurately followed by vehicles driven by pure reactive algorithms. Initial experiments demonstrate the suitability of the method with an Ackermann-steering vehicle model whose severe kinematic constraints cannot be obviated. An important result that sets this work apart from previous research is the finding that employing several families of potential trajectories to expand the tree, which can be done efficiently under the TP-space formalism, improves the optimality of the planned trajectories. A reference C++ implementation has been released as open-source.

  4. Structure and molecular assignment of lactococcal phage TP901-1 baseplate

    DEFF Research Database (Denmark)

    Bebeacua, Cecilia; Bron, Patrick; Lai, Livia

    2010-01-01

    P335 lactococcal phages infect the Gram(+) bacterium Lactococcus lactis using a large multiprotein complex located at the distal part of the tail and termed baseplate (BP). The BP harbors the receptor-binding proteins (RBPs), which allow the specific recognition of saccharidic receptors localized...... on the host cell surface. We report here the electron microscopic structure of the phage TP901-1 wild-type BP as well as those of two mutants bppL (-) and bppU(-), lacking BppL (the RBPs) or both peripheral BP components (BppL and BppU), respectively. We also achieved an electron microscopic reconstruction...... by ORF46 (Dit) hexamers, at its proximal end, and a ORF47 (Tal) trimer at its distal extremity. A total of 54 BppLs (18 RBPs) are thus available to mediate host anchoring with a large apparent avidity. TP901-1 BP exhibits an infection-ready conformation and differs strikingly from the lactococcal phage p...

  5. Mutational hotspots in the TP53 gene and, possibly, other tumor suppressors evolve by positive selection

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2006-01-01

    Full Text Available Abstract Background The mutation spectra of the TP53 gene and other tumor suppressors contain multiple hotspots, i.e., sites of non-random, frequent mutation in tumors and/or the germline. The origin of the hotspots remains unclear, the general view being that they represent highly mutable nucleotide contexts which likely reflect effects of different endogenous and exogenous factors shaping the mutation process in specific tissues. The origin of hotspots is of major importance because it has been suggested that mutable contexts could be used to infer mechanisms of mutagenesis contributing to tumorigenesis. Results Here we apply three independent tests, accounting for non-uniform base compositions in synonymous and non-synonymous sites, to test whether the hotspots emerge via selection or due to mutational bias. All three tests consistently indicate that the hotspots in the TP53 gene evolve, primarily, via positive selection. The results were robust to the elimination of the highly mutable CpG dinucleotides. By contrast, only one, the least conservative test reveals the signature of positive selection in BRCA1, BRCA2, and p16. Elucidation of the origin of the hotspots in these genes requires more data on somatic mutations in tumors. Conclusion The results of this analysis seem to indicate that positive selection for gain-of-function in tumor suppressor genes is an important aspect of tumorigenesis, blurring the distinction between tumor suppressors and oncogenes. Reviewers This article was reviewed by Sandor Pongor, Christopher Lee and Mikhail Blagosklonny.

  6. TP53 p.R337H is a conditional cancer-predisposing mutation: further evidence from a homozygous patient

    International Nuclear Information System (INIS)

    Giacomazzi, Juliana; Hainaut, Pierre; Ashton-Prolla, Patricia; Selistre, Simone; Duarte, Juliana; Ribeiro, Jorge Pinto; Vieira, Paulo JC; Souza Macedo, Gabriel de; Rossi, Cristina; Czepielewski, Mauro; Netto, Cristina Brinkmann Oliveira

    2013-01-01

    Adrenocortical carcinomas (ACCs) are among the most common childhood cancers occurring in infants affected with the Li-Fraumeni and Li- Fraumeni-like (LFS/LFL) syndromes, which are caused by dominant germline mutations in the TP53 gene. In Brazil, a particular mutation, occurring in the tetramerisation domain of the gene, p.R337H, is exceedingly common due to a founder effect and is strongly associated with ACC. In this report, we describe the phenotype and long-term clinical follow-up of a female child diagnosed with ACC and homozygous for the TP53 p.R337H founder mutation. At age 11 months, the patient was diagnosed with a virilising anaplastic adrenal cortical tumour, which was completely excised without disturbing the adrenal capsule. Family history was consistent with an LFL tumour pattern, and genotyping identified the TP53 p.R337H mutation in both alleles in genomic DNA from lymphocytes and fibroblasts. Haplotype analysis confirmed the occurrence of the mutation in the same founder haplotype previously described in other Brazilian patients. No other germline or somatic TP53 mutations or rearrangements were identified. At age 9 years, the child was asymptomatic and had no evidence of endocrine derangements. Full body and brain magnetic resonance imaging (MRI) failed to detect any suspicious proliferative lesions, and cardiopulmonary exercise testing results were within the normal reference for the child’s age, ruling out a major exercise capacity deficiency. This is the first clinical and aerobic functional capacity documentation of a patient who carries two mutant TP53 alleles and no wild-type allele. Our results support the hypothesis that TP53 p.R337H, the most common TP53 mutation ever described in any population, is a conditional mutant. Furthermore, our observations over a long period of clinical follow-up suggest that TP53 p.R337H homozygotes do not have a more severe disease phenotype than do heterozygote carriers of the same mutation. Patients with

  7. Remote intracranial recurrence of IDH mutant gliomas is associated with TP53 mutations and an 8q gain

    Science.gov (United States)

    Nakae, Shunsuke; Kato, Takema; Murayama, Kazuhiro; Sasaki, Hikaru; Abe, Masato; Kumon, Masanobu; Kumai, Tadashi; Yamashiro, Kei; Inamasu, Joji; Hasegawa, Mitsuhiro; Kurahashi, Hiroki; Hirose, Yuichi

    2017-01-01

    Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas (N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions. In addition, diffuse tensor imaging suggested that remote intracranial recurrence in the astrocytomas, IDH-mutant with TP53 mutations may occur along major fiber bundles. Remotely recurrent tumors resulted in a higher mortality and significantly harbored an 8q gain; astrocytomas with an 8q gain resulted in significantly shorter overall survival than those without an 8q gain. OncoScan® arrays and next-generation sequencing revealed specific 8q regions (i.e., between 8q22 and 8q24) show a high copy number. In conclusion, only tumors with TP53 mutations showed patterns of remote recurrence in IDH mutant gliomas. Furthermore, an 8q gain was significantly associated with remote intracranial recurrence and can be considered a poor prognostic factor in astrocytomas, IDH-mutant. PMID:29156679

  8. Remote intracranial recurrence ofIDHmutant gliomas is associated withTP53mutations and an 8q gain.

    Science.gov (United States)

    Nakae, Shunsuke; Kato, Takema; Murayama, Kazuhiro; Sasaki, Hikaru; Abe, Masato; Kumon, Masanobu; Kumai, Tadashi; Yamashiro, Kei; Inamasu, Joji; Hasegawa, Mitsuhiro; Kurahashi, Hiroki; Hirose, Yuichi

    2017-10-17

    Most IDH mutant gliomas harbor either 1p/19q co-deletions or TP53 mutation; 1p/19q co-deleted tumors have significantly better prognoses than tumors harboring TP53 mutations. To investigate the clinical factors that contribute to differences in tumor progression of IDH mutant gliomas, we classified recurrent tumor patterns based on MRI and correlated these patterns with their genomic characterization. Accordingly, in IDH mutant gliomas ( N = 66), 1p/19 co-deleted gliomas only recurred locally, whereas TP53 mutant gliomas recurred both locally and in remote intracranial regions. In addition, diffuse tensor imaging suggested that remote intracranial recurrence in the astrocytomas, IDH-mutant with TP53 mutations may occur along major fiber bundles. Remotely recurrent tumors resulted in a higher mortality and significantly harbored an 8q gain; astrocytomas with an 8q gain resulted in significantly shorter overall survival than those without an 8q gain. OncoScan ® arrays and next-generation sequencing revealed specific 8q regions (i.e., between 8q22 and 8q24) show a high copy number. In conclusion, only tumors with TP53 mutations showed patterns of remote recurrence in IDH mutant gliomas. Furthermore, an 8q gain was significantly associated with remote intracranial recurrence and can be considered a poor prognostic factor in astrocytomas, IDH-mutant.

  9. The expression of TP53 pathway-related proteins in ovarian carcinoma transplanted subcutaneously in nude mice.

    Science.gov (United States)

    Zhang, S-R; Li, D-B; Xue, J-W

    2018-03-01

    Given the important functions of TP53 pathway in various biological processes, this study aimed to investigate the expression of TP53 pathway-related proteins in ovarian carcinoma transplanted subcutaneously in nude mice with and without the presence of p53 inhibitor and to explore possible roles of p53 in the development of ovarian cancer. Thirty BALB/c-nu female nude mice were randomly divided into model group, control group and p53 inhibitor group (Pftα group). There were 10 rats in each group. The nude mice were subcutaneously inoculated with human ovarian cancer cell line SKOV3, and the tumor growth was observed. Morphological changes of tumor tissue were observed by hematoxylin and eosin (HE) staining. The mRNA and protein levels of TP53 pathway related factors-p53, p21 and mouse double minute 2 homolog (MDM2) were detected by RT-PCR and Western blot. p53 inhibitor can increase the growth rate of subcutaneously transplanted tumor in nude mice. p53 inhibitor could decrease the expression of p53 and p21 at both mRNA and protein levels and increase the expression of MDM2 at both mRNA and protein levels in ovarian carcinoma transplanted subcutaneously in nude mice. TP53 pathway may play pivotal roles in the development of ovarian cancer and TP53 pathway may be a new target for the treatment of ovarian cancer.

  10. Defects in mitophagy promote redox-driven metabolic syndrome in the absence of TP53INP1.

    Science.gov (United States)

    Seillier, Marion; Pouyet, Laurent; N'Guessan, Prudence; Nollet, Marie; Capo, Florence; Guillaumond, Fabienne; Peyta, Laure; Dumas, Jean-François; Varrault, Annie; Bertrand, Gyslaine; Bonnafous, Stéphanie; Tran, Albert; Meur, Gargi; Marchetti, Piero; Ravier, Magalie A; Dalle, Stéphane; Gual, Philippe; Muller, Dany; Rutter, Guy A; Servais, Stéphane; Iovanna, Juan L; Carrier, Alice

    2015-06-01

    The metabolic syndrome covers metabolic abnormalities including obesity and type 2 diabetes (T2D). T2D is characterized by insulin resistance resulting from both environmental and genetic factors. A genome-wide association study (GWAS) published in 2010 identified TP53INP1 as a new T2D susceptibility locus, but a pathological mechanism was not identified. In this work, we show that mice lacking TP53INP1 are prone to redox-driven obesity and insulin resistance. Furthermore, we demonstrate that the reactive oxygen species increase in TP53INP1-deficient cells results from accumulation of defective mitochondria associated with impaired PINK/PARKIN mitophagy. This chronic oxidative stress also favors accumulation of lipid droplets. Taken together, our data provide evidence that the GWAS-identified TP53INP1 gene prevents metabolic syndrome, through a mechanism involving prevention of oxidative stress by mitochondrial homeostasis regulation. In conclusion, this study highlights TP53INP1 as a molecular regulator of redox-driven metabolic syndrome and provides a new preclinical mouse model for metabolic syndrome clinical research. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  11. Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively.

    Directory of Open Access Journals (Sweden)

    Lenka Mikalová

    2017-03-01

    Full Text Available Treponema pallidum subsp. endemicum (TEN is the causative agent of endemic syphilis (bejel. An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan.The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE strains, but not to TEN sequences.A detailed analysis of two recombinant loci found in the 11q/j clinical isolate revealed that the recombination event occurred just once, in the TP0488, with the donor sequence originating from a TPA strain. Since TEN Bosnia A and Iraq B were found to contain TPA-like sequences at the TP0548 locus, the recombination at TP0548 took place in a treponeme that was an ancestor to both TEN Bosnia A and Iraq B. The sequence of 11q/j isolate in TP0548 represents an ancestral TEN sequence that is similar to yaws-causing treponemes. In addition to the importance of the 11q/j isolate for reconstruction of the TEN phylogeny, this case emphasizes the possible role of TEN strains in development of syphilis-like lesions.

  12. Human Treponema pallidum 11q/j isolate belongs to subsp. endemicum but contains two loci with a sequence in TP0548 and TP0488 similar to subsp. pertenue and subsp. pallidum, respectively.

    Science.gov (United States)

    Mikalová, Lenka; Strouhal, Michal; Oppelt, Jan; Grange, Philippe Alain; Janier, Michel; Benhaddou, Nadjet; Dupin, Nicolas; Šmajs, David

    2017-03-01

    Treponema pallidum subsp. endemicum (TEN) is the causative agent of endemic syphilis (bejel). An unusual human TEN 11q/j isolate was obtained from a syphilis-like primary genital lesion from a patient that returned to France from Pakistan. The TEN 11q/j isolate was characterized using nested PCR followed by Sanger sequencing and/or direct Illumina sequencing. Altogether, 44 chromosomal regions were analyzed. Overall, the 11q/j isolate clustered with TEN strains Bosnia A and Iraq B as expected from previous TEN classification of the 11q/j isolate. However, the 11q/j sequence in a 505 bp-long region at the TP0488 locus was similar to Treponema pallidum subsp. pallidum (TPA) strains, but not to TEN Bosnia A and Iraq B sequences, suggesting a recombination event at this locus. Similarly, the 11q/j sequence in a 613 bp-long region at the TP0548 locus was similar to Treponema pallidum subsp. pertenue (TPE) strains, but not to TEN sequences. A detailed analysis of two recombinant loci found in the 11q/j clinical isolate revealed that the recombination event occurred just once, in the TP0488, with the donor sequence originating from a TPA strain. Since TEN Bosnia A and Iraq B were found to contain TPA-like sequences at the TP0548 locus, the recombination at TP0548 took place in a treponeme that was an ancestor to both TEN Bosnia A and Iraq B. The sequence of 11q/j isolate in TP0548 represents an ancestral TEN sequence that is similar to yaws-causing treponemes. In addition to the importance of the 11q/j isolate for reconstruction of the TEN phylogeny, this case emphasizes the possible role of TEN strains in development of syphilis-like lesions.

  13. Rotameric transformations in the photochemistry of TpM(CO)2(η(3)-C3H4R), where Tp = tris(pyrazolyl)borate, M = Mo or W, and R = H or Me.

    Science.gov (United States)

    Thornley, Wyatt A; Bitterwolf, Thomas E

    2015-05-07

    Low energy photolysis of TpM(CO)2(η(3)-C3H4R), where Tp = tris(pyrazolyl)borate, M = Mo or W, and R = 2-H or 2-Me in PVC matrices at 85 K results in exo/gauche isomerism of the allyl ligand. This transformation comes in contrast to the behaviour observed in cyclopentadienyl analogues which undergo exo/endo isomerism. DFT computations reveal an η(3) → η(1)* → η(3) mechanism for the allyl rotameric interconversion where the η(1)*-allyl intermediate is generated upon MLCT excitation.

  14. Mutational analysis of two structural genes of the remperate lactococcal bacteriophage TP901-1 involved in tail length determination and baseplate assembly

    DEFF Research Database (Denmark)

    Pedersen, Margit; Østergaard, Solvej; Bresciani, José

    2000-01-01

    Two putative structural genes, orf tmp (tape measure protein) and orf bpp (baseplate protein), of the temperate lactococcal phage TP901-1 were examined by introduction of specific mutations in the prophage strain Lactococcus lactic ssp. cremoris 901-1. The adsorption efficiencies of the mutated...... of the TP901-1 tail and baseplate structure is presented. Author Keywords: Lactococcus bacteriophage; TP901-1; mutagenesis; structural genes; adsorption; tail protein; tape measure protein; baseplate protein...

  15. Mutational analysis of two structural genes of the remperate lactococcal bacteriophage TP901-1 involved in tail length determination and baseplate assembly

    DEFF Research Database (Denmark)

    Pedersen, Margit; Østergaard, Solvej; Bresciani, José

    2000-01-01

    Two putative structural genes, orf tmp (tape measure protein) and orf bpp (baseplate protein), of the temperate lactococcal phage TP901-1 were examined by introduction of specific mutations in the prophage strain Lactococcus lactic ssp. cremoris 901-1. The adsorption efficiencies of the mutated p...... of the TP901-1 tail and baseplate structure is presented. Author Keywords: Lactococcus bacteriophage; TP901-1; mutagenesis; structural genes; adsorption; tail protein; tape measure protein; baseplate protein...

  16. Recurrent TP53 missense mutation in cancer patients of Arab descent.

    Science.gov (United States)

    Zick, Aviad; Kadouri, Luna; Cohen, Sherri; Frohlinger, Michael; Hamburger, Tamar; Zvi, Naama; Plaser, Morasha; Avital, Eilat; Breuier, Shani; Elian, Firase; Salah, Azzam; Goldberg, Yael; Peretz, Tamar

    2017-04-01

    Hereditary cancer comprises more than 10% of all breast cancer cases. Identification of germinal mutations enables the initiation of a preventive program that can include early detection or preventive treatment and may also have a major impact on cancer therapy. Several recurrent mutations were identified in the BRCA1/2 genes in Jewish populations however, in other ethnic groups in Israel, no recurrent mutations were identified to date. Our group established panel sequencing in cancer patients to identify recurrent, founder, and new mutations in the heterogeneous and diverse populations in Israel, We evaluated five breast cancer patients of Arab descent diagnosed with cancer before the age of 50 years and identified the previously described TP53 mutation, c.541C>T, R181C (rs587782596), in two women from unrelated Arab families. The two probands were diagnosed with breast cancer at a young age (27 and 34 years) and had significant family history spanning a wide range of tumors (breast cancer (BC), papillary thyroid cancer, glioblastoma multiform (GBM), colon cancer and leukemia). The R181C variant is expected to disrupt p53 at the ASPP2 binding domain but not the DNA binding domain and is defined by Clinvar as likely pathogenic and in HGMD as disease mutation. We further tested 85 unrelated Arab cancer patients and father of a BC carrier patient for TP53 c.541C>T using a real time polymerase chain reaction (RT-PCR) approach and identified four additional carriers, two with BC one with lung cancer, and the father of a BC carrier patient, diagnosed with GBM. Another carrier suffering from BC was identified using a Myriad panel, suggesting a recurrent mutation in this population with a frequency of 5/42 (11.9%) of our selected BC patients. We suggest testing Arab women with a breast cancer at a young age, Arab patients with multiple malignancies, or with suggestive family history for TP53 c.541C>T.

  17. Steam oxidation of TP 347H FG. Laboratory exposures versus service conditions at the power plant

    Energy Technology Data Exchange (ETDEWEB)

    Hansson, Anette N. [DONG Energy A/S, Copenhagen (Denmark); Montgomery, Melanie [DONG Energy A/S, Copenhagen (Denmark); Technical Univ. of Denmark, Lyngby (Denmark). Dept. of Mechanical Engineering; Vattenfall Heat Nordic, Copenhagen (Denmark)

    2010-07-01

    TP347H FG is often used as final superheater tubing at Danish Power Plants. The oxidation behaviour of TP347H FG in steam was investigated both in laboratory conditions and field conditions. Short time exposures (336 hours) were performed in the laboratory at 500, 600 and 700 C in gasses with 8 or 46% H{sub 2}O and varying oxygen partial pressures. The shortest exposure time at the power plant was 7720 h, the temperature varied between 500 and 650 C. Surprisingly, thicker oxide layers formed within the laboratory facility at 600 and 700 C than during the long time exposures at the power plant. This could not be explained by spallation. Double-layered oxides developed during oxidation. The outer layer consist of Fe-oxides and the inner oxide contained Fe and the remaining alloy elements. Investigations with scanning electron microscopy (SEM) revealed that the morphology of the inner oxide was different for the two types of exposures. However, investigation using transmission electron microscopy (TEM) showed that the inner oxide in both cases consisted of particles of Fe-Mn-Cr spinel embedded in a metallic Fe-Ni matrix in the bulk of the (former) alloy grains and Cr-rich oxide layer along the (former) alloy grain boundaries. The main difference between the layers formed at the two locations is that the Cr-rich oxide layer is thicker for the samples exposed at the power plant than that for the samples exposed at the laboratory conditions. Furthermore, the depth of Cr depletion in the alloy adjacent the oxide layer is greater for the samples exposed at the power plant compared to those exposed in the laboratory. The microstructure investigation suggests that the slower oxidation rate of TP347H FG at the power plant as compared to the laboratory is due to a larger reservoir of Cr for the samples exposed at the power plant probably combined with a higher mobility of Cr within the alloy. (orig.)

  18. Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma.

    Science.gov (United States)

    Gleber-Netto, Frederico O; Zhao, Mei; Trivedi, Sanchit; Wang, Jiping; Jasser, Samar; McDowell, Christina; Kadara, Humam; Zhang, Jiexin; Wang, Jing; William, William N; Lee, J Jack; Nguyen, Minh Ly; Pai, Sara I; Walline, Heather M; Shin, Dong M; Ferris, Robert L; Carey, Thomas E; Myers, Jeffrey N; Pickering, Curtis R

    2018-01-01

    Human immunodeficiency virus-infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non-HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non-HIV-related HNSCC. The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non-HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA-A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups. HIV-related HNSCC revealed a distinct pattern of mutations in comparison with non-HIV-related HNSCC. TP53 mutation frequencies were significantly lower in HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53. HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2018;124:84-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

  19. TP53 Mutation Status of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma with a Wild-type p53 Immunostaining Pattern.

    Science.gov (United States)

    Na, Kiyong; Sung, Ji-Youn; Kim, Hyun-Soo

    2017-12-01

    Diffuse and strong nuclear p53 immunoreactivity and a complete lack of p53 expression are regarded as indicative of missense and nonsense mutations, respectively, of the TP53 gene. Tubo-ovarian and peritoneal high-grade serous carcinoma (HGSC) is characterized by aberrant p53 expression induced by a TP53 mutation. However, our experience with some HGSC cases with a wild-type p53 immunostaining pattern led us to comprehensively review previous cases and investigate the TP53 mutational status of the exceptional cases. We analyzed the immunophenotype of 153 cases of HGSC and performed TP53 gene sequencing analysis in those with a wild-type p53 immunostaining pattern. Immunostaining revealed that 109 (71.3%) cases displayed diffuse and strong p53 expression (missense mutation pattern), while 39 (25.5%) had no p53 expression (nonsense mutation pattern). The remaining five cases of HGSC showed a wild-type p53 immunostaining pattern. Direct sequencing analysis revealed that three of these cases harbored nonsense TP53 mutations and two had novel splice site deletions. TP53 mutation is almost invariably present in HGSC, and p53 immunostaining can be used as a surrogate marker of TP53 mutation. In cases with a wild-type p53 immunostaining pattern, direct sequencing for TP53 mutational status can be helpful to confirm the presence of a TP53 mutation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  20. TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: A non-randomized retrospective study

    Directory of Open Access Journals (Sweden)

    Markowska Janina

    2008-01-01

    Full Text Available Abstract Background Taxane-platinum therapy (TP has replaced platinum-based therapy (PC or PAC, DNA damaging chemotherapy in the postoperative treatment of ovarian cancer patients; however, it is not always effective. TP53 protein plays a differential role in response to DNA-damaging agents and taxanes. We sought to define profiles of patients who benefit the most from TP and also of those who can be treated with PC. Methods We compared the effectiveness of PC/PAC (n = 253 and TP (n = 199 with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease; this was a non-randomized retrospective study. Immunohistochemical analysis was performed on 452 archival tumors; univariate and multivariate analysis by the Cox's and logistic regression models was performed in all patients and in subgroups with [TP53(+] and without TP53 accumulation [TP53(-]. Results The advantage of taxane-platinum therapy over platinum-based therapy was seen in the TP53(+, and not in the TP53(- group. In the TP53(+ group taxane-platinum therapy enhanced the probability of complete remission (p = .018, platinum sensitivity (p = .014, platinum highly sensitive response (p = .038 and longer survival (OS, p = .008. Poor tumor differentiation diminished the advantage from taxane-platinum therapy in the TP53(+ group. In the TP53(- group PC/PAC was at least equally efficient as taxane-platinum therapy and it enhanced the chance of platinum highly sensitive response (p = .010. However, in the TP53(- group taxane-platinum therapy possibly diminished the risk of death in patients over 53 yrs (p = .077. Among factors that positively interacted with taxane-platinum therapy in some analyses were endometrioid and clear cell type, FIGO III stage, bulky residual tumor, more advanced age of patient and moderate tumor differentiation. Conclusion Our results suggest that taxane-platinum therapy is particularly justified in patients with TP53(+ tumors or older

  1. Germline TP53 mutations and single nucleotide polymorphisms in children Mutaciones y polimorfismos de un único nucleótido del gen TP53 en línea germinal en niños

    Directory of Open Access Journals (Sweden)

    Pamela Valva

    2009-02-01

    Full Text Available Mutations in the gene TP53, which codifies the tumor suppressor protein p53, are found in about 50% of tumors. These mutations can occur not only at somatic level, but also in germline. Pediatric cancer patients, mostly with additional family history of malignancy, should be considered as potential TP53 germline mutation carriers. Germline TP53 mutations and polymorphisms have been widely studied to determine their relation with different tumors' pathogenesis. Our aim was to analyze the occurrence frequency of germline TP53 mutations and polymorphisms and to relate these to tumor development in a pediatric series. Peripheral blood mononuclear cell samples from 26 children with solid tumors [PST] and 21 pediatric healthy donors [HD] were analyzed for germline mutations and polymorphisms in TP53 gene spanning from exon 5 to 8 including introns 5 and 7. These PCR amplified fragments were sequenced to determine variations. A heterozygous mutation at codon 245 was found in 1/26 PST and 0/21 HD. Comparative polymorphisms distribution, at position 14181 and 14201(intron 7, between HD and PST revealed a trend of association (p= 0.07 with cancer risk. HD group disclosed a similar polymorphism distribution as published data for Caucasian and Central/South American populations. This is the first study about TP53 variant frequency and distribution in healthy individuals and cancer patients in Argentina.El gen que codifica para la proteína supresora de tumor p53 (TP53 se encuentra mutado en aproximadamente el 50% de los tumores. Estas mutaciones pueden presentarse como somáticas o en línea germinal. Los niños con tumores, sobre todo aquellos con historia familiar de enfermedad oncológica, deben considerarse potenciales portadores de mutaciones en línea germinal. Las mutaciones de TP53 y los polimorfismos son estudiados para determinar su relación con la patogénesis de diferentes tumores. El objetivo del trabajo fue analizar la frecuencia de

  2. Two-neutron stripping in ({sup 18}O, {sup 16}O) and (t,p) reactions

    Energy Technology Data Exchange (ETDEWEB)

    Cavallaro, M.; Agodi, A.; Carbone, D.; Cunsolo, A. [INFN - Laboratori Nazionali del Sud, Via S. Sofia 62, I-95125 Catania (Italy); Bondì, M.; Cappuzzello, F.; Nicolosi, D.; Tropea, S. [INFN - Laboratori Nazionali del Sud, Via S. Sofia 62, I-95125 Catania, Italy and Dipartimento di Fisica e Astronomia, Università di Catania, Via S. Sofia 64, I-95125 Catania (Italy); Borello-Lewin, T.; Rodrigues, M. R. D. [Instituto de Física - Universidade de São Paulo, Rua do Matão Travessa R Nr.187 CEP 05508-090 Cidade Universitária, São Paulo (Brazil); De Napoli, M. [INFN - Sezione di Catania, Via S. Sofia 64, I-95125 Catania (Italy); Garcia, V. N. [Instituto de Física, Universidade Federal Fluminense, Avenida Litoranea s/n, Gragoata, 24210-340, Niteroi, RJ (Brazil); Linares, R.; Lubian, J.; Paes, B. [Instituto de Física, Universidade Federal Fluminense, Avenida Litoranea s/n, Gragoata , 24210-340, Niteroi, RJ (Brazil); Foti, A. [Dipartimento di Fisica e Astronomia, Università di Catania, Via S. Sofia 64, I-95125 Catania, Italy and INFN - Sezione di Catania, Via S. Sofia 64, I-95125 Catania (Italy)

    2014-11-11

    The {sup 12}C({sup 18}O,{sup 16}O){sup 14}C reactions has been investigated at 84 MeV incident energy. The charged ejectiles produced in the reaction have been momentum analyzed and identified by the MAGNEX magnetic spectrometer. Q-value spectra have been extracted with an energy resolution of 160 keV (Full Width at Half Maximum) and several known bound and resonant states of {sup 14}C have been identified up to 15 MeV. In particular, excited states with dominant 2p - 4h configuration are the most populated. The absolute values of the cross sections have been extracted showing a striking similarity with those measured for the same transitions by (t,p) reactions. This indicates that the effect of the {sup 16}O core is negligible in the reaction mechanism.

  3. Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Schildkraut, Joellen M; Goode, Ellen L; Clyde, Merlise A

    2009-01-01

    The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5,206 invasive ovarian cancer cases (2......,829 of which were serous) and 8,790 controls from 13 case-control or nested case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Three of the studies performed independent discovery investigations involving genotyping of up to 23 single nucleotide polymorphisms (SNP.......07-1.57) and rs12951053 (median per allele OR, 1.19; 95% PI, 1.01-1.38). Analyses of other histologic subtypes suggested similar associations with endometrioid but not with mucinous or clear cell cancers. This large study provides statistical evidence for a small increase in risk of ovarian cancer associated...

  4. A new germline TP53 gene mutation in a family with Li-Fraumeni syndrome.

    Science.gov (United States)

    Dockhorn-Dworniczak, B; Wolff, J; Poremba, C; Schäfer, K L; Ritter, J; Gullotta, F; Jürgens, H; Böcker, W

    1996-07-01

    This report describes an unusual clinical presentation of Li-Fraumeni syndrome. Family history revealed a mild aggregation of adult cancers in one generation, and an unusual clustering of brain tumours of early childhood in the following generation. In order to evaluate the genetic basis for cancer predisposition in this family, molecular genetic analysis for the occurrence of germline TP53 tumour suppressor gene mutations was performed on 12 siblings of two generations. Indirect mutation analysis was performed by the single-strand conformation polymorphism (SSCP) technique. Alterations were characterised by automated direct fluorescence sequencing analysis. Tumour material was also examined for p53 protein accumulation by immunohistochemistry. Initially, a TP53 gene germline missense mutation was detected in an 11-year-old kindred with acute myeloid leukaemia (AML) following intensive treatment of a brain tumour. In peripheral blood and bone marrow samples of this proband, a reduction to hemizygosity occurred. During AML treatment, detection of LOH of 17p was used as a marker for clonality and treatment control. The mutation was found to be inherited from the proband's mother, who was diagnosed with breast cancer at the age of 48 years. Further, three siblings were carriers, and two are apparently healthy at the age of 21 and 23 years. Knowledge of germline mutations may allow accurate DNA-based carrier diagnosis which is of important clinical significance for treatment strategy and control. Furthermore, the occurrence of unaffected carriers in this family raises questions about appropriate methods of cancer surveillance and counselling for these people.

  5. Vico y Sarmiento: un caso para el tema de las influencias

    OpenAIRE

    Lértora Mendoza, Celina A.

    1993-01-01

    Sarmiento y la Generación del ‘37 no fueron viquianos, pero realizaron una obra histórica y civilizadora acorde con los ideales de Vico, que vivió y pensó en un contexto muy diferente. El tema de la influencia de Vico en Sarmiento es algo a debatir, lo cual requiere una depuración metodológica y una explicitación teórica de las posibles conexiones. Las cuestiones que solicitan el presente estudio remiten a la pregunta sobre esa posible influencia en el pensador argentino: si hay objetivamente...

  6. La influencia de Gregorio Magno en Alberto Magno: Super Dionysii Mysticam Theologiam et Epistulas

    OpenAIRE

    Anneliese Meis

    2010-01-01

    Si bien la influencia de Gregorio Magno fue decisiva para la historia del pensamiento teológico práctico en la Edad Media, siendo Gregorio el autor más citado en la STh de Tomás de Aquino después de Agustín, su influencia sobre Alberto Magno no ha sido estudiada recientemente. En efecto, Alberto Magno orienta su Comentario al Corpus Dionisiacum de la misma manera que Gregorio por la revelación de este misterio, que busca entender racionalmente. El estudio se detiene en las citas tomadas por e...

  7. Los inicios del astillero de la Habana en el siglo XVIII y la influencia francesa

    OpenAIRE

    Serrano Alvarez,José Manuel

    2011-01-01

    Este trabajo trata de establecer la influencia francesa en los inicios del astillero de La Habana durante el siglo XVIII. Aunque se ha defendido una influencia francesa muy escasa en los aspectos navales, en este trabajo se trata de mostrar cómo las ideas francesas fueron muy influyentes tanto para el ámbito general de la Marina española del siglo XVIII como para el astillero de La Habana en concreto. Las reformas francesas a nivel económico y administrativo fueron claves para entender el éxi...

  8. Impact of Iron and Homocysteine Levels on T Peak-to-End Interval and Tp-e/QT Ratio in Elite Athletes.

    Science.gov (United States)

    Duyuler, Serkan; Türker Duyuler, Pınar; Batur, Mustafa Kemal

    2016-11-01

    Electrocardiography (ECG) is frequently used in preparticipation evaluation of competitive athletes. Repolarization heterogeneities on ECG is a well-known indicator for malignant ventricular arrhythmias and sudden cardiac death. We aimed to investigate the effect of iron and homocysteine levels on arrhythmogenic indicators, T peak-to-end (Tp-e) interval, and Tp-e/QT ratio in elite athletes. A total of 72 players (48 football and 24 basketball) with a mean age of 25.4 ± 5.0 years were included to the analysis. Blood biochemistry, homocysteine level, and iron parameters (transferrin saturation and serum iron) were obtained by standard methods. Duration of QRS, QT interval, and Tp-e interval were measured manually on the precordial leads and Tp-e/QT ratio was calculated. Baseline demographic and clinical characteristics of the study population were compared in two groups according to the median value of Tp-e/QT = 0.219. Both iron and transferrin saturations were higher in the above median group (P = 0.001 and P = 0.002, respectively), however, homocysteine levels were not statistically different among two groups (P = 0.405). In correlation analysis, both serum iron and transferrin saturation were significantly correlated with Tp-e interval (r = 0.368; P = 0.001 and r = 0.394; P = 0.00, respectively) and Tp-e/QT ratio (r = 0.357; P = 0.002 and r = 0.372; P = 0.001, respectively). Multiple stepwise regression analysis revealed that transferrin saturation was an independent predictor of Tp-e interval and Tp-e/QT ratio (β = 0.325; P = 0.002 and β = 0.372; P = 0.001, respectively). This study showed an independent relationship between iron status and Tp-e interval and Tp-e/QT ratios of elite sport players which were also not correlated with serum homocysteine levels. © 2016 Wiley Periodicals, Inc.

  9. DNA methylation patterns of candidate genes regulated by thymine DNA glycosylase in patients with TP53 germline mutations

    Energy Technology Data Exchange (ETDEWEB)

    Fortes, F.P. [CIPE, Laboratrio de Oncogentica Molecular, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Kuasne, H. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Departamento de Urologia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP (Brazil); Marchi, F.A. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Programa Inter-Institucional em Bioinformtica, Instituto de Matemtica e Estatstica, Universidade So Paulo, So Paulo, SP (Brazil); Miranda, P.M. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Rogatto, S.R. [CIPE, Laboratrio NeoGene, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Departamento de Urologia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP (Brazil); Achatz, M.I. [CIPE, Laboratrio de Oncogentica Molecular, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Departamento de Oncogentica, A.C. Camargo Cancer Center, So Paulo, SP (Brazil)

    2015-04-28

    Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder. In Brazil, the p.R337H TP53 founder mutation causes the variant form of LFS, Li-Fraumeni-like syndrome. The occurrence of cancer and age of disease onset are known to vary, even in patients carrying the same mutation, and several mechanisms such as genetic and epigenetic alterations may be involved in this variability. However, the extent of involvement of such events has not been clarified. It is well established that p53 regulates several pathways, including the thymine DNA glycosylase (TDG) pathway, which regulates the DNA methylation of several genes. This study aimed to identify the DNA methylation pattern of genes potentially related to the TDG pathway (CDKN2A, FOXA1, HOXD8, OCT4, SOX2, and SOX17) in 30 patients with germline TP53mutations, 10 patients with wild-type TP53, and 10 healthy individuals. We also evaluated TDG expression in patients with adrenocortical tumors (ADR) with and without the p.R337H TP53 mutation. Gene methylation patterns of peripheral blood DNA samples assessed by pyrosequencing revealed no significant differences between the three groups. However, increased TDG expression was observed by quantitative reverse transcription PCR in p.R337H carriers with ADR. Considering the rarity of this phenotype and the relevance of these findings, further studies using a larger sample set are necessary to confirm our results.

  10. Temporal transcription of the lactococcal temperate phage TP901-1 and DNA sequence of the early promoter region

    DEFF Research Database (Denmark)

    Madsen, Hans Peter Lynge; Hammer, Karin

    1998-01-01

    to a phage repressor, a single-stranded DNA-binding protein, a topoisomerase, a Cro-like protein and two other phage proteins of unknown function were detected. The gene arrangement in the early transcribed region of TP901-1 thus consists of two transcriptional units: one from PR containing four genes...

  11. EEC syndrome, Arg227Gln TP63 mutation and micturition difficulties: Is there a genotype-phenotype correlation?

    NARCIS (Netherlands)

    Maclean, K.; Holme, S.A.; Gilmour, E.; Taylor, M.; Scheffer, H.; Graf, N.; Smith, G.H.; Onikul, E.; Bokhoven, J.H.L.M. van; Moss, C.; Ades, L.C.

    2007-01-01

    We report on two unrelated families with EEC syndrome (ectrodactyly, ectodermal dysplasia, cleft lip/palate), each with an Arg227Gln TP63 gene mutation, where the phenotype overlapped extensively with the allelic disorder, limb-mammary syndrome (LMS). Features common to both families were an

  12. Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in the TP63 Gene

    NARCIS (Netherlands)

    Eisenkraft, A.; Pode-Shakked, B.; Goldstein, N.; Shpirer, Z.; Bokhoven, H. van; Anikster, Y.

    2015-01-01

    Mutations in the TP63 gene have been associated with a variety of ectodermal dysplasia syndromes, among which the clinically overlapping Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) and the Rapp-Hodgkin syndromes. We report a multiplex nonconsanguineous family of Ashkenazi-Jewish

  13. Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert withTP53mutations.

    Science.gov (United States)

    Ajore, Ram; Raiser, David; McConkey, Marie; Jöud, Magnus; Boidol, Bernd; Mar, Brenton; Saksena, Gordon; Weinstock, David M; Armstrong, Scott; Ellis, Steven R; Ebert, Benjamin L; Nilsson, Björn

    2017-04-01

    Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in TP53 -intact tumors ( P  ≪ 10 -10 ), and shRNA-mediated knockdown of RPGs activated p53 in TP53 -wild-type cells. In contrast, we did not see negative selection of RPG deletions in TP53 -mutant tumors. RPGs are conserved with respect to homozygous deletions, and shRNA screening data from 174 cell lines demonstrate that further suppression of hemizygously deleted RPGs inhibits cell growth. Our results establish RPG haploinsufficiency as a strikingly common vulnerability of human cancers that associates with TP53 mutations and could be targetable therapeutically. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

  14. Expression of TP53 and IL-1α in unicystic ameloblastoma predicts the efficacy of marsupialization treatment.

    Science.gov (United States)

    Zhang, Xinyu; Liu, Liu; Yang, Xi; Wang, Lizhen; Zhang, Chenping; Hu, Yongjie

    2018-02-01

    In this study, we evaluated the effects of marsupialization in treating unicystic ameloblastoma (UA) and investigated the relationship between TP53 and interleukin 1 α (IL-1α) expression and the clinical outcome of UA treated with marsupialization.Consecutive patients treated with marsupialization and curettage at Shanghai Ninth People's Hospital were included. According to the unified standard, 48 patients were included in this study. Of these, 20 showed a good response, 10 a partial response, and 18 no response, based on the outcome of the marsupialization procedure. The expression of proteins TP53 and IL-1α was detected with immunohistochemistry (IHC). The clinical and pathological characteristics of the patients were analyzed.Analysis of the clinical and pathological characteristics showed that the effects of marsupialization treatment were significantly associated with lesion location (P < .001) and tumor diameter (P = .01). IHC showed that TP53 expression was significantly higher in the good-response group than in the partial- or no-response group (P = .02), and IL-1α expression was significantly higher in the good-response group than in the partial- and no-response groups (P = .03).Marsupialization is an effective preliminary procedure for treating UA before curettage and peripheral ostectomy. The expression of the TP53 and IL-1α proteins correlates directly with the outcome of UA treated with marsupialization.

  15. Identification of operator sites of the CI repressor of phage TP901-1: evolutionary link to other phages

    International Nuclear Information System (INIS)

    Johansen, Annette H.; Broendsted, Lone; Hammer, Karin

    2003-01-01

    The repressor encoded by the cI gene of the temperate Lactococcus lactis subsp. cremoris bacteriophage TP901-1 has been purified. Gel-retardation and footprinting analyses identified three palindromic operator sites (O R , O L , and O D ). The operator site O R is located between the two divergent early promoters P R and P L , O L overlaps the transcriptional start of the lytic P L promoter, and O D is located downstream of the mor gene, the first gene in the lytic gene cluster. The function of O L was verified by mutational analysis. Binding was found to be specific and cooperative. Multimeric forms of the repressor were observed, thus indicating that the repressor may bind simultaneously to all three operator sites. Inverted repeats with homology to the operator sites of TP901-1 were identified in phage genomes encoding repressors homologous to CI of TP901-1. Interestingly, the locations of these repeats on the phage genomes correspond to those found in TP901-1, indicating that the same system of cooperative repression of early phage promoters has been inherited by modular evolution

  16. TP53 germline mutation may affect response to anticancer treatments: analysis of an intensively treated Li-Fraumeni family.

    Science.gov (United States)

    Kappel, Sonja; Janschek, Elisabeth; Wolf, Brigitte; Rudas, Margaretha; Teleky, Bela; Jakesz, Raimund; Kandioler, Daniela

    2015-06-01

    Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited disorder associated with the occurrence of a wide spectrum of early-onset malignancies, the most prevalent being breast cancer and sarcoma. The presence of TP53 germline mutations in the majority of LFS patients suggests a genetic basis for the cancer predisposition. No special recommendations for the treatment of LFS patients have been made to date, except that of minimizing radiation. We hypothesized that TP53 germline mutations may be associated not only with cancer predisposition, but also with lack of response to chemo- and radiotherapy. Here, we present an Austrian LFS family whose members were intensively treated with chemo- and radiotherapy due to cancers that occurred at a predominantly young age, including eight breast cancers in six patients. Material from seven family members was screened for p53 mutation by Sanger sequencing and immunohistochemistry. A rare missense mutation in the tetramerization domain of exon 10 of the TP53 gene was found to segregate with malignant disease in this family. Lack of response to various chemotherapies and radiotherapy could be ascertained by histopathology of surgical specimens after neoadjuvant treatment, by cancer relapse occurring while receiving adjuvant systemic treatment and by the occurrence of second primaries in areas of adjuvant radiation. Our observations suggest that current standards of cancer treatment may not be valid for patients with LFS. In patients with TP53 germline mutation, cytotoxic treatment may bear not only the risk of tumor induction but also the risk of treatment failure.

  17. TpF1 from Treponema pallidum activates inflammasome and promotes the development of regulatory T cells.

    Science.gov (United States)

    Babolin, Chiara; Amedei, Amedeo; Ozolins, Dzintars; Zilevica, Aija; D'Elios, Mario Milco; de Bernard, Marina

    2011-08-01

    Human syphilis is a multistage disease, with diverse and wide-ranging manifestations caused by Treponema pallidum. Despite the fact that a cell-mediated immune response takes part in the course of syphilis, T. pallidum often manages to evade host immunity and, in untreated individuals, may trigger chronic infection. With this study, we demonstrate for the first time, to our knowledge, that Treponema pallidum induces a regulatory T (Treg) response in patients with secondary syphilis and we found that the miniferritin TpF1, produced by the bacterium, is able to expand this response and promote the production of TGF-β. Accordingly, TpF1 stimulates monocytes to release IL-10 and TGF-β, the key cytokines in driving Treg cell differentiation. Interestingly, we also found that TpF1 stimulates monocytes to synthesize and release several proinflammatory cytokines, such as TNF-α, IL-6, and IL-1β, the latter following the activation of the multiprotein complex inflammasome. Collectively, these data strongly support a central role for TpF1 both in the inflammation process, which occurs in particular during the early stage of syphilis, and in the long-term persistence of the spirochete within the host by promoting Treg response and TGF-β production.

  18. Real-time estimation of TP load in a Mississippi Delta Stream using a dynamic data driven application system

    Science.gov (United States)

    Ying Ouyang; Theodor D. Leininger; Jeff Hatten

    2013-01-01

    Elevated phosphorus (P) in surface waters can cause eutrophication of aquatic ecosystems and can impair water for drinking, industry, agriculture, and recreation. Currently, no effort has been devoted to estimating real-time variation and load of total P (TP) in surface waters due to the lack of suitable and/or cost-effective wireless sensors. However, when considering...

  19. A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor

    DEFF Research Database (Denmark)

    Stecher, Chalotte Willemann; Grønbaek, Kirsten; Hasle, Henrik

    2008-01-01

    A 20-month-old boy presented with precocious puberty due to a Leydig cell tumor, and at the age of 6 years with a primitive neuroectodermal brain-tumor (PNET). A novel splice site mutation of the TP53-gene, likely to be associated with a nonfunctional protein, was found in the proband, his father...

  20. Microstructural investigation of the oxide formed on TP 347H FG during long-term steam oxidation

    DEFF Research Database (Denmark)

    Hansson, Anette Nørgaard; Danielsen, Hilmar Kjartansson; Grumsen, Flemming Bjerg

    2010-01-01

    The long-term oxidation behaviour of TP347H FG in ultra supercritical steam conditions was assessed by exposing the steel in test superheater loops in a Danish coal-fired power plant and characterising the oxide layer with reflective light and electron microscopy. Double layered oxide scales formed...

  1. Structural and dynamics studies of a truncated variant of CI repressor from bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Rasmussen, Kim Krighaar; Frandsen, Kristian E. H.; Erba, Elisabetta Boeri

    2016-01-01

    The CI repressor from the temperate bacteriophage TP901-1 consists of two folded domains, an N-terminal helix-turn-helix DNA-binding domain (NTD) and a C-terminal oligomerization domain (CTD), which we here suggest to be further divided into CTD1 and CTD2. Full-length CI is a hexameric protein...

  2. Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex

    Directory of Open Access Journals (Sweden)

    Zuzana Hořejší

    2014-04-01

    Full Text Available The R2TP cochaperone complex plays a critical role in the assembly of multisubunit machines, including small nucleolar ribonucleoproteins (snoRNPs, RNA polymerase II, and the mTORC1 and SMG1 kinase complexes, but the molecular basis of substrate recognition remains unclear. Here, we describe a phosphopeptide binding domain (PIH-N in the PIH1D1 subunit of the R2TP complex that preferentially binds to highly acidic phosphorylated proteins. A cocrystal structure of a PIH-N domain/TEL2 phosphopeptide complex reveals a highly specific phosphopeptide recognition mechanism in which Lys57 and 64 in PIH1D1, along with a conserved DpSDD phosphopeptide motif within TEL2, are essential and sufficient for binding. Proteomic analysis of PIH1D1 interactors identified R2TP complex substrates that are recruited by the PIH-N domain in a sequence-specific and phosphorylation-dependent manner suggestive of a common mechanism of substrate recognition. We propose that protein complexes assembled by the R2TP complex are defined by phosphorylation of a specific motif and recognition by the PIH1D1 subunit.

