The p53 target protein Wig-1 binds hnRNP A2/B1 and RNA Helicase A via RNA

AbstractThe p53-induced Wig-1 gene encodes a double stranded RNA-binding zinc finger protein. We generated Saos-2 osteosarcoma cells expressing tetracycline-inducible Flag-tagged