  3. Association between TP53 gene Arg72Pro polymorphism and Wilms’ tumor risk in a Chinese population

    Directory of Open Access Journals (Sweden)

    Fu W

    2017-02-01

    Full Text Available Wen Fu,1,2,* Zhen-Jian Zhuo,3,* Wei Jia,1,2 Jinhong Zhu,4 Shi-Bo Zhu,1,2 Ze-Feng Lin,1,2 Feng-Hua Wang,1,2 Huimin Xia,1,2 Jing He,1,2 Guo-Chang Liu1,2 1Department of Pediatric Urology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 2Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 3Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, 4Molecular Epidemiology Laboratory, Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Wilms’ tumor is one of the most prevalent pediatric malignancies, ranking fourth in childhood cancer worldwide. TP53 is a critical tumor suppressor gene, which encodes a 53 kDa protein, p53. The p53 functions to protect against cancer by regulating cell cycle and apoptosis and maintaining DNA integrity. TP53 gene is highly polymorphic. Several TP53 gene polymorphisms have been considered to be associated with cancer risk. Of them, a nonsynonymous polymorphism, Arg72Pro (rs1042522 C>G, has been most extensively studied for the association with cancer risk; however, few studies have investigated its effect on Wilms’ tumor. Because of the central role of p53 in cell cycle control, the TP53 gene Arg72Pro polymorphism is also a good potential candidate predisposition locus for this pediatric cancer. We genotyped this polymorphism in 145 patients and 531 cancer-free controls recruited from Chinese children by Taqman methodology. Overall, our result suggested a lack of association between the TP53 gene Arg72Pro polymorphism and Wilms’ tumor. In the stratified analysis, we found that carriers of CG/GG genotypes had a significantly increased Wilms’ tumor risk in children not older

  4. TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes

    NARCIS (Netherlands)

    Ruijs, M.W.G.; Verhoef, S.; Rookus, M.A.; Pruntel, R.; van der Hout, A.H.; Hogervorst, F.B.L.; Kluijt, I.; Sijmons, R.H.; Aalfs, C.M.; Wagner, A.; Ausems, M.G.E.M.; Hoogerbrugge, N.; van Asperen, C.J.; Gómez García, E.B.; Meijers-Heijboer, H.; ten Kate, L.P.; Menko, F.H.; van 't Veer, L.J.

    2010-01-01

    Background Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome. Most families fulfilling the classical diagnostic criteria harbour TP53 germline mutations. However, TP53 germline mutations may also occur in less obvious phenotypes. As a result, different criteria

  5. Importance of TP53 and RB in the repair of potentially lethal damage and induction of color junctions after exposure to ionizing radiation

    NARCIS (Netherlands)

    Franken, N. A. P.; van Bree, C.; ten Cate, R.; van Oven, C. H.; Haveman, J.

    2002-01-01

    Repair of potentially lethal damage (PLD) was investigated in cells with functional G(1)-phase arrest with wild-type TP53 and wild-type RB and in cells in which G(1)-phase arrest was abrogated by inactivation of TP53 or RB. Confluent cultures of cells were plated for clonogenic survival assay either

  6. Association of the germline TP53 R72P and MDM2 SNP309 variants with breast cancer survival in specific breast tumor subgroups

    NARCIS (Netherlands)

    van den Broek, Alexandra J.; Broeks, Annegien; Horlings, Hugo M.; Canisius, Sander V. M.; Braaf, Linde M.; Langerød, Anita; van't Veer, Laura J.; Schmidt, Marjanka K.

    2011-01-01

    The tumor suppressor gene TP53 and its regulator MDM2 are both important players in the DNA-damage repair "TP53 response pathway". Common germline polymorphisms in these genes may affect outcome in patients with tumors characterized by additional somatic changes in the same or a related pathway. To

  7. TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution.

    Science.gov (United States)

    Hou, H-A; Chou, W-C; Kuo, Y-Y; Liu, C-Y; Lin, L-I; Tseng, M-H; Chiang, Y-C; Liu, M-C; Liu, C-W; Tang, J-L; Yao, M; Li, C-C; Huang, S-Y; Ko, B-S; Hsu, S-C; Chen, C-Y; Lin, C-T; Wu, S-J; Tsay, W; Chen, Y-C; Tien, H-F

    2015-07-31

    The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

  8. The Multifunctional Role of the Pallilysin-Associated Treponema pallidum Protein, Tp0750, in Promoting Fibrinolysis and Extracellular Matrix Component Degradation

    Science.gov (United States)

    Houston, Simon; Russell, Shannon; Hof, Rebecca; Roberts, Alanna K.; Cullen, Paul; Irvine, Kyle; Smith, Derek S.; Borchers, Christoph H.; Tonkin, Michelle L.; Boulanger, Martin J.; Cameron, Caroline E.

    2014-01-01

    Summary The mechanisms that facilitate dissemination of the highly invasive spirochete, Treponema pallidum, are incompletely understood. Previous studies showed the treponemal metalloprotease pallilysin (Tp0751) possesses fibrin clot degradation capability, suggesting a role in treponemal dissemination. In the current study we report characterization of the functionally-linked protein Tp0750. Structural modelling predicts Tp0750 contains a von Willebrand factor type A (vWFA) domain, a protein-protein interaction domain commonly observed in extracellular matrix (ECM)-binding proteins. We report Tp0750 is a serine protease that degrades the major clot components fibrinogen and fibronectin. We also demonstrate Tp0750 cleaves a matrix metalloprotease (MMP) peptide substrate that is targeted by several MMPs, enzymes central to ECM remodelling. Through proteomic analyses we show Tp0750 binds the endothelial fibrinolytic receptor, annexin A2, in a specific and dose-dependent manner. These results suggest Tp0750 constitutes a multifunctional protein that is able to (1) degrade infection-limiting clots by both inhibiting clot formation through degradation of host coagulation cascade proteins and promoting clot dissolution by complexing with host proteins involved in the fibrinolytic cascade and (2) facilitate ECM degradation via MMP-like proteolysis of host components. We propose that through these activities Tp0750 functions in concert with pallilysin to enable T. pallidum dissemination. PMID:24303899

  9. Analysis of the complete DNA sequence of the temperate bacteriophage TP901-1: Evolution, structure, and genome organization of lactococcal bacteriophages

    DEFF Research Database (Denmark)

    Brøndsted, Lone; Østergaard, Solvej; Pedersen, Margit

    2001-01-01

    A complete analysis of the entire genome of the temperate lactococcal bacteriophage TP901-1 has been performed and the function of 21 of 56 TP901-1-encoded ORFs has been assigned. This knowledge has been used to propose 10 functional modules each responsible for specific functions during bacterio...

  10. Oropharyngeal Squamous Cell Carcinoma Treated With Radiotherapy or Radiochemotherapy: Prognostic Role of TP53 and HPV Status

    International Nuclear Information System (INIS)

    Fallai, Carlo; Perrone, Federica; Licitra, Lisa; Pilotti, Silvana; Locati, Laura; Bossi, Paolo; Orlandi, Ester; Palazzi, Mauro; Olmi, Patrizia

    2009-01-01

    Purpose: To study the prognostic value of the TP53 mutation and human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC). Methods and materials: The TP53 mutation and HPV status were analyzed in 78 cases of locoregionally advanced OPSCC. The possible correlation of these factors with locoregiownal control, relapse-free survival, disease-specific survival, and overall survival (OS) was also investigated. Results: Of these 78 cases, 22 had disruptive and 22 had non-disruptive (silent) TP53 mutations; the remaining 34 cases had wild-type (WT) TP53. HPV 16 DNA was found in 9 cases (11%), but all HPV-positive (HPV+) cases carried a functional p53 protein, except for 1 case that had a silent mutation. HPV+ patients fared better than HPV-negative (HPV-) patients in terms of all survival parameters, with highly statistically significant differences between the groups. Specifically, no distant metastases were observed in the HPV+ patients, whereas they occurred in 17% of the HPV- patients. However, no difference was observed between the WT TP53 and mutation group, even when this was analyzed in terms of disruptive and non-disruptive mutations. Regardless, treatment with chemotherapy nearly doubled the 5-year OS rates, both in the mutation (42% vs. 22%) and WT (30 vs. 16%) group, but only the mutation group showed improvement in all survival parameters. In addition, the second tumor-free 5-year survival rate was 72% in HPV- cases, but no second tumors were observed in HPV+ and WT p53 cases. Conclusions: Patients with HPV+ OPSCC have an excellent prognosis after radiochemotherapy, but cisplatin-based chemotherapy may not confer a satisfactory outcome, especially in WT cases, thereby justifying the additional or alternative use of taxanes and epidermal growth factor receptors inhibitors. Uncommon distant metastases and second tumors in the HPV+ group may be cause for clinicians to review the follow-up policies in these patients.

  11. Reduced binding of the endolysin LysTP712 to Lactococcus lactis ΔftsH contributes to phage resistance

    Directory of Open Access Journals (Sweden)

    CLARA eROCES

    2016-02-01

    Full Text Available Absence of the membrane protease FtsH in Lactococcus lactis hinders release of the bacteriophage TP712. In this work we have analysed the mechanism responsible for the non-lytic phenotype of L. lactis ΔftsH after phage infection. The lytic cassette of TP712 contains a putative antiholin-pinholin system and a modular endolysin (LysTP712. Inducible expression of the holin gene demonstrated the presence of a dual start motif which is functional in both wildtype and L. lactis ΔftsH cells. Moreover, simulating holin activity with ionophores accelerated lysis of wildtype cells but not L. lactis ΔftsH cells, suggesting inhibition of the endolysin rather than a role of FtsH in holin activation. However, zymograms revealed the synthesis of an active endolysin in both wildtype and L. lactis ΔftsH TP712 lysogens. A reporter protein was generated by fusing the cell wall binding domain of LysTP712 to the fluorescent mCherry protein. Binding of this reporter protein took place at the septa of both wildtype and L. lactis ΔftsH cells as shown by fluorescence microscopy. Nonetheless, fluorescence spectroscopy demonstrated that mutant cells bound 40 % less protein. In conclusion, the non-lytic phenotype of L. lactis ΔftsH is not due to direct action of the FtsH protease on the phage lytic proteins but rather to a putative function of FtsH in modulating the architecture of the L. lactis cell envelope that contributes to a lower affinity of the phage endolysin to its substrate and, likely to its catalytic activity.

  12. Reduced Binding of the Endolysin LysTP712 to Lactococcus lactis ΔftsH Contributes to Phage Resistance.

    Science.gov (United States)

    Roces, Clara; Campelo, Ana B; Escobedo, Susana; Wegmann, Udo; García, Pilar; Rodríguez, Ana; Martínez, Beatriz

    2016-01-01

    Absence of the membrane protease FtsH in Lactococcus lactis hinders release of the bacteriophage TP712. In this work we have analyzed the mechanism responsible for the non-lytic phenotype of L. lactis ΔftsH after phage infection. The lytic cassette of TP712 contains a putative antiholin-pinholin system and a modular endolysin (LysTP712). Inducible expression of the holin gene demonstrated the presence of a dual start motif which is functional in both wildtype and L. lactis ΔftsH cells. Moreover, simulating holin activity with ionophores accelerated lysis of wildtype cells but not L. lactis ΔftsH cells, suggesting inhibition of the endolysin rather than a role of FtsH in holin activation. However, zymograms revealed the synthesis of an active endolysin in both wildtype and L. lactis ΔftsH TP712 lysogens. A reporter protein was generated by fusing the cell wall binding domain of LysTP712 to the fluorescent mCherry protein. Binding of this reporter protein took place at the septa of both wildtype and L. lactis ΔftsH cells as shown by fluorescence microscopy. Nonetheless, fluorescence spectroscopy demonstrated that mutant cells bound 40% less protein. In conclusion, the non-lytic phenotype of L. lactis ΔftsH is not due to direct action of the FtsH protease on the phage lytic proteins but rather to a putative function of FtsH in modulating the architecture of the L. lactis cell envelope that results in a lower affinity of the phage endolysin to its substrate.

  13. In situ synthesis of Eu(Tp){sub 3} complex inside the pores of mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Malba, Chandrashekhar; Bellotto, Luca; Freris, Isidora [Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari di Venezia, via Torino 155/b, 30170 Venezia-Mestre (Italy); Enrichi, Francesco [CIVEN, Coordinamento Interuniversitario Veneto per le Nanotecnologie, Via delle Industrie 5, 30175 Marghera (Venezia) (Italy); Cristofori, Davide [Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari di Venezia, via Torino 155/b, 30170 Venezia-Mestre (Italy); Riello, Pietro, E-mail: riellop@unive.it [Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari di Venezia, via Torino 155/b, 30170 Venezia-Mestre (Italy); Benedetti, Alvise [Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari di Venezia, via Torino 155/b, 30170 Venezia-Mestre (Italy)

    2013-10-15

    A route for europium (III) tris-pyrazolyl borate complex [Eu(Tp){sub 3}] formation inside the pores of mesoporous silica nanoparticles (MSNs) has been established to yield a highly luminescent nanostructured hybrid. Two different in situ chemical precipitation techniques have been explored for the nanoencapsulation of the Eu{sup 3+} complex [Eu(Tp){sub 3}] inside the pore channels of mesoporous silica nanoparticles, by varying the sequence order of precursor impregnation. In the first method, the Eu salt is introduced into the pores by wet impregnation and removal of the solvent, followed by wet impregnation of the ligand. In the second approach, the addition sequence is reversed. The importance of the addition sequence was demonstrated by the successful formation of the europium (III) tris-pyrazolyl borate complex in the pore network by following the first approach. The observed pyrazol-1-yl borate (Tp) to Eu{sup 3+} intramolecular energy transfer, i.e., the antenna effect, verified the formation of the complex. Photoluminescence spectroscopy, X-ray diffraction, N{sub 2} adsorption, FTIR spectroscopy, and TEM were used to characterize the material. -- Highlights: • In situ formation of Eu(Tp){sub 3} in mesoporous silica nanoparticles is studied. • Pivotal role of the addition sequence of the reagents is demonstrated. • Eu salt adsorption preceded the addition of the ligand proved effective (route A). • Luminescent material is well characterized by several techniques. • We give a possible mechanism for the formation of Eu(Tp){sub 3} complex via route A.

  14. Geochemical Characteristics of TP3 Mine Wastes at the Elizabeth Copper Mine Superfund Site, Orange County, Vermont

    Science.gov (United States)

    Hammarstrom, Jane M.; Piatak, Nadine M.; Seal, Robert R.; Briggs, Paul H.; Meier, Allen L.; Muzik, Timothy L.

    2003-01-01

    Remediation of the Elizabeth mine Superfund site in the Vermont copper belt poses challenges for balancing environmental restoration goals with issues of historic preservation while adopting cost-effective strategies for site cleanup and long-term maintenance. The waste-rock pile known as TP3, at the headwaters of Copperas Brook, is especially noteworthy in this regard because it is the worst source of surface- and ground-water contamination identified to date, while also being the area of greatest historical significance. The U.S. Geological Survey (USGS) conducted a study of the historic mine-waste piles known as TP3 at the Elizabeth mine Superfund site near South Strafford, Orange County, VT. TP3 is a 12.3-acre (49,780 m2) subarea of the Elizabeth mine site. It is a focus area for historic preservation because it encompasses an early 19th century copperas works as well as waste from late 19th- and 20th century copper mining (Kierstead, 2001). Surface runoff and seeps from TP3 form the headwaters of Copperas Brook. The stream flows down a valley onto flotation tailings from 20th century copper mining operations and enters the West Branch of the Ompompanoosuc River approximately 1 kilometer downstream from the mine site. Shallow drinking water wells down gradient from TP3 exceed drinking water standards for copper and cadmium (Hathaway and others, 2001). The Elizabeth mine was listed as a Superfund site in 2001, mainly because of impacts of acid-mine drainage on the Ompompanoosuc River.

  15. CSNK1E/CTNNB1 Are Synthetic Lethal To TP53 in Colorectal Cancer and Are Markers for Prognosis

    Directory of Open Access Journals (Sweden)

    Khong-Loon Tiong

    2014-05-01

    Full Text Available Two genes are called synthetic lethal (SL if their simultaneous mutations lead to cell death, but each individual mutation does not. Targeting SL partners of mutated cancer genes can kill cancer cells specifically, but leave normal cells intact. We present an integrated approach to uncovering SL pairs in colorectal cancer (CRC. Screening verified SL pairs using microarray gene expression data of cancerous and normal tissues, we first identified potential functionally relevant (simultaneously differentially expressed gene pairs. From the top-ranked pairs, ~20 genes were chosen for immunohistochemistry (IHC staining in 171 CRC patients. To find novel SL pairs, all 169 combined pairs from the individual IHC were synergistically correlated to five clinicopathological features, e.g. overall survival. Of the 11 predicted SL pairs, MSH2-POLB and CSNK1E-MYC were consistent with literature, and we validated the top two pairs, CSNK1E-TP53 and CTNNB1-TP53 using RNAi knockdown and small molecule inhibitors of CSNK1E in isogenic HCT-116 and RKO cells. Furthermore, synthetic lethality of CSNK1E and TP53 was verified in mouse model. Importantly, multivariate analysis revealed that CSNK1E-P53, CTNNB1-P53, MSH2-RB1, and BRCA1-WNT5A were independent prognosis markers from stage, with CSNK1E-P53 applicable to early-stage and the remaining three throughout all stages. Our findings suggest that CSNK1E is a promising target for TP53-mutant CRC patients which constitute ~40% to 50% of patients, while to date safety regarding inhibition of TP53 is controversial. Thus the integrated approach is useful in finding novel SL pairs for cancer therapeutics, and it is readily accessible and applicable to other cancers.

  16. Immunohistochemical staining patterns of p53 can serve as a surrogate marker for TP53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis.

    Science.gov (United States)

    Yemelyanova, Anna; Vang, Russell; Kshirsagar, Malti; Lu, Dan; Marks, Morgan A; Shih, Ie Ming; Kurman, Robert J

    2011-09-01

    Immunohistochemical staining for p53 is used as a surrogate for mutational analysis in the diagnostic workup of carcinomas of multiple sites including ovarian cancers. Strong and diffuse immunoexpression of p53 is generally interpreted as likely indicating a TP53 gene mutation. The immunoprofile that correlates with wild-type TP53, however, is not as clear. In particular, the significance of completely negative immunostaining is controversial. The aim of this study was to clarify the relationship of the immunohistochemical expression of p53 with the mutational status of the TP53 gene in ovarian cancer. A total of 57 ovarian carcinomas (43 high-grade serous ovarian/peritoneal carcinomas, 2 malignant mesodermal mixed tumors (carcinosarcomas), 2 low-grade serous carcinomas, 4 clear cell carcinomas, 1 well-differentiated endometrioid carcinoma, and 5 carcinomas with mixed epithelial differentiation) were analyzed for TP53 mutations by nucleotide sequencing (exons 4-9), and subjected to immunohistochemical analysis of p53 expression. Thirty six tumors contained functional mutations and 13 had wild type TP53. Five tumors were found to harbor known TP53 polymorphism and changes in the intron region were detected in three. Tumors with wild-type TP53 displayed a wide range of immunolabeling patterns, with the most common pattern showing ≤10% of positive cells in 6 cases (46%). Mutant TP53 was associated with 60-100% positive cells in 23 cases (64% of cases). This pattern of staining was also seen in three cases with wild-type TP53. Tumors that were completely negative (0% cells staining) had a mutation of TP53 in 65% of cases and wild-type TP53 in 11%. Combining two immunohistochemical labeling patterns associated with TP53 mutations (0% and 60-100% positive cells), correctly identified a mutation in 94% of cases (Povarian carcinomas. In addition to a strong and diffuse pattern of p53 expression (in greater than 60% of cells), complete absence of p53 immunoexpression is

  17. Validación del Cuestionario de Creencias Centrales de los Trastornos de la Personalidad (CCE-TP en población colombiana

    Directory of Open Access Journals (Sweden)

    Nora Helena Londoño A.

    2010-07-01

    Full Text Available Se construyó un cuestionario para evaluar creencias centrales asociadas con los trastornos de la personalidad, fundamentadas en el Modelo de la Terapia Cognitiva. Se realizó el análisis estructural y la validez de contenido de la prueba en población universitaria de la ciudad de Medellín, Colombia. La muestra fue representativa y elegida al azar a través de un procedimiento polietápico. Un número de 809 estudiantes universitarios contestaron el cuestionario de creencias centrales de los trastornos de la personalidad (CCE-TP. Se realizó un análisis factorial exploratorio de la prueba, reagrupándose los ítems en 14 factores (F que representan el 61,3% de la varianza. F1: CCE-TP antisocial (8 ítems, a 0,839; F2: CCE-TP esquizotípico/límite (8 ítems, a 0,846; F3: CCE-TP histriónico/patrón seductor (6 ítems, a 0,833; F4: CCE-TP paranoide (6 ítems, a 0,836; F5: CCE-TP por evitación / autopercepción negativa (5 ítems, a 0,755; F6: CCE-TP por dependencia (5 ítems, a 0,797; F7: CCE-TP histriónico/ dependencia emocional (4 ítems, a 0,755; F8: CCETP obsesivo-compulsivo/perfeccionista (4 ítems, a 0,808; F9: CCE-TP por evitación/hipersensible (4 ítems, a 0,766; F10: CCE-TP obsesivo-compulsivo/ crítico frente a los demás (3 ítems, a 0,851; F11: CCE-TP narcisista (4 ítems, a 0,717; F12: CCE-TP pasivo-agresivo / temor a ser dominado (3 ítems, a 0,719; F13: CCE-TP pasivo-agresivo/crítico frente a la autoridad (3 ítems, a 0,685, y F14: CCE-TP esquizoide (2 ítems, a 0,774. El alfa de Cronbach de la prueba fue de 0,931.

  18. Validación del Cuestionario de Creencias Centrales de los Trastornos de la Personalidad (CCE-TP en población colombiana

    Directory of Open Access Journals (Sweden)

    Diego Castrillón M.

    2007-06-01

    Full Text Available Se construyó un cuestionario para evaluar creencias centrales asociadas con los trastornos de la personalidad, fundamentadas en el Modelo de la Terapia Cognitiva. Se realizó el análisis estructural y la validez de contenido de la prueba en población universitaria de la ciudad de Medellín, Colombia. La muestra fue representativa y elegida al azar a través de un procedimiento polietápico. Un número de 809 estudiantes universitarios contestaron el cuestionario de creencias centrales de los trastornos de la personalidad (CCE-TP. Se realizó un análisis factorial exploratorio de la prueba, reagrupándose los ítems en 14 factores (F que representan el 61,3% de la varianza. F1: CCE-TP antisocial (8 ítems, a 0,839; F2: CCE-TP esquizotípico/límite (8 ítems, a 0,846; F3: CCE-TP histriónico/patrón seductor (6 ítems, a 0,833; F4: CCE-TP paranoide (6 ítems, a 0,836; F5: CCE-TP por evitación / autopercepción negativa (5 ítems, a 0,755; F6: CCE-TP por dependencia (5 ítems, a 0,797; F7: CCE-TP histriónico/dependencia emocional (4 ítems, a 0,755; F8: CCETP obsesivo-compulsivo/perfeccionista (4 ítems, a 0,808; F9: CCE-TP por evitación/hipersensible (4 ítems, a 0,766; F10: CCE-TP obsesivo-compulsivo/ crítico frente a los demás (3 ítems, a 0,851; F11: CCE-TP narcisista (4 ítems, a 0,717; F12: CCE-TP pasivo-agresivo / temor a ser dominado (3 ítems, a 0,719; F13: CCE-TP pasivo-agresivo/crítico frente a la autoridad (3 ítems, a 0,685, y F14: CCE-TP esquizoide (2 ítems, a 0,774. El alfa de Cronbach de la prueba fue de 0,931.

  19. Early occurrence of lung adenocarcinoma and breast cancer after radiotherapy of a chest wall sarcoma in a patient with a de novo germline mutation in TP53.

    Science.gov (United States)

    Ferrarini, Alessandra; Auteri-Kaczmarek, Agnes; Pica, Alessia; Boesch, Nemya; Heinimann, Karl; Schäfer, Stephan C; Vesnaver-Megalo, Sara; Cina, Viviane; Beckmann, Jacques S; Monnerat, Christian

    2011-06-01

    We report a 26-year-old female patient who was diagnosed within 4 years with chest sarcoma, lung adenocarcinoma, and breast cancer. While her family history was unremarkable, DNA sequencing of TP53 revealed a germline de novo non-sense mutation in exon 6 p.Arg213X. One year later, she further developed a contralateral ductal carcinoma in situ, and 18 months later a jaw osteosarcoma. This case illustrates the therapeutic pitfalls in the care of a young cancer patient with TP53 de novo germline mutations and the complications related to her first-line therapy. Suggestion is made to use the less stringent Chompret criteria for germline TP53 mutation screening. Our observation underlines the possibly negative effect of radiotherapy in generating second tumors in patients with a TP53 mutation. We also present a review of six previously reported cases, comparing their cancer phenotypes with those generally produced by TP53 mutations.

  20. Treponema pallidum subsp. pallidum TP0136 protein is heterogeneous among isolates and binds cellular and plasma fibronectin via its NH2-terminal end.

    Science.gov (United States)

    Ke, Wujian; Molini, Barbara J; Lukehart, Sheila A; Giacani, Lorenzo

    2015-03-01

    Adherence-mediated colonization plays an important role in pathogenesis of microbial infections, particularly those caused by extracellular pathogens responsible for systemic diseases, such as Treponema pallidum subsp. pallidum (T. pallidum), the agent of syphilis. Among T. pallidum adhesins, TP0136 is known to bind fibronectin (Fn), an important constituent of the host extracellular matrix. To deepen our understanding of the TP0136-Fn interaction dynamics, we used two naturally-occurring sequence variants of the TP0136 protein to investigate which region of the protein is responsible for Fn binding, and whether TP0136 would adhere to human cellular Fn in addition to plasma Fn and super Fn as previously reported. Fn binding assays were performed with recombinant proteins representing the two full-length TP0136 variants and their discrete regions. As a complementary approach, we tested inhibition of T. pallidum binding to Fn by recombinant full-length TP0136 proteins and fragments, as well as by anti-TP0136 immune sera. Our results show that TP0136 adheres more efficiently to cellular Fn than to plasma Fn, that the TP0136 NH2-terminal conserved region of the protein is primarily responsible for binding to plasma Fn but that binding sites for cellular Fn are also present in the protein's central and COOH-terminal regions. Additionally, message quantification studies show that tp0136 is highly transcribed during experimental infection, and that its message level increases in parallel to the host immune pressure on the pathogen, which suggests a possible role for this protein in T. pallidum persistence. In a time where syphilis incidence is high, our data will help in the quest to identify suitable targets for development of a much needed vaccine against this important disease.

  1. Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    Bazrafshani, Mohammad Reza R; Nowshadi, Pouriaali A; Shirian, Sadegh; Daneshbod, Yahya; Nabipour, Fatemeh; Mokhtari, Maral; Hosseini, Fatemehsadat; Dehghan, Somayeh; Saeedzadeh, Abolfazl; Mosayebi, Ziba

    2016-02-01

    Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation-dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin-fixed paraffin-embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5-8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  2. Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma: A Rereview of Cases Lacking TP53 Mutations in The Cancer Genome Atlas Ovarian Study.

    Science.gov (United States)

    Vang, Russell; Levine, Douglas A; Soslow, Robert A; Zaloudek, Charles; Shih, Ie-Ming; Kurman, Robert J

    2016-01-01

    The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the

  3. Actitudes hacia la influencia de la sociedad en la ciencia y la tecnología

    Directory of Open Access Journals (Sweden)

    Manassero Mas, M.ª Antonia

    1999-01-01

    Full Text Available Not available.La filosofía tradicional de la ciencia presenta ésta como un conocimiento objetivo, aislado de influencias externas, mientras que la moderna sociología y epistemología de la ciencia sostienen la influencia de los factores contextuales. Este estudio analiza las actitudes de estudiantes y profesorado sobre la influencia de la sociedad en la ciencia y tecnología mediante una serie de cuestiones referidas a distintos factores sociales, como el gobierno, las empresas e industrias, el ejército, la cultura, los grupos de especial interés o la educación científica y tecnológica del público. Las actitudes obtenidas muestran diferente intensidad y se fundan en distintas razones justificativas, aunque se observa una tendencia a admitir mayoritariamente esta influencia sobre la ciencia cuando se refiere a un factor general, mientras que cuando la influencia de la sociedad se concreta en factores más concretos, las actitudes no concitan tanta unanimidad. Las diferencias entre estudiantes según el grado de exposición a la ciencia no son tan importantes como cabría esperar, y las diferencias de género, cuando se controla la variable anterior son escasas. El análisis comparativo entre profesorado y alumnado muestra más coincidencias que diferencias, y cuando se comparan los estudiantes canadienses con los españoles existen tantas diferencias como coincidencias. Finalmente, se discuten algunas implicaciones para la enseñanza de las ciencias desde una perspectiva de ciencia-tecnología-sociedad (CTS.

  4. T-p phase diagrams and the barocaloric effect in materials with successive phase transitions

    Science.gov (United States)

    Gorev, M. V.; Bogdanov, E. V.; Flerov, I. N.

    2017-09-01

    An analysis of the extensive and intensive barocaloric effect (BCE) at successive structural phase transitions in some complex fluorides and oxyfluorides was performed. The high sensitivity of these compounds to a change in the chemical pressure allows one to vary the succession and parameters of the transformations (temperature, entropy, baric coefficient) over a wide range and obtain optimal values of the BCE. A comparison of different types of schematic T-p phase diagrams with the complicated T( p) dependences observed experimentally shows that in some ranges of temperature and pressure the BCE in compounds undergoing successive transformations can be increased due to a summation of caloric effects associated with distinct phase transitions. The maximum values of the extensive and intensive BCE in complex fluorides and oxyfluorides can be realized at rather low pressure (0.1-0.3 GPa). In a narrow temperature range around the triple points conversion from conventional BCE to inverse BCE is observed, which is followed by a gigantic change of both \\vertΔ S_BCE\\vert and \\vertΔ T_AD\\vert .

  5. Identification of Quaternary Structure and Functional Domains of the CI Repressor from Bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Pedersen, Margit; Lo Leggio, Leila; Grossmann, J. Günter

    2008-01-01

    -L and the lysogenic promoter PR by binding to multiple operator sites on the DNA. In this study, we used a small bistable genetic switch element from phage TP901-1 to study the effect of cI deletions in vivo and showed that 43 amino acids could be removed from the C-terminal end of Cl without destroying the ability......The bacteriophage-encoded repressor protein plays a key role in determining the life cycle of a temperate phage following infection of a sensitive host. The repressor protein Cl, which is encoded by the temperate lactococcal phage TP901-1, represses transcription from both the lytic promoter P...

  6. Screening of TP53 mutations by DHPLC and sequencing in brain tumours from patients with an occupational exposure to pesticides or organic solvents.

    Science.gov (United States)

    Loyant, V; Jaffré, A; Breton, J; Baldi, I; Vital, A; Chapon, F; Dutoit, S; Lecluse, Y; Loiseau, H; Lebailly, P; Gauduchon, P

    2005-09-01

    The aetiology of brain tumours remains unclear. Occupational exposures to pesticides and organic solvents are suspected risk factors. The case-control study CEREPHY (221 cases, 442 controls) carried in the Departement de la Gironde in France revealed a significantly increased risk of brain tumours for subjects most exposed to pesticides. In some cancers, TP53 mutations could reflect exposure to specific carcinogens. These mutations are present in approximately 30% of astrocytic brain tumours. In a pilot study, we explored the hypothesis that pesticide or solvent exposure could raise the frequency of TP53 mutations in brain tumour cells. We investigated TP53 mutations in exons 2-11 by denaturing high performance liquid chromatography (DHPLC) and sequencing, and p53 accumulation by immunohistochemistry in brain tumour of the 30 patients from CEREPHY study with a history of occupational exposure to pesticides (n = 21) and/or organic solvents (n = 14) for whom tumoral tissue was available. Included cases concerned 27% of CEREPHY cases exposed to pesticides and, based on the cumulative index of occupational exposure, they were more exposed to pesticides. There were 12 gliomas, 6 meningiomas, 7 neurinomas, 2 central nervous system lymphomas and 3 tumours of other histological types. We detected TP53 mutations in three tumours, which is similar to the expected number (3.3) calculated from 46 published studies referenced in the IARC TP53 mutations database, taking into account histological types. Considering TP53 mutations previously detected in the laboratory by DHPLC and the frequency of TP53 polymorphisms detected in this sample (similar to published data), the TP53 mutations rate is probably not underestimated. These preliminary results, even if it was on a limited number of tumours, are not in favour of the role of pesticide or organic solvent exposure in the occurrence of TP53 mutations in brain tumours.

  7. Predictive and prognostic impact of TP53 mutations and MDM2 promoter genotype in primary breast cancer patients treated with epirubicin or paclitaxel.

    Directory of Open Access Journals (Sweden)

    Ranjan Chrisanthar

    Full Text Available BACKGROUND: TP53 mutations have been associated with resistance to anthracyclines but not to taxanes in breast cancer patients. The MDM2 promoter single nucleotide polymorphism (SNP T309G increases MDM2 activity and may reduce wild-type p53 protein activity. Here, we explored the predictive and prognostic value of TP53 and CHEK2 mutation status together with MDM2 SNP309 genotype in stage III breast cancer patients receiving paclitaxel or epirubicin monotherapy. EXPERIMENTAL DESIGN: Each patient was randomly assigned to treatment with epirubicin 90 mg/m(2 (n = 109 or paclitaxel 200 mg/m(2 (n = 114 every 3rd week as monotherapy for 4-6 cycles. Patients obtaining a suboptimal response on first-line treatment requiring further chemotherapy received the opposite regimen. Time from last patient inclusion to follow-up censoring was 69 months. Each patient had snap-frozen tumor tissue specimens collected prior to commencing chemotherapy. PRINCIPAL FINDINGS: While TP53 and CHEK2 mutations predicted resistance to epirubicin, MDM2 status did not. Neither TP53/CHEK2 mutations nor MDM2 status was associated with paclitaxel response. Remarkably, TP53 mutations (p = 0.007 but also MDM2 309TG/GG genotype status (p = 0.012 were associated with a poor disease-specific survival among patients having paclitaxel but not patients having epirubicin first-line. The effect of MDM2 status was observed among individuals harbouring wild-type TP53 (p = 0.039 but not among individuals with TP53 mutated tumors (p>0.5. CONCLUSION: TP53 and CHEK2 mutations were associated with lack of response to epirubicin monotherapy. In contrast, TP53 mutations and MDM2 309G allele status conferred poor disease-specific survival among patients treated with primary paclitaxel but not epirubicin monotherapy.

  8. The prognostic values of the expression of Vimentin, TP53, and Podoplanin in patients with cervical cancer.

    Science.gov (United States)

    Lin, Jiaying; Lu, Jiaqi; Wang, Chao; Xue, Xiaohong

    2017-01-01

    Epithelial-mesenchymal transition (EMT), TP53, and Podoplanin have been implicated in the tumorigenesis and metastasis of human cancers. Nevertheless, the clinical significance of these markers in cancer patients is still not clear. In this study, we sought to determine the prognostic values of Vimentin, TP53, and Podoplanin in patients with cervical cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were performed to determine the messenger RNA and protein expression levels of Vimentin, TP53, and Podoplanin, respectively, in cervical squamous cell carcinoma and adjacent normal cervical tissues. Additionally, the expression levels of Podoplanin were also measured in 130 cervical cancer patients (FIGO stages Ib1-IIa2) using immunohistochemistry (IHC) staining. The mRNA expression levels of Vimentin, TP53, and Podoplanin were considerably elevated in cervical cancer tissues, compared with those in the adjacent normal cervical tissues. Additionally, the protein expression levels of Vimentin were closely correlated with the age of onset (P = 0.007), lymph node metastasis (P = 0.007), lymphatic invasion (P = 0.024), disease recurrence (P < 0.001), and the clinical prognosis of patients with cervical cancer (P < 0.001). Our multivariate analysis also suggests that Vimentin is an independent marker for survival in cervical cancer patients. Furthermore, the expression levels of Vimentin are negatively correlated with the proliferation marker Ki67 expression. Our data show that Vimentin can serve as an independent prognostic marker for cervical cancer patients with primary surgery. Registration number ChiCTR-TRC-06000236 Registered 15 December 2006.

  9. Identical TP53 mutations in pelvic carcinosarcomas and associated serous tubal intraepithelial carcinomas provide evidence of their clonal relationship.

    Science.gov (United States)

    Ardighieri, Laura; Mori, Luigi; Conzadori, Sara; Bugatti, Mattia; Falchetti, Marcella; Donzelli, Carla Maria; Ravaggi, Antonella; Odicino, Franco E; Facchetti, Fabio

    2016-07-01

    Pelvic carcinosarcomas (PCSs) are rare aggressive biphasic tumors that localize in the ovary, fallopian tube, or peritoneum and present frequently as bilateral disease. We undertook a morphological, p53 immunohistochemical and TP53 gene mutational analysis study in a single institution cohort of 16 PCSs in order to investigate the nature of bilateral tumors and to shed light on their origin and pathogenesis. Of the 16 patients, 10 presented with bilateral disease, 6 with a carcinosarcoma in both adnexa, and the remaining cases with a carcinosarcoma in one adnexum and a carcinoma in the opposite. The carcinoma component showed high-grade serous features in 13/16 of cases (81 %). In 10 patients (63 %), a serous tubal intraepithelial carcinoma (STIC) was found, in one case bilateral, making a total of 11 STICs. STIC was found only in cases with a carcinoma component with high-grade serous features. All 10 bilateral tumors and all 11 PCS-associated STICs showed a similar p53 immunostaining pattern. At mutation analysis of the TP53 gene, all five bilateral PCS contained an identical mutation in both localizations. Furthermore, a TP53 mutation was found in 8 of 10 STICs, with an identical mutation in the associated PCS. The finding of similar p53 immunostaining in all bilateral cases and identical TP53 mutations in most PCS-associated STIC provides evidence for a clonal relation between these neoplastic lesions, supporting a metastatic nature of bilateral PCS and suggesting that they have an extraovarian origin in a STIC.

  10. Treponema pallidum Strain Types and Association with Macrolide Resistance in Sydney, Australia: New TP0548 Gene Types Identified.

    Science.gov (United States)

    Read, Phillip; Tagg, Kaitlin A; Jeoffreys, Neisha; Guy, Rebecca J; Gilbert, Gwendolyn L; Donovan, Basil

    2016-08-01

    Strain typing of Treponema pallidum, using the three-target enhanced classification scheme, was performed with 191 samples obtained between 2004 and 2011 in Sydney, Australia. The most common strain type was 14d/g (92/191 samples [48%]). Two new TP0548 gene types were detected (m and n). Strain type was associated with macrolide resistance and possible acquisition outside Australia. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. The Tp0684 (MglB-2) Lipoprotein of Treponema pallidum: A Glucose-Binding Protein with Divergent Topology.

    Science.gov (United States)

    Brautigam, Chad A; Deka, Ranjit K; Liu, Wei Z; Norgard, Michael V

    2016-01-01

    Treponema pallidum, the bacterium that causes syphilis, is an obligate human parasite. As such, it must acquire energy, in the form of carbon sources, from the host. There is ample evidence that the principal source of energy for this spirochete is D-glucose acquired from its environment, likely via an ABC transporter. Further, there is genetic evidence of a D-glucose chemotaxis system in T. pallidum. Both of these processes may be dependent on a single lipidated chemoreceptor: Tp0684, also called TpMglB-2 for its sequence homology to MglB of Escherichia coli. To broaden our understanding of this potentially vital protein, we determined a 2.05-Å X-ray crystal structure of a soluble form of the recombinant protein. Like its namesake, TpMglB-2 adopts a bilobed fold that is similar to that of the ligand-binding proteins (LBPs) of other ABC transporters. However, the protein has an unusual, circularly permuted topology. This feature prompted a series of biophysical studies that examined whether the protein's topological distinctiveness affected its putative chemoreceptor functions. Differential scanning fluorimetry and isothermal titration calorimetry were used to confirm that the protein bound D-glucose in a cleft between its two lobes. Additionally, analytical ultracentrifugation was employed to reveal that D-glucose binding is accompanied by a significant conformational change. TpMglB-2 thus appears to be fully functional in vitro, and given the probable central importance of the protein to T. pallidum's physiology, our results have implications for the viability and pathogenicity of this obligate human pathogen.

  12. [Evaluation of the Recombinant Protein Tp0965 of Treponema Pallidum as Perspective Antigen for the Improved Serological Diagnosis of Syphilis].

    Science.gov (United States)

    Runina, A V; Starovoitova, A S; Deryabin, D G; Kubanov, A A

    2016-01-01

    BACKGRAUND. Treponemal tests based on the detection of antibodies against the Treponema pallidum antigens are the most specific methods for serological diagnosis of syphilis. Due to the inability to cultivate this bacterium in vitro, the most promising sources of antigens for diagnostics are recombinant proteins of T. pallidum. Evaluation of the analytical value of certain T. pallidum proteins is the approach to improve sensitivity, specificity, and reproducibility of syphilis serological tests, including possibilities of differential diagnosis of various forms of the disease. The aim of the research was to evaluate the analytical values (sensitivity and specificity) of recombinant protein Tp0965 of T. pallidum as a candidate antigen for serological diagnosis of syphilis. tp0965 gene was cloned into the expression vector pET28a and the construct was used for the transformation of E. coli BL-21 (DE3) cells and further expression and purification of the recombinant protein. The collected protein was used as T. pallidum antigen for serum analysis (ELISA) of groups of patients with various forms of syphilis (n=84) and the group of healthy donors (n = 25). High frequency of positive ELISA results was shown with serum of patients with syphilis, compared to the group of healthy donors. The sensitivity of serological reactions using recombinant protein Tp0965 was 98.8%, specificity--87.5%. The highest sensitivity (100%) was detected in the groups of patients with primary, secondary and early latent syphilis while in the group of patients with late latent syphilis it decreased to 95.2%. We concluded that due to its specificity T. pallidum recombinant protein Tp0965 can be used as a novel perspective antigen for development of syphilis serological diagnostic assays (for primary and early latent forms).

  13. Novel organization of genes involved in prophage excision identified in the temperate lactococcal bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Breuner, Anne; Brøndsted, Lone; Hammer, Karin

    1999-01-01

    is the only phage protein present. However, 100% excision is observed when the phage protein Orf7 is provided as well as the integrase. Thus, Orf7 is the TP901-1 excisionase, and it is the first excisionase identified that is used during excisive recombination catalyzed by an integrase belonging to the family...... use for many organisms and also for types of deletion events other than excision....

  14. Association of TP53 and MDM2 polymorphisms with survival in bladder cancer patients treated with chemoradiotherapy

    International Nuclear Information System (INIS)

    Shinohara, Asano; Sakano, Shigeru; Hinoda, Yuji; Nishijima, Jun; Kawai, Yoshihisa; Misumi, Taku; Nagao, Kazuhiro; Hara, Takahiko; Matsuyama, Hideyasu

    2009-01-01

    Platinum-based chemoradiotherapy (CRT) as bladder conservation therapy has shown promising results for muscle-invasive bladder cancer. However, CRT might diminish survival as a result of the delay in cystectomy for some patients with non-responding bladder tumors. Because the p53 tumor suppression pathway, including its MDM2 counterpart, is important in chemotherapy- and radiotherapy-associated effects, functional polymorphisms in the TP53 and MDM2 genes could influence the response to treatment and the prognosis following CRT. We investigated associations between two such polymorphisms, and p53 overexpression, and response or survival in bladder cancer patients treated with CRT. The study group comprised 96 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms (SNPs) in TP53 (codon 72, arginine>proline) and MDM2 (SNP3O9, T>G) were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and nuclear expression levels of p53 were examined using immunohistochemistry. None of the genotypes or p53 overexpression was significantly associated with response to CRT. However, patients with MDM2 T/G+G/G genotypes had improved cancer-specific survival rates after CRT (P=0.009). In multivariate analysis, the MDM2 T/G+G/G genotypes, and more than two of total variant alleles in TP53 and MDM2, were independently associated with improved cancer-specific survival (P=0.031 and P=0.015, respectively). In addition, MDM2 genotypes were significantly associated with cystectomy-free survival (P=0.030). These results suggest that the TP53 and MDM2 genotypes might be useful prognostic factors following CRT in bladder cancer, helping patient selection for bladder conservation therapy. (author)

  15. Comparative reactivity of TpRu(L)(NCMe)Ph (L = CO or PMe3): impact of ancillary ligand l on activation of carbon-hydrogen bonds including catalytic hydroarylation and hydrovinylation/oligomerization of ethylene.

    Science.gov (United States)

    Foley, Nicholas A; Lail, Marty; Lee, John P; Gunnoe, T Brent; Cundari, Thomas R; Petersen, Jeffrey L

    2007-05-30

    Complexes of the type TpRu(L)(NCMe)R [L = CO or PMe3; R = Ph or Me; Tp = hydridotris(pyrazolyl)borate] initiate C-H activation of benzene. Kinetic studies, isotopic labeling, and other experimental evidence suggest that the mechanism of benzene C-H activation involves reversible dissociation of acetonitrile, reversible benzene coordination, and rate-determining C-H activation of coordinated benzene. TpRu(PMe3)(NCMe)Ph initiates C-D activation of C6D6 at rates that are approximately 2-3 times more rapid than that for TpRu(CO)(NCMe)Ph (depending on substrate concentration); however, the catalytic hydrophenylation of ethylene using TpRu(PMe3)(NCMe)Ph is substantially less efficient than catalysis with TpRu(CO)(NCMe)Ph. For TpRu(PMe3)(NCMe)Ph, C-H activation of ethylene, to ultimately produce TpRu(PMe3)(eta3-C4H7), is found to kinetically compete with catalytic ethylene hydrophenylation. In THF solutions containing ethylene, TpRu(PMe3)(NCMe)Ph and TpRu(CO)(NCMe)Ph separately convert to TpRu(L)(eta3-C4H7) (L = PMe3 or CO, respectively) via initial Ru-mediated ethylene C-H activation. Heating mesitylene solutions of TpRu(L)(eta3-C4H7) under ethylene pressure results in the catalytic production of butenes (i.e., ethylene hydrovinylation) and hexenes.

  16. Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis.

    Science.gov (United States)

    Jiang, Chuanhao; Xiao, Jinhong; Xie, Yafeng; Xiao, Yongjian; Wang, Chuan; Kuang, Xingxing; Xu, Man; Li, Ranhui; Zeng, Tiebing; Liu, Shuanquan; Yu, Jian; Zhao, Feijun; Wu, Yimou

    2016-02-01

    Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum, and accurate diagnosis is important for the prevention and treatment of syphilis. Here, to identify appropriate diagnostic antigens for serodiagnosis of syphilis, 6 recombinant proteins were expressed in Escherichia coli and purified, including flagellins (FlaB1 [Tp0868], FlaB2 [Tp0792], and FlaB3 [Tp0870]), Tp0463, Tp0751, and Tp1038. The sensitivities were determined by screening sera from individuals with primary (n=82), secondary (n=115), latent (n=105), and congenital (n=65) syphilis. The specificities were determined by screening sera from uninfected controls (n=30) and potentially cross-reactive infections including Lyme disease (n=30), leptospirosis (n=5), and hepatitis B (n=30). Our data showed that FlaB1, FlaB2, FlaB3, Tp0463, and Tp1038 exhibited higher overall sensitivities and specificities for detecting IgG antibody, with 95.4% and 98.9%, 92.6% and 95.8%, 95.1% and 95.8%, 92.6% and 97.9%, and 95.9% and 98.9%, respectively. In contrast, Tp0751 demonstrated only an overall sensitivity of 39.2%. For comparison, the sensitivity and specificity of Architect Syphilis TP were determined to be 98.1% and 93.7%, respectively. In addition, FlaB1, FlaB2, FlaB3, and Tp0463 demonstrated excellent performance for detecting IgM antibody in primary and congenital syphilis, with sensitivities of 76.8% and 83.1%, 72.0% and 87.7%, 74.4% and 89.2%, and 64.6% and 75.3%, respectively. These results indicate that FlaB1, FlaB2, FlaB3, and Tp0463 could be as novel diagnostic candidates for serodiagnosis of syphilis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. TP53 induced glycolysis and apoptosis regulator (TIGAR) knockdown results in radiosensitization of glioma cells

    International Nuclear Information System (INIS)

    Peña-Rico, Miguel A.; Nieves Calvo-Vidal, María; Villalonga-Planells, Ruth; Martínez-Soler, Fina; Giménez-Bonafé, Pepita; Navarro-Sabaté, Àurea; Tortosa, Avelina; Bartrons, Ramon; Manzano, Anna

    2011-01-01

    Background and purpose: The TP53 induced glycolysis and apoptosis regulator (TIGAR) functions to lower fructose-2,6-bisphosphate (Fru-2,6-P 2 ) levels in cells, consequently decreasing glycolysis and leading to the scavenging of reactive oxygen species (ROS), which correlate with a higher resistance to cell death. The decrease in intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic lesions. Given these good prospects of TIGAR for metabolic regulation and p53-response modulation, we analyzed the effects of TIGAR knockdown in U87MG and T98G glioblastoma-derived cell lines. Methods/results: After TIGAR-knockdown in glioblastoma cell lines, different metabolic parameters were assayed, showing an increase in Fru-2,6-P 2 , lactate and ROS levels, with a concomitant decrease in reduced glutathione (GSH) levels. In addition, cell growth was inhibited without evidence of apoptotic or autophagic cell death. In contrast, a clear senescent phenotype was observed. We also found that TIGAR protein levels were increased shortly after irradiation. In addition, avoiding radiotherapy-triggered TIGAR induction by gene silencing resulted in the loss of capacity of glioblastoma cells to form colonies in culture and the delay of DNA repair mechanisms, based in γ-H2AX foci, leading cells to undergo morphological changes compatible with a senescent phenotype. Thus, the results obtained raised the possibility to consider TIGAR as a therapeutic target to increase radiotherapy effects. Conclusion: TIGAR abrogation provides a novel adjunctive therapeutic strategy against glial tumors by increasing radiation-induced cell impairment, thus allowing the use of lower radiotherapeutic doses.

  18. Effect of alloy grain size on the high-temperature oxidation behavior of the austenitic steel TP 347

    Directory of Open Access Journals (Sweden)

    Vicente Braz Trindade

    2005-12-01

    Full Text Available Generally, oxide scales formed on high Cr steels are multi-layered and the kinetics are strongly influenced by the alloy grain boundaries. In the present study, the oxidation behaviour of an austenite steel TP347 with different grain sizes was studied to identify the role of grain-boundaries in the oxidation process. Heat treatment in an inert gas atmosphere at 1050 °C was applied to modify the grain size of the steel TP347. The mass gain during subsequent oxidation was measured using a microbalance with a resolution of 10-5 g. The scale morphology was examined using SEM in combination with energy-dispersive X-ray spectroscopy (EDS. Oxidation of TP347 with a grain size of 4 µm at 750 °C in air follows a parabolic rate law. For a larger grain size (65 µm, complex kinetics is observed with a fast initial oxidation followed by several different parabolic oxidation stages. SEM examinations indicated that the scale formed on specimens with smaller grain size was predominantly Cr2O3, with some FeCr2O4 at localized sites. For specimens with larger grain size the main oxide is iron oxide. It can be concluded that protective Cr2O3 formation is promoted by a high density of fast grain-boundary diffusion paths which is the case for fine-grained materials.

  19. Fuzzy clustering demonstrates that codon 72 SNP rs1042522 of TP53 gene associated with HNSCC but not with prognoses.

    Science.gov (United States)

    Pinheiro, Ugo Borges; Fraga, Carlos Alberto de Carvalho; Mendes, Danilo Cangussu; Farias, Lucyana Conceição; Cardoso, Cláudio Marcelo; Silveira, Christine Mendes; D'Angelo, Marcos Flávio Silveira Vasconcelos; Jones, Kimberly Marie; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena

    2015-12-01

    It is estimated that 7.6 million people will die as a consequence of head and neck squamous cell carcinoma (HNSCC). Genetic predisposition has emerged as an important risk factor in the development and prognosis of HNSCC. Considering this, the aim of the current study is to assess whether codon 72 SNP of the TP53 gene (rs1042522) is associated with an increased odds ratio of developing HNSCC or with a worse prognosis in patients with HNSCC. Analysis of the rs1042522 in HNSCC patients and in control individuals. Differences between the case and control groups were determined using chi-squared tests. Multivariate analysis was performed to evaluate the odds ratio of HNSCC. Fussy C Means Clustering was to cluster HNSCC patients for survival analyses. Time of survival was calculated using the Kaplan-Meier estimator and comparing this to the log rank test. Statistical significance was set at p control group. Logistic regression demonstrated that the Arg/Arg genotype, smoking, and alcohol consumption increase the odds ratio of HNSCC. No association between TP53 codon 72 polymorphism and P53 expression. No association between rs1042522 and survival or prognoses was observed. This study identified that individuals carrying the arginine allele at rs1042522 have an increased odds ratio of HNSCC. However, no association between codon 72 SNP of the TP53 gene and HNSCC prognosis or P53 expression was observed.

  20. Treponema pallidum (syphilis) antigen TpF1 induces angiogenesis through the activation of the IL-8 pathway.

    Science.gov (United States)

    Pozzobon, Tommaso; Facchinello, Nicola; Bossi, Fleur; Capitani, Nagaja; Benagiano, Marisa; Di Benedetto, Giulietta; Zennaro, Cristina; West, Nicole; Codolo, Gaia; Bernardini, Marialina; Baldari, Cosima Tatiana; D'Elios, Mario Milco; Pellegrini, Luca; Argenton, Francesco; de Bernard, Marina

    2016-01-05

    Over 10 million people every year become infected by Treponema pallidum and develop syphilis, a disease with broad symptomatology that, due to the difficulty to eradicate the pathogen from the highly vascularized secondary sites of infection, is still treated with injections of penicillin. Unlike most other bacterial pathogens, T. pallidum infection produces indeed a strong angiogenic response whose mechanism of activation, however, remains unknown. Here, we report that one of the major antigen of T. pallidum, the TpF1 protein, has growth factor-like activity on primary cultures of human endothelial cells and activates specific T cells able to promote tissue factor production. The growth factor-like activity is mediated by the secretion of IL-8 but not of VEGF, two known angiogenic factors. The pathogen's factor signals IL-8 secretion through the activation of the CREB/NF-κB signalling pathway. These findings are recapitulated in an animal model, zebrafish, where we observed that TpF1 injection stimulates angiogenesis and IL-8, but not VEGF, secretion. This study suggests that the angiogenic response observed during secondary syphilis is triggered by TpF1 and that pharmacological therapies directed to inhibit IL-8 response in patients should be explored to treat this disease.

  1. Treponema pallidum Lipoprotein TP0435 Expressed in Borrelia burgdorferi Produces Multiple Surface/Periplasmic Isoforms and mediates Adherence

    Science.gov (United States)

    Chan, Kamfai; Nasereddin, Thayer; Alter, Laura; Centurion-Lara, Arturo; Giacani, Lorenzo; Parveen, Nikhat

    2016-01-01

    The ability of Treponema pallidum, the syphilis spirochete to colonize various tissues requires the presence of surface-exposed adhesins that have been difficult to identify due to the inability to culture and genetically manipulate T. pallidum. Using a Borrelia burgdorferi-based heterologous system and gain-in-function approach, we show for the first time that a highly immunogenic lipoprotein TP0435 can be differentially processed into multiple isoforms with one variant stochastically displayed on the spirochete surface. TP0435 was previously believed to be exclusively located in T. pallidum periplasm. Furthermore, non-adherent B. burgdorferi strain expressing TP0435 acquires the ability to bind to a variety of host cells including placental cells and exhibits slow opsonophagocytosis in vitro similar to poor ex vivo phagocytosis of T. pallidum by host macrophages reported previously. This phenomenon of production of both surface and periplasmic immunogenic lipoprotein isoforms has possible implications in immune evasion of the obligate pathogen T. pallidum during infection. PMID:27161310

  2. Biology of the temperate Streptococcus thermophilus bacteriophage TP-J34 and physical characterization of the phage genome

    International Nuclear Information System (INIS)

    Neve, Horst; Freudenberg, Wiebke; Diestel-Feddersen, Frederike; Ehlert, Regina; Heller, Knut J.

    2003-01-01

    The temperate Streptococcus thermophilus bacteriophage TP-J34 was identified in the lysogenic host strain J34. The majority of phage particles produced upon induction was defective and noninfectious, consisting of DNA-filled heads lacking tails. A physical map (45.6 kb) was established. Analysis of minor restriction bands of the DNA isolated from phage particles as well as the analysis of the protein pattern indicated that phage TP-J34 is a pac-type phage. This was confirmed by immunoelectron microscopy using antisera raised against virulent cos- and pac-type S. thermophilus phages. The lysogenic host J34 but not its noninducible derivate J34-12 contained phage DNA in the nonintegrated state and exhibited autolysis at elevated temperatures. Prophage-carrying strains grew homogeneously while 16 of 20 prophage-cured derivatives aggregated and sedimented rapidly. When phage TP-J34 was propagated lytically on a prophage-cured host strain, a 2.7-kb site-specific deletion occurred in the phage genome. This deletion was also identified in the prophage DNAs of relysogenized strains

  3. The first two confirmed sub-Saharan African families with germline TP53 mutations causing Li-Fraumeni syndrome.

    Science.gov (United States)

    Macaulay, Shelley; Goodyear, Quintin Clive; Kruger, Mia; Chen, Wenlong; Essop, Fahmida; Krause, Amanda

    2018-02-01

    Li-Fraumeni syndrome is a rare inherited cancer syndrome characterised by the early onset of specific cancers. Li-Fraumeni syndrome (LFS) is associated with germline mutations in the tumour suppressor gene, TP53. This study reports the first cases of molecularly confirmed LFS germline mutations in sub-Saharan Africa. Three black African patients, all with LFS-associated cancers, were seen through the Clinical and Counselling Section of the Division of Human Genetics at the National Health Laboratory Service and University of the Witwatersrand in Johannesburg, South Africa, during 2011-2012. All three patients (two were related) were recruited into this research study. Sequence analysis of the coding region of the TP53 gene identified a Class IV (likely pathogenic) variant, c.326T > C (p.Phe109Ser), in the two related patients, and a known pathogenic mutation, c.1010G > A (p.Arg337His), also referred to as the Brazilian founder mutation, in the other patient. A confirmed diagnosis in these patients will assist in tailored medical management (it is recommended that individuals carrying a germline TP53 mutation avoid radiotherapy as this might cause secondary radiotherapy-induced malignancies) and in addition, genetic testing of at-risk family members can be offered. Very little is known and documented on LFS in African individuals. Despite the small number of patients in this study, the results support the need for diagnostic genetic testing for LFS in South Africa.

  4. Genotyping of Human Papillomavirus and TP53 Mutaions at Exons 5 to 7 in Lung Cancer Patients from Iran

    Directory of Open Access Journals (Sweden)

    Hossein Jafari

    2013-06-01

    Full Text Available Introduction: There is a powerful relationship between high-risk human papillomaviruses and lung cancer. In fact, inactivation of p53 is the most common genetic abnormality in lung cancer. Indeed, the frequency of HPV types and TP53 mutations in squamous cell carcinoma of lung, among patients from the northwest of Iran has been evaluated in this article. Methodes: Fifty Paraffin embedded blocks of lung SCC were selected for detection of HPV DNA by Nested PCR, and then DNA was sequenced for HPV typing. Equal numbers of positive and negative samples for the HPV DNA were examined for the presence of mutations in exons 5-7 of the TP53 gene by PCR and direct sequencing. Results: Overtly 9 (18% of 50 samples presented the HPV DNA: eight were HPV-18 and one was HPV-6. TP53 mutations were found in 5 samples (27.7%. Of these, 4 cases showed mutations in exon 5 and one case contained a mutation in exon 7.The most frequent mutation in exon 5 was the C to G transversion (c.409C>G, and also the T to A tansversion (c.770T>A in exon 7. Conclusion: This study showed that HPV-18 is more likely to conscequence in the development of lung cancer among some communities. Genetic alterations, alongside with environmental factors, all play a significant role in the pathogenesis of lung cancer.

  5. Pyrazole cleavage of tris(3,5-dimethylpyrazolyl)borate with Ruthenium(II) complexes: Synthesis, structural characterization and DFT studies

    Science.gov (United States)

    Kharbani, Donkupar; Deb, Debojit Kumar; Mawnai, Ibaniewkor L.; Kurbah, Sunshine D.; Sarkar, Biplab; Rymmai, E. K.

    2017-04-01

    The reaction of [Ru(H)(Cl)(CO)(PPh3)3] (1) with KTp* (KTp* = Potassium tris(3,5-dimethylpyrazolyl)borate) in a refluxing toluene yields a mixture of [RuTp*(H)(CO)(PPh3)] (2), [Ru(H)(Cl)(pz*H)(CO)(PPh3)2] (3), and [H(pz*)B(μ-pz*)2B(pz*)H] (4) (pz*H = 3,5-dimethylpyrazole). The products (3) and (4) were obtained by the degradation of the scorpionate ligand, Tp*. These complexes were characterised by IR, 1H NMR, UV, X-ray crystallography and DFT calculations.

  6. Inhibition of A2A Adenosine Receptor Signaling in Cancer Cells Proliferation by the Novel Antagonist TP455

    Directory of Open Access Journals (Sweden)

    Stefania Gessi

    2017-12-01

    Full Text Available Several evidences indicate that the ubiquitous nucleoside adenosine, acting through A1, A2A, A2B, and A3 receptor (AR subtypes, plays crucial roles in tumor development. Adenosine has contrasting effects on cell proliferation depending on the engagement of different receptor subtypes in various tumors. The involvement of A2AARs in human A375 melanoma, as well as in human A549 lung and rat MRMT1 breast carcinoma proliferation has been evaluated in view of the availability of a novel A2AAR antagonist, with high affinity and selectivity, named as 2-(2-furanyl-N5-(2-methoxybenzyl[1,3]thiazolo[5,4-d]pyrimidine-5,7-diammine (TP455. Specifically, the signaling pathways triggered in the cancer cells of different origin and the antagonist effect of TP455 were investigated. The A2AAR protein expression was evaluated through receptor binding assays. Furthermore, the effect of A2AAR activation on cell proliferation at 24, 48 and 72 hours was studied. The selective A2AAR agonist 2-p-(2-carboxyethylphenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS21680, concentration-dependently induced cell proliferation in A375, A549, and MRMT1 cancer cells and the effect was potently antagonized by the A2AAR antagonist TP455, as well as by the reference A2AAR blocker 4-(2-[7-amino-2-(2-furyl[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethylphenol (ZM241385. As for the signaling pathway recruited in this response we demonstrated that, by using the specific inhibitors of signal transduction pathways, the effect of A2AAR stimulation was induced through phospholipase C (PLC and protein kinase C-delta (PKC-δ. In addition, we evaluated, through the AlphaScreen SureFire phospho(p protein assay, the kinases enrolled by A2AAR to stimulate cell proliferation and we found the involvement of protein kinase B (AKT, extracellular regulated kinases (ERK1/2, and c-Jun N-terminal kinases (JNKs. Indeed, we demonstrated that the CGS21680 stimulatory effect on kinases was

  7. La danza y su influencia en la percepción de plenitud y bienestar psicoemocional.

    OpenAIRE

    Rengifo Rodríguez, Lorelcris; Carrero Planes, Virginia

    2016-01-01

    Introducción: Desde los resultados obtenidos en diversas investigaciones que han identificado la influencia del trabajo corporal sobre la inteligencia emocional y otras variables psicológicas, se derivó el interés por descubrir los efectos o beneficios de la danza sobre las habilidades emocionales u otros procesos psicosociales asociados al bienestar y plenitud. El trabajo que se presenta tiene como objetivo explorar la vivencia de personas que practican danza, de manera profes...

  8. Influencia de la adición del filler calizo sobre el fraguado del cemento

    Directory of Open Access Journals (Sweden)

    Menéndez, Ignacio

    1993-09-01

    Full Text Available The present paper deals about the infuence that addition of calcareous "filler" has on the set of portland cement which rates are from 0 up to 50% of filler.

    En el presente artículo se estudia la influencia que la adición de "filler" calizo ejerce sobre el fraguado del cemento portland, al que se le añaden porcentajes desde O al 50% en filler.

  9. La influencia portuguesa en el arte autóctono del Golfo de Guinea

    OpenAIRE

    Sanz Serrano, María Jesús

    2010-01-01

    Atrio: Revista de historia del arte nº 15-16 (2010), p. 187-198 Los viajes de exploración, intercambios comerciales y colonización portugueses desde el siglo XV en las costas africanas del Golfo de Guinea supusieron la influencia de los nuevos motivos representativos portugueses en las creaciones artísticas de las culturas africanas indígenas de la zona. Versión del editor

  10. Transportability Testing of the Family of Medium Tactical Vehicles (FMTV) 10-Ton Dump Truck, TP-94-01, Rev. 2, June 2004, "Transportability Testing Procedures"

    National Research Council Canada - National Science Library

    Barickman, Philip W

    2007-01-01

    ... (FMTV) 10-ton dump truck manufactured by Stewart and Stevenson Systems, Inc., Sealy, Texas. The testing was conducted in accordance with TP-94-01, Revision 2, June 2004 "Transportability Testing Procedures...

  11. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Wu, Lin; Visco, Carlo

    2012-01-01

    TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. ...

  12. The long non-coding RNA TP73-AS1 modulates HCC cell proliferation through miR-200a-dependent HMGB1/RAGE regulation.

    Science.gov (United States)

    Li, Shaling; Huang, Yan; Huang, Yun; Fu, Yongming; Tang, Daolin; Kang, Rui; Zhou, Rongrong; Fan, Xue-Gong

    2017-04-12

    P73 antisense RNA 1 T (non-protein coding), also known as TP73-AS1, is a long non-coding RNA (lncRNA) which is involved in cell proliferation and the development of tumors. However, the exact effects and molecular mechanisms of TP73-AS1 in hepatocellular carcinoma (HCC) progression are still unknown. The present study is aimed to investigate the detailed functions and the mechanism of TP73-AS1 in regulation of HCC cell proliferation. TP73-AS1 expression in HCC tissues and cell lines was determined using real-time PCR assays; the correlation of TP73-AS1 expression with clinicopathological features of HCC was analyzed. The functions of TP73-AS1 in regulation of HCC cell proliferation was evaluated using MTT and BrdU assays. The candidate upstream miRNAs of HMGB1 were screened using miRcode, miRWalk, miRanda and Target scan, verified using real-time PCR assays. The interaction between TP73-AS1 and miR-200a was confirmed using Luciferase report gene assays. The proten levels of HMGB1 signaling-related factors in response to co-processing TP73-AS1 knockdown and miR-200a inhibition were determined using Western blot assays and ELISA. Further, miR-200a, HMGB1 mRNA and RAGE mRNA and their correlations in HCC tissues were determined. TP73-AS1 was upregulated in HCC tissues and cell lines. High TP73-AS1 expression was correlated with worse clinicopathological features, poorer prognosis and shorter survival. Knockdown of TP73-AS1 inhibited the HCC proliferation and the expression levels of HMGB1, RAGE and NF-κB in HCC cells. By using online tools, we screened out several candidate upstream miRNAs of HMGB1, among which miR-200a overexpression inhibited HMGB1 mRNA expression the most significantly. By using luciferase assays, we confirmed that miR-200a could directly bind to TP73-AS1 and the 3'UTR of HMGB1; TP73-AS1 competed with HMGB1 for miR-200a binding. MiR-200a inhibition could up-regulate HMGB1, RAGE, NF-κB expression as well as NF-κB regulated cytokines levels, which

  13. Human Papillomavirus 16 Infection and TP53 Mutation: Two Distinct Pathogeneses for Oropharyngeal Squamous Cell Carcinoma in an Eastern Chinese Population

    OpenAIRE

    Wang, Zhen; Xia, Rong-Hui; Ye, Dong-Xia; Li, Jiang

    2016-01-01

    Objectives To investigate the clinicopathological characteristics, human papillomavirus (HPV) infection, p53 expression, and TP53 mutations in oropharyngeal squamous cell carcinoma (OPSCC) and determine their utility as prognostic predictors in a primarily eastern Chinese population. Methods The HPV infection status was tested via p16INK4A immunohistochemistry and validated using PCR, reverse blot hybridization and in situ hybridization (ISH) in 188 OPSCC samples. p53 expression levels and TP...

  14. The anti-microbial peptide TP359 attenuates inflammation in human lung cells infected with Pseudomonas aeruginosa via TLR5 and MAPK pathways

    Science.gov (United States)

    Emeh, Robert O.; Dixit, Saurabh; Bakeer, Mona K.; Coats, Mamie T.; Owen, Donald R.; Pillai, Shreekumar R.; Singh, Shree R.; Dennis, Vida A.

    2017-01-01

    Pseudomonas aeruginosa infection induces vigorous inflammatory mediators secreted by epithelial cells, which do not necessarily eradicate the pathogen. Nonetheless, it reduces lung function due to significant airway damage, most importantly in cystic fibrosis patients. Recently, we published that TP359, a proprietary cationic peptide had potent bactericidal effects against P. aeruginosa, which were mediated by down-regulating its outer membrane biogenesis genes. Herein, we hypothesized that TP359 bactericidal effects could also serve to regulate P. aeruginosa-induced lung inflammation. We explored this hypothesis by infecting human A549 lung cells with live P. aeruginosa non-isogenic, mucoid and non-mucoid strains and assessed the capacity of TP359 to regulate the levels of elicited TNFα, IL-6 and IL-8 inflammatory cytokines. In all instances, the mucoid strain elicited higher concentrations of cytokines in comparison to the non-mucoid strain, and TP359 dose-dependently down-regulated their respective levels, suggesting its regulation of lung inflammation. Surprisingly, P. aeruginosa flagellin, and not its lipopolysaccharide moiety, was the primary inducer of inflammatory cytokines in lung cells, which were similarly down-regulated by TP359. Blocking of TLR5, the putative flagellin receptor, completely abrogated the capacity of infected lung cells to secrete cytokines, underscoring that TP359 regulates inflammation via the TLR5-dependent signaling pathway. Downstream pathway-specific inhibition studies further revealed that the MAPK pathway, essentially p38 and JNK are necessary for induction of P. aeruginosa elicited inflammatory cytokines and their down-regulation by TP359. Collectively, our data provides evidence to support exploring the relevancy of TP359 as an anti-microbial and anti-inflammatory agent against P. aeruginosa for clinical applications. PMID:28467446

  15. The profile and contribution of rare germline copy number variants to cancer risk in Li-Fraumeni patients negative for TP53 mutations

    OpenAIRE

    Silva, Amanda G; Krepischi, Ana Cristina Victorino; Pearson, Peter Lees; Hainaut, Pierre; Rosenberg, Carla; Achatz, Maria Isabel

    2014-01-01

    Background: The Li-Fraumeni syndrome (LFS) is an inherited rare cancer predisposition syndrome characterized by a variety of early-onset tumors. Although germline mutations in the tumor suppressor gene TP53 account for over 50% of the families matching LFS criteria, the lack of TP53 mutation in a significant proportion of LFS families, suggests that other types of inherited alterations must contribute to their cancer susceptibility. Recently, increases in copy number variation (CN...

  16. Identification of a novel germ-line mutation in the TP53 gene in a Mexican family with Li-Fraumeni syndrome

    OpenAIRE

    Taja-Chayeb, Lucia; Vidal-Mill?n, Silvia; Guti?rrez-Hern?ndez, Olga; Trejo-Becerril, Catalina; P?rez-C?rdenas, Enrique; Ch?vez-Blanco, Alma; de la Cruz-Hern?ndez, Erick; Due?as-Gonz?lez, Alfonso

    2009-01-01

    Abstract Background Germ-line mutations of the TP53 gene are known to cause Li-Fraumeni syndrome, an autosomal, dominantly inherited, high-penetrance cancer-predisposition syndrome characterized by the occurrence of a variety of cancers, mainly soft tissue sarcomas, adrenocortical carcinoma, leukemia, breast cancer, and brain tumors. Methods Mutation analysis was based on Denaturing high performance liquid chromatography (DHPLC) screening of exons 2-11 of the TP53 gene, sequencing, and clonin...

  17. An identical, complex TP53 mutation arising independently in two unrelated families with diverse cancer profiles: the complexity of interpreting cancer risk in carriers

    OpenAIRE

    Pinto, E M; Ribeiro, R C; Li, J; Taja-Chayeb, L; Carrasco, L F; de Lourdes Peña-Torres, M; Vidal-Millán, S; Maldonado-Mtz, H; Dueñas-González, A; McGregor, L; Zambetti, G P

    2012-01-01

    Most inherited TP53 mutations have been identified in individuals with a family cancer predisposition syndrome, in which the activity of p53 mutants is severely reduced. However, germline p53 mutants in children with ‘sporadic' adrenocortical or choroid plexus tumors exhibit a wide range of functional activity. Here, we demonstrate the occurrence of a complex germline TP53 mutation in two unrelated families with different cancer phenotypes, neither fulfilling the classic criteria for Li-Fraum...

  18. The anti-microbial peptide TP359 attenuates inflammation in human lung cells infected with Pseudomonas aeruginosa via TLR5 and MAPK pathways.

    Science.gov (United States)

    Dosunmu, Ejovwoke F; Emeh, Robert O; Dixit, Saurabh; Bakeer, Mona K; Coats, Mamie T; Owen, Donald R; Pillai, Shreekumar R; Singh, Shree R; Dennis, Vida A

    2017-01-01

    Pseudomonas aeruginosa infection induces vigorous inflammatory mediators secreted by epithelial cells, which do not necessarily eradicate the pathogen. Nonetheless, it reduces lung function due to significant airway damage, most importantly in cystic fibrosis patients. Recently, we published that TP359, a proprietary cationic peptide had potent bactericidal effects against P. aeruginosa, which were mediated by down-regulating its outer membrane biogenesis genes. Herein, we hypothesized that TP359 bactericidal effects could also serve to regulate P. aeruginosa-induced lung inflammation. We explored this hypothesis by infecting human A549 lung cells with live P. aeruginosa non-isogenic, mucoid and non-mucoid strains and assessed the capacity of TP359 to regulate the levels of elicited TNFα, IL-6 and IL-8 inflammatory cytokines. In all instances, the mucoid strain elicited higher concentrations of cytokines in comparison to the non-mucoid strain, and TP359 dose-dependently down-regulated their respective levels, suggesting its regulation of lung inflammation. Surprisingly, P. aeruginosa flagellin, and not its lipopolysaccharide moiety, was the primary inducer of inflammatory cytokines in lung cells, which were similarly down-regulated by TP359. Blocking of TLR5, the putative flagellin receptor, completely abrogated the capacity of infected lung cells to secrete cytokines, underscoring that TP359 regulates inflammation via the TLR5-dependent signaling pathway. Downstream pathway-specific inhibition studies further revealed that the MAPK pathway, essentially p38 and JNK are necessary for induction of P. aeruginosa elicited inflammatory cytokines and their down-regulation by TP359. Collectively, our data provides evidence to support exploring the relevancy of TP359 as an anti-microbial and anti-inflammatory agent against P. aeruginosa for clinical applications.

  19. IRC +10 216 in 3D: morphology of a TP-AGB star envelope

    Science.gov (United States)

    Guélin, M.; Patel, N. A.; Bremer, M.; Cernicharo, J.; Castro-Carrizo, A.; Pety, J.; Fonfría, J. P.; Agúndez, M.; Santander-García, M.; Quintana-Lacaci, G.; Velilla Prieto, L.; Blundell, R.; Thaddeus, P.

    2018-02-01

    During their late pulsating phase, AGB stars expel most of their mass in the form of massive dusty envelopes, an event that largely controls the composition of interstellar matter. The envelopes, however, are distant and opaque to visible and NIR radiation: their structure remains poorly known and the mass-loss process poorly understood. Millimeter-wave interferometry, which combines the advantages of longer wavelength, high angular resolution and very high spectral resolution is the optimal investigative tool for this purpose. Mm waves pass through dust with almost no attenuation. Their spectrum is rich in molecular lines and hosts the fundamental lines of the ubiquitous CO molecule, allowing a tomographic reconstruction of the envelope structure. The circumstellar envelope IRC +10 216 and its central star, the C-rich TP-AGB star closest to the Sun, are the best objects for such an investigation. Two years ago, we reported the first detailed study of the CO(2-1) line emission in that envelope, made with the IRAM 30-m telescope. It revealed a series of dense gas shells, expanding at a uniform radial velocity. The limited resolution of the telescope (HPBW 11″) did not allow us to resolve the shell structure. We now report much higher angular resolution observations of CO(2-1), CO(1-0), CN(2-1) and C4H(24-23) made with the SMA, PdB and ALMA interferometers (with synthesized half-power beamwidths of 3″, 1″ and 0.3″, respectively). Although the envelope appears much more intricate at high resolution than with an 11″ beam, its prevailing structure remains a pattern of thin, nearly concentric shells. The average separation between the brightest CO shells is 16″ in the outer envelope, where it appears remarkably constant. Closer to the star (formation zone, the gas appears to expand radially at a constant velocity, 14.5 km s-1, with small turbulent motions. Based on that property, we have reconstructed the 3D structure of the outer envelope and have derived

  20. Polimorfismo do gene tp53 no códon 72 em pacientes com suspeita de LMC Codon 72 polymorphism of the TP53 gene in patients suspected to have CML

    Directory of Open Access Journals (Sweden)

    Camila S. Hamú

    2007-12-01

    Full Text Available A leucemia mielóide crônica (LMC é uma doença proliferativa do sistema hematopoiético, caracterizada pela expansão clonal de uma célula-tronco primitiva e pluripotente denominada stem cell. Este tipo de leucemia está associado, em 90% dos casos, à translocação t(9;22(q34;q11. Essa alteração cromossômica estrutural codifica para uma proteína quimérica BCR-ABL, que confere às células leucêmicas uma alta resistência à morte, independente do agente indutor desse processo. A proteína p53 é uma reguladora transcricional induzida por danos no DNA, fato que resulta na parada do ciclo celular com conseqüente ativação de mecanismos de reparo ou mesmo na indução à apoptose. As mutações no gene TP53 são as alterações genéticas mais comuns em tumores malignos humanos. O presente estudo teve como objetivo genotipar e determinar a freqüência alélica do polimorfismo do TP53 no códon 72 (arginina - Arg e prolina - Pro, em pacientes com suspeita de LMC, pela Reação em Cadeia da Polimerase. Desta forma, os resultados indicaram que 73,4% (23/30 dos pacientes apresentaram homozigose para arginina (Arg/Arg e 26,6% (7/30 heterozigose (Arg/Pro. Não foi encontrado nenhum paciente homozigoto para prolina (Pro/Pro. Os resultados obtidos sugerem que o polimorfismo do gene TP53 no códon 72 não é um fator de risco importante para a iniciação, promoção e progressão da LMC.Chronic myeloid leukemia (CML is a proliferative disorder of the hematopoietic system characterized by clonal expansion of a primitive and pluripotent stem cell. In this type of leukemia, up to 90% of all cases is associated to a specific chromosomal translocation, t(9;22(q34;q11. The genomic alteration results in a chimeric protein, BCR-ABL, that confers a high resistance leukemia cells to death, independent of the induction mechanism of this process. Protein p53 is a transcriptional factor expressed after DNA damage which ceases cell cycle progression and

  1. The profile and contribution of rare germline copy number variants to cancer risk in Li-Fraumeni patients negative for TP53 mutations.

    Science.gov (United States)

    Silva, Amanda G; Krepischi, Ana C V; Pearson, Peter L; Hainaut, Pierre; Rosenberg, Carla; Achatz, Maria Isabel

    2014-04-28

    The Li-Fraumeni syndrome (LFS) is an inherited rare cancer predisposition syndrome characterized by a variety of early-onset tumors. Although germline mutations in the tumor suppressor gene TP53 account for over 50% of the families matching LFS criteria, the lack of TP53 mutation in a significant proportion of LFS families, suggests that other types of inherited alterations must contribute to their cancer susceptibility. Recently, increases in copy number variation (CNV) have been reported in LFS individuals, and are also postulated to contribute to LFS phenotypic variability. Seventy probands from families fulfilling clinical criteria for either Li-Fraumeni or Li-Fraumeni-like (LFS/LFL) syndromes and negative for TP53 mutations were screened for germline CNVs. We found a significantly increased number of rare CNVs, which were smaller in size and presented higher gene density compared to the control group. These data were similar to the findings we reported previously on a cohort of patients with germline TP53 mutations, showing that LFS/LFL patients, regardless of their TP53 status, also share similar CNV profiles. These results, in conjunction with our previous analyses, suggest that both TP53-negative and positive LFS/LFL patients present a broad spectrum of germline genetic alterations affecting multiple loci, and that the genetic basis of LFS/LFL predisposition or penetrance in many cases might reside in germline transmission of CNVs.

  2. An identical, complex TP53 mutation arising independently in two unrelated families with diverse cancer profiles: the complexity of interpreting cancer risk in carriers.

    Science.gov (United States)

    Pinto, E M; Ribeiro, R C; Li, J; Taja-Chayeb, L; Carrasco, L F; de Lourdes Peña-Torres, M; Vidal-Millán, S; Maldonado-Mtz, H; Dueñas-González, A; McGregor, L; Zambetti, G P

    2012-02-20

    Most inherited TP53 mutations have been identified in individuals with a family cancer predisposition syndrome, in which the activity of p53 mutants is severely reduced. However, germline p53 mutants in children with 'sporadic' adrenocortical or choroid plexus tumors exhibit a wide range of functional activity. Here, we demonstrate the occurrence of a complex germline TP53 mutation in two unrelated families with different cancer phenotypes, neither fulfilling the classic criteria for Li-Fraumeni syndrome. The TP53 mutation consists of a duplication of 7 bp in exon 4, resulting in a frame shift and premature stop signal. Haplotype analysis indicated that the mutation arose independently in the two families. Analysis of the DNA secondary structure predicts the TP53 mutation occurred within a hairpin loop. Additional germline complex mutations occurring within the same region of exon 4 have been identified in the IARC database. Our findings suggest that certain TP53 regions are prone to intrinsic genetic alterations, possibly through defects in DNA replication or repair. Further, carriers of the same TP53 mutation can have diverse cancer profiles, illustrating the complexity of genetic counseling and risk prediction.

  3. Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.

    Science.gov (United States)

    Alsbeih, Ghazi A; Al-Harbi, Najla M; Bin Judia, Sara S; Khoja, Hatim A; Shoukri, Mohamed M; Tulbah, Asma M

    2017-07-01

    Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  4. Probing the reaction mechanism of spore photoproduct lyase (SPL) via diastereoselectively labeled dinucleotide SP TpT substrates

    Science.gov (United States)

    Yang, Linlin; Lin, Gengjie; Liu, Degang; Dria, Karl J.; Telser, Joshua; Li, Lei

    2011-01-01

    5-thyminyl-5,6-dihydrothymine (commonly called spore photoproduct or SP) is the exclusive DNA photo-damage product in bacterial endospores. It is generated in the bacterial sporulation phase and repaired by a radical SAM enzyme, spore photoproduct lyase (SPL), at the early germination phase. SPL utilizes a special [4Fe-4S] cluster to reductively cleave S-adenosylmethionine (SAM) to generate a reactive 5′-dA radical. The 5′-dA radical is proposed to abstract one of the two H atoms at the C6 carbon of SP to initiate the repair process. Via organic synthesis and DNA photochemistry, we selectively labeled the 6-HproS or 6-HproR position with a deuterium in a dinucleotide SP TpT substrate. Monitoring the deuterium migration in enzyme catalysis (employing Bacillus subtilis SPL) revealed that it is the 6-HproR atom of SP that is abstracted by the 5′-dA radical. Surprisingly, the abstracted deuterium was not returned to the resulting TpT after enzymatic catalysis, an H atom from the aqueous buffer was incorporated into TpT instead. This result questions the currently hypothesized SPL mechanism which excludes the involvement of protein residue(s) in SPL reaction, suggesting that some protein residue(s), which is capable of exchanging a proton with the aqueous buffer, is involved in the enzyme catalysis. Moreover, evidence has been obtained for a possible SAM regeneration after each catalytic cycle; however, such a regeneration process is more complex than currently thought, with one or even more protein residues involved as well. These observations have enabled us to propose a modified reaction mechanism for this intriguing DNA repair enzyme. PMID:21671623

  5. Recent declines in DIN:TP in Swedish lakes driven by changes in N deposition and climate

    Science.gov (United States)

    Isles, P. D.; Bergström, A. K.; Jonsson, A.

    2017-12-01

    Atmospheric nitrogen (N) deposition has changed dramatically over the past several decades as a result of human activities. These changes, coupled with ongoing changes in climate, have the potential to alter the nutrient limitation status of freshwater ecosystems. In this study we compared time-series data of dissolved inorganic N (DIN), total phosphorus (TP), DIN:TP, and total organic carbon (TOC) from 92 nutrient-poor lakes and 78 headwater streams in Sweden with corresponding estimates of N-deposition, temperature, and precipitation from 1998-2013 to assess trends in, and potential drivers of, lake N:P ratios. We also conducted nutrient limitation assays along a gradient of N deposition and DOC in 27 lakes at different times of year to examine seasonal changes in nutrient limitation. We found that long-term trends in nutrients were variable at the scale of individual lakes but were highly synchronous at the regional scale, suggesting underlying control by broad-scale drivers mediated by site-specific characteristics. Seasonally, some lakes were P limited early in the season, but all lakes experienced increasingly severe N limitation over the course of the growing season. Overall, we observed a dramatic change in DIN:TP throughout Sweden over the monitoring period, with 33% of lakes strongly N-limited and 44% co-limited during the summer at the beginning of the study period, and 64% of lakes strongly N-limited and 20% co-limited at the end, suggesting that N limitation is likely to become more widespread and severe if recent trends continue.

  6. Breast cancer phenotype in women with TP53 germline mutations: a Li-Fraumeni syndrome consortium effort.

    Science.gov (United States)

    Masciari, Serena; Dillon, Deborah A; Rath, Michelle; Robson, Mark; Weitzel, Jeffrey N; Balmana, Judith; Gruber, Stephen B; Ford, James M; Euhus, David; Lebensohn, Alexandra; Telli, Melinda; Pochebit, Stephen M; Lypas, Georgios; Garber, Judy E

    2012-06-01

    Breast cancer is the most common tumor in women with Li-Fraumeni Syndrome (LFS), an inherited cancer syndrome associated with germline mutations in the TP53 tumor suppressor gene. Their lifetime breast cancer risk is 49% by age 60. Breast cancers in TP53 mutation carriers recently have more often been reported to be hormone receptor and HER-2 positive by immunohistochemistry and FISH in small series. We seek to complement the existing small literature with this report of a histopathologic analysis of breast cancers from women with documented LFS. Unstained slides and paraffin-embedded tumor blocks from breast cancers from 39 germline TP53 mutation carriers were assembled from investigators in the LFS consortium. Central histology review was performed on 93% of the specimens by a single breast pathologist from a major university hospital. Histology, grade, and hormone receptor status were assessed by immunohistochemistry; HER-2 status was defined by immunohistochemistry and/or FISH. The 43 tumors from 39 women comprise 32 invasive ductal carcinomas and 11 ductal carcinomas in situ (DCIS). No other histologies were observed. The median age at diagnosis was 32 years (range 22-46). Of the invasive cancers, 84% were positive for ER and/or PR; and 81% were high grade. Sixty three percent of invasive and 73% of in situ carcinomas were positive for Her2/neu (IHC 3+ or FISH amplified). Of the invasive tumors, 53% were positive for both ER and HER2+; other ER/PR/HER2 combinations were observed. The DCIS were positive for ER and HER2 in 27% of the cases. This report of the phenotype of breast cancers from women with LFS nearly doubles the literature on this topic. Most DCIS and invasive ductal carcinomas in LFS are hormone receptor positive and/or HER-2 positive. These findings suggest that modern treatments may result in improved outcomes for women with LFS-associated breast cancer.

  7. Unambiguous detection of multiple TP53 gene mutations in AAN-associated urothelial cancer in Belgium using laser capture microdissection.

    Directory of Open Access Journals (Sweden)

    Selda Aydin

    Full Text Available In the Balkan and Taiwan, the relationship between exposure to aristolochic acid and risk of urothelial neoplasms was inferred from the A>T genetic hallmark in TP53 gene from malignant cells. This study aimed to characterize the TP53 mutational spectrum in urothelial cancers consecutive to Aristolochic Acid Nephropathy in Belgium. Serial frozen tumor sections from female patients (n=5 exposed to aristolochic acid during weight-loss regimen were alternatively used either for p53 immunostaining or laser microdissection. Tissue areas with at least 60% p53-positive nuclei were selected for microdissecting sections according to p53-positive matching areas. All areas appeared to be carcinoma in situ. After DNA extraction, mutations in the TP53 hot spot region (exons 5-8 were identified using nested-PCR and sequencing. False-negative controls consisted in microdissecting fresh-frozen tumor tissues both from a patient with a Li-Fraumeni syndrome who carried a p53 constitutional mutation, and from KRas mutated adenocarcinomas. To rule out false-positive results potentially generated by microdissection and nested-PCR, a phenacetin-associated urothelial carcinoma and normal fresh ureteral tissues (n=4 were processed with high laser power. No unexpected results being identified, molecular analysis was pursued on malignant tissues, showing at least one mutation in all (six different mutations in two patients, with 13/16 exonic (nonsense, 2; missense, 11 and 3/16 intronic (one splice site mutations. They were distributed as transitions (n=7 or transversions (n=9, with an equal prevalence of A>T and G>T (3/16 each. While current results are in line with A>T prevalence previously reported in Balkan and Taiwan studies, they also demonstrate that multiple mutations in the TP53 hot spot region and a high frequency of G>T transversion appear as a complementary signature reflecting the toxicity of a cumulative dose of aristolochic acid ingested over a short period

  8. Study of the onset of deformation and shape coexistence in $^{46}$Ar via the inverse kinematics ($t,p$) reaction

    CERN Multimedia

    Reiter, P; Blazhev, A A; Nardelli, S; Stora, T; Tengborn, E A; Kruecken, R; Voulot, D; Korten, W; Srebrny, J; Clement, E; Lo bianco, G; Sorlin, O H; Habs, D; Fraile prieto, L M; Chapman, R; Nilsson, T; Diriken, J V J; Jenkins, D G; Wady, P T; Kroell, T; Patronis, N; Angus, L J; Iwanicki, J S

    We plan to study states in $^{46}$ Ar via the (t,p) two-neutron transfer reaction in inverse kinematics in order to identify and characterize excited states and to gain insights into the onset of deformation and the possible occurrence of shape-coexistence in this region where the N = 28 shell closure may be weakening. The experiment will be performed using accelerated beams from REX-ISOLDE and the T-REX particle detector set-up inside MINIBALL. We request a total of 30 shifts + 3 shifts for beam commissioning.

  9. Identification of the Treponema pallidum subsp. pallidum TP0092 (RpoE) Regulon and Its Implications for Pathogen Persistence in the Host and Syphilis Pathogenesis

    Science.gov (United States)

    Denisenko, Oleg; Tompa, Martin; Centurion-Lara, Arturo

    2013-01-01

    Bacteria often respond to harmful environmental stimuli with the induction of extracytoplasmic function (ECF) sigma (σ) factors that in turn direct RNA polymerase to transcribe specific groups of response genes (or regulons) to minimize cellular damage and favor adaptation to the changed extracellular milieu. In Treponema pallidum subsp. pallidum, the agent of syphilis, the TP0092 gene is predicted to code for the pathogen's only annotated ECF σ factor, homologous to RpoE, known in Escherichia coli to control a key transduction pathway for maintenance of envelope homeostasis in response to external stress and cell growth. Here we have shown that TP0092 is highly transcribed during experimental syphilis. Furthermore, TP0092 transcription levels significantly increase as infection progresses toward immune clearance of the pathogen, suggesting a role for TP0092 in helping T. pallidum respond to harmful stimuli in the host environment. To investigate this hypothesis, we determined the TP0092 regulon at two different time points during infection using chromatin immunoprecipitation followed by high-throughput sequencing. A total of 22 chromosomal regions, all containing putative TP0092-binding sites and corresponding to as many T. pallidum genes, were identified. Noteworthy among them are the genes encoding desulfoferrodoxin and thioredoxin, involved in detoxification of reactive oxygen species (ROS). Because T. pallidum does not possess other enzymes for ROS detoxification, such as superoxide dismutase, catalase, or glutathione peroxidase, our results suggest that the TP0092 regulon is important in protecting the syphilis spirochete from damage caused by ROS produced at the site of infection during the inflammatory response. PMID:23243302

  10. Transcription of TP0126, Treponema pallidum putative OmpW homolog, is regulated by the length of a homopolymeric guanosine repeat.

    Science.gov (United States)

    Giacani, Lorenzo; Brandt, Stephanie L; Ke, Wujian; Reid, Tara B; Molini, Barbara J; Iverson-Cabral, Stefanie; Ciccarese, Giulia; Drago, Francesco; Lukehart, Sheila A; Centurion-Lara, Arturo

    2015-06-01

    An effective mechanism for introduction of phenotypic diversity within a bacterial population exploits changes in the length of repetitive DNA elements located within gene promoters. This phenomenon, known as phase variation, causes rapid activation or silencing of gene expression and fosters bacterial adaptation to new or changing environments. Phase variation often occurs in surface-exposed proteins, and in Treponema pallidum subsp. pallidum, the syphilis agent, it was reported to affect transcription of three putative outer membrane protein (OMP)-encoding genes. When the T. pallidum subsp. pallidum Nichols strain genome was initially annotated, the TP0126 open reading frame was predicted to include a poly(G) tract and did not appear to have a predicted signal sequence that might suggest the possibility of its being an OMP. Here we show that the initial annotation was incorrect, that this poly(G) is instead located within the TP0126 promoter, and that it varies in length in vivo during experimental syphilis. Additionally, we show that TP0126 transcription is affected by changes in the poly(G) length consistent with regulation by phase variation. In silico analysis of the TP0126 open reading frame based on the experimentally identified transcriptional start site shortens this hypothetical protein by 69 amino acids, reveals a predicted cleavable signal peptide, and suggests structural homology with the OmpW family of porins. Circular dichroism of recombinant TP0126 supports structural homology to OmpW. Together with the evidence that TP0126 is fully conserved among T. pallidum subspecies and strains, these data suggest an important role for TP0126 in T. pallidum biology and syphilis pathogenesis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. Conservation of the Host-Interacting Proteins Tp0750 and Pallilysin among Treponemes and Restriction of Proteolytic Capacity to Treponema pallidum.

    Science.gov (United States)

    Houston, Simon; Taylor, John S; Denchev, Yavor; Hof, Rebecca; Zuerner, Richard L; Cameron, Caroline E

    2015-11-01

    The spirochete Treponema pallidum subsp. pallidum is the causative agent of syphilis, a chronic, sexually transmitted infection characterized by multiple symptomatic and asymptomatic stages. Although several other species in the genus are able to cause or contribute to disease, T. pallidum differs in that it is able to rapidly disseminate via the bloodstream to tissue sites distant from the site of initial infection. It is also the only Treponema species able to cross both the blood-brain and placental barriers. Previously, the T. pallidum proteins, Tp0750 and Tp0751 (also called pallilysin), were shown to degrade host proteins central to blood coagulation and basement membrane integrity, suggesting a role for these proteins in T. pallidum dissemination and tissue invasion. In the present study, we characterized Tp0750 and Tp0751 sequence variation in a diversity of pathogenic and nonpathogenic treponemes. We also determined the proteolytic potential of the orthologs from the less invasive species Treponema denticola and Treponema phagedenis. These analyses showed high levels of sequence similarity among Tp0750 orthologs from pathogenic species. For pallilysin, lower levels of sequence conservation were observed between this protein and orthologs from other treponemes, except for the ortholog from the highly invasive rabbit venereal syphilis-causing Treponema paraluiscuniculi. In vitro host component binding and degradation assays demonstrated that pallilysin and Tp0750 orthologs from the less invasive treponemes tested were not capable of binding or degrading host proteins. The results show that pallilysin and Tp0750 host protein binding and degradative capability is positively correlated with treponemal invasiveness. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma

    Science.gov (United States)

    Arnhold, Viktor; Schmelz, Karin; Proba, Jutta; Winkler, Annika; Wünschel, Jasmin; Toedling, Joern; Deubzer, Hedwig E.; Künkele, Annette; Eggert, Angelika; Schulte, Johannes H.; Hundsdoerfer, Patrick

    2018-01-01

    Fewer than 50% of patients with high-risk neuroblastoma survive five years after diagnosis with current treatment protocols. Molecular targeted therapies are expected to improve survival. Although MDM2 has been validated as a promising target in preclinical models, no MDM2 inhibitors have yet entered clinical trials for neuroblastoma patients. Toxic side effects, poor bioavailability and low efficacy of the available MDM2 inhibitors that have entered phase I/II trials drive the development of novel MDM2 inhibitors with an improved risk-benefit profile. We investigated the effect of the novel MDM2 small molecular inhibitor, DS-3032b, on viability, proliferation, senescence, migration, cell cycle arrest and apoptosis in a panel of six neuroblastoma cell lines with different TP53 and MYCN genetic backgrounds, and assessed efficacy in a murine subcutaneous model for high-risk neuroblastoma. Re-analysis of existing expression data from 476 primary neuroblastomas showed that high-level MDM2 expression correlated with poor patient survival. DS-3032b treatment enhanced TP53 target gene expression and induced G1 cell cycle arrest, senescence and apoptosis. CRISPR-mediated MDM2 knockout in neuroblastoma cells mimicked DS-3032b treatment. TP53 signaling was selectively activated by DS-3032b in neuroblastoma cells with wildtype TP53, regardless of the presence of MYCN amplification, but was significantly reduced by TP53 mutations or expression of a dominant-negative TP53 mutant. Oral DS-3032b administration inhibited xenograft tumor growth and prolonged mouse survival. Our in vitro and in vivo data demonstrate that DS-3032b reactivates TP53 signaling even in the presence of MYCN amplification in neuroblastoma cells, to reduce proliferative capacity and cause cytotoxicity. PMID:29416773

  13. MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer.

    Science.gov (United States)

    García-García, Celina; Rivas, Martín A; Ibrahim, Yasir H; Calvo, María Teresa; Gris-Oliver, Albert; Rodríguez, Olga; Grueso, Judit; Antón, Pilar; Guzmán, Marta; Aura, Claudia; Nuciforo, Paolo; Jessen, Katti; Argilés, Guillem; Dienstmann, Rodrigo; Bertotti, Andrea; Trusolino, Livio; Matito, Judit; Vivancos, Ana; Chicote, Irene; Palmer, Héctor G; Tabernero, Josep; Scaltriti, Maurizio; Baselga, José; Serra, Violeta

    2015-12-15

    PI3K pathway activation occurs in concomitance with RAS/BRAF mutations in colorectal cancer, limiting the sensitivity to targeted therapies. Several clinical studies are being conducted to test the tolerability and clinical activity of dual MEK and PI3K pathway blockade in solid tumors. In the present study, we explored the efficacy of dual pathway blockade in colorectal cancer preclinical models harboring concomitant activation of the ERK and PI3K pathways. Moreover, we investigated if TP53 mutation affects the response to this therapy. Dual MEK and mTORC1/2 blockade resulted in synergistic antiproliferative effects in cell lines bearing alterations in KRAS/BRAF and PIK3CA/PTEN. Although the on-treatment cell-cycle effects were not affected by the TP53 status, a marked proapoptotic response to therapy was observed exclusively in wild-type TP53 colorectal cancer models. We further interrogated two independent panels of KRAS/BRAF- and PIK3CA/PTEN-altered cell line- and patient-derived tumor xenografts for the antitumor response toward this combination of agents. A combination response that resulted in substantial antitumor activity was exclusively observed among the wild-type TP53 models (two out of five, 40%), but there was no such response across the eight mutant TP53 models (0%). Interestingly, within a cohort of 14 patients with colorectal cancer treated with these agents for their metastatic disease, two patients with long-lasting responses (32 weeks) had TP53 wild-type tumors. Our data support that, in wild-type TP53 colorectal cancer cells with ERK and PI3K pathway alterations, MEK blockade results in potent p21 induction, preventing apoptosis to occur. In turn, mTORC1/2 inhibition blocks MEK inhibitor-mediated p21 induction, unleashing apoptosis. Clin Cancer Res; 21(24); 5499-510. ©2015 AACR. ©2015 American Association for Cancer Research.

  14. Transcription of TP0126, Treponema pallidum Putative OmpW Homolog, Is Regulated by the Length of a Homopolymeric Guanosine Repeat

    Science.gov (United States)

    Brandt, Stephanie L.; Ke, Wujian; Reid, Tara B.; Molini, Barbara J.; Iverson-Cabral, Stefanie; Ciccarese, Giulia; Drago, Francesco; Lukehart, Sheila A.; Centurion-Lara, Arturo

    2015-01-01

    An effective mechanism for introduction of phenotypic diversity within a bacterial population exploits changes in the length of repetitive DNA elements located within gene promoters. This phenomenon, known as phase variation, causes rapid activation or silencing of gene expression and fosters bacterial adaptation to new or changing environments. Phase variation often occurs in surface-exposed proteins, and in Treponema pallidum subsp. pallidum, the syphilis agent, it was reported to affect transcription of three putative outer membrane protein (OMP)-encoding genes. When the T. pallidum subsp. pallidum Nichols strain genome was initially annotated, the TP0126 open reading frame was predicted to include a poly(G) tract and did not appear to have a predicted signal sequence that might suggest the possibility of its being an OMP. Here we show that the initial annotation was incorrect, that this poly(G) is instead located within the TP0126 promoter, and that it varies in length in vivo during experimental syphilis. Additionally, we show that TP0126 transcription is affected by changes in the poly(G) length consistent with regulation by phase variation. In silico analysis of the TP0126 open reading frame based on the experimentally identified transcriptional start site shortens this hypothetical protein by 69 amino acids, reveals a predicted cleavable signal peptide, and suggests structural homology with the OmpW family of porins. Circular dichroism of recombinant TP0126 supports structural homology to OmpW. Together with the evidence that TP0126 is fully conserved among T. pallidum subspecies and strains, these data suggest an important role for TP0126 in T. pallidum biology and syphilis pathogenesis. PMID:25802057

  15. Reversion of apoptotic resistance of TP53-mutated Burkitt lymphoma B-cells to spindle poisons by exogenous activation of JNK and p38 MAP kinases.

    Science.gov (United States)

    Farhat, M; Poissonnier, A; Hamze, A; Ouk-Martin, C; Brion, J-D; Alami, M; Feuillard, J; Jayat-Vignoles, C

    2014-05-01

    Defects in apoptosis are frequently the cause of cancer emergence, as well as cellular resistance to chemotherapy. These phenotypes may be due to mutations of the tumor suppressor TP53 gene. In this study, we examined the effect of various mitotic spindle poisons, including the new isocombretastatin derivative isoNH2CA-4 (a tubulin-destabilizing molecule, considered to bind to the colchicine site by analogy with combretastatin A-4), on BL (Burkitt lymphoma) cells. We found that resistance to spindle poison-induced apoptosis could be reverted in tumor protein p53 (TP53)-mutated cells by EBV (Epstein Barr virus) infection. This reversion was due to restoration of the intrinsic apoptotic pathway, as assessed by relocation of the pro-apoptotic molecule Bax to mitochondria, loss of mitochondrial integrity and activation of the caspase cascade with PARP (poly ADP ribose polymerase) cleavage. EBV sensitized TP53-mutated BL cells to all spindle poisons tested, including vincristine and taxol, an effect that was systematically downmodulated by pretreatment of cells with inhibitors of p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases. Exogenous activation of p38 and JNK pathways by dihydrosphingosine reverted resistance of TP53-mutated BL cells to spindle poisons. Dihydrosphingosine treatment of TP53-deficient Jurkat and K562 cell lines was also able to induce cell death. We conclude that activation of p38 and JNK pathways may revert resistance of TP53-mutated cells to spindle poisons. This opens new perspectives for developing alternative therapeutic strategies when the TP53 gene is inactivated.

  16. La polémica influencia de Adolfo Posada en el pensamiento de los catedráticos de derecho de la generación del 900

    Directory of Open Access Journals (Sweden)

    Raquel García Bouzas

    2014-10-01

    Full Text Available Contenido: Las razones de la influencia de Posada entre los juristas rioplatenses. Un particular enfoque del krausismo. Receptividad y difusión de su pensamiento. Concepción organicista del estado. El sufragio como un deber.Valoración de su influencia en nuestra historia intelectual

  17. Assessment of the potential for conversion of TP-108 boilers to firing natural gas and fuel oil

    Science.gov (United States)

    Tugov, A. N.; Supranov, V. M.; Izyumov, M. A.; Vereshchetin, V. A.; Usman, Yu. M.; Natal'in, A. S.

    2017-03-01

    TP-108 boilers were initially designed to burn milled peat. In the 1980s, they were reconstructed for conversion to burning natural gas as well. However, operation of these boilers revealed problems due to low reheat temperature and great air inleakage in the furnace. The initial design of the boiler and its subsequent reconstruction are described in the paper. Measures are presented for further modernization of TP-108 boilers to eliminate the above-mentioned problems and enable natural gas or fuel oil only to be burned in them. Thermal design calculations made using a specially developed adapted model (AM) suggest that replacement of the existing burners with new oil/gas burners, installation of steam-to-steam heat exchangers (SSHE), and sealing of the boiler gas path to make it gas tight will allow the parameters typical of gas-and-oil fired boilers to be attained. It is demonstrated that SSHEs can yield the design secondary steam reheat temperature, although this solution is not typical for natural circulation boilers with steam reheat. The boiler equipped with SSHEs can operate on fuel oil or natural gas with flue gas recirculation or without it. Moreover, operation of the boiler with flue gas recirculation to the air duct in combination with staged combustion enables the required environmental indicators to be attained.

  18. Material problems related to large scale firing of biomass. Steam oxidation of TP 347H FG and X20

    Energy Technology Data Exchange (ETDEWEB)

    Noergaard Hansson, A.

    2009-07-01

    TP 347 H and X20 is often used as construction material in biomass-fired boilers. The corrosion rate of the alloys is affected by the metal temperature. In this project, the oxidation behaviour of TP 347H FG and X20 is studied by field-testing, laboratory exposures, and thermodynamic/kinetic modelling. The long term oxidation behaviour of TP 347H FG at ultra supercritical steam conditions was assessed by exposing the steel in 4 test superheater loops in a coal-fired power plant. The steel was exposed for 7720, 22985, 29588, and 57554 h at metal temperatures between 499 and 650 deg. C. In the laboratory furnace, the oxidation behaviour of TP 347H FG, TP 347H CG, and X20 was studied in water vapour containing environments (8 or 46%) in the temperature range 500-700 deg. C. Air, Ar and Ar+7% H{sub 2} were used as carrier gas. The microstructure of the oxide layer and the subjacent alloy was investigated with X-ray diffraction (XRD), reflective light microscopy (RLM), scanning electron microscopy (SEM) equipped with energy dispersive spectroscopy (EDS), and transmission electron microscopy (TEM) equipped with electron diffraction (ED) and EDS. Double-layered oxides developed during steam oxidation of TP 347H FG both during field-testing and during laboratory exposures. TEM investigation suggested that the interior of the alloy grain was oxidised internally, forming particles of metallic Ni/Fe and Fe-Cr spinel. A FeCr{sub 2}O{sub 4} layer developed along the former alloy grain boundaries. Cr{sub 2}O{sub 3} developed in between this layer and the alloy during field-testing, and its formation was promoted by higher temperature. The morphology of the inner layer for the samples oxidised below and above approx. 585 deg. C looked very different in SEM (field-testing). It is suggested that more Cr is incorporated into the oxide layer at higher temperature, gradually transforming the morphology of the inner oxide layer. The alloy beneath the oxide layer was depleted in Cr

  19. Isolated human and rat cerebral arteries constrict to increases in flow: role of 20-HETE and TP receptors

    Science.gov (United States)

    Toth, Peter; Rozsa, Bernadett; Springo, Zsolt; Doczi, Tamas; Koller, Akos

    2011-01-01

    Elevation of intraluminal pressure increases vasomotor tone, which thought to have a substantial role in regulation of cerebral blood flow (CBF). Interestingly, responses of cerebral vessels to increases in flow varied and have not been studied in human cerebral arteries. We hypothesized that increases in flow elicit constrictions of isolated human and rat cerebral arteries and aimed to elucidate the underlying mechanisms. Human cerebral arteries and rat middle cerebral arteries constricted to increases in flow (P<0.05). Simultaneous increase in intraluminal flow+pressure further reduced the diameter compared with pressure-induced changes (P<0.05), leading to constant estimated CBF. Flow-induced constrictions were abolished by HET0016 (inhibitor of synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) or inhibition of COXs or blocking TP (thromboxane A2/prostaglandin H2, receptors and attenuated by scavenging reactive oxygen species (ROS). Flow-enhanced ROS formation was significantly reduced by HET0016. In conclusion, in human and rat cerebral arteries (1) increases in flow elicit constrictions, (2) signaling mechanism of flow-induced constriction of cerebral arteries involves enhanced production of ROS, COX activity, and mediated by 20-HETE via TP receptors, and (3) we propose that simultaneous operation of pressure- and flow-induced constrictions is necessary to provide an effective autoregulation of CBF. PMID:21610722

  20. The genetic switch regulating activity of early promoters of the temperate lactococcal bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Madsen, P.L.; Johansen, Annette Helle; Hammer, Karin

    1999-01-01

    A functional analysis of open reading frame 4 (ORF4) and ORF5 from the temperate lactococcal phage TP901-1 was performed by mutant and deletion analysis combined with transcriptional studies of the early phage promoters p(R) and p(L). ORF4 (180 amino acids) was identified as a phage repressor...... necessary for repression of both promoters. Furthermore, the presence of ORF4 confers immunity of the host strain to TP901-1. ORF5 (72 amino acids) was found to be able to inhibit repression of the lytic promoter p(L) by ORF4. Upon transformation with a plasmid containing both ORF4 and ORF5...... and their cognate promoters, clonal variation is observed: in each transformant, either p(L) is open and p(R) is closed or vice versa. The repression is still dependent on ORF4, and the presence of ORF5 is needed for the clonal variation. Induction of a repressed p(L) fusion containing orf4 and orf5 was obtained...

  1. Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population.

    Science.gov (United States)

    Rivu, Sanzana Fareen; Apu, Mohd Nazmul Hasan; Shabnaz, Samia; Nahid, Noor Ahmed; Islam, Md Reazul; Al-Mamun, Mir Md Abdullah; Nahar, Zabun; Rabbi, Sikder Nahidul Islam; Ahmed, Maizbha Uddin; Islam, Mohammad Safiqul; Hasnat, Abul

    2017-08-01

    Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160Ccolorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR=2.58, 95% CI=1.77-3.77, pcolorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (pcolorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR=2.02, 95% CI=1.42-2.87, pcolorectal cancer development in Bangladeshi population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. High-resolution structural analysis shows how Tah1 tethers Hsp90 to the R2TP complex.

    Science.gov (United States)

    Back, Régis; Dominguez, Cyril; Rothé, Benjamin; Bobo, Claude; Beaufils, Chrystel; Moréra, Solange; Meyer, Philippe; Charpentier, Bruno; Branlant, Christiane; Allain, Frédéric H-T; Manival, Xavier

    2013-10-08

    The ubiquitous Hsp90 chaperone participates in snoRNP and RNA polymerase assembly through interaction with the R2TP complex. This complex includes the proteins Tah1, Pih1, Rvb1, and Rvb2. Tah1 bridges Hsp90 to R2TP. Its minimal TPR domain includes two TPR motifs and a capping helix. We established the high-resolution solution structures of Tah1 free and in complex with the Hsp90 C-terminal peptide. The TPR fold is similar in the free and bound forms and we show experimentally that in addition to its solvating/stabilizing role, the capping helix is essential for the recognition of the Hsp90 (704)EMEEVD(709) motif. In addition to Lys79 and Arg83 from the carboxylate clamp, this helix bears Tyr82 forming a π/S-CH3 interaction with Hsp90 M(705) from the peptide 310 helix. The Tah1 C-terminal region is unfolded, and we demonstrate that it is essential for the recruitment of the Pih1 C-terminal domain and folds upon binding. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Tsc1-Tp53 loss induces mesothelioma in mice, and evidence for this mechanism in human mesothelioma

    Science.gov (United States)

    Guo, Yanan; Chirieac, Lucian R.; Bueno, Raphael; Pass, Harvey; Wu, Wenhao; Malinowska, Izabela A.; Kwiatkowski, David J.

    2014-01-01

    Mesothelioma is diagnosed in approximately 2,500 patients in the United States every year, most often arising in the pleural space, but also occurring as primary peritoneal mesothelioma. The vast majority of patients with mesothelioma die from their disease within 3 years. We developed a new mouse model of mesothelioma by bladder or intra-peritoneal injection of adenovirus Cre into mice with conditional alleles of each of Tp53 and Tsc1. Such mice began to develop malignant ascites about 6 months after injection, which was due to peritoneal mesothelioma, based on tumor morphology and immunohistochemical staining. Mesothelioma cell lines were established which showed loss of both Tsc1 and Tp53, with mTORC1 activation. Treatment of mice with malignant ascites due to mesothelioma with rapamycin led to a marked reduction in ascites, extended survival, and a 95–99% reduction in mesothelioma tumor volume, in comparison to vehicle-treated mice. To see if TSC1/TSC2 loss was a common genetic event in human mesothelioma, we examined 9 human mesothelioma cell lines, and found that 4 of 9 showed persistent activation of mTORC1 though none had loss of TSC1 or TSC2. A tissue microarray analysis of 198 human mesothelioma specimens showed that 33% of cases had reduced TSC2 expression and 60% showed activation of mTOR, indicating that mTOR activation is common in human mesothelioma and suggesting that it is a potential therapeutic target. PMID:23851502

  4. La influencia de Gregorio Magno en Alberto Magno: Super Dionysii Mysticam Theologiam et Epistulas

    Directory of Open Access Journals (Sweden)

    Anneliese Meis

    2010-01-01

    Full Text Available Si bien la influencia de Gregorio Magno fue decisiva para la historia del pensamiento teológico práctico en la Edad Media, siendo Gregorio el autor más citado en la STh de Tomás de Aquino después de Agustín, su influencia sobre Alberto Magno no ha sido estudiada recientemente. En efecto, Alberto Magno orienta su Comentario al Corpus Dionisiacum de la misma manera que Gregorio por la revelación de este misterio, que busca entender racionalmente. El estudio se detiene en las citas tomadas por el Doctor Universalis de los Moralia en SMT II, la Ep I, la Ep V y la Ep IX, para descubrir cuál es, concretamente, la influencia de Gregorio Magno sobre Alberto Magno en la intelección del problema razón y revelación.Although the influence of Gregory Magnus was crucial for the history of practical theological thought in the Middle Ages -being the most cited author in Thomas Aquinas' STh after Augustine- his influence over Albertus Magnus has not been studied recently. In effect, Albertus Magnus's Commentary on Corpus Di-onysiacum is guided, in the same way as Gregory, by the revelation of this mystery, which he seeks to understand rationally. This study focuses on the citations from the Moralia that Doctor Universalis uses in SMT II (Super Mysticam Theologiam Dionysii, the Ep. I, the Ep.V and the Ep. IX, in an effort to concretely discover what Gregory Magnus' influence was over Albertus Magnus in his understanding of the problem of reason and revelation.

  5. Construction of halide-bridged tungsten-copper-sulfide double cubanelike clusters from a new precursor [(Tp*WS2)2(μ-S2)].

    Science.gov (United States)

    Wei, Li-Pei; Ren, Zhi-Gang; Zhu, Lian-Wen; Yan, Wen-Yan; Sun, Sha; Wang, Hui-Fang; Lang, Jian-Ping; Sun, Zhen-Rong

    2011-05-16

    Treatment of [Et(4)N][Tp*WS(3)] (1) (Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate) with 2 equiv of AgSCN in MeCN afforded a novel neutral compound [(Tp*WS(2))(2)(μ-S(2))] (2). Reactions of 2 with excess CuX (X = Cl, Br, I) in MeCN and CH(2)Cl(2) or CHCl(3) formed three neutral W/Cu/S clusters [{Tp*W(μ(3)-S)(3)Cu(3)(μ-Cl)}(2)Cu(μ-Cl)(2)(μ(7)-Cl)(MeCN)](2) (3), [{Tp*W(μ(3)-S)(3)Cu(3)}(2)Br(μ-Br)(2)(μ(4)-Br)(MeCN)] (4), and [{Tp*W(μ(3)-S)(3)Cu(3)}(2){Cu(2)(μ-I)(4)(μ(3)-I)(2)}] (5), respectively. On the other hand, treatment of 2 with CuX (X = Cl, Br) in the presence of Et(4)NX (X = Cl, Br) produced two anionic W/Cu/S clusters [Et(4)N][{Tp*W(μ(3)-S)(3)Cu(3)X}(2)(μ-X)(2)(μ(4)-X)] (6: X = Cl; 7 X = Br). Compounds 2-7 were characterized by elemental analysis, IR, UV-vis, (1)H NMR, electrospray ionization (ESI) mass spectra, and single-crystal X-ray crystallography. The dimeric structure of 2 can be viewed as two [Tp*WS(2)] fragments in which two W atoms are connected by one S(2)(2-) dianion. Compounds 3-7 all possess unique halide-bridged double cubanelike frameworks. For 3, two [Tp*W(μ(3)-S)(3)Cu(3)](2+) dications are linked via a μ(7)-Cl(-) bridge, two μ-Cl(-) bridges, and a [Cu(MeCN)(μ-Cl)(2)](+) bridge. For 4, one [Tp*W(μ(3)-S)(3)Cu(3)(MeCN)](2+) dication and one [Tp*W(μ(3)-S)(3)Cu(3)Br](+) cation are linked via a μ(4)-Br(-) and two μ-Br(-) bridges. For 5, the two [Tp*W(μ(3)-S)(3)Cu(3)](2+) dications are bridged by a linear [(μ-I)(2)Cu(μ(3)-I)(2)Cu(μ-I)(2)](4+) species. For 6 and 7, two [Tp*W(μ(3)-S)(3)Cu(3)X](+) cations are linked by a μ(4)-X(-) and two μ-X(-) bridges (X = Cl, Br). In addition, the third-order nonlinear optical (NLO) properties of 2-7 in MeCN/CH(2)Cl(2) were investigated by using femtosecond degenerate four-wave mixing (DFWM) technique.

  6. Conocimientos sobre sexualidad y su influencia en el embarazo en adolescentes

    OpenAIRE

    Carmina Alexandra García Macías; Leticia Remón Ramírez; Josefa Margarita Miranda Vázquez; Silvia Rosana Defaz Taipe

    2017-01-01

    Introducción: El embarazo en la adolescencia es en la actualidad un problema de salud que genera serias consecuencias personales, sociales y económicas, con repercusión en la salud individual, familiar y colectiva. Objetivo: Identificar los conocimientos sobre la sexualidad y su influencia en el embarazo en la adolescencia. Métodos: Se realizó un estudio observacional analítico, transversal, en un universo de 80 adolescentes de 15 a 19 años del Equipo Urbano de Salud 23 Latacunga, a q...

  7. INFLUENCIA DEL DESARROLLO MOTRIZ EN EL APRENDIZAJE DE LA ESCRITURA, ASÍ COMO EN LAS COMPETENCIAS

    OpenAIRE

    Soto-Ruiz, María del Pilar

    2012-01-01

    La idea central de esta investigación fue examinar el desarrollo de los patrones motrices básicos en niños de infantil y su posible influencia en el proceso de aprendizaje, concretamente en la escritura. La metodología empleada fue de tipo exploratoria-descriptiva y correlacional, dirigida a una muestra de 40 niños de 5 años, a los cuales se les aplicó una serie de pruebas para valorar la motricidad, escritura y calificaciones escolares. El análisis e interpretación de los resu...

  8. Influencia de la familia en los trastornos alimenticios (Estudio de un caso clínico)

    OpenAIRE

    González Gómez, Dulce María

    2016-01-01

    Los trastornos de la conducta alimentaria son un conjunto de patologías cuya prevalencia no deja de aumentar, encontrando casos cada vez a edades más tempranas y siendo mucho más frecuentes en mujeres. Su tratamiento no es nada fácil, pues la curación completa suele conllevar años y en un gran número de casos se produce cronificación o recaídas. Su etiología, como en muchas enfermedades, es el resultado de una compleja interacción entre factores genéticos e influencia del ambiente exter...

  9. Influencia de la humedad en el ensayo de resistencia de los ladrillos de suelo-cemento

    OpenAIRE

    Lima, José I.; Escobar Martín, Dunia

    1994-01-01

    A través de un diseño experimental adecuado se pretende mostrar la influencia de la humedad en el ensayo a compresión de los ladrillos de suelo-cemento, obteniendo las ecuaciones que muestran esta relación. Su generalización posterior permitió elaborar una matriz de correlación de las resistencias con las diferentes humedades de ensayo, de forma tal que se pueda ensayar con una humedad dada y estimar la resistencia que tendrá esa muestra para diferentes valores de humedad, con un buen nive...

  10. La motivación laboral y su influencia en la empresa

    OpenAIRE

    Jiménez Cacho, Raquel

    2017-01-01

    Este proyecto se centra en un tema de gran interés como es la motivación laboral y su influencia en la empresa. Como sabemos este tema no es nuevo y se ha analizado y estudiado desde hace mucho tiempo, debido a la incidencia que tiene en el mundo laboral, económico y social. La motivación laboral lleva una trayectoria positiva en cuanto a su estudio e importancia, gracias a su estrecha relación con los problemas, soluciones, costes, beneficios y ventajas competitivas de las empresas. Para ...

  11. Estructura portante y estructura formal: Mies Van Der Rohe y su influencia sobre la arquitectura paulista

    OpenAIRE

    Mahfuz, Edson da Cunha

    2014-01-01

    El artículo trata de la posible influencia de Mies van der Rohe sobre la arquitectura paulista. Su característica más evidente es el rol de la estructura portante en la construcción de la forma. El uso de un número reducido de soportes busca liberar el suelo para actividades colectivas. The article describes the possible influence of Mies van der Rohe on the architecture practiced in São Paulo. Its most noticeable feature is the role of the structure on the definition of the overall art...

  12. Influencia del aceite de coco en enfermos de alzhéimer a nivel cognitivo.

    OpenAIRE

    De la Rubia Ortí, Jose Enrique; Sánchez Álvarez, Carmen; Selvi Sabater, Pablo; Bueno Cayo, Alma María; Sancho Castillo, Sandra; Julián Rochina, Mariano; Hu Yang, Iván

    2017-01-01

    La enfermedad de Alzheimer es a día de hoy la demencia neurodegenerativa con mayor prevalencia en el primer mundo. Este hecho, unido a la falta de tratamiento farmacológico que cure la enfermedad, hace que se estudien nuevas estrategias terapéuticas no farmacológicas como es la administración de nutrientes. En este sentido, destaca la posible influencia del aceite de coco como fuente energética alternativa, capaz de frenar la muerte neuronal que se produce de modo progresivo en esta enfermeda...

  13. La influencia de las guerras civiles sobre la represión estatal en posguerras

    OpenAIRE

    Herreros, Francisco

    2014-01-01

    En este artículo se analizan los determinantes de la represión estatal en posguerras. Su argumento principal es que ciertas dinámicas de las guerras civiles explican la variación en represión estatal en la posguerra. Para comprobar la influencia de las guerras civiles en la represión estatal, se emplea una base de datos que incluye a todos los países que han experimentado una guerra civil en el período 1976-2009. Los resultados muestran que una victoria rebelde en la guerra o un compromiso en...

  14. Influencia del tempo de la música en las emociones

    Directory of Open Access Journals (Sweden)

    Jonathan Azael Caballero-Meneses

    2010-01-01

    exposición de 24 estudiantes de licenciatura a treinta extractos musicales de distinto tempo. Además se evaluó la posible modulación de la relación tempo-valencia por el rasgo de personalidad extroversión/introversión. Los resultados confirmaron la influencia del tempo sobre el arousal, pero no sobre la valencia, así como una posible mediación de la dimensión de personalidad introversión-extroversión sobre la valencia.

  15. Culpabilidad sexual en jóvenes: influencia de las actitudes y la experiencia sexual

    OpenAIRE

    Juan Carlos Sierra; Felipe Perla; Pablo Santos-Iglesias

    2011-01-01

    La culpabilidad sexual es un factor determinante de la conducta sexual. El objetivo del presente estudio fue analizar la culpabilidad sexual en una muestra de 594 jóvenes salvadoreños con edades comprendidas entre 14 y 18 años, seleccionados mediante un procedimiento no aleatorio, con el propósito de determinar la influencia que sobre la misma tienen una serie de variables sociodemográficas y de actitudes hacia la sexualidad. Los participantes contestaron el Inventario de Culpabilidad Sexual ...

  16. Absceso paravalvular en la endocarditis bacteriana: influencia en el pronóstico postoperatorio

    OpenAIRE

    Varela Barca, Laura; López Menéndez, Jose; Martín García, Miren; Redondo Palacios, Ana; Centella Hernández, Tomasa; Miguelena Hycka, Javier; Muñoz Pérez, Rafael; Rodríguez-Roda Stuart, Jorge

    2017-01-01

    Objetivo: El absceso paravalvular (AbP) aumenta la mortalidad, la complejidad y las complicaciones asociadas a la cirugía de endocarditis infecciosa (EI). Analizamos la influencia del AbP en las distintas formas de presentación de endocarditis bacteriana. Métodos: Estudio retrospectivo, observacional, incluyendo a todos los pacientes intervenidos de EI entre 2002 y 2015, y realizando seguimiento clínico tras el alta. Resultados: Se intervino a 169 pacientes, presentando AbP el 33% de lo...

  17. La influencia del apego y del trauma infantil en la psicopatología del adulto

    OpenAIRE

    Marrodán Muro, Isabel

    2015-01-01

    En el presente trabajo se hace una revisión bibliográfica de la influencia de dos factores personales de la infancia, apego y trauma infantil, en la psicopatología de la edad adulta. En la primera parte se analiza cómo afecta el apego a la hora de sufrir trastornos mentales en un futuro, y se demuestra que un apego inseguro es un factor de riesgo a la hora de sufrir psicopatologías. La segunda parte trata de cómo influye el trauma infantil (abuso sexual, maltrato físico o psicológico o violen...

  18. La influencia de la musicoterapia en ni??os con disfemia

    OpenAIRE

    P??rez Bazoco, M??nica

    2015-01-01

    En este trabajo se pretende realizar una peque??a investigaci??n sobre la influencia que tiene la musicoterapia en los ni??os que presentan disfemia. La musicoterapia es un medio de rehabilitaci??n que incide tanto desde el punto de vista fisiol??gico (como puede ser la ejercitaci??n de la voz), como desde la perspectiva emocional e intelectual, proporcionando un desarrollo afectivo y cognoscitivo. Por tanto, la din??mica planteada de modelos mel??dicos y r??tmicos parece repercutir en el des...

  19. Las organizaciones contemporáneas tipo MP3 y su influencia cultural

    OpenAIRE

    Macías Cardona, Hugo

    2011-01-01

    En este artículo se hace una reflexión sobre la influencia cultural de organizaciones contemporáneas con estructuras des-jerarquizadas y procesos internos no secuenciales, que el profesor Richard Sennet ha llamado organizaciones MP3. A partir de las estructuras organizacionales descritas por Álvaro Zapata, la distinción entre trabajo y labor de Hannah Arendt, los mecanismos de vigilancia foucaultianos y una contextualización en Colombia, se analiza la baja lealtad institucional, la disminució...

  20. Uso e influencia de la televisión en la infancia

    OpenAIRE

    Arroyo Jiménez, Isabel

    2012-01-01

    Esta investigación está contextualizada en torno al uso e influencia que ejerce la televisión en la infancia. En concreto hemos escogido un grupo de niños del tercer ciclo de Educación Primaria (10-12 años). Primeramente, tratamos de comprobar el uso que hacen de la televisión los alumnos que hemos tomado como muestra así como el tipo de programas que ven. Posteriormente, analizaremos una pequeña muestra de esos programas más seguidos por nuestros alumnos encuestados. Para ello, partire...

  1. Influencia de la electroestimulación y lesión del ligamento cruzado anterior

    OpenAIRE

    Nuñez, Alberto

    2011-01-01

    En este trabajo se estudio en profundidad la lesión del ligamento cruzado anterior (LCA) y la influencia de la electroestimulación. En la primer parte del trabajo se desarrolló un protocolo para aplicar electroestimulación a diez pacientes que sufrieron lesión del LCA y que habían sido sometidos a cirugía. En la segunda parte, se indagó en profundidad a dichos pacientes a través de una entrevista sobre las causas de la lesión, el contexto en que ocurrió la lesión, el proceso pr...

  2. INFLUENCIA DEL CULTIVO INTERCALADO EN LA PRODUCCIÓN Y CALIDAD DEL FRUTO DE TOMATE CEREZA

    OpenAIRE

    Fabricio Rossi; Edmilson José Ambrosano; Eliana Aparecida Schammass; Glaucia María Bovi Ambrosano; Nivaldo Guirado; Fabio Luis Ferreira Días; Roberto Antonio Arévalo; Edna Ivani Bertoncini

    2013-01-01

    El presente trabajo tiene por objetivo determinar la influencia en la cosecha y calidad de los frutos de Solanum lycopersicum L. (1753) cv. cereza [Lycopersicum esculentum Mill. 1768] (tomate) en convivencia con cultivos intercalares de cinco Fabaceae, plantas auxiliadoras en la agricultura y dos tratamientos con y sin residuos de cosecha de Zea mayz L. El estudio fue im- plantado en el Polo Centro Sul, Piracicaba-SP. Brasil, en suelo Argisol rojo-amarillo distrófico. El diseño experimental f...

  3. Las organizaciones contemporáneas tipo mp3 y su influencia cultural

    Directory of Open Access Journals (Sweden)

    Hugo Macías Cardona

    2011-06-01

    Full Text Available En este artículo se hace una reflexión sobre la influencia cultural de organizaciones contemporáneas con estructuras des-jerarquizadas y procesos internos no secuenciales, que el profesor Richard Sennet ha llamado organizaciones MP3. A partir de las estructuras organizacionales descritas por Álvaro Zapata, la distinción entre trabajo y labor de Hannah Arendt, los mecanismos de vigilancia foucaultianos y una contextualización en Colombia, se analiza la baja lealtad institucional, la disminución de la confianza informal entre quienes laboran y el debilitamiento del conocimiento institucional.

  4. Base damage, local sequence context and TP53 mutation hotspots: a molecular dynamics study of benzo[a]pyrene induced DNA distortion and mutability.

    Science.gov (United States)

    Menzies, Georgina E; Reed, Simon H; Brancale, Andrea; Lewis, Paul D

    2015-10-30

    The mutational pattern for the TP53 tumour suppressor gene in lung tumours differs to other cancer types by having a higher frequency of G:C>T:A transversions. The aetiology of this differing mutation pattern is still unknown. Benzo[a]pyrene,diol epoxide (BPDE) is a potent cigarette smoke carcinogen that forms guanine adducts at TP53 CpG mutation hotspot sites including codons 157, 158, 245, 248 and 273. We performed molecular modelling of BPDE-adducted TP53 duplex sequences to determine the degree of local distortion caused by adducts which could influence the ability of nucleotide excision repair. We show that BPDE adducted codon 157 has greater structural distortion than other TP53 G:C>T:A hotspot sites and that sequence context more distal to adjacent bases must influence local distortion. Using TP53 trinucleotide mutation signatures for lung cancer in smokers and non-smokers we further show that codons 157 and 273 have the highest mutation probability in smokers. Combining this information with adduct structural data we predict that G:C>T:A mutations at codon 157 in lung tumours of smokers are predominantly caused by BPDE. Our results provide insight into how different DNA sequence contexts show variability in DNA distortion at mutagen adduct sites that could compromise DNA repair at well characterized cancer related mutation hotspots. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. Computational screening and molecular dynamic simulation of breast cancer associated deleterious non-synonymous single nucleotide polymorphisms in TP53 gene.

    Directory of Open Access Journals (Sweden)

    Kumaraswamy Naidu Chitrala

    Full Text Available Breast cancer is one of the most common cancers among the women around the world. Several genes are known to be responsible for conferring the susceptibility to breast cancer. Among them, TP53 is one of the major genetic risk factor which is known to be mutated in many of the breast tumor types. TP53 mutations in breast cancer are known to be related to a poor prognosis and chemo resistance. This renders them as a promising molecular target for the treatment of breast cancer. In this study, we present a computational based screening and molecular dynamic simulation of breast cancer associated deleterious non-synonymous single nucleotide polymorphisms in TP53. We have predicted three deleterious coding non-synonymous single nucleotide polymorphisms rs11540654 (R110P, rs17849781 (P278A and rs28934874 (P151T in TP53 with a phenotype in breast tumors using computational tools SIFT, Polyphen-2 and MutDB. We have performed molecular dynamics simulations to study the structural and dynamic effects of these TP53 mutations in comparison to the wild-type protein. Results from our simulations revealed a detailed consequence of the mutations on the p53 DNA-binding core domain that may provide insight for therapeutic approaches in breast cancer.

  6. Allele-specific wild-type TP53 expression in the unaffected carrier parent of children with Li-Fraumeni syndrome.

    Science.gov (United States)

    Buzby, Jeffrey S; Williams, Shirley A; Schaffer, Lana; Head, Steven R; Nugent, Diane J

    2017-02-01

    Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder where an oncogenic TP53 germline mutation is passed from parent to child. Tumor protein p53 is a key tumor suppressor regulating cell cycle arrest in response to DNA damage. Paradoxically, some mutant TP53 carriers remain unaffected, while their children develop cancer within the first few years of life. To address this paradox, response to UV stress was compared in dermal fibroblasts (dFb) from an affected LFS patient vs. their unaffected carrier parent. UV induction of CDKN1A/p21, a regulatory target of p53, in LFS patient dFb was significantly reduced compared to the unaffected parent. UV exposure also induced significantly greater p53[Ser15]-phosphorylation in LFS patient dFb, a reported property of some mutant p53 variants. Taken together, these results suggested that unaffected parental dFb may express an increased proportion of wild-type vs. mutant p53. Indeed, a significantly increased ratio of wild-type to mutant TP53 allele-specific expression in the unaffected parent dFb was confirmed by RT-PCR-RFLP and RNA-seq analysis. Hence, allele-specific expression of wild-type TP53 may allow an unaffected parent to mount a response to genotoxic stress more characteristic of homozygous wild-type TP53 individuals than their affected offspring, providing protection from the oncogenesis associated with LFS. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability.

    Science.gov (United States)

    Horejsí, Zuzana; Takai, Hiroyuki; Adelman, Carrie A; Collis, Spencer J; Flynn, Helen; Maslen, Sarah; Skehel, J Mark; de Lange, Titia; Boulton, Simon J

    2010-09-24

    TEL2 interacts with and is essential for the stability of all phosphatidylinositol 3-kinase-related kinases (PIKKs), but its mechanism of action remains unclear. Here, we show that TEL2 is constitutively phosphorylated on conserved serines 487 and 491 by casein kinase 2 (CK2). Proteomic analyses establish that the CK2 phosphosite of TEL2 confers binding to the R2TP/prefoldin-like complex, which possesses chaperon/prefoldin activities required during protein complex assembly. The PIH1D1 subunit of the R2TP complex binds directly to the CK2 phosphosite of TEL2 in vitro and is required for the TEL2-R2TP/prefoldin-like complex interaction in vivo. Although the CK2 phosphosite mutant of TEL2 retains association with the PIKKs and HSP90 in cells, failure to interact with the R2TP/prefoldin-like complex results in instability of the PIKKs, principally mTOR and SMG1. We propose that TEL2 acts as a scaffold to coordinate the activities of R2TP/prefoldin-like and HSP90 chaperone complexes during the assembly of the PIKKs. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Single nucleotide variation in the TP53 3' untranslated region in diffuse large B-cell lymphoma treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Li, Yong; Gordon, Michael W; Xu-Monette, Zijun Y

    2013-01-01

    We identified multiple single nucleotide variants (SNVs) in the TP53 3' untranslated region (3'UTR) in tumor specimens from 244 patients with diffuse large B-cell lymphoma (DLBCL). Patients carrying a wild-type TP53 coding sequence (CDS) and 1 or more 3'UTR SNVs had a better 5-year survival rate...... as a validation set. Altogether, we identified 187 novel SNVs; 36 occurred at least twice. Most of the newly identified 3'UTR SNVs were located at sites that are complementary to seed sequences of microRNAs (miRNAs) that are predicted or experimentally known to target TP53. Three SNVs disrupt the seed match...... between miR-125b and the TP53 3'UTR, thereby impeding suppression of p53 by this miRNA. In addition, a germline SNV (rs78378222) located in the TP53 polyadenylation signal resulted in downregulation of both p53 messenger RNA and protein levels and reduction of cellular apoptosis. This study is the first...

  9. Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor.

    Science.gov (United States)

    Pinto, Emilia M; Ribeiro, Raul C; Kletter, Gad B; Lawrence, John P; Jenkins, Jesse J; Wang, Jinling; Shurtleff, Sheila; McGregor, Lisa; Kriwacki, Richard W; Zambetti, Gerard P

    2011-03-01

    Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome. In fact, about two-thirds of children with ACT have a TP53 mutation. However, less than 10% of pediatric ACT cases occur in Li-Fraumeni syndrome, suggesting that inherited low-penetrance TP53 mutations play an important role in pediatric adrenal cortex tumorigenesis. We identified a novel inherited germline TP53 mutation affecting the acceptor splice site at intron 10 in a child with an ACT and no family history of cancer. The lack of family history of cancer and previous information about the carcinogenic potential of the mutation led us to further characterize it. Bioinformatics analysis showed that the non-natural and highly hydrophobic C-terminal segment of the frame-shifted mutant p53 protein may disrupt its tumor suppressor function by causing misfolding and aggregation. Our findings highlight the clinical and genetic counseling dilemmas that arise when an inherited TP53 mutation is found in a child with ACT without relatives with Li-Fraumeni-component tumors.

  10. A comparison among HER2, TP53, PAI-1, angiogenesis, and proliferation activity as prognostic variables in tumours from 408 patients diagnosed with early breast cancer

    DEFF Research Database (Denmark)

    Offersen, Birgitte Vrou; Alsner, Jan; Olsen, Karen Ege

    2008-01-01

    analysis and DNA sequencing. RESULTS: Ninety one patients (22%) were HER2 positive. TP53 was mutated in 101 cases (25%). Median PAI-1, Chalkley and MIB-1 was 0.72 ng/mg protein (range, 0-90 ng/mg protein), 5.00 (range, 2.67-12.00) and 15% (range, 1-83%). MIB-1 was correlated with HER2+, Chalkley counts, TP......BACKGROUND: The prognostic potential of HER2, TP53 mutations, PAI-1 protein levels, angiogenesis and proliferation were investigated in tumours from 408 patients with early breast cancer followed >10 years. One hundred and sixty seven patients (41%) died from breast cancer. MATERIALS AND METHODS.......0001) were prognostic markers. Among node-negative patients, HER2+ (p =0.0002), mutated TP53 (p =0.001), high PAI-1 levels (p =0.02), and grade (p =0.03) indicated poor DSS. In node-positive patients, HER2+ (p =0.0002), mutated TP53 (p

  11. La influencia externa en las políticas educativas de Argentina, Brasil y Chile (1990-2006)

    OpenAIRE

    Rambla, Francesc Xavier,

    2009-01-01

    El objetivo del artículo es analizar el papel que juega la influencia internacional en el diseño y aplicación de políticas educativas en el Cono Sur. Específicamente pretende explorar el proceso a través del cual las ideas, recomendaciones y metas globales modelan las políticas educativas latinoamericanas. Para ello, el artículo se centra en el programa de Educación para Todos en el Acuerdo General de Comercio de Servicios, analizando los mecanismos de influencia externa que intervienen en ca...

  12. Relaciones sociales y trayectorias biográficas : hacia un enfoque comprensivo de los modos de influencia

    OpenAIRE

    Bourdon, Sylvain

    2009-01-01

    El objetivo del presente texto es proponer algunos elementos para un enfoque comprensivo de la influencia de las relaciones en las trayectorias biográficas. El análisis se apoya en los datos de un estudio longitudinal sobre el papel que desempeñan la familia y las redes en la perseverancia en los estudios, realizado con 96 jóvenes que inician su trayectoria postsecundaria. En lugar de abordar la influencia en términos de características sociales, o a partir de un enfoque estructural de las re...

  13. Thermo-chemotherapy of GP or TP for Advanced Non-small Cell Lung Cancer: 
A Systematic Review

    Directory of Open Access Journals (Sweden)

    Denghai MI

    2012-08-01

    Full Text Available Background and objective Advanced non-small cell lung cancer (NSCLC is characterized by poor treatment efficacy and short survival time. Clinical trials have shown that the combination of chemotherapy with thermotherapy exhibits strong efficacy. We performed this meta-analysis to evaluate the clinical efficacy and safety of gemcitabine plus cisplatin (GP and paclitaxel plus cisplatin (TP combined with thermotherapy in the treatment of NSCLC, as well as to provide reference for clinical practice and future research. Methods We searched international (Cochrane Library, PubMed, and EMBASE and Chinese (CBM, CNKI, VIP and Wanfang databases for relevant articles and imported other retrievable sources, such as tracing-related references. We also corresponded with other authors to obtain certain inaccessible information. Data from all relevant randomized controlled trials (RCT were collected to compare GP or TP thermochemotherapy with GP or TP chemotherapy alone. The quality of the included studies was assessed by adequate outcome-based standards and clinical circumstances. The meta-analysis was conducted using RevMan 5.1. Results Fifteen RCTs involving 952 patients were included in this meta-analysis. The results showed that the thermochemotherapy group had higher rates of improvement in quality of life (OR=3.84, 95%CI: 2.61-5.64, survival at 1 year (HR=1.94, 95%CI: 1.21-3.12, and survival at 2 years (HR=2.05, 95%CI: 1.18-3.58 compared with the chemotherapy group, with the differences between them being significant. However, these groups did not differ in other indicators of treatment effectiveness, such as myelosuppression, alimentary canal reactions, hepatic lesions, and diarrhea. Conclusion Compared with chemotherapy alone, thermochemotherapy can improve survival rates and curative effects, ameliorate symptoms, and enhance the quality of life of patients with advanced NSCLC, and it has an acceptable safety profile. The results of this meta

  14. Wee1 Kinase Inhibitor AZD1775 Radiosensitizes Hepatocellular Carcinoma Regardless of TP53 Mutational Status Through Induction of Replication Stress

    Energy Technology Data Exchange (ETDEWEB)

    Cuneo, Kyle C., E-mail: kcuneo@umich.edu; Morgan, Meredith A.; Davis, Mary A.; Parcels, Leslie A.; Parcels, Joshua; Karnak, David; Ryan, Caila; Liu, Na; Maybaum, Jonathan; Lawrence, Theodore S.

    2016-06-01

    Purpose: Wee1 kinase inhibitors are effective radiosensitizers in cells lacking a G{sub 1} checkpoint. In this study we examined the potential effect of Wee1 kinase inhibition on inducing replication stress in hepatocellular carcinoma (HCC). Methods and Materials: Five independent datasets from the Oncomine database comparing gene expression in HCC compared to normal tissue were combined and specific markers associated with Wee1 sensitivity were analyzed. We then performed a series of in vitro experiments to study the effect of Wee1 inhibition on irradiated HCC cell lines with varying p53 mutational status. Clonogenic survival assays and flow cytometry using anti-γH2AX and phospho-histone H3 antibodies with propidium iodide were performed to study the effect of AZD1775 on survival, cell cycle, and DNA repair. Additionally, nucleoside enriched medium was used to examine the effect of altering nucleotide pools on Wee1 targeted radiation sensitization. Results: Our analysis of the Oncomine database found high levels of CDK1 and other cell cycle regulators indicative of Wee1 sensitivity in HCC. In our in vitro experiments, treatment with AZD1775 radiosensitized and chemosensitized Hep3B, Huh7, and HepG2 cell lines and was associated with delayed resolution of γH2AX foci and the induction of pan-nuclear γH2AX staining. Wee1 inhibition attenuated radiation-induced G{sub 2} arrest in the Hep3B (TP53 null) and Huh7 (TP53 mutant) cell lines but not in the TP53 wild-type cell line HepG2. Supplementation with nucleosides reversed the radiation-sensitizing effect of AZD1775 and reduced the amount of cells with pan-nuclear γH2AX staining after radiation. Conclusions: Radiation sensitization with Wee1 inhibition occurs in cells regardless of their p53 mutational status. In this study we show for the first time that replication stress via the overconsumption of nucleotides plays an important role in AZD1775-induced radiation sensitization.

  15. Influencias platónicas en el pensamiento de clemente de alejandría

    Directory of Open Access Journals (Sweden)

    José Antonio Llamas Martínez

    2001-01-01

    Full Text Available Las obras de Clemente de Alejandría son el reflejo más exacto de la filosofía platónica. La influencia de Platón fue bastante evidente durante el periodo helenístico. Clemente de Alejandría es un intelectual formado a la luz de diversas escuelas helenísticas. Sin embargo, esta razón no es suficiente para confirmar tal influencia. Es cierto que Clemente elige a Platón y no a Aristóteles como inspiración de su pensamiento cristiano. Hubo otros intelectuales que, no sólo no hicieron referencia a ningún filósofo, sino que losrechazaron abiertamente. Clemente admira tanto a Platón que identifica su filosofía como un auténtico testamento, con un valor realmente propedéutico, como hubiera sido el testamento para la nueva filosofía cristiana

  16. El seminario de Wachsmann en Japón: Las influencias compartidas

    Directory of Open Access Journals (Sweden)

    Martino Peña Fernández-Serrano

    2017-11-01

    Full Text Available En 1955 Konrad Wachsmann, arquitecto alemán de origen judío y establecido en Estados Unidos, impartió el seminario denominado The Wachsmann Seminar en Japón. En el taller de Wachsmann se ejemplifican las influencias directas que el maestro transmite a una joven generación de estudiantes japoneses de arquitectura entre los cuales se encontraban algunos de los futuros componentes del grupo Metabolista. Kenzo Tange es el organizador del taller y a través de él se materializó el resultado en el edifico denominado Big Roof, situado en la exposición universal que se celebró en Osaka en 1970. Esta edificación, que sirve de entrada al complejo, aloja varias exposiciones entre las que se encuentraba la denominada ciudad aérea, donde arquitectos colocaron sus artefactos. En esta exposición se utiliza la cubierta como gran contenedor de células habitacionales diseñadas por algunos componentes del grupo Metabolista y otros grupos internacionales como Archigram. Se constatan por tanto las influencias directas e indirectas de una generación de arquitectos sobre otra más joven, y a su vez entre ellos, derivadas del seminario de Wachsmann que fue posible gracias al inicio de los viajes aéreos comerciales que siguen a los militares.

  17. INFLUENCIA DEL TEMPO DE LA MÚSICA EN LAS EMOCIONES

    Directory of Open Access Journals (Sweden)

    Jonathan Azael Caballero-Meneses

    2010-01-01

    Full Text Available Se sabe que la música puede influir en dos componentes de lasemociones: el arousal y la valencia. En particular, se ha reportadoque el tempo o rapidez de la música está directamenterelacionado con el arousal, aunque su relación con la valenciao medida de afecto no es aún clara. En este trabajo se analizóla influencia del tempo en ambos componentes mediante laexposición de 24 estudiantes de licenciatura a treinta extractosmusicales de distinto tempo. Además se evaluó la posiblemodulación de la relación tempo-valencia por el rasgo de personalidadextroversión/introversión. Los resultados confirmaronla influencia del tempo sobre el arousal, pero no sobrela valencia, así como una posible mediación de la dimensiónde personalidad introversión-extroversión sobre la valencia.

  18. De la influencia al poder: elementos para una mirada foucaultiana al Liderazgo

    Directory of Open Access Journals (Sweden)

    Juan Javier Saavedra Mayorga

    2013-10-01

    Full Text Available El artículo tiene como objetivo contribuir a la construcción de una mirada crítica al liderazgo. Examina la posibilidad de estudiar el problema central del liderazgo, el de la influencia, desde un punto de vista más amplio, el de las relaciones de poder entre los individuos, y en particular desde la teoría del poder de Michel Foucault. El artículo hace una revisión de la obra de Michel Foucault y de su utilización por parte de los estudios organizacionales, y propone la tesis según la cual su filosofía, que señala una estrecha relación entre el discurso y los dispositivos para el ejercicio del poder, puede contribuir a la comprensión de los mecanismos a través de los cuales se ejerce la influencia en las organizaciones. Para desarrollar esta tesis de exploran tres formas complementarias de estudiar el liderazgo desde la perspectiva de Foucault: el liderazgo como discurso, como tecnología de poder y como técnica del yo.

  19. La influencia de la televisión en una campaña electoral

    Directory of Open Access Journals (Sweden)

    ELISABETH NOELLE-NEUMANN

    1978-01-01

    Full Text Available Se examina el efecto de los medios de comunicación de masas sobre las elecciones en base a datos relativos las elecciones federales de la República Federal de Alemania que tuvieron lugar en 1965, 1972 y 1976. Se sugiere que durante una campaña electoral la opinión pública seguirá las expectativas mostradas por los medios y la visibilidad que éstos dan a las diferentes partes. Se perfilan los cambios en la opinión pública que alteran el clima político mediante el análisis de datos recabados en varios períodos. Dichos análisis revelan que no se puede demostrar la existencia de una relación causal entre las sentencias políticas que aparecen en la televisión y la opinión pública. Si bien parece que la televisión tenga alguna influencia en el clima de opinión, el problema de cómo verificar dicha influencia permanece irresuelto.

  20. Influencia de la estrategia "toma de decisiones" en el autoconcepto de adolescentes consumidores de alcohol

    Directory of Open Access Journals (Sweden)

    Reyna Isabel Hernández Pedroza

    2015-12-01

    Full Text Available El objetivo de esta investigación fue determinar la influencia de la estrategia "toma de decisiones" en el autoconcepto de adolescentes consumidores de alcohol. Se aplicó un estudio longitudinal, pre-experimental. Se incluyeron 30 adolescentes, previo consentimiento informado de estudiantes y padres. La recolección de datos se realizo con AUDIT, test de conflicto decisional y The Tennessee Self-Concep Scale (TSCS. Se encontró que la edad promedio fue 16.56 ± 0.85 años, 60% hombres, el 100% de los adolescentes presentaron conflicto decisional. El 100% habían consumido alcohol alguna vez en su vida. No se encontró diferencia estadísticamente significativa entre el autoconcepto pre y post intervención (p = 0.27, excepto en la dimensión Yo moral (p = 0.01. Se concluye de acuerdo a los resultados obtenidos en la pre y post intervención que la estrategia de intervención tuvo una influencia en la dimensión del autoconcepto Yo Moral del adolescente consumidor de alcohol. Es posible que esto influyera en la percepción de sí mismo al encontrarse con la realidad de que por primera vez consideraba su capacidad o incapacidad para tomar decisiones.

  1. La influencia social de los medios de comunicación en Twitter

    Directory of Open Access Journals (Sweden)

    Karines Rodríguez Díaz

    2017-06-01

    Full Text Available En este artículo se expone cómo se desarrolla la influencia social de los medios de comunicación sobre los usuarios en Twitter, durante la celebración de la VII Cumbre de la Asociación de Estados del Caribe (AEC. La investigación parte del análisis de un corpus de 1500 tuits con las etiquetas temáticas #CubaCaribe, #VIICumbreAEC, #CumbreAEC. Utilizando el análisis del discurso mediado por computador, los resultados muestran la habilidad de influencia de los medios de comunicación a través de patrones de repetición-reacción y en la construcción del consenso sobre la valoración del acontecimiento. El reporte de caso explica cómo los parlamentos mediáticos repercuten en la comunidad de usuarios en el contexto microblogging.

  2. Factores determinantes de la actividad en el mercado laboral gallego. Influencia del género

    Directory of Open Access Journals (Sweden)

    Mª Carmen Sánchez Sellero

    2013-04-01

    Full Text Available En este trabajo se estudian las características personales que determinan la actividad (ocupación o paro en la población gallega. Para ello se construye el modelo de actividad, en el cual se estima la probabilidad de que una persona en edad de trabajar forme parte de la población activa.Una vez estimados los parámetros del modelo mediante regresión logística binaria, se calculan las probabilidades de actividad condicionadas a distintas características personales, para evaluar la influencia real de las mismas en la forma en que un individuo se integra en el mercado de trabajo. Del análisis empírico se obtiene que la característica más destacada es el sexo, y que la influencia de las demás variables sobre las distintas probabilidades varía en función del sexo de la persona analizada.

  3. An extensive molecular cytogenetic characterization in high-risk chronic lymphocytic leukemia identifies karyotype aberrations and TP53 disruption as predictors of outcome and chemorefractoriness

    Science.gov (United States)

    Cavallari, Maurizio; Quaglia, Francesca Maria; Lista, Enrico; Urso, Antonio; Guardalben, Emanuele; Martinelli, Sara; Saccenti, Elena; Bassi, Cristian; Lupini, Laura; Bardi, Maria Antonella; Volta, Eleonora; Tammiso, Elisa; Melandri, Aurora; Negrini, Massimo

    2017-01-01

    We investigated whether karyotype analysis and mutational screening by next generation sequencing could predict outcome in 101 newly diagnosed chronic lymphocytic leukemia patients with high-risk features, as defined by the presence of unmutated IGHV gene and/or 11q22/17p13 deletion by FISH and/or TP53 mutations. Cytogenetic analysis showed favorable findings (normal karyotype and isolated 13q14 deletion) in 30 patients, unfavorable (complex karyotype and/or 17p13/11q22 deletion) in 34 cases and intermediate (all other abnormalities) in 36 cases. A complex karyotype was present in 21 patients. Mutations were detected in 56 cases and were associated with unmutated IGHV status (p = 0.040) and complex karyotype (p = 0.047). TP53 disruption (i.e. TP53 mutations and/or 17p13 deletion by FISH) correlated with the presence of ≥ 2 mutations (p = 0.001) and a complex karyotype (p = 0.012). By multivariate analysis, an advanced Binet stage (p karyotype (p = 0.001) predicted a shorter time to first treatment. TP53 disruption (p = 0.019) and the unfavorable karyotype (p = 0.028) predicted a worse overall survival. A shorter time to chemorefractoriness was associated with TP53 disruption (p = 0.001) and unfavorable karyotype (p = 0.025). Patients with both unfavorable karyotype and TP53 disruption presented a dismal outcome (median overall survival and time to chemorefractoriness of 28.7 and 15.0 months, respectively). In conclusion, karyotype analysis refines risk stratification in high-risk CLL patients and could identify a subset of patients with highly unfavorable outcome requiring alternative treatments. PMID:28427204

  4. TP53 gene status and human papilloma virus infection in response to platinum plus taxane-based chemotherapy of epithelial ovarian carcinomas.

    Science.gov (United States)

    Malisic, E; Jankovic, R; Jakovljevic, K; Radulovic, S

    2011-01-01

    Lack of symptoms in early stages of disease and resistance to chemotherapy make epithelial ovarian carcinomas one of the most lethal neoplasms among gynaecological malignancies. The aim of this study was to analyse the impact of TP53 mutations, codon 72 polymorphism and human papillomavirus (HPV) infection on the response to platinum-taxane combination chemotherapy in patients with epithelial ovarian carcinomas. The study was conducted on 26 ovarian carcinoma patients who received carboplatin plus paclitaxel combination chemotherapy. DNA was isolated by salting-out procedure. Mutations in exons 4-8 of TP53 gene were detected by PCR-SSCP and confirmed by automatic DNA sequencing. Codon 72 polymorphism was assessed by the RFLP method. HPV infection was detected through amplification of one part of L1 viral gene. Genotyping was performed by DNA sequencing. Fisher's exact and log-rank tests were used for statistical analysis. TP53 mutations were present in 5/26 (19.2%) ovarian carcinomas. The distribution of codon 72 TP53 genotypes was: Arg/Arg 38.5%, Arg/Pro 50.0%, Pro/Pro 11.5%. HPV was present in 4/26 (15.4%) ovarian carcinomas. All HPV-positive tumors were HPV16 type. Patients with mutations in TP53 gene, Arg/Arg genotype of codon 72 and absence of HPV infection experienced the highest tumor response rate to platinum-taxane chemotherapy. However, no significant correlation between progression free interval (PFI) and the examined biomarkers was observed. Our results indicate that, based on the TP53 gene status and the presence/absence of HPV infection, the subgroups of patients having better initial response to platinum-taxane therapy could be distinguished. This might contribute to more adequate treatment and individual therapeutic approach.

  5. TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

    International Nuclear Information System (INIS)

    Kringen, Pedro; Wang, Yun; Dumeaux, Vanessa; Kristensen, Gunnar; Borresen-Dale, Anne-Lise; Dorum, Anne

    2005-01-01

    Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive. DNA was extracted from paraffin embedded formalin fixed tissues for the familial cases, and from fresh frozen specimen from the sporadic cases. All cases were treated at our hospital according to protocol. Mutation analyses of exon 2 – 11 were performed using TTGE, followed by sequencing. Survival rates for BRCA1-familial cases with TP53 mutations were not significantly lower than for familial cases without TP53 mutations (p = 0.25, RR = 1.64, 95% CI [0.71–3.78]). Median age at diagnosis for sporadic (59 years) and familial (49 years) cases differed significantly (p < 0.001) with or without TP53 mutations. Age at diagnosis between the two types of familial carriers were not significantly different, with median age of 47 for 1675delA and 52.5 for 1135insA carriers (p = 0.245). For cases ≥50 years at diagnosis, a trend toward longer survival for sporadic over familial cases was observed (p = 0.08). The opposite trend was observed for cases <50 years at diagnosis. There do not seem to be a protective advantage for familial BRCA1 carriers without TP53 mutations over familial cases with TP53 mutations. However, there seem to be a trend towards initial advantage in survival for familial cases compared to sporadic cases diagnosed before the age of 50 both with and without TP53 mutations. However, this trend diminishes over time and for cases diagnosed ≥50 years the sporadic cases show a trend towards an advantage in survival over familial cases. Although this data set is small, if confirmed, this may be a link in the evidence that the differences in ovarian cancer survival reported, are

  6. Chromatin enrichment of histone marks H4Ac and H3K9me3 in TP53 gene domain in breast cells

    OpenAIRE

    Santos G. C. Jr; Goes A. C. S.; de Moura Gallo C. V.

    2014-01-01

    In non-cancerous breast cell lines HB2 and MCF10A the TP53 gene is localized inside a relatively small ~ 50 kb loop domain delimited by two S/MARs. Aim. To analyze the chromatin markers H4Ac and H3K9me3 of these two S/MARs and of the TP53 gene P1 promoter in different breast cells lines. Methods. We used chromatin immunoprecipitation (ChIP) to characterize the chromatin status of these S/MARs elements in breast non-cancerous cell lines HB2 and MCF10A and cancerous MCF-7, MDA-MB-231, BT-474 an...

  7. Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor

    OpenAIRE

    Pinto, Emilia M.; Ribeiro, Raul C.; Kletter, Gad B.; Lawrence, John P.; Jenkins, Jesse J.; Wang, Jinling; Shurtleff, Sheila; McGregor, Lisa; Kriwacki, Richard W.; Zambetti, Gerard P.

    2010-01-01

    Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome. In fact, about two-thirds of children with ACT have a TP53 mutation. However, less than 10% of pediatric ACT cases occur in Li-Fraumeni syndrome, suggesting that inherited low-p...

  8. Modelling of bubbly and annular two-phase flow in subchannel geometries with BACCHUS-3D/TP

    International Nuclear Information System (INIS)

    Bottoni, M.; Lyczkowski, R.W.

    1992-01-01

    The theoretical and computational bases of the BACCHUS-3D/TP computer program are reviewed. The computer program is used for thermal-hydraulic analyses of nuclear fuel bundles under normal and accident conditions. The present program combines two models and solution procedures previously used separately, namely, the Improved Slip Model (ISM) and the Separated-Phases Model (SPM). The former model uses mixture equations with accounting for slip between the phases, whereas the latter uses separate continuity and momentum equations. At the present stage of development, both assume thermodynamic equilibrium. Techniques used to affect smooth transition between the two models are described. including treatment of frictional pressure drop and solution of the Poisson and momentum equations. A detailed derivation of the computation of mass transfer between the phases is given because it is a central and novel feature of the model

  9. SV40 large T-p53 complex: evidence for the presence of two immunologically distinct forms of p53

    International Nuclear Information System (INIS)

    Milner, J.; Gamble, J.

    1985-01-01

    The transforming protein of SV40 is the large T antigen. Large T binds a cellular protein, p53, which is potentially oncogenic by virtue of its functional involvement in the control of cell proliferation. This raises the possibility that p53 may mediate, in part, the transforming function of SV40 large T. Two immunologically distinct forms of p53 have been identified in normal cells: the forms are cell-cycle dependent, one being restricted to nondividing cells (p53-Go) and the second to dividing cells (p53-G divided by). The authors have now dissociated and probed the multimeric complex of SV40 large T-p53 for the presence of immunologically distinct forms of p53. Here they present evidence for the presence of p53-Go and p53-G divided by complexed with SV40 large T

  10. Visualizing a Complete Siphoviridae Member by Single-Particle Electron Microscopy: the Structure of Lactococcal Phage TP901-1

    Science.gov (United States)

    Bebeacua, Cecilia; Lai, Livia; Vegge, Christina Skovgaard; Brøndsted, Lone; van Heel, Marin

    2013-01-01

    Tailed phages are genome delivery machines exhibiting unequaled efficiency acquired over more than 3 billion years of evolution. Siphophages from the P335 and 936 families infect the Gram-positive bacterium Lactococcus lactis using receptor-binding proteins anchored to the host adsorption apparatus (baseplate). Crystallographic and electron microscopy (EM) studies have shed light on the distinct adsorption strategies used by phages of these two families, suggesting that they might also rely on different infection mechanisms. Here, we report electron microscopy reconstructions of the whole phage TP901-1 (P335 species) and propose a composite EM model of this gigantic molecular machine. Our results suggest conservation of structural proteins among tailed phages and add to the growing body of evidence pointing to a common evolutionary origin for these virions. Finally, we propose that host adsorption apparatus architectures have evolved in correlation with the nature of the receptors used during infection. PMID:23135714

  11. The Structure of Treponema pallidum Tp0624 Reveals a Modular Assembly of Divergently Functionalized and Previously Uncharacterized Domains.

    Science.gov (United States)

    Parker, Michelle L; Houston, Simon; Wetherell, Charmaine; Cameron, Caroline E; Boulanger, Martin J

    2016-01-01

    Treponema pallidum subspecies pallidum is the causative agent of syphilis, a chronic, multistage, systemic infection that remains a major global health concern. The molecular mechanisms underlying T. pallidum pathogenesis are incompletely understood, partially due to the phylogenetic divergence of T. pallidum. One aspect of T. pallidum that differentiates it from conventional Gram-negative bacteria, and is believed to play an important role in pathogenesis, is its unusual cell envelope ultrastructure; in particular, the T. pallidum peptidoglycan layer is chemically distinct, thinner and more distal to the outer membrane. Established functional roles for peptidoglycan include contributing to the structural integrity of the cell envelope and stabilization of the flagellar motor complex, which are typically mediated by the OmpA domain-containing family of proteins. To gain insight into the molecular mechanisms that govern peptidoglycan binding and cell envelope biogenesis in T. pallidum we report here the structural characterization of the putative OmpA-like domain-containing protein, Tp0624. Analysis of the 1.70 Å resolution Tp0624 crystal structure reveals a multi-modular architecture comprised of three distinct domains including a C-terminal divergent OmpA-like domain, which we show is unable to bind the conventional peptidoglycan component diaminopimelic acid, and a previously uncharacterized tandem domain unit. Intriguingly, bioinformatic analysis indicates that the three domains together are found in all orthologs from pathogenic treponemes, but are not observed together in genera outside Treponema. These findings provide the first structural insight into a multi-modular treponemal protein containing an OmpA-like domain and its potential role in peptidoglycan coordination and stabilization of the T. pallidum cell envelope.

  12. Transitions at CpG dinucleotides, geographic clustering of TP53 mutations and food availability patterns in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Fabio Verginelli

    Full Text Available BACKGROUND: Colorectal cancer is mainly attributed to diet, but the role exerted by foods remains unclear because involved factors are extremely complex. Geography substantially impacts on foods. Correlations between international variation in colorectal cancer-associated mutation patterns and food availabilities could highlight the influence of foods on colorectal mutagenesis. METHODOLOGY: To test such hypothesis, we applied techniques based on hierarchical clustering, feature extraction and selection, and statistical pattern recognition to the analysis of 2,572 colorectal cancer-associated TP53 mutations from 12 countries/geographic areas. For food availabilities, we relied on data extracted from the Food Balance Sheets of the Food and Agriculture Organization of the United Nations. Dendrograms for mutation sites, mutation types and food patterns were constructed through Ward's hierarchical clustering algorithm and their stability was assessed evaluating silhouette values. Feature selection used entropy-based measures for similarity between clusterings, combined with principal component analysis by exhaustive and heuristic approaches. CONCLUSION/SIGNIFICANCE: Mutations clustered in two major geographic groups, one including only Western countries, the other Asia and parts of Europe. This was determined by variation in the frequency of transitions at CpGs, the most common mutation type. Higher frequencies of transitions at CpGs in the cluster that included only Western countries mainly reflected higher frequencies of mutations at CpG codons 175, 248 and 273, the three major TP53 hotspots. Pearson's correlation scores, computed between the principal components of the datamatrices for mutation types, food availability and mutation sites, demonstrated statistically significant correlations between transitions at CpGs and both mutation sites and availabilities of meat, milk, sweeteners and animal fats, the energy-dense foods at the basis of

  13. High-throughput interrogation of PIK3CA, PTEN, KRAS, FBXW7 and TP53 mutations in primary endometrial carcinoma.

    Science.gov (United States)

    Garcia-Dios, Diego A; Lambrechts, Diether; Coenegrachts, Lieve; Vandenput, Ingrid; Capoen, An; Webb, Penelope M; Ferguson, Kaltin; Akslen, Lars A; Claes, Bart; Vergote, Ignace; Moerman, Philippe; Van Robays, Johan; Marcickiewicz, Janusz; Salvesen, Helga B; Spurdle, Amanda B; Amant, Frédéric

    2013-02-01

    Endometrial cancer patients may benefit from systemic adjuvant chemotherapy, alone or in combination with targeted therapies. Prognostic and predictive markers are needed, however, to identify patients amenable for these therapies. Primary endometrial tumors were genotyped for >100 hot spot mutations in genes potentially acting as prognostic or predictive markers. Mutations were correlated with tumor characteristics in a discovery cohort, replicated in independent cohorts and finally, confirmed in the overall population (n=1063). PIK3CA, PTEN and KRAS mutations were most frequently detected, respectively in 172 (16.2%), 164 (15.4%) and 161 (15.1%) tumors. Binary logistic regression revealed that PIK3CA mutations were more common in high-grade tumors (OR=2.03; P=0.001 for grade 2 and OR=1.89; P=0.012 for grade 3 compared to grade 1), whereas a positive TP53 status correlated with type II tumors (OR=11.92; P<0.001) and PTEN mutations with type I tumors (OR=19.58; P=0.003). Conversely, FBXW7 mutations correlated with positive lymph nodes (OR=3.38; P=0.045). When assessing the effects of individual hot spot mutations, the H1047R mutation in PIK3CA correlated with high tumor grade and reduced relapse-free survival (HR=2.18; P=0.028). Mutations in PIK3CA, TP53, PTEN and FBXW7 correlate with high tumor grade, endometrial cancer type and lymph node status, whereas PIK3CA H1047R mutations serve as prognostic markers for relapse-free survival in endometrial cancer patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Evolución de la inmunología e influencia en los trasplantes de órganos

    OpenAIRE

    Carretero Vegas, Luz María

    2012-01-01

    Se profundiza en el conocimiento sobre los mecanismos del sistema inmunológico y la evolución histórica de los mismos para conocer la influencia de la inmunología en los trasplantes y las medidas preventivas más adecuadas para evitar las complicaciones

  15. Exploratory Analysis of TP53 Mutations in Circulating Tumour DNA as Biomarkers of Treatment Response for Patients with Relapsed High-Grade Serous Ovarian Carcinoma: A Retrospective Study.

    Directory of Open Access Journals (Sweden)

    Christine A Parkinson

    2016-12-01

    Full Text Available Circulating tumour DNA (ctDNA carrying tumour-specific sequence alterations may provide a minimally invasive means to dynamically assess tumour burden and response to treatment in cancer patients. Somatic TP53 mutations are a defining feature of high-grade serous ovarian carcinoma (HGSOC. We tested whether these mutations could be used as personalised markers to monitor tumour burden and early changes as a predictor of response and time to progression (TTP.We performed a retrospective analysis of serial plasma samples collected during routine clinical visits from 40 patients with HGSOC undergoing heterogeneous standard of care treatment. Patient-specific TP53 assays were developed for 31 unique mutations identified in formalin-fixed paraffin-embedded tumour DNA from these patients. These assays were used to quantify ctDNA in 318 plasma samples using microfluidic digital PCR. The TP53 mutant allele fraction (TP53MAF was compared to serum CA-125, the current gold-standard response marker for HGSOC in blood, as well as to disease volume on computed tomography scans by volumetric analysis. Changes after one cycle of treatment were compared with TTP. The median TP53MAF prior to treatment in 51 relapsed treatment courses was 8% (interquartile range [IQR] 1.2%-22% compared to 0.7% (IQR 0.3%-2.0% for seven untreated newly diagnosed stage IIIC/IV patients. TP53MAF correlated with volumetric measurements (Pearson r = 0.59, p 32 cm3, ctDNA was detected at ≥20 amplifiable copies per millilitre of plasma. In 49 treatment courses for relapsed disease, pre-treatment TP53MAF concentration, but not CA-125, was associated with TTP. Response to chemotherapy was seen earlier with ctDNA, with a median time to nadir of 37 d (IQR 28-54 compared with a median time to nadir of 84 d (IQR 42-116 for CA-125. In 32 relapsed treatment courses evaluable for response after one cycle of chemotherapy, a decrease in TP53MAF of >60% was an independent predictor of TTP in

  16. La influencia de la cultura política de la Revolución Francesa en los liberalismos europeos (1789-1848)

    OpenAIRE

    López Alcañiz, Vladimir

    2006-01-01

    Conferències impartides en el curs de doctorat La influencia de la cultura política de la Revolución Francesa en los liberalismos europeos (1789-1848). Conferencias del curso de doctorado La influencia de la cultura política de la Revolución Francesa en los liberalismos europeos (1789-1848). Seminar postgraduate courses La influencia de la cultura política de la Revolución Francesa en los liberalismos europeos (1789-1848).

  17. Association of polymorphism in TP53 gene with susceptibility and radiation sensitivity of non-small-cell-lung cancer in Chinese population

    International Nuclear Information System (INIS)

    Shao Guoguang; Liu Linlin; Xu Chuanjie

    2005-01-01

    Objective: To study the association of polymorphism in TP53 gene with the susceptibility and radiation sensitivity of non-small-cell-lung cancer (NSCLC) of the population in the North of China. Methods: Using RFLP-PCR assays, TP53 genotypes were detected by amplifying DNA fragments with sequence specific primers and digested by FnuD II enzyme in 88 patients with NSCLC as well as 112 healthy controls. Results: The C/C allele frequency was significantly higher in NSCLC patients than that in the healthy controls (χ 2 =5.65, P=0.017). The C/C genotype frequency was significantly higher in NSCLC patients than that of the healthy controls (χ 2 =9.33, P=0.0023). The risk of C/C homozygotes in NSCLC patients was about 2.7 times against G/G homozygotes with odds ratio of 2.43(95% CI=1.32-4.51). Conclusion: In the population in the North of China, TP53 C/C genotype is closely associated with the susceptibility of NSCLC. There is no significant relationship between the polymorphism in TP53 gene and radiation sensitivity in NSCLC. (authors)

  18. Microstructure and creep characteristics of dissimilar T91/TP316H martensitic/austenitic welded joint with Ni-based weld metal

    Czech Academy of Sciences Publication Activity Database

    Falat, L.; Svoboda, Milan; Výrostková, A.; Petryshynets, I.; Sopko, M.

    2012-01-01

    Roč. 72, OCT (2012), s. 15-23 ISSN 1044-5803 Institutional support: RVO:68081723 Keywords : martensitic/austenitic weldment * T91/TP316H * Ni-based weld metal Subject RIV: JG - Metallurgy Impact factor: 1.880, year: 2012

  19. Chromatin enrichment of histone marks H4Ac and H3K9me3 in TP53 gene domain in breast cells

    Directory of Open Access Journals (Sweden)

    Santos G. C. Jr

    2014-05-01

    Full Text Available In non-cancerous breast cell lines HB2 and MCF10A the TP53 gene is localized inside a relatively small ~ 50 kb loop domain delimited by two S/MARs. Aim. To analyze the chromatin markers H4Ac and H3K9me3 of these two S/MARs and of the TP53 gene P1 promoter in different breast cells lines. Methods. We used chromatin immunoprecipitation (ChIP to characterize the chromatin status of these S/MARs elements in breast non-cancerous cell lines HB2 and MCF10A and cancerous MCF-7, MDA-MB-231, BT-474 and T47D cell lines, by chromatin enrichment of H4Ac and H3K9me3 epigenetic markers, hallmarks of open and closed chromatin, respectively. Results. We found that these chromatin epigenetic markers are differentially distributed in S/MARs for all analyzed breast cell lines. Conclusions. We found no correlation between S/MARs and chromatin epige- netic status, suggesting that nuclear matrix fixation and chromatin status can be independent. High enrichment of H3K9me3 in the TP53 gene P1 promoter region in MCF-7, could explain lower levels of the TP53 expression, described earlier by our group.

  20. Construction of specific erythromycin resistance mutations in the temperate lactococcal bacteriophage TP901-1 and their use in studies of phage biology

    DEFF Research Database (Denmark)

    Koch, Birgit; Christiansen, Bettina; Evison, Tim

    1997-01-01

    A method for the construction and isolation of specifically designed mutations of the temperate lactococcal phage TP901-1 has been developed. Two different erm-labeled mutants were isolated. One was shown to be defective in lysogenization and excision. The other, showing normal lysogenization, wa...

  1. The TP0796 lipoprotein of Treponema pallidum is a bimetal-dependent FAD pyrophosphatase with a potential role in flavin homeostasis.

    Science.gov (United States)

    Deka, Ranjit K; Brautigam, Chad A; Liu, Wei Z; Tomchick, Diana R; Norgard, Michael V

    2013-04-19

    Treponema pallidum, an obligate parasite of humans and the causative agent of syphilis, has evolved the capacity to exploit host-derived metabolites for its survival. Flavin-containing compounds are essential cofactors that are required for metabolic processes in all living organisms, and riboflavin is a direct precursor of the cofactors FMN and FAD. Unlike many pathogenic bacteria, Treponema pallidum cannot synthesize riboflavin; we recently described a flavin-uptake mechanism composed of an ABC-type transporter. However, there is a paucity of information about flavin utilization in bacterial periplasms. Using a discovery-driven approach, we have identified the TP0796 lipoprotein as a previously uncharacterized Mg(2+)-dependent FAD pyrophosphatase within the ApbE superfamily. TP0796 probably plays a central role in flavin turnover by hydrolyzing exogenously acquired FAD, yielding AMP and FMN. Biochemical and structural investigations revealed that the enzyme has a unique bimetal Mg(2+) catalytic center. Furthermore, the pyrophosphatase activity is product-inhibited by AMP, indicating a possible role for this molecule in modulating FMN and FAD levels in the treponemal periplasm. The ApbE superfamily was previously thought to be involved in thiamine biosynthesis, but our characterization of TP0796 prompts a renaming of this superfamily as a periplasmic flavin-trafficking protein (Ftp). TP0796 is the first structurally and biochemically characterized FAD pyrophosphate enzyme in bacteria. This new paradigm for a bacterial flavin utilization pathway may prove to be useful for future inhibitor design.

  2. [18F]FLT PET for Non-Invasive Assessment of Tumor Sensitivity to Chemotherapy: Studies with Experimental Chemotherapy TP202377 in Human Cancer Xenografts in Mice

    DEFF Research Database (Denmark)

    Jensen, Mette Munk; Erichsen, Kamille Dumong; Björkling, Fredrik

    2012-01-01

    3'-deoxy-3'-[¹⁸F]fluorothymidine ([18F]FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use [18F]FLT positron emission tomography (PET) to study non-invasively early anti-proliferative effects of the experimental chemotherapeutic agent TP202377 in both...

  3. Radiomics Strategy for Molecular Subtype Stratification of Lower-Grade Glioma: Detecting IDH and TP53 Mutations Based on Multimodal MRI.

    Science.gov (United States)

    Zhang, Xi; Tian, Qiang; Wang, Liang; Liu, Yang; Li, Baojuan; Liang, Zhengrong; Gao, Peng; Zheng, Kaizhong; Zhao, Bofeng; Lu, Hongbing

    2018-02-02

    Noninvasive detection of isocitrate dehydrogenase (IDH) and TP53 mutations are meaningful for molecular stratification of lower-grade gliomas (LrGG). To explore potential MRI features reflecting IDH and TP53 mutations of LrGG, and propose a radiomics strategy for detecting them. Retrospective, radiomics. A total of 103 LrGG patients were separated into development (n = 73) and validation (n = 30) cohorts. T 1 -weighted (before and after contrast-enhanced), T 2 -weighted, and fluid-attenuation inversion recovery images from 1.5T (n = 37) or 3T (n = 66) scanners. After data preprocessing, high-throughput features were derived from patients' volumes of interests of different sequences. The support vector machine-based recursive feature elimination (SVM-RFE) was adopted to find the optimal features for IDH and TP53 mutation detection. SVM models were trained and tested on development and validation cohort. The commonly used metric was used for assessing the efficiency. One-way analysis of variance (ANOVA), chi-square, or Fisher's exact test were applied on clinical characteristics to confirm whether significant differences exist between three molecular subtypes decided by IDH and TP53 status. Intraclass correlation coefficients were calculated to assess the robustness of the radiomics features. The constituent ratio of histopathologic subtypes was significantly different among three molecular subtypes (P = 0.017). SVM models for detecting IDH and TP53 mutation were established using 12 and 22 optimal features selected by SVM-RFE. The accuracies and area under the curves for IDH and TP53 mutations on the development cohort were 84.9%, 0.830, and 92.0%, 0.949, while on the validation cohort were 80.0%, 0.792, and 85.0%, 0.869, respectively. Furthermore, the stratified accuracies of three subtypes were 72.8%, 71.9%, and 70%, respectively. Using a radiomics approach integrating SVM model and multimodal MRI features, molecular subtype stratification of

  4. The association of TP53 mutations with the resistance of colorectal carcinoma to the insulin-like growth factor-1 receptor inhibitor picropodophyllin

    International Nuclear Information System (INIS)

    Wang, Quan; Wei, Feng; Lv, Guoyue; Li, Chunsheng; Liu, Tongjun; Hadjipanayis, Costas G; Zhang, Guikai; Hao, Chunhai; Bellail, Anita C

    2013-01-01

    There is growing evidence indicating the insulin-like growth factor 1 receptor (IGF-1R) plays a critical role in the progression of human colorectal carcinomas. IGF-1R is an attractive drug target for the treatment of colon cancer. Picropodophyllin (PPP), of the cyclolignan family, has recently been identified as an IGF-1R inhibitor. The aim of this study is to determine the therapeutic response and mechanism after colorectal carcinoma treatment with PPP. Seven colorectal carcinoma cell lines were treated with PPP. Following treatment, cells were analyzed for growth by a cell viability assay, sub-G1 apoptosis by flow cytometry, caspase cleavage and activation of AKT and extracellular signal-regulated kinase (ERK) by western blot analysis. To examine the in vivo therapeutic efficacy of PPP, mice implanted with human colorectal carcinoma xenografts underwent PPP treatment. PPP treatment blocked the phosphorylation of IGF-1R, AKT and ERK and inhibited the growth of TP53 wild-type but not mutated colorectal carcinoma cell lines. The treatment of PPP also induced apoptosis in TP53 wild-type cells as evident by the presence of sub-G1 cells and the cleavage of caspase-9, caspase-3, DNA fragmentation factor-45 (DFF45), poly (ADP-ribose) polymerase (PARP), and X-linked inhibitor of apoptosis protein (XIAP). The loss of BAD phosphorylation in the PPP-treated TP53 wild type cells further suggested that the treatment induced apoptosis through the BAD-mediated mitochondrial pathway. In contrast, PPP treatment failed to induce the phosphorylation of AKT and ERK and caspase cleavage in TP53 mutated colorectal carcinoma cell lines. Finally, PPP treatment suppressed the growth of xenografts derived from TP53 wild type but not mutated colorectal carcinoma cells. We report the association of TP53 mutations with the resistance of treatment of colorectal carcinoma cells in culture and in a xenograft mouse model with the IGF-1R inhibitor PPP. TP53 mutations often occur in colorectal

  5. BRCA1-mutated and basal-like breast cancers have similar aCGH profiles and a high incidence of protein truncating TP53 mutations

    International Nuclear Information System (INIS)

    Holstege, Henne; Horlings, Hugo M; Velds, Arno; Langerød, Anita; Børresen-Dale, Anne-Lise; Vijver, Marc J van de; Nederlof, Petra M; Jonkers, Jos

    2010-01-01

    Basal-like breast cancers (BLBC) are aggressive breast cancers for which, so far, no targeted therapy is available because they typically lack expression of hormone receptors and HER2. Phenotypic features of BLBCs, such as clinical presentation and early age of onset, resemble those of breast tumors from BRCA1-mutation carriers. The genomic instability of BRCA1-mutated tumors can be effectively targeted with DNA-damaging agents and poly-(ADP-ribose) polymerase 1 (PARP1) inhibitors. Molecular similarities between BLBCs and BRCA1-mutated tumors may therefore provide predictive markers for therapeutic response of BLBCs. There are several known molecular features characteristic for BRCA1-mutated breast tumors: 1) increased numbers of genomic aberrations, 2) a distinct pattern of genomic aberrations, 3) a high frequency of TP53 mutations and 4) a high incidence of complex, protein-truncating TP53 mutations. We compared the frequency of TP53 mutations and the pattern and amount of genomic aberrations between BRCA1-mutated breast tumors, BLBCs and luminal breast tumors by TP53 gene sequencing and array-based comparative genomics hybridization (aCGH) analysis. We found that the high incidence of protein truncating TP53 mutations and the pattern and amount of genomic aberrations specific for BRCA1-mutated breast tumors are also characteristic for BLBCs and different from luminal breast tumors. Complex, protein truncating TP53 mutations in BRCA1-mutated tumors may be a direct consequence of genomic instability caused by BRCA1 loss, therefore, the presence of these types of TP53 mutations in sporadic BLBCs might be a hallmark of BRCAness and a potential biomarker for sensitivity to PARP inhibition. Also, our data suggest that a small subset of genomic regions may be used to identify BRCA1-like BLBCs. BLBCs share molecular features that were previously found to be specific for BRCA1-mutated breast tumors. These features might be useful for the identification of tumors with

  6. Haplotype analysis of TP53 polymorphisms, Arg72Pro and Ins16, in BRCA1 and BRCA2 mutation carriers of French Canadian descent

    International Nuclear Information System (INIS)

    Cavallone, Luca; Arcand, Suzanna L; Maugard, Christine; Ghadirian, Parviz; Mes-Masson, Anne-Marie; Provencher, Diane; Tonin, Patricia N

    2008-01-01

    The TP53 polymorphisms Arg72Pro (Ex4+199 G>C) and Ins16 (IVS3+24 ins16) have been proposed to modify risk of breast cancer associated with germline BRCA1 and BRCA2 mutations. Allele frequencies of these polymorphisms were investigated to determine if they modify risk in BRCA mutation carriers in breast cancer cases drawn from French Canadian cancer families, a population shown to exhibit strong founder effects. The frequencies of the TP53 alleles, genotypes and haplotypes of 157 index breast cancer cases comprised of 42 BRCA1 mutation carriers, 57 BRCA2 mutation carriers, and 58 BRCA mutation-negative cases, where each case was drawn from independently ascertained families were compared. The effect of TP53 variants on the age of diagnosis was also investigated for these groups. The TP53 polymorphisms were also investigated in 112 women of French Canadian descent with no personal history of cancer. The BRCA mutation-positive groups had the highest frequency of homozygous carriers of the 72Pro allele compared with mutation-negative group. The TP53 polymorphisms exhibited linkage disequilibrium (p < 0.001), where the 72Arg and Ins16minus alleles occurred in strong disequilibrium. The highest frequency of carriers of Ins16minus-72Arg haplotype occurred in the BRCA mutation-negative groups. The BRCA1 mutation carriers homozygous for the 72Pro allele had the youngest ages of diagnosis of breast cancer. However none of these observations were statistically significant. In contrast, the BRCA2 mutation carriers homozygous for the 72Pro allele had a significantly older age of diagnosis of breast cancer (p = 0.018). Moreover, in this group, the mean age of diagnosis of breast cancer in carriers of the Ins16minus-72Arg haplotype was significantly younger than that of the individuals who did not this carry this haplotype (p = 0.009). We observed no significant association of breast cancer risk with TP53 genetic variants based on BRCA1/2 mutation carrier status. Although the

  7. Entretenimiento, espiritualidad, familia y la influencia de pares universitarios en el consumo de drogas

    Directory of Open Access Journals (Sweden)

    Aydee Rivera de Parada

    2015-01-01

    Full Text Available El objetivo del estudio fue examinar la relación de los factores socio-culturales de familia, entretenimiento y espiritualidad y la influencia de pares y el consumo de drogas entre los estudiantes universitarios. Estudio es multicéntrico, con un diseño transversal, participaron 250 estudiantes de una universidad en San Salvador, El Salvador. Se realizaron análisis porcentuales, pruebas de asociación y correlación. Se encontró que los factores socioculturales de familia y espiritualidad podrían estar protegiendo ya que la mayoría 80% valoran positivamente estos dos valores. La mayoría de estudiantes consumen muy poco drogas ilícitas, marihuana 2%, cocaína 1% y anfetaminas 1.2%; pero consume más las drogas lícitas alcohol 42%, tabaco 21%.

  8. Influencia del yeso sobre la velocidad de hidratación del cemento portland

    Directory of Open Access Journals (Sweden)

    Yamaguchi, G.

    1961-12-01

    Full Text Available Not availablePara esclarecer la Influencia del yeso sobre el fraguado y endurecimiento del cemento, los autores estudiaron el grado de hidratación de los cuatro principales minerales del clínker de cemento Portland y el efecto del yeso sobre ellas. Haciendo uso del análisis cuantitativo de rayos X, se determinó la porción no hidratada. Simultáneamente, se determinaron los tiempos de fraguado y las resistencias. Los ensayos se llevaron a cabo sobre tres clínkeres sintéticos de diferentes composiciones y sobre dos clínkeres de cemento Portland comerciales.

  9. La Doctrina del Secondary Meaning, su influencia en los sistemas constitutivos de derechos marcarios.

    Directory of Open Access Journals (Sweden)

    Javier Romero Calero

    2009-06-01

    Full Text Available El presente trabajo aborda, teniendo como referencia la legislación cubana, la esencia de la doctrina del secondary meaning o distintividad sobrevenida, así como su influencia en el sistema constitutivo de derecho marcario, considerándose acertado el hecho de que el legislador nacional prevea en el articulado del decreto Ley 203 de marcas y otros signos distintivos de 2000, que dos de las prohibiciones absolutas establecidas en dicho cuerpo legal puedan ser convalidadas, por adquirir el signo, que ad initio fue denegado, aptitud distintiva con relación a los productos o servicios a los que se destina dado el uso de éste en el comercio, sin que esto entre en contradicción con el sistema constitutivo de adquisición de derechos que prevalece en el ordenamiento jurídico nacional.

  10. Influencia de curso pre cálculo en ecuaciones diferenciales y desarrollo de pensamiento variacional

    Directory of Open Access Journals (Sweden)

    Mawency Vergel Ortega

    2018-01-01

    Full Text Available La investigación sigue un enfoque cuantitativo con apoyo del enfoque cualitativo, descriptivo, diseño cuasi experimental. En esta investigación se plantearon los objetivos: estudiar si mejoran las competencias en pensamiento variacional y didácticas de los estudiantes con la utilización de curso precálculo utilizando plataforma virtual respecto a enseñanza tradicional; examinar la influencia en desarrollo del pensamiento matemático y su enseñanza; así como analizar qué tipología de alumnos obtiene mejores resultados en relación a su nivel de competencia digital. Se han obtenido los siguientes avances: el grupo experimental ha obtenido una mejora estadísticamente significativa de sus competencias interpretativas y de pensamiento matemático respecto al grupo control.

  11. La influencia del liderazgo sobre el aprendizaje. El papel mediador del contexto organizativo

    Directory of Open Access Journals (Sweden)

    Susana Pérez López

    2012-09-01

    Full Text Available En este trabajo se analiza la relación existente entre liderazgo y aprendizaje organizativo. Con apoyo en investigaciones previas, se plantea un modelo cuya premisa básica es que la relación entre ambos conceptos es directa e indirecta, en la medida en que el liderazgo influye sobre el contexto organizativo en que se desarrolla el aprendizaje. El presente modelo teórico ha sido contrastado empíricamente a partir de una muestra de 162 empresas españolas, confirmándose la influencia del liderazgo sobre la cultura organizativa y el desarrollo de las políticas de recursos humanos, factores que, a su vez, influyen sobre el aprendizaje. Sin embargo, la relación directa entre liderazgo y aprendizaje organizativo no se confirma. Las implicaciones del estudio, limitaciones y futuras líneas de investigación son discutidas en el trabajo.

  12. Influencia de variables psicológicas en el rendimiento de jugadores amateurs de golf

    Directory of Open Access Journals (Sweden)

    Susana Irazusta

    2006-01-01

    Full Text Available El propósito de la presente investigación es analizar las variaciones del estado de ánimo intracompetición en los jugadores amateurs de golf, así como analizar la influencia que tiene el grado de confianza y otras variables motivacionales en el resultado de la competición. Se realizó la investigación con un total de 296 jugadores y se pasaron los cuestionarios a cada jugador en tres momentos, antes, durante y después de la competición.Una vez analizados los datos se constató que existen grandes fluctuaciones en el estado de ánimo de los jugadores y que el resultado esperado sufre modificaciones a lo largo de la competición.

  13. Human Papillomavirus 16 Infection and TP53 Mutation: Two Distinct Pathogeneses for Oropharyngeal Squamous Cell Carcinoma in an Eastern Chinese Population.

    Science.gov (United States)

    Wang, Zhen; Xia, Rong-Hui; Ye, Dong-Xia; Li, Jiang

    2016-01-01

    To investigate the clinicopathological characteristics, human papillomavirus (HPV) infection, p53 expression, and TP53 mutations in oropharyngeal squamous cell carcinoma (OPSCC) and determine their utility as prognostic predictors in a primarily eastern Chinese population. The HPV infection status was tested via p16INK4A immunohistochemistry and validated using PCR, reverse blot hybridization and in situ hybridization (ISH) in 188 OPSCC samples. p53 expression levels and TP53 gene mutations were assessed through immunohistochemistry and sequencing, respectively. Clinicopathological characteristics and follow-up information were collected. Overall survival was estimated using the Log-rank test. Overall, 22 of the 188 OPSCC samples were associated with HPV infection. HPV16 was identified in all 22 samples, whereas no samples were positive for HPV18. All 22 HPV-associated OPSCC samples were p53 negative and lacked TP53 mutations. HPV16 positivity, female patients, non-smokers, and patients with histological grade I and stage N0 diseases showed better overall survival (p = 0.009, 0.003, 0.048, 0.009, and 0.004, respectively). No significant differences in overall survival between smoking and non-smoking patients were observed in the HPV-associated OPSCC group. Patients without mutations in TP53 exons 5-8 had better prognoses (p = 0.031) among the 43 sequenced specimens. Multivariate analysis indicated that HPV16 infection status (p = 0.011), histological grade (p = 0.017), and N stage (p = 0.019) were independent prognostic factors for patients with OPSCC. Distinct from the situation in Europe and America, for the patients with OPSCC in this study, HPV16 infection was relatively low, although it was still the most important independent prognostic predictor for the disease. In addition to the high smoking and drinking rate in this population, HPV16 infection and TP53 dysfunction appear to be two distinct pathogens for OPSCC patients in the eastern Chinese population.

  14. TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma—evidence supporting the clonal relationship of the two lesions

    Science.gov (United States)

    Kuhn, Elisabetta; Kurman, Robert J; Vang, Russell; Sehdev, Ann Smith; Han, Guangming; Soslow, Robert; Wang, Tian-Li; Shih, Ie-Ming

    2016-01-01

    Serous tubal intraepithelial carcinomas (STICs) have been proposed to be the most likely precursor of ovarian, tubal and ‘primary peritoneal’ (pelvic) high-grade serous carcinoma (HGSC). As somatic mutation of TP53 is the most common molecular genetic change of ovarian HGSC, occurring in more than 95% of cases, we undertook a mutational analysis of 29 pelvic HGSCs that had concurrent STICs to demonstrate the clonal relationship of STICs and HGSCs. In addition, we correlated the mutational data with p53 immunostaining to determine the role of p53 immunoreactivity as a surrogate for TP53 mutations in histological diagnosis. Somatic TP53 mutations were detected in all 29 HGSCs analysed and the identical mutations were detected in 27 of 29 pairs of STICs and concurrent HGSCs. Missense mutations were observed in 61% of STICs and frameshift/splicing junction/nonsense mutations in 39%. Interestingly, there were two HGSCs with two distinctly different TP53 mutations each, but only one of the mutations was detected in the concurrent STICs. Missense mutations were associated with intense and diffuse (≥ 60%) p53 nuclear immunoreactivity, while most of the null mutations were associated with complete loss of p53 staining (p STIC and pelvic HGSC and demonstrate the utility of p53 immunostaining as a surrogate for TP53 mutation in the histological diagnosis of STIC. In this regard, it is important to appreciate the significance of different staining patterns. Specifically, strong diffuse staining correlates with a missense mutation, whereas complete absence of staining correlates with null mutations. PMID:21990067

  15. TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma--evidence supporting the clonal relationship of the two lesions.

    Science.gov (United States)

    Kuhn, Elisabetta; Kurman, Robert J; Vang, Russell; Sehdev, Ann Smith; Han, Guangming; Soslow, Robert; Wang, Tian-Li; Shih, Ie-Ming

    2012-02-01

    Serous tubal intraepithelial carcinomas (STICs) have been proposed to be the most likely precursor of ovarian, tubal and 'primary peritoneal' (pelvic) high-grade serous carcinoma (HGSC). As somatic mutation of TP53 is the most common molecular genetic change of ovarian HGSC, occurring in more than 95% of cases, we undertook a mutational analysis of 29 pelvic HGSCs that had concurrent STICs to demonstrate the clonal relationship of STICs and HGSCs. In addition, we correlated the mutational data with p53 immunostaining to determine the role of p53 immunoreactivity as a surrogate for TP53 mutations in histological diagnosis. Somatic TP53 mutations were detected in all 29 HGSCs analysed and the identical mutations were detected in 27 of 29 pairs of STICs and concurrent HGSCs. Missense mutations were observed in 61% of STICs and frameshift/splicing junction/nonsense mutations in 39%. Interestingly, there were two HGSCs with two distinctly different TP53 mutations each, but only one of the mutations was detected in the concurrent STICs. Missense mutations were associated with intense and diffuse (≥ 60%) p53 nuclear immunoreactivity, while most of the null mutations were associated with complete loss of p53 staining (p STIC and pelvic HGSC and demonstrate the utility of p53 immunostaining as a surrogate for TP53 mutation in the histological diagnosis of STIC. In this regard, it is important to appreciate the significance of different staining patterns. Specifically, strong diffuse staining correlates with a missense mutation, whereas complete absence of staining correlates with null mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. TP53 hot spot mutations in ovarian cancer: selective resistance to microtubule stabilizers in vitro and differential survival outcomes from The Cancer Genome Atlas.

    Science.gov (United States)

    Seagle, Brandon-Luke L; Yang, Chia-Ping Huang; Eng, Kevin H; Dandapani, Monica; Odunsi-Akanji, Oluwatosin; Goldberg, Gary L; Odunsi, Kunle; Horwitz, Susan Band; Shahabi, Shohreh

    2015-07-01

    To test if TP53 hot spot mutations (HSMs) confer differential chemotherapy resistance or survival outcomes, the effects of microtubule stabilizers on human ovarian carcinoma cells (OCCs) expressing TP53 HSMs were studied in vitro. Survival outcomes of patients with high grade serous epithelial ovarian carcinoma (HGS EOC) expressing matched HSMs were compared using The Cancer Genome Atlas (TCGA) data. Growth inhibition of OCCs transfected with a HSM (m175, m248 or m273) was measured during treatment with paclitaxel, epothilone B (epoB), or ixabepilone. Effects of epoB on p53 expression, phosphorylation, and acetylation, as well as p53-regulated expression of p21 and mdm2 proteins, were determined by Western blot analysis. Expression of p53 target genes P21, GADD45, BAX, PIDD, NF-kB2, PAI-1, and MDR1 was measured by RT-PCR. cBioPortal.org identified patients with codon R175, R248 or R273 HSMs from TCGA data. Survival outcomes were characterized. p53-m248 confers chemoresistance and is not acetylated during epoB treatment. m273 demonstrated high MDR1 expression and resistance to paclitaxel. P21, GADD45 and PAI-1 expression were down-regulated in mutant OCCs. Optimally cytoreduced patients with codon R273 (n=17), R248 (n=13), R175 (n=7) HSMs, or any other TP53 mutation demonstrated median 14.9, 17.6, 17.8 and 16.9months (p=0.806) progression free survival and 84.1, 33.6, 62.1 and 44.5months (p=0.040) overall survival, respectively. Human OCCs harboring different TP53 HSMs were selectively resistant to microtubule stabilizers. Patients with different HSMs had significantly different overall survival. Both in vitro data and clinical experience support further studying the outcomes of particular TP53 HSMs. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Lack of relationship between PTEN 32-bp and TP53 16-bp Ins/Del polymorphisms and chronic hepatitis B virus infection.

    Science.gov (United States)

    Eskandari, Ebrahim; Dahmardeh, Tayebeh; Dahmardeh, Fatemeh; Pahlevani, Elham; Metanat, Malihe

    2017-09-01

    TP53 and phosphate and tension homolog (PTEN) are two tumor suppressor genes that regulate cell proliferation, migration, and death. P53 and PTEN deficiency has been associated with hepatic fibrosis, a prominent pathological feature associated with chronic hepatitis B (CHB). The present study is aimed to assess the association of PTEN 32-bp Ins/Del (rs34421660) and TP53 16-bp Ins/Del polymorphisms with CHB infection susceptibility. A total of 411 subjects were recruited in this case-control study of 213 patients with CHB infection and 198 healthy individuals as controls. PTEN and TP53 deletions were detected by polymerase chain reaction method. We found no significant association between PTEN 32-bp Ins/Del polymorphism and the risk for CHB using either of codominant (Ins/Del vs. Ins/Ins: P  = 0.427; Del/Del vs. Ins/Ins: P  = 0.235), dominant (Ins/Del + Del/Del vs. Ins/Ins P  = 0.343) or recessive genetic model (Del/Del vs. Ins/Ins + Ins/Del: P  = 0.516). At allelic level although the PTEN Del variant allele was more common in CHB patients compared to controls (55 vs. 51), but the difference did not reach the statistical significant range (OR 0.87, P  = 0.327). Similarly, no association was observed between TP53 16-bp Ins/Del and the risk for CHB infection at both genotype and allele levels ( P  > 0.05). In summary, our study demonstrated that the PTEN 32-bp and TP53 16-bp Ins/Del polymorphisms did not affect the risk of CHB infection in the Iranian population.

  18. Influencia del medio familiar en niños con conductas agresivas

    Directory of Open Access Journals (Sweden)

    Nilo Valentín Noroño Morales

    2002-06-01

    Full Text Available Se realizó un estudio descriptivo, sobre la influencia del medio familiar en niños de 9 a 11 años, con conductas agresivas, evaluados y diagnosticados en el Departamento de Psicología del Policlínico " Dr. Tomás Romay"; la muestra estuvo conformada además, por los padres de estos niños. A todos ellos se les aplicó una serie de técnicas con el objetivo principal de describir las características del medio familiar y su influencia en las conductas agresivas de los infantes. Se concluyó en que como características del medio familiar predominaron las familias disfuncionales incompletas, con manifestaciones de agresividad, alcoholismo, mala integración social y familiar, rechazo hacia los hijos e irresponsabilidad en su cuidado y atención.A descriptive study of the influence of the family environment on children aged 9-11 years old, evaluated and diagnosed at the Psychology Department of "Dr Tomás Romay" polyclinics, was carried out. The children´s parents were also part of the sample. All of them were applied a series of techniques to find out the characteristics of the family environment and its influence on children´s aggressive behaviors. It was concluded that the predominant characteristics were uncompleted dysfunctional families with manifestations of aggressiveness, alcoholism, poor social and family integration, rejection to children and lack of responsibility in relation to their care and attention.

  19. Influencia del clima escolar y familiar en adolescentes, víctimas de ciberacoso

    Directory of Open Access Journals (Sweden)

    Jessica Ortega Barón

    2016-01-01

    Full Text Available El ciberacoso es un fenómeno de creciente preocupación social que afecta cada vez más a niños y adolescentes de todos los países desarrollados. A diferencia de la considerable literatura que hay sobre las relaciones entre el acoso escolar y el contexto familiar y escolar, todavía hay pocos trabajos sobre la influencia de estos entornos sociales en el problema del ciberacoso. Mediante una metodología cuantitativa, el objetivo principal del presente estudio fue analizar la influencia del contexto escolar y familiar en víctimas de ciberacoso. La muestra estuvo formada por 1.062 adolescentes (51,5% chicos y 48,5% chicas, de edades comprendidas entre los 12 y los 18 años (M=14,5; DT=1,62. Se establecieron tres grupos de contraste: cibervíctimas severas, cibervíctimas moderadas y no víctimas de ciberacoso. Los resultados del análisis de varianza indicaron que las cibervíctimas severas en comparación con las no víctimas puntúan significativamente más alto en conflicto familiar y obtienen puntuaciones más bajas en el resto de variables familiares (autoestima familiar, cohesión y expresividad, y variables escolares (implicación, afiliación y ayuda al profesor, consideradas en el estudio. Los análisis de regresión revelaron que la autoestima académica y familiar y algunas dimensiones del clima familiar y escolar predicen la cibervictimización en la adolescencia. Estos novedosos resultados muestran la importancia de incluir a la familia y a la escuela en los programas de prevención del ciberacoso.

  20. Influencia de la actividad física y la alimentación equilibrada en la mejora de la calidad de vida /

    OpenAIRE

    Vidaurrazaga Dobaran, Andoni

    2013-01-01

    Se estudia la influencia que la actividad física tiene en la calidad de vida de las personas. Es de sobra conocido que vivir de forma saludable es beneficioso para la salud pero se trata de esclarecer qué entendemos por “vivir de forma saludable” y cuál puede ser su influencia en el mantenimiento y mejora de la calidad de vida de las personas

  1. Frequent mutations in EGFR, KRAS and TP53 genes in human lung cancer tumors detected by ion torrent DNA sequencing.

    Directory of Open Access Journals (Sweden)

    Xin Cai

    Full Text Available Lung cancer is the most common malignancy and the leading cause of cancer deaths worldwide. While smoking is by far the leading cause of lung cancer, other environmental and genetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive lung cancer molecular profile is essential for developing more effective, tailored therapies. Until recently, personalized DNA sequencing to identify genetic mutations in cancer was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 76 human lung cancer samples. The sequencing analysis revealed missense mutations in KRAS, EGFR, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

  2. Precipitation behavior and martensite lath coarsening during tempering of T/P92 ferritic heat-resistant steel

    Science.gov (United States)

    Xu, Lin-qing; Zhang, Dan-tian; Liu, Yong-chang; Ning, Bao-qun; Qiao, Zhi-xia; Yan, Ze-sheng; Li, Hui-jun

    2014-05-01

    Tempering is an important process for T/P92 ferritic heat-resistant steel from the viewpoint of microstructure control, as it facilitates the formation of final tempered martensite under serving conditions. In this study, we have gained deeper insights on the mechanism underlying the microstructural evolution during tempering treatment, including the precipitation of carbides and the coarsening of martensite laths, as systematically analyzed by optical microscopy, transmission electron microscopy, and high-resolution transmission electron microscopy. The chemical composition of the precipitates was analyzed using energy dispersive X-ray spectroscopy. Results indicate the formation of M3C (cementite) precipitates under normalized conditions. However, they tend to dissolve within a short time of tempering, owing to their low thermal stability. This phenomenon was substantiated by X-ray diffraction analysis. Besides, we could observe the precipitation of fine carbonitrides (MX) along the dislocations. The mechanism of carbon diffusion controlled growth of M23C6 can be expressed by the Zener's equation. The movement of Y-junctions was determined to be the fundamental mechanism underlying the martensite lath coarsening process. Vickers hardness was estimated to determine their mechanical properties. Based on the comprehensive analysis of both the micro-structural evolution and hardness variation, the process of tempering can be separated into three steps.

  3. TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients

    Science.gov (United States)

    Caceres, Gisela; McGraw, Kathy; Yip, Bon Ham; Pellagatti, Andrea; Johnson, Joseph; Zhang, Ling; Liu, Kenian; Zhang, Lan Min; Fulp, William J.; Lee, Ji-Hyun; Al Ali, Najla H.; Basiorka, Ashley; Smith, Larry J.; Daugherty, F. Joseph; Littleton, Neil; Wells, Richard A.; Sokol, Lubomir; Wei, Sheng; Komrokji, Rami S.; Boultwood, Jacqueline; List, Alan F.

    2013-01-01

    Stabilization of p53 in erythroid precursors in response to nucleosomal stress underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically active 20-mer antisense oligonucleotide complementary to TP53 exon10, could suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced cellular p53 and p53-up-regulated modulator of apoptosis expression compared with controls, accompanied by a significant reduction in apoptosis and increased cell proliferation. In a two-stage erythroid differentiation assay, cenersen significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from patients with del(5q) MDS, whereas erythroid burst recovery increased proportionally to the magnitude of p53 suppression without evidence of del(5q) clonal suppression (r = −0.6; P = 0.005). To explore the effect of p53 suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor-dependent p53 antagonist, was added to lenalidomide treatment in eight lower-risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance. Transfusion independence was restored in five patients accompanied by expansion of erythroid precursors and decreased cellular p53 expression. We conclude that targeted suppression of p53 could support effective erythropoiesis in lenalidomide-resistant del(5q) MDS. PMID:24043769

  4. Kinetic rates and mass balance of COD, TKN, and TP using SBR treating domestic and industrial wastewater.

    Science.gov (United States)

    Warodomrungsimun, Chaowalit; Fongsatitkul, Prayoon

    2009-12-01

    To assess the performance of SBR to treat three different types of wastewater from domestic, hospital, slaughterhouse and investigate the kinetic rates of active biomass. Mass balance calculation of COD, TKN and TP was further performed to explain the mechanisms of the biological nutrient removals processed in the SBR system. The measured kinetic rates were in turn used to evaluate the process performances under different types of wastewater. Experimental research involving 3 similar SBR lab-scales were installed and operated at the Sanitary Engineering Laboratory. The reactors were seeded with sludge biomass obtained from the Sri-Phraya Domestic Wastewater Treatment Plant in Bangkok. The slaughterhouse, hospital and domestic wastewaters were treated by SBR system for biological organic carbon (COD), nitrogen (TKN) and phosphorus removals. Biological methods for kinetic rates evaluation were conducted in five replicated batch tests. The removal efficiencies of COD and TKN were greater than 90% for all three types of wastewater while the biological phosphorus removal for domestic and hospital wastewaters were less than 60% and phosphorus removal for slaughterhouse exceeded 95%. The kinetic rates of nitrification and denitrification of hospital wastewater was lower than those the domestic and slaughterhouse wastewaters. Phosphorus release and uptake rates of slaughterhouse wastewater were high but domestic and hospital wastewaters were very low. The result of system removal efficiency and batch test for kinetic rates confirmed that the domestic and hospital wastewaters were in deficiency of organic carbon with respect to its ability to support successful biological phosphorus removal.

  5. A Homology Model Reveals Novel Structural Features and an Immunodominant Surface Loop/Opsonic Target in the Treponema pallidum BamA Ortholog TP_0326.

    Science.gov (United States)

    Luthra, Amit; Anand, Arvind; Hawley, Kelly L; LeDoyt, Morgan; La Vake, Carson J; Caimano, Melissa J; Cruz, Adriana R; Salazar, Juan C; Radolf, Justin D

    2015-06-01

    We recently demonstrated that TP_0326 is a bona fide rare outer membrane protein (OMP) in Treponema pallidum and that it possesses characteristic BamA bipartite topology. Herein, we used immunofluorescence analysis (IFA) to show that only the β-barrel domain of TP_0326 contains surface-exposed epitopes in intact T. pallidum. Using the solved structure of Neisseria gonorrhoeae BamA, we generated a homology model of full-length TP_0326. Although the model predicts a typical BamA fold, the β-barrel harbors features not described in other BamAs. Structural modeling predicted that a dome comprised of three large extracellular loops, loop 4 (L4), L6, and L7, covers the barrel's extracellular opening. L4, the dome's major surface-accessible loop, contains mainly charged residues, while L7 is largely neutral and contains a polyserine tract in a two-tiered conformation. L6 projects into the β-barrel but lacks the VRGF/Y motif that anchors L6 within other BamAs. IFA and opsonophagocytosis assay revealed that L4 is surface exposed and an opsonic target. Consistent with B cell epitope predictions, immunoblotting and enzyme-linked immunosorbent assay (ELISA) confirmed that L4 is an immunodominant loop in T. pallidum-infected rabbits and humans with secondary syphilis. Antibody capture experiments using Escherichia coli expressing OM-localized TP_0326 as a T. pallidum surrogate further established the surface accessibility of L4. Lastly, we found that a naturally occurring substitution (Leu(593) → Gln(593)) in the L4 sequences of T. pallidum strains affects antibody binding in sera from syphilitic patients. Ours is the first study to employ a "structure-to-pathogenesis" approach to map the surface topology of a T. pallidum OMP within the context of syphilitic infection. Previously, we reported that TP_0326 is a bona fide rare outer membrane protein (OMP) in Treponema pallidum and that it possesses the bipartite topology characteristic of a BamA ortholog. Using a homology

  6. INFLUENCIA DE LA PRESIÓN ATMOSFÉRICA EN LAS TRANSMISIONES A FRECUENCIA 2.4 GHz

    OpenAIRE

    González Romero, Pedro Vicente; Espina Ávila, Luis Gerardo

    2012-01-01

    La presente investigación se planteó como propósito fundamental determinar la influencia de la presión atmosférica sobre una señal transmitida en una frecuencia de 2.4 GHz. La investigación es de tipo explicativa, con diseño metodológico experimental. Mediante ella se obtiene la atenuación de una señal de 2.4GHz a diferentes presiones atmosféricas y se determinan las gráficas que muestran el comportamiento observado. Como resultado de esta investigación se observó que sí existe una influencia...

  7. Influencia de la autoestima y del apoyo social percibido sobre el bienestar psicológico de estudiantes universitarios chilenos

    Directory of Open Access Journals (Sweden)

    Enrique Barra Almagia

    2012-01-01

    Full Text Available El presente estudio, de tipo correlacional transeccional, examinó la influencia de la autoestima y del apoyo social percibido sobre el bienestar psicológico, en una muestra de 450 estudiantes de ambos sexos de la Universidad de Concepción, Chile, quienes respondieron las Escalas de Autoestima de Rosenberg, de Bienestar Psicológico de Ryff y el Cuestionario de Apoyo Social Percibido. Se encontró que la autoestima tenía una influencia mayor sobre el bienestar psicológico que el apoyo social percibido. Aunque no hubo diferencias de sexo en el bienestar psicológico global, se observaron diferencias a favor de los hombres en las dimensiones de autoaceptación y autonomía, y a favor de las mujeres, en crecimiento personal, así como diferencias a favor de los hombres en autoestima y a favor de las mujeres en apoyo socialpercibido.

  8. ROL DE LOS RIOS TRIBUTARIOS EN LOS SISTEMAS LACUSTRE Y MARINO COSTERO NOR-PATAGONICOS BAJO INFLUENCIA ANTROPICA

    OpenAIRE

    LEON MUÑOZ, JORGE EDUARDO

    2011-01-01

    Primer Capítulo se abordó la hipótesis específica Hl, analizándose la variabilidad interanual (años 1944- 2007) del régimen hidrológico del río Puelo (41.5°S, Q = 650 m3/seg) y su influencia en la capa superficial del fiordo Reloncaví, uno de los sistemas costeros más importantes para la salmonicultura nacional. La importancia del estudio radicó en analizar la relación río/fiordo en escenarios contrastantes de caudal, ésto permitió registrar cómo la influencia del río Puelo es altamente...

  9. INFLUENCIA DE LOS INVERSIONISTAS INSTITUCIONALES EN LAS DECISIONES DE ESTRUCTURA DE CAPITAL DE LA EMPRESA. Evidencia para un mercado emergente

    Directory of Open Access Journals (Sweden)

    Felipe Araya Sepúlveda

    2015-01-01

    Full Text Available Este artículo analiza empíricamente la influencia de las Administradoras de Fondos de Pensión (AFP como principales accionistas institucionales, sobre las decisiones de estructura de capital de la empresa chilena. Estos inversionistas pueden influir en la estructura de capital mediante distintos papeles como los de monitoreo a la gestión y de recopilación y transferencia de información al mercado. El análisis es desarrollado durante el periodo 2009-2011 para una muestra de 109 empresas chilenas que cotizan en la bolsa. Las AFP no sólo participan en el mercado accionario sino que también compiten por la deuda pública, por lo que nuestros resultados son relevantes al indicar la positiva influencia de este tipo de inversionistas en la contratación y emisión de deuda, particularmente la pública.

  10. Influencia de Las Cargas Térmicas Sobre Flujos de Aire Generados en Una Habitacíon

    DEFF Research Database (Denmark)

    Olmedo, Inés; Ruiz de Adana Santiago, Manuel; Nielsen, Peter V.

    2011-01-01

    El flujo de aire en el interior de un local generado con un sistema de ventilación y difusión de aire puede verse afectado por las cargas térmicas internas del local. En este trabajo, se estudia la influencia de las cargas térmicas internas debidas a personas en el flujo de aire interior de un lo...

  11. Estudio de influencia de variables en la polimerización de bisfenol-acetofenona con difenilcarbonato

    OpenAIRE

    Ginestá Anzola, Anahí

    2008-01-01

    El enfoque de este estudio consiste en determinar experimentalmente la influencia que las distintas variables de operación (temperatura, concentración del catalizador y relación entre reactantes)ejercen en el procesol de policondensación entre el bisfenol acetofenona (AP) y el DPC, para que de esta manera puedan obtenerse las constantes cinéticas de esta reacción. Escuela Técnica Superior de Ingeniería Industrial

  12. Cambios espaciales y su influencia en la configuración territorial de Aguazul y Tauramena 1974–2005

    Directory of Open Access Journals (Sweden)

    Claudia Yolima Devia Acosta

    2011-09-01

    una periodización basada en el cambio en las actividades económicas y en los cambios político-administrativos en la configuración territorial de estos municipios. El artículo centra el análisis en la influencia de la actividad petrolera en la región, y en su capacidad directa e indirecta de transformar el territorio.

  13. Celos y violencia en alumnos de enseñanza secundaria. Influencia de los estilos educativos familiares

    OpenAIRE

    Aymerich Navarro, Mª del Milagro

    2016-01-01

    El objetivo de la tesis consiste en establecer la relación entre los celos en la adolescencia y la influencia de los estilos educativos familiares a la hora de explicar la violencia entre iguales, las reacciones emocionales y las conductas desajustadas de los adolescentes. Las reacciones emocionales se miden con las variables: celos, ansiedad y hostilidad. En cuanto a las reacciones conductuales se maneja como variable el bullying o victimización entre iguales. Con respecto a la variable e...

  14. Influencia del carbono y el cromo en el comportamiento tribológico de aleaciones férreas

    Directory of Open Access Journals (Sweden)

    García, A.

    2005-12-01

    Full Text Available This study compares the abrasive wear resistance of a carbon steel, used in the linings of coal mills, and ferrous alloys with different chromium and carbon content. It also analyses the influence of chromium and carbon content on mechanical properties, such as hardness, and microstructure. The abrasive wear resistance of the different materials was determined by means of ASTM G 105, "Standard Test Method for Conducting Wet Sand/Rubber Wheel Abrasion Test". A blasting test was used to study erosive wear resistance.

    En este estudio se analiza la influencia, en las propiedades tribológicas, del contenido en carbono para distintas aleaciones férreas con similares contenidos en cromo, así como la influencia del cromo cuando el contenido en carbono es semejante. También, se analizó la influencia de estos elementos en propiedades como la dureza y en la microestructura de las aleaciones. Para el estudio tribológico se llevaron a cabo dos ensayos, el ensayo descrito en la norma ASTM G105: Standard Test Method for Conducting Wet Sand/Rubber Wheel Abrasion Test y ensayos de chorreo.

  15. Entretenimiento, espiritualidad, familia y su relación con la influencia de pares en el consumo

    Directory of Open Access Journals (Sweden)

    Rolando Salazar Sarmiento

    2015-01-01

    Full Text Available El presente estudio fue una investigación de tipo exploratorio quantitativa. Examina la relación entre el uso de drogas en estudiantes universitarios de una universidad en Bogotá, Colombia y la influencia del grupo de pares, en torno al efecto moderador de factores socio-culturales como las relaciones familiares, el entretenimiento y la espiritualidad en dicho consumo. La muestra non probabilistica fue conformada por 350 estudiantes. El 89,4% de los jóvenes encuestados reportaran que consumen drogas ilícitas y el 82,2% aceptaran la influencia que los pares en este tipo de conductas. Los más altos consumos se presentan en alcohol con un 91,1% y tabaco con un 37,4%, las drogas de más bajo consumo son la cocaína y las anfetaminas. El consumo de drogas en estudiantes presenta índices elevados, y la influencia de los grupos entre los jóvenes es determinante de muchos de sus comportamientos.

  16. Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia.

    Science.gov (United States)

    Le Bris, Yannick; Struski, Stéphanie; Guièze, Romain; Rouvellat, Caroline; Prade, Naïs; Troussard, Xavier; Tournilhac, Olivier; Béné, Marie C; Delabesse, Eric; Ysebaert, Loïc

    2017-12-01

    Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder of remarkable heterogeneity as demonstrated by cytogenetics and molecular analyses. Complex karyotype (CK), TP53 deletions and/or mutations (TP53 disruption), IGVH mutational status, and, more recently, recurrent somatic mutations have been identified as prognostic markers in CLL. On a cohort of 110 patients with CLL treated with first-line fludarabin, cyclophosphamide, and rituximab treatment compared with 33 untreated (watch and wait) patients with CLL, we report more frequent complex karyotypes (34 vs 15%; P = .05), unmutated IGHV (70 vs 21%; P karyotyping therefore appears to be of value, CK being an additional factor, undetectable in classical FISH, in patients with CLL at the stage when therapy becomes required. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Investigation of single-strand conformational polymorphism of the TP53 gene in women with a family history of breast cancer

    Directory of Open Access Journals (Sweden)

    R.R. Burbano

    2000-11-01

    Full Text Available Breast cancer in families with germ line mutations in the TP53 gene has been described in the medical literature. Mutation screening for susceptibility genes should allow effective prophylactic and preventive measures. Using single-strand conformational polymorphism, we screened for mutations in exons 5, 6, 7 and 8 of gene TP53 in the peripheral blood of 8 young non-affected members (17 to 36 years old of families with a history of breast cancer. Studies of this type on young patients (mean age, 25 years are very rare in the literature. The identification of these mutations would contribute to genetic counseling of members of families with predisposition to breast cancer. The results obtained did not show any polymorphism indicating mutation. In our sample, the familial tumorigenesis is probably related to other gene etiologies.

  18. Advanced Running Performance by Genetic Predisposition in Male Dummerstorf Marathon Mice (DUhTP Reveals Higher Sterol Regulatory Element-Binding Protein (SREBP Related mRNA Expression in the Liver and Higher Serum Levels of Progesterone.

    Directory of Open Access Journals (Sweden)

    Daniela Ohde

    Full Text Available Long-term-selected DUhTP mice represent a non-inbred model for inborn physical high-performance without previous training. Abundance of hepatic mRNA in 70-day male DUhTP and control mice was analyzed using the Affymetrix mouse array 430A 2.0. Differential expression analysis with PLIER corrected data was performed using AltAnalyze. Searching for over-representation in biochemical pathways revealed cholesterol metabolism being most prominently affected in DUhTP compared to unselected control mice. Furthermore, pathway analysis by AltAnalyze plus PathVisio indicated significant induction of glycolysis, fatty acid synthesis and cholesterol biosynthesis in the liver of DUhTP mice versus unselected control mice. In contrast, gluconeogenesis was partially inactivated as judged from the analysis of hepatic mRNA transcript abundance in DUhTP mice. Analysis of mRNA transcripts related to steroid hormone metabolism inferred elevated synthesis of progesterone and reduced levels of sex steroids. Abundance of steroid delta isomerase-5 mRNA (Hsd3b5, FC 4.97 was increased and steroid 17-alpha-monooxygenase mRNA (Cyp17a1, FC -11.6 was massively diminished in the liver of DUhTP mice. Assessment of steroid profiles by LC-MS revealed increased levels of progesterone and decreased levels of sex steroids in serum from DUhTP mice versus controls. Analysis of hepatic mRNA transcript abundance indicates that sterol regulatory element-binding protein-1 (SREBP-1 may play a major role in metabolic pathway activation in the marathon mouse model DUhTP. Thus, results from bioinformatics modeling of hepatic mRNA transcript abundance correlated with direct steroid analysis by mass spectrometry and further indicated functions of SREBP-1 and steroid hormones for endurance performance in DUhTP mice.

  19. TBL1XR1/TP63: a novel recurrent gene fusion in B-cell non-Hodgkin lymphoma | Office of Cancer Genomics

    Science.gov (United States)

    Recently, the landscape of single base mutations in diffuse large B-cell lymphoma (DLBCL) was described. Here we report the discovery of a gene fusion between TBL1XR1 and TP63, the only recurrent somatic novel gene fusion identified in our analysis of transcriptome data from 96 DLBCL cases. Based on this cohort and a further 157 DLBCL cases analyzed by FISH, the incidence in de novo germinal center B cell-like (GCB) DLBCL is 5% (6 of 115).

  20. Adrenocortical carcinoma with extension to the inferior vena cava and right atrium: 20-month-old girl with TP53 mutation

    Directory of Open Access Journals (Sweden)

    Terry L. Levin, MD

    2015-01-01

    Full Text Available A 20-month-old female presented with respiratory distress and a right adrenal mass extending into the inferior vena cava and right atrium. The mass was initially thought to be neuroblastoma. Pathology later revealed adrenocortical carcinoma. Inferior vena cava extension is far more common in adrenocortical carcinoma than neuroblastoma, and its presence should prompt clinical and laboratory evaluation for an adrenocortical tumor. The genetic findings in TP53 associated with this disease are discussed.

  1. Whole-exome analysis of a Li-Fraumeni family trio with a novel TP53 PRD mutation and anticipation profile.

    Science.gov (United States)

    Franceschi, Sara; Spugnesi, Laura; Aretini, Paolo; Lessi, Francesca; Scarpitta, Rosa; Galli, Alvaro; Congregati, Caterina; Caligo, Maria Adelaide; Mazzanti, Chiara Maria

    2017-09-01

    Li-Fraumeni syndrome is a clinically heterogeneous familial cancer predisposition syndrome with autosomal-dominant inheritance caused by heterozygous germline mutations in the TP53 gene. We here analyze the genetic background of a family with a 4-year-proband presented with a Li-Fraumeni tumor. The mother developed breast cancer at age 37 and the proband died at age 8. We performed Sanger sequencing and whole-exome sequencing on peripheral blood DNA from proband and relatives. Data analysis selected only high-quality score and depth reads, rare variants and protein impact involving missense, non-sense, frameshift and splice disrupt mutations. Disease implicated variants and predicted deleterious alterations were also chosen. TP53 genetic testing revealed a never reported TP53 deletion arose as de novo mutation in the mother and inherited by the proband. We then performed whole-exome analysis of the trio to uncover inherited variants from the father that potentially worsen the already altered genetic background in the proband. No pathogenic variants were inherited in autosomal recessive, de novo dominant or X-linked recessive manner. Comparing proband and father exome we detected 25 predicted deleterious variants including a nonsense mutation in ERCC3. Those inherited mutations are possible candidate modifiers linked to TP53, explaining the proband accelerated tumor onset compared to the mother and providing a possible explanation of the genetic anticipation event in this Li-Fraumeni family. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Analysis of the roles of E6 binding to E6TP1 and nuclear localization in the human papillomavirus type 31 life cycle

    International Nuclear Information System (INIS)

    Lee, Choongho; Wooldridge, Tonia R.; Laimins, Laimonis A.

    2007-01-01

    The E6 oncoproteins of high-risk human papillomaviruses provide important functions not only for malignant transformation but also in the productive viral life cycle. E6 proteins have been shown to bind to a number of cellular factors, but only a limited number of analyses have investigated the effects of these interactions on the viral life cycle. In this study, we investigated the consequences of HPV 31 E6 binding to E6TP1, a putative Rap1 GAP protein. HPV 16 E6 has been shown to bind as well as induce the rapid turnover of E6TP1, and similar effects were observed with HPV 31 E6. Mutation of amino acid 128 in HPV 31 E6 was found to abrogate the ability to bind and degrade E6TP1 but did not alter binding to another α-helical domain protein, E6AP. When HPV 31 genomes containing mutations at amino acid 128 were transfected into human keratinocytes, the viral DNAs were not stably maintained as episomes indicating the importance of this residue for pathogenesis. Many E6 binding partners including E6TP1 are cytoplasmic proteins, but E6 has been also reported to be localized to the nucleus. We therefore investigated the importance of E6 localization to the nucleus in the viral life cycle. Using a fusion of E6 to Green Fluorescent Protein, we mapped one component of the nuclear localization sequences to residues 121 to 124 of HPV 31 E6. Mutation of these residues in the context of the HPV 31 genome abrogated the ability for episomes to be stably maintained and impaired the ability to extend the life span of cells. These studies identify two activities of HPV 31 E6 that are important for its function in the viral life cycle and for extension of cell life span

  3. Distribution of GSTM1, GSTT1, GSTP1 and TP53 disease-associated gene variants in native and urban Venezuelan populations.

    Science.gov (United States)

    Chiurillo, Miguel Angel; Griman, Pedro; Santiago, Laskhmi; Torres, Keila; Moran, Yeinmy; Borjas, Lisbeth

    2013-11-15

    The contemporary Venezuelan population is the product of major admixture process across various historical events, which has provided it a particular genetic background. The aim of this study concerns the analysis of glutathione S-transferase (GST) GSTM1, GSTP1 and GSTT1 genetic variants and five polymorphisms at the TP53 gene, which are related to cancer susceptibility, in an urban/admixed population and five Amerindian tribes (Bari, Panare, Pemon, Warao and Wayuu) from Venezuela. Genotyping was carried out in 120 individuals from an urban sample and 188 Amerindians. The analysis performed on TP53 haplotype and GST allele distribution showed a close correlation for Pemon and Warao populations, while Bari group appears isolated from the other populations. GSTT1 null variant frequency in our admixed (11%) and native samples (0.0-11.4%) was lower when compared with Caucasians, Africans and Asians. Frequency of the GSTP1*Val cancer-associated allele found in Bari (88.6%) and Panare (63.0%) is of the highest so far reported. Fourteen TP53 haplotypes were observed in the admixed populations, whereas only 3 to 5 in Amerindians. To our knowledge this is the first report of GST polymorphisms and TP53 haplotype distribution in Venezuelans. The distribution of most of analyzed polymorphisms in the urban sample is consistent with the admixed origin of the present-day population of Venezuela. While, the inter-ethnic variations in genetic polymorphisms found in Native American tribes seem to be the result of the influence of demographic factors. These results provide additional data for undertaking ethnographic and disease association studies in Venezuela. © 2013.

  4. Influencia do indice de massa corporal no equilibrio e na configuracao plantar em obesos adultos

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    Liu Chiao Yi

    2014-01-01

    Full Text Available INTRODUÇÃO: A obesidade é uma doença crônica degenerativa multifatorial que pode levar a alterações do sistema musculoesquelético, como mudança do centro de gravidade e sobrecarga mecânica sobre os membros inferiores. OBJETIVOS: Correlacionar o índice de massa corporal (IMC com o equilíbrio corporal e verificar associação entre o IMC e a configuração plantar. MÉTODOS: Foram avaliados 30 obesos, de ambos os gêneros, com IMC maior ou igual a 30 Kg/m². Inicialmente, os voluntários foram submetidos às avaliações de medidas antropométricas a fim de calcular o valor do IMC. Em seguida, foram submetidos ao teste de equilíbrio corporal estático Balance Error Scoring System (BESS e a plantigrafia para a identificação da impressão plantar. Por meio do método de Viladot, os voluntários foram classificados em grupos: pé plano (GPP, pé cavo (GPC e pé neutro (GPN. A correlação entre as variáveis IMC e BESS foi calculada por meio do coeficiente de correlação linear de Pearson e associação entre o IMC e a configuração plantar foi realizada por meio da análise de variância (Anova. Para todas as análises, nível de significância considerado foi p < 0,05. RESULTADOS: Os valores da correlação entre o IMC e o BESS foram r = - 0,1 e p = 0,59. Os valores da associação do IMC entre GPN - GPP; GPN - GPC; GPP - GPC foram respectivamente: p = 0,76; p = 0,001; p = 0,07. CONCLUSÃO: O índice de massa corporal de adultos obesos não influencia o equilíbrio corporal, porém influencia na configuração plantar.

  5. Identification of the TP53-induced glycolysis and apoptosis regulator in various stages of colorectal cancer patients

    Science.gov (United States)

    AL-KHAYAL, KHAYAL; ABDULLA, MAHA; AL-OBEED, OMAR; KATTAN, WAEL AL; ZUBAIDI, AHMAD; VAALI-MOHAMMED, MANSOOR-ALI; ALSHEIKH, ABDULMALIK; AHMAD, REHAN

    2016-01-01

    The TP53-induced glycolysis and apoptosis regulator (TIGAR) is a p53 target gene known to regulate glycolysis by acting as fructose bis-phosphatase (FBPase) and modulate reactive oxygen species. TIGAR expression has been implicated in oncogenesis and progression of several human cancers. However, TIGAR expression is not known in various stages of colorectal cancer (CRC). There is an increase in the colorectal cancer incidence in Saudi Arabia. We sought to analyze TIGAR expression in this ethnic group. The aim of this study was to investigate the TIGAR expression in colorectal cancer (CRC) patients from Saudi Arabia. Tissue microarray (TMA) was constructed from 22 matched colorectal tumor tissues and adjacent normal tissues. TIGAR expression was examined in TMA slide using immunohistochemistry. TIGAR mRNA was determined in 14 matched tumor tissue and adjacent normal tissue. TIGAR protein expression was also examined in CRC tumor tissues and cell lines. Statistical analyses (t-test) were applied to evaluate the significance of TIGAR expression. TIGAR mRNA level was upregulated significantly in stage II (pcolorectal cancer. Strong TIGAR positive staining was found in 68% (15/22) of the tumor samples with nuclear localization. TIGAR staining was found to be significantly increased in early stage (stage I and II) CRC (pcolorectal cancer tissues and CRC cell lines. These findings indicate that TIGAR is highly expressed at the mRNA and protein levels in colorectal cancer with prominent nuclear localization. TIGAR expression may be used as a bio-marker for detection of colorectal cancer and can be used as a target for developing therapeutics for the treatment of colorectal cancer. PMID:26675982

  6. TP53-induced glycolysis and apoptosis regulator protects from spontaneous apoptosis and predicts poor prognosis in chronic lymphocytic leukemia.

    Science.gov (United States)

    Hong, Ming; Xia, Yi; Zhu, Yu; Zhao, Hui-Hui; Zhu, Han; Xie, Yue; Fan, Lei; Wang, Li; Miao, Kou-Rong; Yu, Hui; Miao, Yu-Qing; Wu, Wei; Zhu, Hua-Yuan; Chen, Yao-Yu; Xu, Wei; Qian, Si-Xuan; Li, Jian-Yong

    2016-11-01

    Circulating chronic lymphocytic leukemia (CLL) cells appear not to be overly utilizing aerobic glycolysis. However, recurrent contact with CLL cells in a stromal microenvironment leads to increased aerobic glycolysis and the cells' overall glycolytic capacity, which promotes cell survival and proliferation. TP53-induced glycolysis and apoptosis regulator (TIGAR) has been directly implicated in cellular metabolism in the control of glycolysis. TIGAR inhibits glycolysis and protects cells from intracellular reactive oxygen species (ROS)-associated apoptosis. TIGAR mRNA expression was investigated by quantitative PCR in 102 newly diagnosed CLL patients. Furthermore, the relationship between the expression of TIGAR and its clinical characteristics and prognosis were investigated. Moreover, we also investigated the correlation between TIGAR expression and apoptosis in primary CLL cells. Our data revealed that TIGAR overexpression was correlated with the protection from spontaneous apoptosis in CLL cells, and is strongly associated with advanced Binet stage, unmutated immunoglobulin heavy-chain variable region (IGHV) status, CD38 positivity, β2-microglobulin and p53 aberrations. Higher expression of TIGAR was associated with shorter treatment-free survival (median: three months vs. 51 months, P=0.0108), worse overall survival (median: 74 months vs. not reached, P=0.0242), and the diverse responses to fludarabine-based chemotherapy. TIGAR expression in patients resistant to chemotherapy was significantly higher than in patients sensitive to chemotherapy (mean: 0.3859±0.1710 vs. 0.0974±0.0291, P=0.0290). Taken together, our findings revealed that high TIGAR expression is closely correlated with worse clinical outcome in CLL patients, and depicted how bioenergetic characteristics could be therapeutically exploited in CLL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. A Novel Interaction of Ecdysoneless (ECD) Protein with R2TP Complex Component RUVBL1 Is Required for the Functional Role of ECD in Cell Cycle Progression.

    Science.gov (United States)

    Mir, Riyaz A; Bele, Aditya; Mirza, Sameer; Srivastava, Shashank; Olou, Appolinaire A; Ammons, Shalis A; Kim, Jun Hyun; Gurumurthy, Channabasavaiah B; Qiu, Fang; Band, Hamid; Band, Vimla

    2015-12-28

    Ecdysoneless (ECD) is an evolutionarily conserved protein whose germ line deletion is embryonic lethal. Deletion of Ecd in cells causes cell cycle arrest, which is rescued by exogenous ECD, demonstrating a requirement of ECD for normal mammalian cell cycle progression. However, the exact mechanism by which ECD regulates cell cycle is unknown. Here, we demonstrate that ECD protein levels and subcellular localization are invariant during cell cycle progression, suggesting a potential role of posttranslational modifications or protein-protein interactions. Since phosphorylated ECD was recently shown to interact with the PIH1D1 adaptor component of the R2TP cochaperone complex, we examined the requirement of ECD phosphorylation in cell cycle progression. Notably, phosphorylation-deficient ECD mutants that failed to bind to PIH1D1 in vitro fully retained the ability to interact with the R2TP complex and yet exhibited a reduced ability to rescue Ecd-deficient cells from cell cycle arrest. Biochemical analyses demonstrated an additional phosphorylation-independent interaction of ECD with the RUVBL1 component of the R2TP complex, and this interaction is essential for ECD's cell cycle progression function. These studies demonstrate that interaction of ECD with RUVBL1, and its CK2-mediated phosphorylation, independent of its interaction with PIH1D1, are important for its cell cycle regulatory function. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. The Putative Role of TP53 Alterations and p53 Expression in Borderline Ovarian Tumors - Correlation with Clinicopathological Features and Prognosis: A Mini-Review

    Science.gov (United States)

    Semczuk, Andrzej; Gogacz, Marek; Semczuk-Sikora, Anna; Jóźwik, Maciej; Rechberger, Tomasz

    2017-01-01

    Borderline ovarian tumors (BOTs) represent an independent group among ovarian malignancies, being diagnosed at clinical stage earlier than invasive ovarian carcinomas (OCs) and characterized by a rather favorable outcome after careful surgical management. Data published worldwide showed a substantial discordance of p53 expression in BOTs. The purpose of this work was to present the current status of knowledge on the significance of TP53 gene and p53 protein product alterations in BOTs. In general, higher p53 expression patterns were reported for ovarian malignancies compared to BOTs. Serous, mucinous, and endometrioid BOTs differ substantially in relation to p53 immunostaining, but data concerning the relationship between the protein's immunoreactivity and other clinico-pathological variables are scarce. Finally, reports published to date support the view that TP53 alterations may not be commonly associated with the borderline phenotype of ovarian tumors but they probably occur during the development of invasive OCs. In light of these uncertainties, the impact of TP53 alterations and p53 expression on overall survival in women affected by BOTs requires further multi-institutional studies in large cohorts of patients. PMID:28928856

  9. A mutation screening of oncogenes, tumor suppressor gene TP53 and nuclear encoded mitochondrial complex I genes in oncocytic thyroid tumors.

    Science.gov (United States)

    Evangelisti, Cecilia; de Biase, Dario; Kurelac, Ivana; Ceccarelli, Claudio; Prokisch, Holger; Meitinger, Thomas; Caria, Paola; Vanni, Roberta; Romeo, Giovanni; Tallini, Giovanni; Gasparre, Giuseppe; Bonora, Elena

    2015-03-21

    Thyroid neoplasias with oncocytic features represent a specific phenotype in non-medullary thyroid cancer, reflecting the unique biological phenomenon of mitochondrial hyperplasia in the cytoplasm. Oncocytic thyroid cells are characterized by a prominent eosinophilia (or oxyphilia) caused by mitochondrial abundance. Although disruptive mutations in the mitochondrial DNA (mtDNA) are the most significant hallmark of such tumors, oncocytomas may be envisioned as heterogeneous neoplasms, characterized by multiple nuclear and mitochondrial gene lesions. We investigated the nuclear mutational profile of oncocytic tumors to pinpoint the mutations that may trigger the early oncogenic hit. Total DNA was extracted from paraffin-embedded tissues from 45 biopsies of oncocytic tumors. High-resolution melting was used for mutation screening of mitochondrial complex I subunits genes. Specific nuclear rearrangements were investigated by RT-PCR (RET/PTC) or on isolated nuclei by interphase FISH (PAX8/PPARγ). Recurrent point mutations were analyzed by direct sequencing. In our oncocytic tumor samples, we identified rare TP53 mutations. The series of analyzed cases did not include poorly- or undifferentiated thyroid carcinomas, and none of the TP53 mutated cases had significant mitotic activity or high-grade features. Thus, the presence of disruptive TP53 mutations was completely unexpected. In addition, novel mutations in nuclear-encoded complex I genes were identified. These findings suggest that nuclear genetic lesions altering the bioenergetics competence of thyroid cells may give rise to an aberrant mitochondria-centered compensatory mechanism and ultimately to the oncocytic phenotype.

  10. Regulatory Activities of the President of the Office of Electronic Communications versus competitiveness and fi nancial situation of the enterprises on the example of TP Group

    Directory of Open Access Journals (Sweden)

    Ewa M. Kwiatkowska

    2014-09-01

    Full Text Available Purpose: The aim of this paper is to present the regulatory obligations imposed by the President of the Office of Electronic Communications (hereafter: President of UKE on telecom enterprises with significant market power in the retail and wholesale telecommunications markets. Methodology: The decisions addressed to TP Group entities were analyzed as well as the fi nancial statements presenting the economic volume achieved for the period 2006–2013. Findings: In the analyzed period for entities of the TP Group were applied a range of regulatory obligations, that should result in disabling the use of their monopoly position and transfer their position between telecommunications markets. Regulatory obligations imposed by the President of UKE on TP Group entities did not affect to a significant extent the situation of the group. Fluctuations of analyzed financial f gures seem to be primarily the result of internal management decisions rather than a comprehensive range of sector-specific regulation in telecommunications. These researches indicate the need for a deeper analysis of the perception of the effects of regulatory actions by stakeholders in the telecommunications sector.

  11. Identification of a novel germ-line mutation in the TP53 gene in a Mexican family with Li-Fraumeni syndrome.

    Science.gov (United States)

    Taja-Chayeb, Lucia; Vidal-Millán, Silvia; Gutiérrez-Hernández, Olga; Trejo-Becerril, Catalina; Pérez-Cárdenas, Enrique; Chávez-Blanco, Alma; de la Cruz-Hernández, Erick; Dueñas-González, Alfonso

    2009-12-17

    Germ-line mutations of the TP53 gene are known to cause Li-Fraumeni syndrome, an autosomal, dominantly inherited, high-penetrance cancer-predisposition syndrome characterized by the occurrence of a variety of cancers, mainly soft tissue sarcomas, adrenocortical carcinoma, leukemia, breast cancer, and brain tumors. Mutation analysis was based on Denaturing high performance liquid chromatography (DHPLC) screening of exons 2-11 of the TP53 gene, sequencing, and cloning of DNA obtained from peripheral blood lymphocytes. We report herein on Li Fraumeni syndrome in a family whose members are carriers of a novel TP53 gene mutation at exon 4. The mutation comprises an insertion/duplication of seven nucleotides affecting codon 110 and generating a new nucleotide sequence and a premature stop codon at position 150. With this mutation, the p53 protein that should be translated lacks the majority of the DNA binding domain. To our knowledge, this specific alteration has not been reported previously, but we believe it is the cause of the Li-Fraumeni syndrome in this family.

  12. Identification of a novel germ-line mutation in the TP53 gene in a Mexican family with Li-Fraumeni syndrome

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    de la Cruz-Hernández Erick

    2009-12-01

    Full Text Available Abstract Background Germ-line mutations of the TP53 gene are known to cause Li-Fraumeni syndrome, an autosomal, dominantly inherited, high-penetrance cancer-predisposition syndrome characterized by the occurrence of a variety of cancers, mainly soft tissue sarcomas, adrenocortical carcinoma, leukemia, breast cancer, and brain tumors. Methods Mutation analysis was based on Denaturing high performance liquid chromatography (DHPLC screening of exons 2-11 of the TP53 gene, sequencing, and cloning of DNA obtained from peripheral blood lymphocytes. Results We report herein on Li Fraumeni syndrome in a family whose members are carriers of a novel TP53 gene mutation at exon 4. The mutation comprises an insertion/duplication of seven nucleotides affecting codon 110 and generating a new nucleotide sequence and a premature stop codon at position 150. With this mutation, the p53 protein that should be translated lacks the majority of the DNA binding domain. Conclusion To our knowledge, this specific alteration has not been reported previously, but we believe it is the cause of the Li-Fraumeni syndrome in this family.

  13. The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like kindreds.

    Science.gov (United States)

    Siddiqui, Rina; Onel, Kenan; Facio, Flavia; Nafa, Kedoudja; Diaz, Louis Robles; Kauff, Noah; Huang, Helen; Robson, Mark; Ellis, Nathan; Offit, Kenneth

    2005-01-01

    Li-Fraumeni syndrome (LFS) is a dominantly inherited cancer predisposition syndrome characterized by a wide spectrum of neoplasms occurring at young age. Germline mutations in the TP53 tumor suppressor gene have been identified in approximately 71 of LFS patients and 22 of Li-Fraumeni-like (LFL) patients. Mutations within the cell cycle checkpoint gene CHEK2 have also been reported in some patients with LFS, LFL, and phenotypically suggestive of LFS (PS-LFS) not carrying a TP53 mutation. In this study, we show that 7 of the 23 patients with LFS/LFL tested positive for deleterious mutations in p53. Fifteen of the remaining sixteen were not found to carry the CHEK2* 1100delCmutation. These results indicate that CHEK2*1100delC is not a common cause of LFS, LFL, or PS-LFS in North American kindreds not carrying a TP53 mutation. Of note, two patients were found to carry p53* R72P, which is of unknown clinical significance. Lack of segregation of this allele in one of these kindreds provides strong evidence that the R72P allele is not disease-causing. While mutations in p53 account for a proportion of patients with LFS/LFL, future studies are needed to determine if other genes are responsible for LFS/LFL families not carrying germline p53 mutations.

  14. [Description of a new TP53 gene germline mutation in a family with the Li-Fraumeni syndrome. Genetic counselling to healthy mutation carriers].

    Science.gov (United States)

    Balmaña, Judith; Nomdedéu, Josep; Díez, Orland; Sabaté, Josep Maria; Balil, Anna; Pericay, Carles; López López, Juan José; Brunet, Joan; Baiget, Montse; Alonso, Carmen

    2002-10-19

    Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, soft-tissue sarcomas and osteosarcomas, acute leukemia, adrenocortical neoplasms and central nervous system tumors. Germline mutations in gene TP53 are identified in a percentage of affected families. Eight families with aggregation of childhood sarcomas, brain tumors, breast cancers in pre-menopausal women, and renal tumors were screened for TP53 germ-line mutations. SSCP and posterior direct sequencing were performed for genetic analysis. We also report a previously undescribed family with the Li-Fraumeni syndrome carrying a germline mutation. Seven families fulfilled so-called Li-Fraumeni like criteria and one fulfilled classical criteria. A new germ-line mutation in codon 238 at exon 7 of the gene TP53 was identified in the family fulfilling classical criteria. This mutation has not been previously reported. The clinical heterogeneity as well as the molecular complexity and consequences of mutation analysis and genetic counseling make it necessary to develop protocols in this area. A multidisciplinary approach is needed; this approach should be coordinated by a Familial Cancer Genetic Counseling Unit.

  15. Germ-line TP53 mutations in Finnish cancer families exhibiting features of the Li-Fraumeni syndrome and negative for BRCA1 and BRCA2.

    Science.gov (United States)

    Huusko, P; Castrén, K; Launonen, V; Soini, Y; Pääkkönen, K; Leisti, J; Vähäkangas, K; Winqvist, R

    1999-07-01

    Mutations in BRCA1 and BRCA2 account for a large portion of the inherited predisposition to breast and ovarian cancer. It was recently discovered that mutations in these two genes are less common in the Finnish population than expected. Because the genetic background of breast cancer, in particular, is largely obscure, it became necessary to search for mutations in other susceptibility genes. Because seven of our BRCA1 and BRCA2 mutation-negative families fulfilled the criteria of either Li-Fraumeni syndrome (LFS) or Li-Fraumeni-like syndrome (LFL), we decided to screen them for germ-line TP53 mutations in exons 5-8 using a dual-temperature single-strand conformation polymorphism assay (SSCP). Two missense mutations (Asn235Ser and Tyr220Cys) were identified. The clinical significance of these findings was evaluated by comparison to previously reported germ-line TP53 mutation data, and by using the tumor loss of heterozygosity (LOH) analysis. In addition, an immunohistochemical analysis of tumor specimens from mutation-positive individuals was performed. Our results suggest that the observed missense mutations confer susceptibility to cancer, and that germ-line TP53 mutations would therefore explain an additional fraction of hereditary breast cancer in Finland.

  16. Further evidence for pathogenicity of the TP53 tetramerization domain mutation p.Arg342Pro in Li-Fraumeni syndrome.

    Science.gov (United States)

    Etzold, Anna; Schröder, Julia C; Bartsch, Oliver; Zechner, Ulrich; Galetzka, Danuta

    2015-03-01

    Li-Fraumeni syndrome (LFS) is a rare genetic disease with a highly significant predisposition to multiple early-onset neoplasms. These neoplasms include adrenocortical carcinoma, sarcoma, leukemia and CNS tumors in children and sarcoma, breast cancer and lung cancer in adults. LFS is inherited in an autosomal dominant manner. In most patients germline mutations in the tumor suppressor gene TP53 are found. As the majority of known mutations affect the DNA-binding domain of the p53 protein, there are only a few case reports showing the clinical presentation of mutations outside of this mutational hotspot. Here we present a family with a typical LFS pedigree with patients suffering from early-onset lung cancer, bilateral breast cancer and osteosarcoma. TP53 sequence analysis of the index patient revealed the germline mutation c.1025G > C in a heterozygous state, resulting in an amino acid exchange from arginine to proline (p.Arg342Pro) in the tetramerization domain of p53. Using DNA from an old bedside blood typing test, the same mutation was found in the mother of the index patient, who had died of breast cancer 29 years ago. In conclusion, we provide evidence for the co-segregation of a TP53 tetramerization domain mutation and cancer phenotypes, but also report pre-symptomatic mutation carriers within the family. We review published recommendations for clinical management and surveillance of high-risk members in Li-Fraumeni kindreds.

  17. Biotransformation of gabapentin in surface water matrices under different redox conditions and the occurrence of one major TP in the aquatic environment.

    Science.gov (United States)

    Henning, Nina; Kunkel, Uwe; Wick, Arne; Ternes, Thomas A

    2018-06-15

    Laboratory-scale incubation experiments in water/sediment systems were conducted to test the transformation behavior of the anticonvulsant gabapentin (GBP) under different environmental conditions (aerobic, anaerobic, with abiotic controls). GBP was transformed by biological processes as it was eliminated quickly under aerobic conditions (dissipation time 50% of initial concentration (DT 50 ): 2-7 days) whereas no decrease was observed under anaerobic conditions. Measurements via high resolution mass spectrometry (LC-Orbitrap-MS) revealed eight biological transformation products (TPs). Three of them were identified with reference standards (GBP-Lactam, TP186, TP213), while for the other five TPs tentative structures were proposed from information by MS 2 /MS 3 experiments. Furthermore, the quantitatively most relevant TP GBP-Lactam was formed via intramolecular amidation (up to 18% of initial GBP concentration). Incubation experiments with GBP-Lactam revealed a higher stability against biotic degradation (DT 50 : 12 days) in contrast to GBP, while it was stable under anaerobic and abiotic conditions. Besides GBP, GBP-Lactam was detected in surface water in the μg L -1 range. Finally, GBP and GBP-Lactam were found in potable water with concentrations up to 0.64 and 0.07 μg L -1 , respectively. According to the elevated environmental persistence of GBP-Lactam compared to GBP and its presumed enhanced toxicity, we recommend to involve GBP-Lactam into monitoring programs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. August Cover 09 Tp

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    In this section of Resonance, we invite readers to pose questions likely to be raised in a classroom situation. We may suggest strategies for dealing with them, or invite responses, or both. “Classroom” is equally a forum for raising broader issues and sharing personal experiences and viewpoints on matters related to ...

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    The course will cover topics selected mostly from post-graduate curriculum in the broad areas of classical and quantum mechanics, electrodynamics, special relativity, mathematical methods, and statistical physics. The lectures will be supplemented by discussion and problem sessions. Teachers who wish to participate may ...

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    Indian Academy of Sciences (India)

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    virus, which causes myeloblastic anemia in young chickens, was used for the following two reasons. First, upon his return to UCSF, Levinson had evaluated the efficacy of the Cu++-INH complex on RSV-induced tumors in susceptible chickens, and had found that it suppressed tumor formation. Second, it was important to ...

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    Indian Academy of Sciences (India)

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    455 The Major Players in Adaptive Immunity. Humoral Immunity. Asama Ahmed, Banishree Saha, Anand Patwardhan,. Shwetha Shivaprasad and Dipankar Nandi. 472 The Saga of the HIV Controversy. Nobel Prize in Physiology or Medicine – 2008. Udaykumar Ranga. 430. 416. 508 ...

  2. INFLUENCIA DE LA LONGITUD DEL CONO DE UN CICLÓN SOBRE LAS VARIABLES DE FLUJO

    Directory of Open Access Journals (Sweden)

    Horacio A. Petit

    2012-01-01

    Full Text Available Los ciclones son separadores gas-polvo ampliamente empleados en la industria. Su eficiencia depende de las variables geométricas de diseño y de las condiciones de operación. En este trabajo se estudia el efecto de la longitud de la parte cónica sobre la eficiencia de recolección de polvo. Se realiza la simulación del flujo turbulento presente en los ciclones para analizar la distribución de velocidades tangenciales y determinar la caída de presión. Se utiliza el modelo LES (Large Eddy Simulation y se aplican las técnicas de fluidodinámica computacional (CFD: Computacional Fluid Dynamics. Empleando el modelo del número de vórtices para determinar la eficiencia fraccional, se pudo establecer que los ciclones con mayor largo de cono presentan mejor eficiencia de separación y menor caída de presión. Esto ocurre para cualquier diámetro de partícula y en todo el rango de temperaturas estudiado, siendo la influencia del largo del cono mayor para las menores temperaturas.

  3. Influencia de los Roles de Equipo en las Actividades del Desarrollador de Software

    Directory of Open Access Journals (Sweden)

    Elsa Estrada Guzmán

    2013-05-01

    Full Text Available Uno de los roles básicos en el proceso del software es precisamente el de desarrollador, también denominado ingeniero de software, cuyas actividades principales son: el análisis, diseño, programación y pruebas del producto a desarrollar. Estas actividades, dependiendo generalmente del tamaño del proyecto y de la metodología, pueden estar a cargo de diferentes personas o bien de un grupo de desarrolladores que en conjunto las llevan todas a cabo; en este último caso, estaríamos hablando de trabajo en equipo entre iguales o pares. Por otro lado, de acuerdo con la teoría de roles de equipo, las personas tienden a comportarse de manera regular en forma distintiva cuando colaboran, estas formas particulares de colaborar es probable que influyan en el desempeño del equipo de desarrolladores de software. En este documento se presenta un caso de estudio con la finalidad de entender la influencia de los roles de equipo en ciertas actividades involucradas en el proceso de desarrollo de software.

  4. La influencia de la Revolución Cultural en las mujeres chinas

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    María Gómez y Patiño

    2013-11-01

    Full Text Available Si todos los procesos de transición política influyen en la ciudadanía en general, las mujeres suelen sufrir sus consecuencias doblemente: primero, a título individual, y segundo, como mujer. La influencia que la Revolución Cultural tuvo en China persiste en la mentalidad y en la vida de las mujeres del país asiático emergente par excellence. Este artículo presenta diez entrevistas personales realizadas in situ, a mujeres de distintos orígenes, edades, estatus social y nivel cultural, cuya vida se vio afectada por uno de los procesos políticos más fuertes que la historia universal ha recogido. El análisis y la interpretación de estas entrevistas ofrecen una perspectiva inédita de su visión del mundo, así como un testimonio oral de ese capítulo de la historia.

  5. La influencia de los rasgos psicológicos en las actitudes hacia el empleo

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    Antonia Mercedes García Cabrera

    2008-01-01

    Full Text Available Esta investigación explica la influencia que el rasgo psicológico locus de control, conjuntamente con las variables que definen el capital humano de un país -género, edad y educación-, ejercen sobre las actitudes hacia el empleo en la República de Cabo Verde. De entre estos rasgos demográficos del individuo, el género es analizado más profundamente debido al interés actual por reducir las desigualdades en razón de género en el mercado laboral. Los 448 cuestionarios recabados muestran que, en este país, los atributos demográficos edad y nivel de estudios, así como el rasgo de personalidad locus de control, son importantes determinantes de las actitudes hacia el empleo de la población activa. Los resultados ofrecen las bases sobre las que redirigir las políticas de empleo en Cabo Verde para afrontar los puntos débiles que limitan el desarrollo del mercado de trabajo y amenazan la integración social.

  6. El fantasma del abstencionismo y la influencia mediática

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    Lic. Edith Barajas

    2001-01-01

    Full Text Available Nadie duda, en el inicio de un nuevo milenio, de la influencia y el impacto de los medios masivos de comunicación. La prensa, la radio, la televisión y, contemporáneamente Internet, juegan un papel clave en la nueva era de la humanidad, donde la paradoja es tener información a mansalva para un ser actual dominado por fenómenos como el cortoplacismo, los antimodelos, las guerras, el esoterismo, la hambruna, la religión y la violencia, todo englobado, a su vez, en una economía mundializada que rompe y descarna las fronteras de las naciones, y en donde los futurólogos citan las dos grandes vías: la era digital y la era biológica.En el llamado "control de masas", el medio masivo, especialmente el electrónico, desarrolla un actor importante dentro del mundo global, pues mantiene a la mayoría de la población concentrada en temas que no son precisamente los del orden de mayor interés (en nuestro país, podemos considerar el escándalo Trevi-Andrade como un elemento distractor, sobre los problemas que aquejan al país; es decir, la opinión pública se concentra en ese enfoque, antes de irse a lo medular

  7. Influencia del polvo del horno de cemento sobre plantas y animales

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    Pajenkamp, H.

    1963-06-01

    Full Text Available Not availableEl pretendido «polvo de cemento» de los alrededores de las fábricas no es de cemento, sino que se compone, en su mayor parte, de caliza molida muy fina. Es, por tanto, un producto intermedio de la fabricación del cemento. Sería mucho más correcto llamarle «polvo del horno de cemento». Continuamente alegan los agricultores que este «polvo del horno de cemento» es dañino para plantas y animales, y en los últimos años, para probar la validez de tales asertos, se han llevado a cabo numerosas investigaciones científicas para estudiar los efectos de este polvo. Estamos hoy día en posesión de una serie· de trabajos muy completos que dan una idea clara sobre el efecto del polvo del horno de cemento. Los animales domésticos útiles (por ejemplo: corderos, vacas de leche no sufren ningún perjuicio clínico, ninguna deficiencia de su estado general, a pesar de serie administradas grandes dosis de polvo. Los ensayos agrícolas con plantas útiles (avena, trébol, remolacha azucarera, pastos que han sido efectuados durante varios años, han demostrado que ni siquiera cantidades elevadas de polvo provocan perjuicios ni influencias nefastas sobre el crecimiento y sobre la recolección.

  8. La influencia del conocimiento político en las decisiones de voto

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    Marta FRAILE

    2007-01-01

    Full Text Available Este trabajo discute y compara dos lógicas explicativas del comportamiento electoral: el voto por resultados y el voto ideológico. En concreto, el trabajo pone a prueba uno de los principales supuestos de ambas teorías: que las reglas que guían las decisiones de voto de los ciudadanos son las mismas independientemente de su nivel de interés, conocimiento e información sobre los temas políticos. Para ello se analiza material empírico proveniente de encuestas postelectorales en cuatro democracias: España, Portugal, Hungría y Polonia. Los datos pertenecen al segundo módulo del programa de Estudio Comparado de Sistemas Electorales (CSES, 2005, que contiene información sobre el comportamiento electoral y el conocimiento político de los ciudadanos. Los resultados apuntan a que mientras la influencia del conocimiento político en la lógica del voto por resultados es clara y contundente, resulta mucho menos concluyente en el caso del voto ideológico. Todo ello sugiere que el control democrático de los gobiernos a través de la sanción de su rendimiento requiere unos niveles mínimos de conocimiento e información sobre la política por parte de la ciudadanía.

  9. Mejora de la calidad del acero obtenido por colada continua mediante influencias electrofísicas

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    Shklyar, V.

    1998-12-01

    Full Text Available Laboratory tests with tin smelted in a crucible and industrial tests with crude steel poured in moulds had been carried out. These metals were subjected to electrophysical influences. As a result of the applied electric field, it is observed in tin that during the solidification, the crystalization temperature and the solidification time are changed. Crystal growth in the electric field direction and an increase of the fracture limit in the steel ingot are observed.

    Se han realizado ensayos de laboratorio con estaño fundido en crisol y a escala industrial con acero líquido vertidos en moldes, sometiendo estos metales a influencias electrofísicas. Como resultado del campo aplicado, en el estaño se observa que durante la solidificación varía la temperatura de cristalización y el tiempo de solidificación. En el lingote de acero se observa un crecimiento de los cristales en dirección del campo eléctrico y un aumento del límite de rotura.

  10. Influencia de las diferentes etapas de procesamiento sobre la microestructura de dispositivos multicapa basados en PZT

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    Solera, E.

    2002-02-01

    Full Text Available A comparative study of the influence of both rheological and processing parameters on the microstructure and reliability of multilayer ceramic chips based on PZT has been conducted. The multilayer chips were obtained by tape casting. Viscosity measurements of different slurries with various solids content have been correlated with both the thickness and the green density of the casted layers. The critical points of the thermal treatments, organics burn-out and sintering, have been identified. The green microstructure of the layers and the final microstructure of the sintered chips have been studied by SEM.

    Se ha realizado un estudio comparativo de la influencia de los parámetros reológicos y de procesamiento sobre la microestructura y consistencia de chips multicapa de PZT obtenidos mediante un proceso de colado en cinta. Para ello se han realizado medidas de viscosidad de distintas barbotinas con diferente contenido en sólidos y su relación con el espesor y densidad en verde de las cintas obtenidas, se han identificado los puntos críticos del ciclo de quemado-sinterización y, mediante MEB se ha estudiado la microestructura en verde de las láminas coladas y la microestructura final de los chips multicapa fabricados.

  11. Influencia familiar sobre las actitudes ante el consumo de drogas en adolescentes españoles

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    María de la Villa Moral Jiménez

    2013-08-01

    Full Text Available En la cultura mediterránea la familia sigue siendo la agencia socializadora por excelencia, a pesar de diversos cambios referenciales y en la intensidad de los afectos, así como en los estilos disciplinares característicos de nuevas tipologías de familias postmodernas. La influencia y modelado familiar sobre las actitudes ante el consumo de sustancias psicoactivas en adolescentes está bien establecida en indicadores tales como experiencias paternas con las drogas, apego y supervisión parental, clima afectivo, dinámica sociofamiliar, etc. Nuestro objeto de estudio se centra en el análisis psicosocial de tales indicadores, así como en ofrecer un análisis diferencial de la valoración de la relación paterno-filial en relación con las actitudes ante el consumo de drogas en un colectivo de adolescentes españoles. Se ha confirmado una mayor permisividad actitudinal y menor concienciación ante los efectos dañinos de las drogas en los hijos de padres consumidores de sustancias psicoactivas tanto legales como ilegales. Se confirma la importancia psicosocial del Apoyo más valorado por los adolescentes que no consumen drogas, así como la percepción diferencial del empleo del Castigo-Coerción y de la Reprobación en adolescentes consumidores que presentan niveles de mayor permisividad actitudinal.

  12. Las nuevas plataformas televisivas en España y su influencia en el mercado

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    JV García Santamaría

    2014-06-01

    Full Text Available Introducción. Los procesos de absorción de las cadenas Cuatro y La Sexta por Telecinco y Antena 3, respectivamente, han configurado un nuevo mapa audiovisual en España. Las dos nuevas plataformas mediáticas, denominadas ahora Mediaset España y Atresmedia, han acumulado un considerable poder en la facturación televisiva, la configuración de las audiencias y la gestión publicitaria de la televisión en abierto. El objetivo es analizar las causas de estas integraciones, su influencia en el mercado televisivo español, y comprobar si afectan —en cuanto a “mercados relevantes”—, a la supervivencia de otros concurrentes. Metodología. Parte de la Economía Política de la Comunicación, que proporciona un marco teórico integrado, que se centra especialmente en la propiedad y la concentración de los medios de comunicación. Resultados y conclusiones. La conclusión general es que, desde el año 2010, fecha de la primera operación, el mercado audiovisual ha visto modificadas sus condiciones de competencia.

  13. Gene-gene interaction between MSX1 and TP63 in Asian case-parent trios with nonsyndromic cleft lip with or without cleft palate.

    Science.gov (United States)

    Liu, Dongjing; Schwender, Holger; Wang, Mengying; Wang, Hong; Wang, Ping; Zhu, Hongping; Zhou, Zhibo; Li, Jing; Wu, Tao; Beaty, Terri H

    2018-03-01

    Small ubiquitin-like modification, also known as sumoylation, is a crucial post-translational regulatory mechanisms involved in development of the lip and palate. Recent studies reported two sumoylation target genes, MSX1 and TP63, to have achieved genome-wide level significance in tests of association with nonsyndromic clefts. Here, we performed a candidate gene analysis considering gene-gene and gene-environment interaction for SUMO1, MSX1, and TP63 to further explore the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P). A total of 130 single-nucleotide polymorphisms (SNPs) in or near SUMO1, MSX1, and TP63 was analyzed among 1,038 Asian NSCL/P trios ascertained through an international consortium. Conditional logistic regression models were used to explore gene-gene (G × G) and gene-environment (G × E) interaction involving maternal environmental tobacco smoke and multivitamin supplementation. Bonferroni correction was used for G × E analysis and permutation tests were used for G × G analysis. While transmission disequilibrium tests and gene-environment interaction analysis showed no significant results, we did find signals of gene-gene interaction between SNPs near MSX1 and TP63. Three pairwise interactions yielded significant p values in permutation tests (rs884690 and rs9290890 with p = 9.34 × 10 -5 and empirical p = 1.00 × 10 -4 , rs1022136 and rs4687098 with p = 2.41 × 10 -4 and empirical p = 2.95 × 10 -4 , rs6819546 and rs9681004 with p = 5.15 × 10 -4 and empirical p = 3.02 × 10 -4 ). Gene-gene interaction between MSX1 and TP63 may influence the risk of NSCL/P in Asian populations. Our study provided additional understanding of the genetic etiology of NSCL/P and underlined the importance of considering gene-gene interaction in the etiology of this common craniofacial malformation. © 2018 Wiley Periodicals, Inc.

  14. Human Papillomavirus 16 Infection and TP53 Mutation: Two Distinct Pathogeneses for Oropharyngeal Squamous Cell Carcinoma in an Eastern Chinese Population.

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    Zhen Wang

    Full Text Available To investigate the clinicopathological characteristics, human papillomavirus (HPV infection, p53 expression, and TP53 mutations in oropharyngeal squamous cell carcinoma (OPSCC and determine their utility as prognostic predictors in a primarily eastern Chinese population.The HPV infection status was tested via p16INK4A immunohistochemistry and validated using PCR, reverse blot hybridization and in situ hybridization (ISH in 188 OPSCC samples. p53 expression levels and TP53 gene mutations were assessed through immunohistochemistry and sequencing, respectively. Clinicopathological characteristics and follow-up information were collected. Overall survival was estimated using the Log-rank test.Overall, 22 of the 188 OPSCC samples were associated with HPV infection. HPV16 was identified in all 22 samples, whereas no samples were positive for HPV18. All 22 HPV-associated OPSCC samples were p53 negative and lacked TP53 mutations. HPV16 positivity, female patients, non-smokers, and patients with histological grade I and stage N0 diseases showed better overall survival (p = 0.009, 0.003, 0.048, 0.009, and 0.004, respectively. No significant differences in overall survival between smoking and non-smoking patients were observed in the HPV-associated OPSCC group. Patients without mutations in TP53 exons 5-8 had better prognoses (p = 0.031 among the 43 sequenced specimens. Multivariate analysis indicated that HPV16 infection status (p = 0.011, histological grade (p = 0.017, and N stage (p = 0.019 were independent prognostic factors for patients with OPSCC.Distinct from the situation in Europe and America, for the patients with OPSCC in this study, HPV16 infection was relatively low, although it was still the most important independent prognostic predictor for the disease. In addition to the high smoking and drinking rate in this population, HPV16 infection and TP53 dysfunction appear to be two distinct pathogens for OPSCC patients in the eastern Chinese

  15. Identification of colorectal cancer patients with tumors carrying the TP53 mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy

    International Nuclear Information System (INIS)

    Godai, Ten-i; Sakuma, Yuji; Tsuchiya, Eiju; Kameda, Yoichi; Akaike, Makoto; Miyagi, Yohei; Suda, Tetsuji; Sugano, Nobuhiro; Tsuchida, Kazuhito; Shiozawa, Manabu; Sekiguchi, Hironobu; Sekiyama, Akiko; Yoshihara, Mitsuyo; Matsukuma, Shoichi

    2009-01-01

    Although postoperative chemotherapy is widely accepted as the standard modality for Dukes' stage C or earlier stage colorectal cancer (CRC) patients, biomarkers to predict those who may benefit from the therapy have not been identified. Previous in vitro and clinical investigations reported that CRC patients with wild-type p53 gene (TP53)-tumors benefit from 5-fluorouracil (5-FU) based chemotherapy, while those with mutated TP53-tumors do not. However, these studies evaluated the mutation-status of TP53 by immunohistochemistry with or without single-strand conformation polymorphism, and the mutation frequency was different from study to study. In addition, the polymorphic status at p53 codon 72, which results in arginine or proline residues (R72P) and is thought to influence the function of the protein significantly, was not examined. To evaluate the significance of the TP53 mutation as a molecular marker to predict the prognosis of CRC patients, especially those who received postoperative chemotherapy, we examined the mutation by direct sequencing from fresh CRC tumors and evaluated the R72P polymorphism of the mutated TP53 by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR). The TP53 mutation occurred in 147 (70%) of 211 Japanese CRC tumors. The mutation was observed in 93 (63%) tumors on the R72 allele and in 54 (37%) tumors on the P72 allele. Although the alterations to TP53 have no prognostic significance for CRC patients overall, we found that Dukes' stage C CRC patients who did not receive postoperative chemotherapy and carried the mutated TP53-R72 showed significantly longer survival times than those with the mutated TP53-P72 when evaluated by overall survival (p = 0.012). Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the TP53 mutated allele in Japanese CRC patients. We raised a possibility that Dukes' stage C colorectal cancer

  16. Identification of colorectal cancer patients with tumors carrying the TP53 mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU based postoperative chemotherapy

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    Tsuchiya Eiju

    2009-12-01

    Full Text Available Abstract Background Although postoperative chemotherapy is widely accepted as the standard modality for Dukes' stage C or earlier stage colorectal cancer (CRC patients, biomarkers to predict those who may benefit from the therapy have not been identified. Previous in vitro and clinical investigations reported that CRC patients with wild-type p53 gene (TP53-tumors benefit from 5-fluorouracil (5-FU based chemotherapy, while those with mutated TP53-tumors do not. However, these studies evaluated the mutation-status of TP53 by immunohistochemistry with or without single-strand conformation polymorphism, and the mutation frequency was different from study to study. In addition, the polymorphic status at p53 codon 72, which results in arginine or proline residues (R72P and is thought to influence the function of the protein significantly, was not examined. Methods To evaluate the significance of the TP53 mutation as a molecular marker to predict the prognosis of CRC patients, especially those who received postoperative chemotherapy, we examined the mutation by direct sequencing from fresh CRC tumors and evaluated the R72P polymorphism of the mutated TP53 by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR. Results The TP53 mutation occurred in 147 (70% of 211 Japanese CRC tumors. The mutation was observed in 93 (63% tumors on the R72 allele and in 54 (37% tumors on the P72 allele. Although the alterations to TP53 have no prognostic significance for CRC patients overall, we found that Dukes' stage C CRC patients who did not receive postoperative chemotherapy and carried the mutated TP53-R72 showed significantly longer survival times than those with the mutated TP53-P72 when evaluated by overall survival (p = 0.012. Conclusion Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the TP53 mutated allele in Japanese CRC patients. We raised a possibility

  17. La influencia católica en la configuración del sistema político y educativo nacional argentino a fines del siglo XIX

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    Oscar Daniel Duarte

    2014-05-01

    Full Text Available El presente artículo describe las diferentes corrientes de pensamiento que influenciaron en el proceso de conformación estatal argentino. Sobresalen entre ellas la línea liberal y la línea católica de fuerte influencia en la elite dirigente del país. A partir de allí realizamos un análisis sobre la orientación política tomada por el Estado y la influencia impelida por el catolicismo particularmente en el debate sobre la conformación del aparato educativo nacional. La conclusión a la que arribamos en este estudio explica el por qué del sometimiento político e ideológico al que se vio sujeto el Estado argentino respecto a la influencia del Vaticano.

  18. La influencia de la televisión en los niños

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    Laura PERLADO EKMAN

    2009-11-01

    Full Text Available RESUMEN: En este artículo se exponen los resultados más relevantes de una investigación que pretendía analizar la influencia que ejerce el medio televisivo en los niños con edades comprendidas entre los 6, 7 y 8 años. Un cuestionario conformado por 55 preguntas, agrupadas en diferentes dimensiones y de opciones múltiples fue aplicado a una muestra de 432 niños con edades de 6, 7 y 8 años procedentes de 8 centros educativos de Zaragoza (España, acerca de la influencia que la televisión genera en ellos. Para el análisis de los resultados se utilizaron las pruebas pertinentes. Como conclusiones más relevantes de esta investigación se puede constatar que: los niños muestran interés por todos los programas infantiles que incluyen escenas de acción y violencia, relegando a segundo término los educativos; la publicidad moldea decisivamente la mente de estos niños, los niños pasan la mayoría de su tiempo libre sentados frente al televisor, la publicidad de los juguetes es percibida por ellos como engañosa. Les cuesta distinguir entre ficción y realidad. Resulta injustificable que no exista una mayor regulación y un control seguro sobre publicidad y programas infantiles.ABSTRACT: In this article I report the results of an investigation which tried to detect the effects of television in eight Primary Schools. The study was performed in eight Primary Schools from Zaragoza (Spain with 432 children. Theirs ages are 6, 7 and 8 years old. The children answered to 55 questions about the programs of television. Data was analyse using the stadistic program SPSS. The analysis of the investigation results showing that the children are specially interested in violent programs and the children don't like didactic programs very much. The children are very often sitting in front of television.RÉSUMÉ: Dans cet article je donne une information sur une recherche qui prétendait détecter l'influence.de la télévision dans huits Écoles Primaires

  19. Influencia del estudio personal en la adquisición de conocimientos

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    Josep Nebot-Cegarra

    Full Text Available Introducción. La actividad del docente suele ser la primera influencia formativa que recibe el alumno en el proceso de aprendizaje de un determinado tema, pero se consolida mediante el estudio personal. En el presente trabajo se ha determinado el grado de mejora obtenido tras el estudio personal en la puntuación alcanzada en una serie de cuestiones, que fueron previamente evaluadas justo después de ser enseñadas¹. Material y Métodos. Se efectuó una prueba a 66 alumnos inmediatamente después de realizar una actividad teoricopráctica de la asignatura Biología del Desarrollo y Teratogenia, que la repitieron días después. Se valoró la existencia de diferencias significativas en el grado de mejoría en función de las características de las cuestiones planteadas y del tiempo transcurrido entre ambas pruebas. Resultados. Hubo mejora en todos los tipos de cuestiones siendo significativa para las cuestiones en que los alumnos precisaron durante la sesión docente una actitud más activa que aquellas otras en que solamente debían observar. De estas últimas mejoraron más las de percepción auditiva. En las respuestas que requerían nombrar, la mejora significativa fue inversamente proporcional a la complejidad de los términos, pero los mejores resultados se obtuvieron en los términos con dificultad fonética alta. Los días transcurridos entre las pruebas no influyeron significativamente en los incrementos de la nota global. Conclusiones. El estudio personal permite una mejora general en la comprensión de los contenidos, independientemente de su grado de dificultad en el aprendizaje a corto plazo.

  20. Influencia del microsite en la imagen de marca a través de experiencias significativas

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    Belinda de Frutos Torres

    2012-04-01

    Full Text Available Las empresas e instituciones, actualmente, son conscientes del potencial que ofrece internet como instrumento para mantener una relación activa con sus públicos de interés. Con este propósito diseñan estrategias de comunicación específicamente destinadas a que el usuario pueda establecer una relación interactiva con la marca. Una de las formas de estar presente en la red es a través del microsite que se perfilan como una solución para estrechar los lazos entre el usuario y la marca.El objetivo del estudio es valorar la influencia del microsite como herramienta de comunicación corporativa y su importancia en la construcción de la imagen de marca. Para ello se ha llevado a cabo un estudio empírico a partir de tres acciones de comunicación reales de tres marcas conocidas representativas de tres estrategias de comunicación. Las tres acciones se llevaron a cabo con microsites y fueron visitados y evaluados por una muestra de 41 personas. Los resultados muestran que la valoración global hacia el microsite puede explicarse en torno a tres dimensiones su grado de entretenimiento, su valor informativo y el agrado asociado. Se comprueba que la experiencia generada por el microsite es diferente dependiendo de la estrategia de comunicación utilizada y contribuye de forma distinta a explicar la actitud hacia la marca. Cada estrategia constituye una experiencia diferenciada para el usuario sin embargo la implicación del usuario con la categoría del producto obtiene un papel determinante en  la relación con la imagen de marca.

  1. Influencia de habitos alimentarios sobre las concentraciones de pesticidas organoclorados en tejido adiposo

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    Costabeber Ijoni

    2002-01-01

    Full Text Available Fueron evaluados los niveles de residuos de pesticidas organoclorados (p,p'-DDE, HCB, gamma-HCH, aldrín presentes en 123 muestras de tejido adiposo mamario obtenidas de mujeres residentes en Córdoba (España. Además, se investigó la influencia de hábitos alimentarios y edad de las donantes sobre los niveles de organoclorados encontrados en el tejido. El p,p'-DDE fue el compuesto encontrado en concentraciones más altas (1,848myg/g, seguido de HCB (0,235mg/g, aldrín (0,005myg/g y gamma-HCH (0,003myg/g. Las donantes mayores presentaron niveles de p,p'-DDE, aldrín y HCB superiores que las más jóvenes. Sin embargo, la edad no influyó en los niveles de gamma-HCH. La mayoría de las donantes (40,65% indicaron las frutas como el alimento más consumido, seguido de la alimentación variada (34,15%, los legumbres (6,50%, los guisos y potajes (6,50%, las verduras (4,88%, la leche (3,25%, el pescado (2,44% y la carne (1,63%. Una correlación no significativa fue observada entre los niveles de organoclorados en el tejido adiposo y los hábitos alimentarios de las donantes.

  2. Influencia de la humedad en el ensayo de resistencia de los ladrillos de suelo-cemento

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    Lima, José I.

    1994-02-01

    Full Text Available The article seeks to show the influence of humidity on the compression test of the soil-cement bricks through an adapted experimental design. The equations showing this relation are obtained. The subsequent generalization provides the possibility of making a pattern of correlation of strengths with different test humidities. Thus, the tests could be performed with a given humidity and the strength of the particular specimen for different humidity values could be estimated with a high degree of certainty. This makes possible the comparison of strength between tested elements in different humidity conditions, verification of fulfillment of recommended strength values and their expressing in terms of a basic humidity value, which is what the currently valid Technical Instructions lack.

    A través de un diseño experimental adecuado se pretende mostrar la influencia de la humedad en el ensayo a compresión de los ladrillos de suelo-cemento, obteniendo las ecuaciones que muestran esta relación. Su generalización posterior permitió elaborar una matriz de correlación de las resistencias con las diferentes humedades de ensayo, de forma tal que se pueda ensayar con una humedad dada y estimar la resistencia que tendrá esa muestra para diferentes valores de humedad, con un buen nivel de confianza. Esto posibilita que se puedan realizar comparaciones de resistencia entre elementos ensayados en condiciones desiguales de humedad, verificar el cumplimiento de los valores recomendados de resistencia y referirlos a un valor de humedad base, defecto actual de las Instrucciones Técnicas vigentes.

  3. Influencia de la reserva cognitiva en la calidad de vida en sujetos con enfermedad de Alzheimer

    Directory of Open Access Journals (Sweden)

    Juan L. Sánchez-Rodríguez

    2013-10-01

    Full Text Available La calidad de vida (CV se define como la percepción personal que un individuo tiene de su situación vital. Dentro de los factores que pueden influir en la CV, se encuentra la Reserva Cognitiva (RC, que podría entenderse como la capacidad del cerebro para hacer frente al daño cerebral generado por la patología, mediante procesos cognitivos preexistentes o compensatorios. El objetivo principal de este estudio, consiste en analizar, como influye la RC en la auto-percepción subjetiva de la CV en sujetos diagnosticados de Enfermedad de Alzheimer (EA y comprobar si existen perfiles diferenciales en función de la sintomatología depresiva y el estado cognitivo de los mismos. La muestra utilizada estaba formada por 112 sujetos que se distribuyeron en dos grupos: uno de 74 sujetos diagnosticados de EA, y otro de 38 sujetos sanos. Se ha utilizado el cuestionario SF-36 para evaluar la CV. En relación a la variable RC, destacar que los sujetos con mayor RC, puntuaron más alto en cada una de las dimensiones del SF-36. La RC podría ser una fuente de influencia en la percepción de la CV de las personas con EA, en la medida en que sus diversos componentes conducirían a la consecución de una capacidad funcional más óptima y una aceptación del estado cognitivo.

  4. Asistencia respiratoria mecánica: Influencia de la edad en la evolución

    Directory of Open Access Journals (Sweden)

    Felipe J. Chertcoff

    2011-02-01

    Full Text Available No existe un concepto definido sobre la influencia de la edad en la mortalidad de la asistencia respiratoria mecánica. Realizamos un trabajo prospectivo-observacional para determinar si la edad es un factor independiente de mortalidad de la asistencia respiratoria mecánica. Se incluyeron 200 pacientes internados en la Unidad de Cuidados Intensivos del Hospital Británico de Buenos Aires. Se registraron características y comorbilidades al ingreso, al inicio de la asistencia respiratoria mecánica, complicaciones y evolución en el Hospital y a los 6 meses. Los 200 pacientes incluidos fueron divididos en dos grupos: Grupo 1 (n = 164 menores de 80 años y Grupo 2 (n = 36 de 80 años o más. No hubo diferencias en la mortalidad en la Unidad de Cuidados Intensivos y en el Hospital entre los pacientes menores de 80 años y los de 80 años o más. (55.56% vs. 41.46% y 58.33% vs. 42.68%. La supervivencia a los 6 meses de los = 80 años fue significativamente menor (22.22% vs. 48.17%, p = 0.0051. En el análisis multivariado solamente un APACHE II > 20 (p = 0.0007 o la ausencia de vida autónoma (p = 0.0028 conservaron poder predictivo independiente. Los pacientes añosos que reciben asistencia respiratoria mecánica no presentan una mayor mortalidad por el sólo hecho de ser ancianos. La restricción de los cuidados terapéuticos invasivos no parece justificada por la edad avanzada.

  5. Influencia del enfoque teórico en el estilo personal del terapeuta

    Directory of Open Access Journals (Sweden)

    Leandro Martín Casari Cobo

    2013-01-01

    Full Text Available Abstract This research paper aims to study the theoretical and technical influences on therapists backgrounds (PST based on his/her own personal style, and also keeping in mind the common and particular features imposed in their tasks, beyond the scope of their work and the specific requirements they completed for their work. For this research, an PST-Q (Fernandez-Alvarez & Garcia, 1998 questionnaire is applied to a sample of 106 psychotherapists from Argentina. Significant differences in their personal style (PST (between psychoanalytic therapists and psychologists with different theoretical orientation are found. The results are analyzed and future aspects of research are created. Resumen El estilo personal del terapeuta se refiere a características habituales que cada uno impone en su tarea como resultado de su peculiar manera de ser, más allá del enfoque de trabajo que utilice y de los requerimientos específicos que le exija la intervención. El objetivo de este artículo de investigación consistió en estudiar la influencia de la orientación téorico-técnica en el desarrollo del Estilo Personal del Terapeuta (EPT. Para ello, se administró el cuestionario EPT-C (Fernández-Álvarez & García, 1998 a una muestra de 106 psicoterapeutas de Argentina, encontrándose diferencias significativas en las funciones del EPT en los terapeutas psicoanalistas en comparación con los psicólogos de otras orientaciones teóricas. Se analizan los resultados y se plantean futuras líneas de investigación.

  6. Influencia del espesor de adhesivo de poliuretano en la resistencia de uniones sometidas a cortadura

    Directory of Open Access Journals (Sweden)

    García-Ledesma, R.

    2005-02-01

    Full Text Available The thickness of adhesive layers in metallic bonded joints has direct influence in the performance and mechanical behaviour of these joints. The aim of this study was to analyse the strength and strain properties of steel overlap joints bonded with polyurethane adhesive layers with different thickness. The results show that the strength is maximum when the thickness of the adhesive layer is very thin, 0.1 mm. When the thickness growth to 1 mm the strength goes down rapidly. For layers from 1 to 1.5 mm the strength goes down slower and from 1.5 to 4 mm the strength is nearly constant. In other hand, the joint strain increase uniformly with adhesive layer thickness growth.

    El espesor de la capa de adhesivo en las uniones por adhesión de materiales metálicos, tiene una influencia notable en el comportamiento y las propiedades mecánicas de dichas uniones. El objeto de este trabajo fue analizar las propiedades de resistencia y desplazamiento, presentadas por uniones a solape de acero, unidas con capas de diferentes espesores de un adhesivo de poliuretano. Los resultados obtenidos muestran que la resistencia mecánica es máxima para capas de adhesivo de espesor muy delgado: 0,1 mm. Cuando el espesor crece de 0,1 hasta 1 mm la resistencia disminuye rápidamente. Para capas desde 1 hasta 1,5 mm la resistencia disminuye más lentamente y, a partir de 1,5 mm, la resistencia permanece prácticamente constante. Por otro lado, los desplazamientos de la unión aumentan uniformemente a medida que crece el espesor de la capa de adhesivo.

  7. Influencia de la betarraga (Beta vulgaris var. cruenta en el aumento de leucocitos, en ratones

    Directory of Open Access Journals (Sweden)

    Jony Amaro

    2014-01-01

    Full Text Available Introducción: La betarraga es una planta oriunda del Mediterráneo utilizada para fines alimenticios y medicinales. Contiene flavonoides. Objetivos: Determinar la influencia del consumo del extracto de Beta vulgaris var. cruenta en el incremento de leucocitos, en el ratón albino. Diseño: Estudio experimental. Lugar: Bioterio de la Institución Educativa 1182. Material biológico: Veinte ratones albinos de la cepa balb/c, machos, de peso promedio 24 g. Intervenciones: Se formó dos grupos, experimental y control, cada uno de diez ratones. Al grupo experimental se le administró vía oral extracto de Beta vulgaris var. cruenta en dosis de 250 mg/kg, volumen de 2 mL, cada cinco horas durante una semana, alternando con nutrientes, y al grupo control solo se le administró nutrientes. Principales medidas de resultados: Recuento de leucocitos. Resultados: Dentro del periodo de acondicionamiento, se observó un ligero incremento en la media de leucocitos del grupo control (3 681 ± 431,1 frente al grupo experimental (3 579 ± 473,5, cuya diferencia no fue significativa. Luego de administrar al grupo experimental el extracto de Beta vulgaris var. cruenta, alternando con sus nutrientes respectivos, se observó diferencia significativa de la media (7 961 ± 275,4 frente al grupo control (3 693 ± 414,7 (t student p<0,05. Conclusiones: En condiciones experimentales, el consumo del extracto de Beta vulgaris var. cruenta incrementó significativamente el número de leucocitos.

  8. Conocimientos sobre sexualidad y su influencia en el embarazo en adolescentes

    Directory of Open Access Journals (Sweden)

    Carmina Alexandra García Macías

    2017-06-01

    Full Text Available Introducción: El embarazo en la adolescencia es en la actualidad un problema de salud que genera serias consecuencias personales, sociales y económicas, con repercusión en la salud individual, familiar y colectiva. Objetivo: Identificar los conocimientos sobre la sexualidad y su influencia en el embarazo en la adolescencia. Métodos: Se realizó un estudio observacional analítico, transversal, en un universo de 80 adolescentes de 15 a 19 años del Equipo Urbano de Salud 23 Latacunga, a quienes se les aplicó una encuesta sobre sexualidad y métodos anticonceptivos; los datos fueron procesados en el programa SPSS, el análisis se realizó mediante el test de Chi Cuadrado con un nivel de significación de p<0.05. Resultados: La mayoría de los adolescentes presentó conocimientos insuficientes sobre sexualidad (n=50 62.5%. El inicio de las relaciones sexuales predominó a los 15 años (n=11 13.7%; el uso de métodos anticonceptivos en la primera relación sexual fue bajo (n=30 37.5%; el método anticonceptivo más utilizado fue el condón con un (n=22 27.5%, a continuación, se ubicaron los anticonceptivos naturales.  Conclusiones: Predominó el desconocimiento sobre sexualidad y métodos anticonceptivos, a la vez fue temprano el inicio de la vida sexual con un poco utilización de métodos de anticoncepción.

  9. Educación para la salud. Influencia en ancianos hipertensos

    Directory of Open Access Journals (Sweden)

    Regla Ledia González Sánchez

    1999-01-01

    Full Text Available Se realizó estudio descriptivo longitudinal, sobre la influencia de la Educación para Salud en la adquisición de conocimientos y cambios de actitud y control de la enfermedad en ancianos hipertensos de 2 consultorios del Policlínico California, en el año 1977. El universo lo constituyeron 126 ancianos, a los que se les aplicó MINI-MENTAL-TEST, resultando aptos para la investigación 92 gerontes, a éstos se le realizó encuesta y resultó que el mayor porcentaje tenía conocimientos sobre su enfermedad evaluados de regular, al igual que la actitud ante la misma. Estos aspectos mejoraron después de la técnica educativa, incrementándose también el número de pacientes controlados de su enfermedad. Se formularon recomendaciones.A descriptive and longitudinal study about the influence of health education on the acquisition of knowledge and changes of attitude and control of hypertension was conducted among the elderly from 2 family physician offices of the "California" Polyclinic, in 1997. The MINI-MENTAL-TEST was applied to the 126 aged people who took part in this study. According to the results, 92 of them proved to be apt. After surveying them, it was observed that most of them knew about their disease and were evaluated as fair. They received the same evaluation for their attitude towards the disease. These aspects improved when the aducative technique was used. The number of patients under control increased, too. Recommendations were made.

  10. Influencia de las relaciones familiares sobre el aborto provocado en adolescentes

    Directory of Open Access Journals (Sweden)

    Jully Calderón S

    2006-10-01

    Full Text Available Objetivos: Determinar la influencia de las relaciones familiares sobre el aborto provocado en adolescentes. Materiales y métodos: Estudio de casos y controles; los casos fueron 58 adolescentes con aborto provocado que acudieron al Hospital Regional Docente de Trujillo, por hemorragia, y el grupo control fueron 58 adolescentes pareadas según edad de la paciente, edad gestacional y nivel socioeconómico, que continuaron con el embarazo y acudieron al control prenatal en el mismo hospital. Resultados: Sólo 20% de los casos comunicó a sus padres sobre el embarazo, a diferencia del 62% de los controles (p<0,001, la falta de confianza hacia los padres estuvo asociada con el aborto provocado (OR: 4,5; IC95: 1,7-12,3, no se encontró asociación con el antecedente familiar de aborto o con la violencia intrafamiliar. Las reacciones negativas (violencia, retirar a la afectada de los estudios o hacerla trabajar de los padres ante la noticia del aborto fueron más frecuentes en el grupo con aborto (OR: 14,1; IC95: 3,9-50,9; así como la presentación de molestias y discusiones entre los miembros de las familias de los casos (OR: 23,9; IC95: 12,4-208,7. Conclusión: La comunicación y el nivel de confianza con los padres, así como reacciones negativas ante la noticia del embarazo están fuertemente relacionados con el aborto provocado, en las adolescentes de Trujillo.

  11. INFLUENCIA DEL CULTIVO INTERCALADO EN LA PRODUCCIÓN Y CALIDAD DEL FRUTO DE TOMATE CEREZA

    Directory of Open Access Journals (Sweden)

    Fabricio Rossi

    2013-12-01

    Full Text Available El presente trabajo tiene por objetivo determinar la influencia en la cosecha y calidad de los frutos de Solanum lycopersicum L. (1753 cv. cereza [Lycopersicum esculentum Mill. 1768] (tomate en convivencia con cultivos intercalares de cinco Fabaceae, plantas auxiliadoras en la agricultura y dos tratamientos con y sin residuos de cosecha de Zea mayz L. El estudio fue im- plantado en el Polo Centro Sul, Piracicaba-SP. Brasil, en suelo Argisol rojo-amarillo distrófico. El diseño experimental fue en bloque al azar con cinco repeticiones y ocho tratamientos en con- vivencia con plantas de tomate con:1 Sin residuos de ZEAMA-Zea mayz L.;2 Con residuos de ZEAMA- Zea mayz L. cv.cativerde 2; 3 CANEN- Canavalia ensiformis (L. DC.; 4CRO- JU- Crotalaria juncea L.; 5 MUCPR- Mucuna pruriens (L. DC. cv. arbusto (enana o anã; 6 VIGRA- Vigna radiata L. 7 LUPAL- Lupinus albus L.; 8 VIGUN- Vigna unguiculata (L. Walp. Los resultados mostraron que la producción y calidad de los frutos de tomate fue normal, sin ataque de plagas y no se aplicó ningún agrotóxico. El abono verde, así como la presencia o ausencia de residuos de cosecha de maíz, no interfiere en la temporada de cosecha. En cuanto al análisis de sólidos solubles totales (SST y acidez (pH no difirió entre los tratamientos.

  12. Una nueva ultraestructura de ópalo CT en silcretas. Posible indicador de influencia bacteriana

    Directory of Open Access Journals (Sweden)

    Bustillo, Mª A.

    1995-04-01

    Full Text Available Electron microscope observations of opaline silcretes found in the playa of a Miocene shallow lake reveal new opal CT microstructures. These microstructures are made up of fibres, filaments or rods, which are formed, in tum by coalesced microspheres or microhemispheres (0,1-0,2 µ diameter. They are up to 10 µ in length although larger ones could exist. They are straight, bent, wavy or even hairpin shaped. These microstructures comprise part of the opaline mass of the silcretes and are very similar to both neogenic opaline structures which are formed by bacterial intluence and to silicified biofilms. Therefore microbial mediation could exist in the genesis of this opal CT, although a possible inorganic origin by silicification of sepiolite is also considered.Un estudio mediante MEB de silcretas miocenas opalinas formadas por silicificación de playas en un ambiente de «playa-lake» pone de manifiesto la existencia de una nueva microestructura de ópalo CT. Esta microestructura denominada en general fibrosa, se manifiesta por la presencia de multitud de fibras, filamentos o varillas formadas por la alineación de microesferas o microhemisferas que presentan un diámetro entre 0,1 y 0,2 µ. Las fibras, filamentos o varillas tienen formas variables: rectas, curvadas, onduladas y «en horquilla», y presentan longitudes de hasta 10 µ, aunque podrían existir longitudes mayores. La disposición organizada de las microesferas en filamentos o fibras, constituyendo la masa general del ópalo, y su parecido con microestructuras opalinas que han sido formadas por influencia bacteriana, hacen considerar esta hipótesis, aunque no se puede descartar totalmente un origen inorgánico por silicificación de sepiolita.

  13. La influencia de la responsabilidad social en la intención de compra de los consumidores de detergentes

    OpenAIRE

    Murt Prats, Patrícia

    2009-01-01

    En este trabajo se realiza un estudio para determinar la relación entre la responsabilidad social corporativa en la publicidad y el comportamiento de los consumidores. Así, se propone un modelo que comprara la influencia de la responsabilidad social y otras características de la imagen de marca sobre la intención de compra. El sector de productos elegido para el desarrollo del estudio empírico es el de detergentes para lavar ropa, en concreto se analiza el peso de la responsabi...

  14. Influencia de los estilos de crianza en el desarrollo de conductas adictivas hacia el consumo de drogas

    OpenAIRE

    Sarabia Cadaya, Eva María

    2015-01-01

    Dado que el consumo de drogas supone un importante problema a nivel social, y la prevalencia del mismo en la adolescencia es significativamente elevada, el propósito fundamental de este proyecto ha sido destacar la influencia que ejerce la familia, en general, y los estilos parentales, en particular, sobre los hijos en el desarrollo de conductas adictivas hacia las drogas. Además de hacer referencia a la investigación de Baumrind (1971,1991), pionera en los estudios sobre estilos parent...

  15. Influencia de la movilización del plexo sacro en pacientes con esclerosis múltiple

    OpenAIRE

    Ulecia Barrios, Miriam

    2016-01-01

    INTRODUCCIÓN: La esclerosis múltiple se considera la mayor causa no traumática de discapacidad en adultos jóvenes, presentando un 80% de los pacientes espasticidad. La movilización neural, considerando el sistema nervioso como un único sistema continuo, mejora las condiciones fisiológicas del sistema. OBJETIVOS: Determinar la influencia de la movilización del plexo sacro en la fatiga, en la espasticidad, en el rango articular de la flexión de cadera y en la velocidad y segurida...

  16. El lenguaje de los programas deportivos en televisión y su influencia en el lenguaje juvenil actual

    OpenAIRE

    Sastre-García, Ángel

    2012-01-01

    El trabajo planteado pretende demostrar la implantación del lenguaje deportivo en el lenguaje juvenil y la importancia del lenguaje de los periodistas deportivos en televisión. Hemos intentado evidenciar asimismo la influencia de las nuevas redes sociales de internet en los programas deportivos televisivos. Para ello hemos repasado la importancia del deporte en la evolución de la televisión en España, así como los principales géneros y formatos a lo largo del tiempo. A partir de esta intro...

  17. Entretenimiento, espiritualidad, familia y su relación con la influencia de pares en el consumo

    OpenAIRE

    Rolando Salazar Sarmiento; Rocío Morales; Samuel Noh; Bruna Brands; Hayley Hamilton; Denise Gastaldo; Maria da Gloria Miotto Wright; Francisco Cumsille; Akwatu Khenti

    2015-01-01

    El presente estudio fue una investigación de tipo exploratorio quantitativa. Examina la relación entre el uso de drogas en estudiantes universitarios de una universidad en Bogotá, Colombia y la influencia del grupo de pares, en torno al efecto moderador de factores socio-culturales como las relaciones familiares, el entretenimiento y la espiritualidad en dicho consumo. La muestra non probabilistica fue conformada por 350 estudiantes. El 89,4% de los jóvenes encuestados rep...

  18. Entretenimiento, espiritualidad, familia y su relación con la influencia de pares en el consumo

    OpenAIRE

    Sarmiento, Rolando Salazar; Morales, Rocío; Noh, Samuel; Brands, Bruna; Hamilton, Hayley; Gastaldo, Denise; Wright, Maria da Gloria Miotto; Cumsille, Francisco; Khenti, Akwatu

    2015-01-01

    El presente estudio fue una investigación de tipo exploratorio quantitativa. Examina la relación entre el uso de drogas en estudiantes universitarios de una universidad en Bogotá, Colombia y la influencia del grupo de pares, en torno al efecto moderador de factores socio-culturales como las relaciones familiares, el entretenimiento y la espiritualidad en dicho consumo. La muestra non probabilistica fue conformada por 350 estudiantes. El 89,4% de los jóvenes encuestados reportaran que consumen...

  19. Influencia del estrés académico en el sistema binocular en universitarios de la UVA

    OpenAIRE

    López Gómez, Alejandra

    2017-01-01

    Objetivo: El estrés visual, tras trabajo prolongado en cerca, produce modificaciones en el sistema binocular. Esta hipótesis ha sido poco contrastada experimentalmente. El objetivo principal es medir la influencia del estrés académico en estudiantes universitarios de la UVA mediante la medida de la foria. Métodos: Se ha medido la foria en 22 estudiantes, con su corrección habitual, antes y después de un examen, mediante tres métodos: técnica de la varilla de Maddox, técnica de Von Graefe y...

  20. Influencia del flujo de tráfico vehicular en la contaminación sonora del Cercado de Lima

    OpenAIRE

    Visaga Fernández, Sandra Indira; E. P. de Ingeniería Ambiental, Universidad Peruana Unión - Lima

    2016-01-01

    En este trabajo, se ha realizado una medición experimental de los niveles de ruido en 61 puntos estratégicos previamente definidos mediante una evaluación de la distribución espacial del Cercado de Lima, y a la vez en estosmismos puntos se ha recolectado información sobre el flujo del tráfico vehicular para determinar su influencia en la contaminación sonora. Para la recolección de data de campo; niveles de ruido y flujo de tráfico vehicular, se hadeterminado una distribución temporal, compre...

  1. Los gremios económicos y su influencia en la creación de ventajas competitivas sectoriales

    OpenAIRE

    López Padilla, Carlos Andrés

    2006-01-01

    La presente investigación se centra en un discernimiento teórico sobre el papel de los gremios económicos y su influencia en la creación de ventajas competitivas sectoriales, a la luz de la teoría de la ventaja competitiva y las teorías microeconómicas de mercado, presentando herramientas teóricas que inciden en la propuesta de modelos de gestión orientados a la creación sostenimiento y avance de las ventajas competitivas sectoriales. Los principales disertaciones aquí desarrolladas se centra...

  2. Influencia de los rasgos de personalidad en la aplicación de la Terapia de Juego no Directiva

    OpenAIRE

    Luna, María Augusta

    2013-01-01

    Esta investigación nace de la necesidad de estudiar la aplicación del Modelo Integrativo en el ámbito infantil. Específicamente, busca analizar y relacionar la influencia de los rasgos de personalidad en la aplicación de la terapia de juego no directiva centrada en el niño, como lo sostiene la Psicoterapia Integrativa focalizada en la personalidad. La metodología utilizada es el análisis de casos, que resultó efectiva para poder concluir que la terapia de juego no directiva centrada en el niñ...

  3. La influencia del género en los estilos de liderazgo y dirección

    OpenAIRE

    García Ruiz, Luna

    2013-01-01

    Este Trabajo Fin de Máster (TFM) pretende llevar a cabo un análisis de la influencia del género en los estilos de liderazgo y en los estilos de dirección empleados por los directores/as que ocupan cargos de responsabilidad, a través de la revisión y estudio de diversas publicaciones. En primer lugar, y con el fin de poder llegar a concluir si el género puede ser un factor influyente en los estilos de liderazgo y dirección, hemos tratado de establecer a través de las definiciones aportadas ...

  4. Influencia del evento el niño-oscilacion del sur sobre las precipitaciones en cinco ciudades del litoral ecuatoriano

    OpenAIRE

    Espol; Rodriguez Aguilar, Jose Antonio; Luna Rodriguez, Javier Alejandro

    2017-01-01

    La investigación se realizó con el objetivo de evaluar la influencia del fenómeno enos, caracterizado por los índices oni e icen, sobre las precipitaciones ocurridas en el período de 1975-2016 en ciudades del litoral ecuatoriano, con la finalidad de que contribuya al diseño de lineamientos para mejorar la respuesta de la población ante la posible presencia del evento Guayaquil MAGISTER EN CAMBIO CLIMATICO

  5. TENSIONES DE CRECIMIENTO EN Eucalyptus globulus DE GALICIA (ESPAÑA): INFLUENCIA DE LA SILVICULTURA Y ESTRATEGIAS DE ASERRADO

    OpenAIRE

    Touza Vázquez,Manuel C

    2001-01-01

    El eucalipto blanco (Eucalyptus globulus Labill) constituye el principal recurso forestal de las áreas de influencia atlántica de la Península Ibérica, donde ocupa una franja costera que da forma a los bosques más productivos de Europa. De forma paralela a la expansión de las plantaciones orientadas hacia la producción de fibra, numerosos industriales están interesados en diversificar las aplicaciones de la madera de eucalipto. No obstante, el mayor problema para procesar eucaliptos es la apa...

  6. Influencia que tienen los programas de televisión infantil en los argumentos del juego simbólico

    OpenAIRE

    Jácome R., María Esther

    2004-01-01

    La influencia negativa de los programas televisivos dirigidos ó no a niños de 4 a 5 años determinan los argumentos del juego infantil, esta situación se evidencia en las repetidas manifestaciones de agresividad en el entorno escolar y familiar; en el uso de términos despectivos que descalifican y ridiculizan a compañeros y amigos; en los argumentos de conversación frente al juego; en el rechazo a las actividades físicas que impliquen movimiento; en la asunción de roles y postur...

  7. Evaluación de la influencia en el desarrollo infantil de un proyecto de educación musical

    OpenAIRE

    Casas Lloret, Jara

    2015-01-01

    Esta investigación pretende determinar si hay influencias entre un proyecto de Educación Musical Infantil y el desarrollo integral de los niños/as que participan en el mismo, siguiendo el modelo de inteligencias múltiples de Gardner. Se evalúan niños/as entre 3 y 7 años de 7 colegios de Sevilla. Se hace un recorrido por el desarrollo humano, viendo sus diferentes dimensiones, centrándonos posteriormente en el desarrollo emocional. Se revisa la legislación actual para ver qué base teórica tien...

  8. La Influencia de la educación sobre la participación política

    OpenAIRE

    Jorge, José Eduardo; Leguizamón, Mara; Steciow, Ulises

    2013-01-01

    La investigación de la cultura política muestra que el nivel educativo de los ciudadanos tiene una influencia crucial sobre la magnitud y la calidad de su participación política. El artículo aborda los aspectos teóricos de la relación entre educación e implicación política, examina los datos disponibles para la Argentina que surgen de estudios por encuesta de alcance nacional y regional y contrasta las principales hipótesis causales. Facultad de Periodismo y Comunicación Social

  9. INFLUENCIA DE LA TEMPERATURA Y EL PORCENTAJE DEL CATALIZADOR EN LA ETANÓLISIS DEL ACEITE DE PALMA

    OpenAIRE

    Paulo César Narváez; Francisco Sánchez Castellanos; Jesús Alfonso Torres; Luisa Fernanda Ponce de León

    2008-01-01

    En este artículo se presenta la influencia de la temperatura y el porcentaje de catalizador sobre la etanólisis del aceite de palma, y los resultados se comparan con los obtenidos para la metanólisis del mismo aceite. Se realizaron ensayos a 60, 70 y 75 ºC, empleando como catalizador NaOH. Los porcentajes en peso de catalizadorcon respecto al aceite de palma fueron 0,20; 0,50 y 1,00. Los resultados muestran que incrementos en la temperaturay en el porcentaje de catal...

  10. Efecto de la altura de poda en Leucaena leucocephala y su influencia en el rebrote y rendimiento de Panicum maximum

    OpenAIRE

    H. M. Bacab; F. J. Solorio; S. B. Solorio

    2012-01-01

    Una de las prácticas importantes de manejo en los sistemas de Leucaena leucocephala asociada con pastos tropicales, como Panicum maximum, es la poda; en la actualidad se continúan los estudios para determinar los efectos de esta práctica en el componente arbóreo y herbáceo. Por todo ello, en el presente trabajo se evaluó el efecto de tres alturas de poda en Leucaena leucocephala cv. Cunningham y su influencia en la pastura asociada (Panicum maximum cv. Tanzania). El estudio se realizó en la é...

  11. Plan de gestión integral del riego en la zona de influencia de la acequia de Tabacundo

    OpenAIRE

    Ochoa Mármol, Alexis Mauricio

    2013-01-01

    El presente producto consistió en la elaboración de plan integral de riego de la acequia Tabacundo el cual consta de un diagnóstico situacional en la zona de influencia, identificación de problemas, análisis del medio interno y externo, identificación de actores, planteamiento de la misión, visión, objetivos y estrategias para mejorar la gestión del agua de riego en la acequia Tabacundo dentro de los ámbitos socio-organizativo, técnico, económico productivo y ambiental. Este producto se ...

  12. Influencia del status social subjetivo en la salud de las mujeres inmigrantes latinoamericanas residentes en la Comunidad de Canabria

    OpenAIRE

    Sanchón Macías, Maria Visitación

    2012-01-01

    El propósito de la tesis es estudiar las características socioeconómicas y el estatus social subjetivo de las mujeres inmigrantes y analizar su relación con la salud. Así como, explorar los determinantes del estatus social subjetivo y como las mujeres explican la influencia de los mismos en sus trayectorias de salud. El estudio utilizó metodología cuantitativa y cualitativa. Se observó una asociación débil entre las medidas del estatus socioeconómico y la salud percibida. El estatus soc...

  13. Influencia de la solidez en un aerogenerador VAWT con rotor H-Darrieus y perfiles simétricos

    OpenAIRE

    Alonso Gómez, Álvaro

    2016-01-01

    Mediante el empleo de la Mecánica Computacional de Fluidos, se estudia la influencia que tiene el grado de solidez en el comportamiento de un aerogenerador. Se estudia un aerogenerador de eje vertical con rotor H-Darrieus y tres perfiles simétricos en el que se analizan tres grados de solidez diferentes, generándose por lo tanto tres modelos, para cada uno de los cuales se obtiene la curva de rendimiento correspondiente. Para construir la curva se van realizando simulaciones a diferentes ve...

  14. Influencia del sistema de explotación del ganado ovino sobre la calidad de la leche

    OpenAIRE

    Sanjuan Iglesias, David

    2014-01-01

    Estudio para determinar la influencia del sistema de explotación de ganado ovino (intensivo, semi-intensivo, semi-extensivo y orgánico) sobre la calidad de la leche mediante el análisis de la composición de ácidos grasos, vitaminas y actividad antioxidante de la leche de oveja procedente de 20 explotaciones ganaderas de Castilla y León a lo largo de 12 meses. Ingeniería Agrícola y Foresta Máster en Calidad, Desarrollo e Innovación de Alimentos

  15. Influencia de costos totales en los presupuestos de ventas en MYPEs confeccionistas textiles en Los Olivos 2016

    OpenAIRE

    Guevara Hermoza, Luis Alberto

    2017-01-01

    Esta investigación tiene el interés de demostrar la influencia de los costos totales en el presupuesto de ventas de productos terminados en las empresas MYPEs textiles de confecciones. Estas empresas son dirigidas por sus dueños quienes no cuentan o tienen escasa formación para los negocios y, en consecuencia, enfrentan problemas sin herramientas adecuadas para resolverlos. Usualmente cuando el director de la MYPE se encuentra con poco efectivo o sus ganancias son muy reduci...

  16. The Presence of Telomere Fusion in Sporadic Colon Cancer Independently of Disease Stage, TP53/KRAS Mutation Status, Mean Telomere Length, and Telomerase Activity

    Directory of Open Access Journals (Sweden)

    Hiromi Tanaka

    2014-10-01

    Full Text Available Defects in telomere maintenance can result in telomere fusions that likely play a causative role in carcinogenesis by promoting genomic instability. However, this proposition remains to be fully understood in human colon carcinogenesis. In the present study, the temporal sequence of telomere dysfunction dynamics was delineated by analyzing telomere fusion, telomere length, telomerase activity, hotspot mutations in KRAS or BRAF, and TP53 of tissue samples obtained from 18 colon cancer patients. Our results revealed that both the deficiency of p53 and the shortening of mean telomere length were not necessary for producing telomere fusions in colon tissue. In five cases, telomere fusion was observed even in tissue adjacent to cancerous lesions, suggesting that genomic instability is initiated in pathologically non-cancerous lesions. The extent of mean telomere attrition increased with lymph node invasiveness of tumors, implying that mean telomere shortening correlates with colon cancer progression. Telomerase activity was relatively higher in most cancer tissues containing mutation(s in KRAS or BRAF and/or TP53 compared to those without these hotspot mutations, suggesting that telomerase could become fully active at the late stage of colon cancer development. Interestingly, the majority of telomere fusion junctions in colon cancer appeared to be a chromatid-type containing chromosome 7q or 12q. In sum, this meticulous correlative study not only highlights the concept that telomere fusion is present in the early stages of cancer regardless of TP53/KRAS mutation status, mean telomere length, and telomerase activity, but also provides additional insights targeting key telomere fusion junctions which may have significant implications for colon cancer diagnoses.

  17. Different TP53 mutants in p53 overexpressed epithelial ovarian carcinoma can be associated both with altered and unaltered glycolytic and apoptotic profiles.

    Science.gov (United States)

    Antoun, Stephanie; Atallah, David; Tahtouh, Roula; Alaaeddine, Nada; Moubarak, Malak; Khaddage, Abir; Ayoub, Eliane Nasr; Chahine, George; Hilal, George

    2018-01-01

    p53 is a tumor suppressor and key regulator of glycolysis in cancer cells, however highly mutated in tumors. In ovarian cancer, studies concerning p53 mutations focus on the DNA binding domain since the majority of hotspot mutations affects this region. Yet, mutations in other regions such as the proline rich domain may also affect the protein's expression and activity. The aim of this study is to investigate the effect of various positions of mutations in TP53 gene on glycolysis, apoptosis and transcription of p53 target genes. Mutations frequency and their effect on p53 expression were assessed by PCR-SSCP, sequencing and immunohistochemistry on 30 ovarian cancer biopsies. Six tumors were cultured, as well as SK-OV-3, OVCAR-3 and Igrov-1. SK-OV-3 cells were transfected with 2 TP53 mutants. p53 transcriptional activity was assayed by qPCR, apoptosis by flow cytometry and glycolysis by glucose and lactate measurements, with quantification of glycolytic enzymes expression. Our results showed a high frequency of the P72R mutant, associated with p53 overexpression in the ovarian biopsies. However, P72R mutant cells showed similar apoptosis and glycolysis as WT cells. DNA binding domain mutations decreased the transcriptional activity of the protein and increased glucose consumption and lactate production. Despite the overexpression of the P72R mutated protein in the biopsies, it showed a similar apoptotic activity and glucose regulation ability as WT p53. Knowing that p53 expression status is used for chemotherapeutic approaches and prognosis in ovarian cancer, the results obtained highlight the importance of locating TP53 mutations.

  18. Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

    Science.gov (United States)

    Al-Shamsi, Humaid O.; Jones, Jeremy; Fahmawi, Yazan; Dahbour, Ibrahim; Tabash, Aziz; Abdel-Wahab, Reham; Abousamra, Ahmed O. S.; Shaw, Kenna R.; Xiao, Lianchun; Hassan, Manal M.; Kipp, Benjamin R.; Kopetz, Scott; Soliman, Amr S.; McWilliams, Robert R.; Wolff, Robert A.

    2016-01-01

    Background The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. Methods Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher’s exact test was used to determine the association between mutation status and clinical features. Results A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. Conclusions This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation. PMID:28078112

  19. Comprehensive analysis of BRCA1, BRCA2 and TP53 germline mutation and tumor characterization: a portrait of early-onset breast cancer in Brazil.

    Directory of Open Access Journals (Sweden)

    Dirce Maria Carraro

    Full Text Available Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC and TP53 genes was performed in 54 unrelated patients <35 y; their tumors were investigated with respect to transcriptional and genomic profiles as well as hormonal receptors and HER2 expression/amplification. Germline mutations were detected in 12 out of 54 patients (22% [7 in BRCA1 (13%, 4 in BRCA2 (7% and one in TP53 (2% gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes. Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients.

  20. Comprehensive Analysis of BRCA1, BRCA2 and TP53 Germline Mutation and Tumor Characterization: A Portrait of Early-Onset Breast Cancer in Brazil

    Science.gov (United States)

    Carraro, Dirce Maria; Koike Folgueira, Maria Aparecida Azevedo; Garcia Lisboa, Bianca Cristina; Ribeiro Olivieri, Eloisa Helena; Vitorino Krepischi, Ana Cristina; de Carvalho, Alex Fiorini; de Carvalho Mota, Louise Danielle; Puga, Renato David; do Socorro Maciel, Maria; Michelli, Rodrigo Augusto Depieri; de Lyra, Eduardo Carneiro; Grosso, Stana Helena Giorgi; Soares, Fernando Augusto; de Souza Waddington Achatz, Maria Isabel Alves; Brentani, Helena; Moreira-Filho, Carlos Alberto; Brentani, Maria Mitzi

    2013-01-01

    Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC) and TP53 genes was performed in 54 unrelated patients BRCA1 (13%), 4 in BRCA2 (7%) and one in TP53 (2%) gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes). Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients. PMID:23469205

  1. Association between copper excess, zinc deficiency, and TP53 mutations in esophageal squamous cell carcinoma from Kashmir Valley, India--a high risk area.

    Science.gov (United States)

    Dar, Nazir Ahmad; Mir, Mohammad Muzaffar; Salam, Irfana; Malik, Mushtaq Ahmad; Gulzar, Ghulam Mohammad; Yatoo, Ghulam Nabi; Ahmad, Aquil; Shah, Azra

    2008-01-01

    Trace element deficiency or excess is implicated in the development or progression in some cancers. Here we report the elevated level of copper and low level of zinc in the plasma of esophageal cancer patients in Kashmir India--a high incidence area. The average level of copper was significantly higher (P gender and age in patients as compared to controls. Similarly, smokers depicted a significant increase in serum copper (N = 39, P = 0.002) and a decrease in serum zinc approaching level of significance in the patient group as compared to controls. The copper and zinc levels were significantly altered in patients (N = 40) when compared to controls as a function of snuff consumption. The differences in the levels of copper and zinc showed significant association with the consumption of local salted tea up to 1,500 ml per day, but the changes were insignificant beyond that. Patients with poorly differentiated tumors (N = 7) had a higher copper concentration than those with moderately or well-differentiated tumors (P imbalance in copper and zinc levels may lead to higher prevalence of TP53 mutations, we compared the 3 variables, and no association was found between copper concentration and TP53 mutation status; but patients with TP53 mutant tumor had lower zinc levels than those with no mutation. In conclusion, our results point toward a role of the trace element imbalance in the esophageal tumorigenesis in high-risk Kashmiri population exposed to a range of nitroso compounds or their precursors. Further prospective cohort studies are warranted to determine whether change in the plasma zinc and copper homeostasis may represent an independent risk factor for this malignancy as well as a possible target for preventive intervention.

  2. Association of the highly prevalent TP53 R337H mutation with pediatric choroid plexus carcinoma and osteosarcoma in southeast Brazil.

    Science.gov (United States)

    Seidinger, Ana Luiza; Mastellaro, Maria José; Paschoal Fortes, Fernanda; Godoy Assumpção, Juliana; Aparecida Cardinalli, Izilda; Aparecida Ganazza, Mônica; Correa Ribeiro, Raul; Brandalise, Silvia Regina; Dos Santos Aguiar, Simone; Yunes, José Andrés

    2011-05-15

    The inherited, low-penetrance arginine-to-histidine substitution at codon 337 (R337H) of the tumor protein 53 gene (TP53) is clustered in southeast Brazil (estimated frequency, 0.3%). Although its tumorigenic effect initially appeared to be tissue-specific, recent evidence suggests its association with a broader range of tumors. Therefore, the authors of this report investigated the spectrum of pediatric malignancies associated with the TP53 R337H mutation at a single referral institution in southeast Brazil. Genomic DNA samples from 493 children with malignancies were screened for the R337H mutation. Available tumor samples from carriers were investigated for loss of heterozygosity (LOH) and nuclear p53 accumulation. Clinical data were obtained from medical records. Sixty-five of 70 patients (93%) with adrenocortical tumors (ACTs), 9 of 13 patients (69%) with choroid plexus carcinoma (CPC), and 3 of 41 patients (7.3%) with osteosarcoma carried the mutation. The proportion of CPC to choroid plexus papilloma (CPP) was much higher than that reported elsewhere. Osteosarcoma in carriers had a significantly poorer outcome (P = .02). The mutation was not identified in patients who had acute lymphoblastic leukemia (ALL) (n = 187), recurrent ALL (n = 49), acute myeloid leukemia (n = 44), lymphoma (n = 30), non-CPC central nervous system tumors (n = 26), Ewing sarcoma (n = 25), or rhabdomyosarcoma (n = 8). Among the tumors that were available for analysis, LOH with retention of the mutant allele was confirmed in 21 of 21 ACTs, in 2 of 2 CPCs, and in 2 of 3 osteosarcomas that were positive for R337H. CPCs and osteosarcomas that were positive for R337H had marked nuclear accumulation of p53. The current findings demonstrated compellingly that the TP53 R337H mutation is associated not only with ACT but also with CPC and, to a lesser extent, with osteosarcoma, both of which are core-component tumors of the Li-Fraumeni syndrome. 2010 American Cancer Society.

  3. TP53 mutations, human papilloma virus DNA and inflammation markers in esophageal squamous cell carcinoma from the Rift Valley, a high-incidence area in Kenya

    Directory of Open Access Journals (Sweden)

    Martel-Planche Ghislaine

    2011-10-01

    Full Text Available Abstract Background Squamous Cell Carcinoma of Esophagus is one of the most common malignancies in both men and women in eastern and south-eastern Africa. In Kenya, clinical observations suggest that this cancer is frequent in the Rift Valley area. However, so far, there has been no report on the molecular characteristics of esophageal squamous cell carcinoma (ESCC in this area. Results We have analyzed TP53 mutations, the presence of human papilloma virus (HPV DNA and expression of inflammation markers Cyclooxygenase 2 (Cox-2 and Nitrotyrosine (NTyR in 28 cases (13 males and 15 females of archived ESCC tissues collected at the Moi Teaching and Referral Hospital in Eldoret, Kenya. Eleven mutations were detected in TP53 exons 5 to 8 (39%. All ESCC samples were negative for HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 70, 73 and 82. Immunohistochemical analysis of Cox-2 and NTyR showed a low proportion of positive cases (17.4% and 39.1%, respectively. No association between the above markers and suspected risk factors (alcohol or tobacco use, hot tea drinking, use of charcoal for cooking was found. Conclusion Our findings suggest that mechanisms of esophageal carcinogenesis in eastern Africa might be different from other parts of the world. Low prevalence of TP53 mutation compared with other intermediate or high incidence areas of the world highlights this hypothesis. Our data did not support a possible ole of HPV in this series of cases. Further studies are needed to assess and compare the molecular patterns of ESCC from Kenya with those of high-incidence areas such as China or Central Asia.

  4. A novel de novo missense mutation in TP63 underlying germline mosaicism in AEC syndrome: implications for recurrence risk and prenatal diagnosis.

    Science.gov (United States)

    Barbaro, Vanessa; Nardiello, Paola; Castaldo, Giuseppe; Willoughby, Colin E; Ferrari, Stefano; Ponzin, Diego; Amato, Felice; Bonifazi, Ernesto; Parekh, Mohit; Calistri, Arianna; Parolin, Cristina; Di Iorio, Enzo

    2012-08-01

    Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant ectodermal dysplasia syndrome. It is caused by heterozygous mutations in TP63, encoding a transcriptional factor of the p53 family. Mutations in TP63, mainly missense in exons 13 and 14 encoding the sterile alpha motif (SAM) and the transactivation inhibitory (TI) domains, account for 99% of mutations in individuals with AEC syndrome. Of these, ≥70% are de novo mutations, present in the affected patient, but not in parents nor in healthy siblings. However, when a mutation appears de novo, it is not possible to differentiate between a sporadic mutation, or germline mosaicism in the parents. In this latter case, there is a risk of having additional affected offspring. We describe two sisters with AEC syndrome, whose parents were unaffected. Both patients carried the heterozygous c.1568T>C substitution in exon 13 of TP63, resulting in a p.L523P change in the SAM domain of the protein. Analyses of DNA from parental blood cells, seminal fluid (from the father) and maternal cells (buccal, vaginal, and cervical) did not reveal the mutation, suggesting that the mosaicism may involve a very low percentage of cells (very low grade somatic mosaicism) or, more likely, maternal gonadal mosaicism. Mosaicism must be considered for the assessment of recurrence risk during genetic counseling in AEC syndrome, and pre-implantation/prenatal genetic diagnosis should be offered to all couples, even when the mutation is apparently de novo. Copyright © 2012 Wiley Periodicals, Inc.

  5. Influencia de las hormonas metabólicas y la nutrición en el desarrollo folicular en el ganado bovino: implicaciones prácticas

    OpenAIRE

    Piedad Cristina Rivas López; Álvaro Suárez Londoño; Eugenio Ramírez Cardona

    2011-01-01

    La nutrición tiene una influencia en el comportamiento reproductivo de la hembra bovina, pero el mecanismo por el cual se ve afectado dicho desempeño es poco conocido. Aunque las investigaciones se han centrado en la influencia de la nutrición sobre el eje hipotálamo-hipófisis, estudios más recientes han probado la hipótesis que las hormonas metabólicas, como señales nutricionales, ejercen un efecto directo en el ovario. En el ganado, el tratamiento con somatotropina bovina recombinante (rGH)...

  6. DIAGNÓSTICO INTEGRAL DEL ÁREA DE INFLUENCIA DE LA UNIVERSIDAD NACIONAL DE LUJÁN. Una herramienta para la gestión.

    OpenAIRE

    Rey, Alicia; Becerra, Rosa María; Pereira, Nélida da Costa; Goldwaser, Beatriz; Monterroso, Elda; Néspolo, Eugenia; Schulman, Diana; Testa, Amalia

    2007-01-01

    Se presenta en esta ponencia el trabajo de configuración del programa “DIAGNÓSTICO INTEGRAL DEL AREA DE INFLUENCIA DE LA UNIVERSIDAD NACIONAL DE LUJAN: Evaluación e impacto de acciones y servicios hacia la comunidad”. La labor en equipo, que está avalada por disposición 688/06 del Consejo Directivo Departamental de Ciencias Sociales de la Universidad Nacional de Luján (UNLu.), tiene como meta perfilar el área de influencia de la UNLu para establecer un diagnóstico de los territorios involucra...

  7. Influencia de la localización en los patrones de movilidad metropolitana; análisis comparado según tipologia de encuesta.

    OpenAIRE

    Monzón de Cáceres, Andrés; La Paix Puello, Lissy Cesarina; Delgado Iglesias, Miguel Angel; Fernández Heredia, Álvaro

    2008-01-01

    Este trabajo de investigación ha tenido como primer objetivo analizar la influencia de la tipología de encuesta en el ratio de movilidad, comparando la basada en los viajes, con la basada en las actividades realizadas, que es la más utilizada internacionalmente. Los resultados muestran que la encuesta de actividades recoge más viajes. El segundo objetivo fue analizar la influencia de la localización en la generación de viajes y su distribución modal. A estos efectos se realizaron encuestas en...

  8. Influencias literarias y filosóficas en “La Lámpara Maravillosa” de Ramón del Valle-Inclán

    OpenAIRE

    Monge López, Jesús Mª

    2015-01-01

    La presente tesis doctoral sobre las Influencias Literarias y Filosóficas en La lámpara maravillosa de Ramón del Valle-Inclán consta de dos partes. En la primera, se estudian las influencias filosóficas heterodoxas en las que se sustenta el ensayo, con especial incidencia en el movimiento espiritista, de gran desarrollo en España y sin embargo poco estudiado. Conceptos fundamentales en el ensayo valleinclaniano como la reencarnación o la ley de retribución o del karma se hallan en los círculo...

  9. INFLUENCIA DE LA LATERALIDAD Y MOTRICIDAD EN LA ESCRITURA EN NIÑOS DE 2º DE EDUCACIÓN PRIMARIA. PROGRAMA DE INTERVENCIÓN.

    OpenAIRE

    Rosario-Ferández, María Dolores

    2012-01-01

    En el presente trabajo se estudia la influencia que ejerce la lateralidad y motricidad en la escritura en niños de 2º de Educación Primaria. Para el estudio se realizaron pruebas de lateralidad, motricidad gruesa y escritura a una muestra de 37 alumnos de un Colegio Público. El objetivo de esta investigación fue comprobar cómo la lateralidad y motricidad tienen una gran influencia en la escritura y el grado de correlación que existe entre los diferentes patrones motrices y la escritura....

  10. Assembly of new Mo/Cu/S clusters from [Et4N][Tp*MoS(S4)] and Cu(I) salts: syntheses, structures and third-order nonlinear optical properties.

    Science.gov (United States)

    Zhang, Zhi-Yuan; Gong, Wei-Jie; Wang, Fan; Chen, Min-Min; Zhou, Li-Kuan; Ren, Zhi-Gang; Sun, Zhen-Rong; Lang, Jian-Ping

    2013-07-14

    Reactions of [Et4N][Tp*MoS(S)4] (Tp* = hydridotris(3,5-dimethylpyrazol-1-yl)borate) (1) with 3 equiv. of CuX (X = Cl, Br, I, CN) or [Cu(MeCN)4]ClO4 in CH2Cl2-MeCN or CH2Cl2-DMF afforded [Et4N]2[Tp*Mo(μ3-S)3(CuCl)3(μ3-Cl)] (2), [Et4N][Tp*Mo(μ3-S)3(CuX)3] (3: X = Br; 4: X = I), [Et4N][Tp*MoO(μ-S)2(CuX)] (5: X = I; 6: X = CN) and [Tp*Mo(μ3-S)3Cu3(μ3-S')]4 (7). Compounds 2-7 were characterized by elemental analysis, IR spectra, UV-vis spectra, (1)H NMR, electrospray ion mass spectra (ESI-MS) and X-ray crystallography. The cluster dianion of 2 has a complete cubane-like [Tp*Mo(μ3-S)3(CuCl)3(μ3-Cl)] structure while the anion of 3 or 4 consists of an incomplete cubane-like [Tp*Mo(μ3-S)3(CuX)3] structure. The anion of 5 or 6 has a binuclear structure, in which one [Tp*MoO(μ-S)2] moiety and one CuX unit are linked by a pair of μ-S atoms. The structure of 7 may be considered as a supercube whose eight corners are occupied by four incomplete cubane-like [Tp*Mo(μ3-S)3Cu3] fragments and four μ3-S' atoms. The third-order nonlinear optical (NLO) properties of 2-6 in DMF were investigated by femtosecond degenerate four-wave mixing (DFWM) technique with a 80 fs pulse width at 800 nm. Compounds 2-6 exhibited good NLO performances and their NLO responses were enhanced relative to that of 1.

  11. Different TP53 mutants in p53 overexpressed epithelial ovarian carcinoma can be associated both with altered and unaltered glycolytic and apoptotic profiles

    OpenAIRE

    Antoun, Stephanie; Atallah, David; Tahtouh, Roula; Alaaeddine, Nada; Moubarak, Malak; Khaddage, Abir; Ayoub, Eliane Nasr; Chahine, George; Hilal, George

    2018-01-01

    Background p53 is a tumor suppressor and key regulator of glycolysis in cancer cells, however highly mutated in tumors. In ovarian cancer, studies concerning p53 mutations focus on the DNA binding domain since the majority of hotspot mutations affects this region. Yet, mutations in other regions such as the proline rich domain may also affect the protein’s expression and activity. The aim of this study is to investigate the effect of various positions of mutations in TP53 gene on glycolysis, ...

  12. SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma – a Nordic Lymphoma Group study

    DEFF Research Database (Denmark)

    Nordström, Lena; Sernbo, Sandra; Eden, Patrik

    2014-01-01

    Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI......-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating...

  13. Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones

    Czech Academy of Sciences Publication Activity Database

    Malinová, Anna; Cvačková, Zuzana; Matějů, Daniel; Hořejší, Zuzana; Abeza, C.; Vandermoere, F.; Bertrand, E.; Staněk, David; Verheggen, C.

    2017-01-01

    Roč. 216, č. 6 (2017), s. 1579-1596 ISSN 0021-9525 R&D Projects: GA ČR GPP301/12/P425; GA ČR GA15-00790S; GA ČR(CZ) GA14-34264S; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : dominant retinitis-pigmentosa * splicing factor prp8 * rna-polymerase-ii * structural basis * spliceosomal snrnps * coiled bodies * cajal bodies * r2tp complex * mutations * biogenesis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 7.955, year: 2016

  14. A Resolvase-like Protein is required for the Site-Specific Integration of the Temperate Lactococcal Bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Christiansen, Bettina; Brøndsted, Lone; Vogensen, Finn K.

    1996-01-01

    showed 38-44 % similarity to the resolvase group of site-specific integrases, while no similarity to known proteins was found in the C-terminal end. Bacteriophage TP901-1 therefore contains a unique integration system, not resembling the Int-class of site-specific integrases usually found in temperate...... bacteriophages. The constructed integration vector pBC170, integrates into the chromosomal attachment site very efficiently and forms stable transformants with a frequency corresponding to 20 % of the transformation efficiency....

  15. TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy

    DEFF Research Database (Denmark)

    Munch-Petersen, Helga D; Asmar, Fazila; Dimopoulos, Konstantinos

    2016-01-01

    that hotspot/direct DNA contact MUT-TP53 was predictive of poor outcome in CCT-treated PCNSL patients, P = 0.012 and P = 0.008; HR: 1.86 and 1.95, for OS and PFS, respectively. MIR34A, MIR34B/C, and DAPK promoter methylation were detected in 53/93 (57.0 %), 80/84 (95.2 %), and 70/75 (93.3 %) of the PCNSL...

  16. A resolvase-like protein is requered for the site-specific integration of the temperate lactococcal bacteriophage TP901-1

    DEFF Research Database (Denmark)

    Christiansen, Bettina; Brøndsted, Lone; Vogensen, Finn K.

    1996-01-01

    upstream of attP. The N-terminal 150 to 1180 amino acids of Orf1 showed 38 to 44% similarity to the resolvase group of site-specific integrases, while no similarity to know proteins was found in the C-terminal end. Bacteriophage 'TP901-1 therefore contains a unique integration system that does not resemble...... the Int class of site-specific integrases usually found in temperate bacteriophages. The constructed integration vector, pBC170, integrates into the chromosomal attachment site very efficiently and forms stable transformants with a frequency corresponding to 20% of the transformation efficiency....

  17. Influencia del contenido graso y de otras variables sobre la capacidad de fusión del queso Cremoso Argentino

    Directory of Open Access Journals (Sweden)

    Zalazar, Carlos A.

    2004-09-01

    Full Text Available The influence of the fat content, pH, the ripening degree and the incorporation of whey proteins, by two different methods, on the meltability of Cremoso Argentino cheese was examined. Different experimental cheeses were made at pilot plant scale and their meltabilities were determined by a modified Schreiber test. Ripening degree and fat content showed a good correlation with the meltability. Though, cheeses with incorporation of whey proteins showed poor meltability, despite their yields increased. No correlation was found between pH and meltability inside the pH working range studied.En el presente trabajo se estudió la influencia del contenido de materia grasa, pH, grado de maduración e incorporación de proteínas de suero mediante dos vías diferentes sobre la capacidad de fusión del queso Cremoso Argentino. Utilizando una técnica modificada del test de Schreiber se analizó la capacidad de fusión de distintos quesos experimentales elaborados a escala piloto. El contenido graso y el grado de maduración afectaron positivamente la capacidad de fusión. La incorporación de proteínas de suero produjo mayores rendimientos pero la capacidad de fusión se vio fuertemente disminuida. No se observó una influencia clara del pH dentro de los límites estudiados

  18. La influencia social de la televisión: fuentes y métodos de estudio

    Directory of Open Access Journals (Sweden)

    MANUEL MARTÍN SERRANO

    1982-01-01

    Full Text Available Se propone una teoría de la influencia de la televisión, basada en valores de objetividad social. Se analizan como defectuosos los estudios previos sobre el papel de la televisión como mediadora de las relaciones entre el productor, el consumidor y el votante, llevados a cabo por empresas de mercadotecnia porque no promueven un mayor uso social de la televisión. La publicidad se basa en la falsificación y ocultamiento de la realidad. La publicidad política compromete a la democracia al apelar a las emociones más que a la discusión racional. El papel de la televisión en los procesos de socialización esta en función de los modelos significativos de ambos, la televisión y su audiencia: donde estos sistemas de valores y referencia coinciden, la influencia de la televisión será fuerte. Se sugiere que el efecto básico de la televisión no puede ser cambiado sin cambios correlativos en la organización social.

  19. Influencia sobre el extractable de níquel de los minerales oxidados del yacimiento Punta Gorda

    Directory of Open Access Journals (Sweden)

    Antonio R. Chang-Cardona

    2014-12-01

    Full Text Available El propósito fue validar, a escala industrial, una metodología para períodos largos en una loza de 8 hornos en la empresa productora de níquel Comandante Ernesto Che Guevara, con el fin de crear una base de datos de producción confiable para su procesamiento estadístico y demostrar la influencia del contenido de los principales minerales oxidados sobre el extractable de níquel y la tendencia en el comportamiento del extractable de cobalto. Se demostró, mediante experimentos, durante tres meses de monitoreo, la efectividad del software COMPRAC para obtener la composición racional de 100 kg de varios tipos de mena laterítica que entran a los hornos de reducción. A partir de la base de datos creada se obtuvo, por primera vez, las gráficas que reflejan la influencia del contenido de los principales minerales sobre los extractables de níquel y de cobalto; en el caso del níquel con suficiente sensibilidad y confiabilidad para la toma de decisiones operacionales eficaces en el circuito tecnológico Mina-Preparación de Mineral-Hornos de Reducción

  20. La influencia de la publicidad infantil de alimentos: antecedentes y estado de la cuestión

    Directory of Open Access Journals (Sweden)

    Cristina González Díaz

    2013-11-01

    Full Text Available Actualmente estamos asistiendo a un incesante bombardeo de noticias que nos muestran el tipo de productos que la publicidad de alimentos, dirigida específicamente al target infantil, publicita: productos hipercalóricos, con altos niveles en azúcares y sal, etc; en definitiva, productos poco recomendables en la dieta del niño. Al mismo tiempo, no cesan de publicarse investigaciones académicas sobre el poder persuasivo y la capacidad de influencia que este tipo concreto de publicidad posee sobre el niño. Bajo este contexto, este artículo trata de abordar los estudios académicos más significativos que han investigado la posible relación entre la publicidad de alimentos dirigida a niños y la problemática de la obesidad, o más a grandes rasgos, la influencia que la publicidad específica de este sector puede tener en la ingesta de alimentos poco saludables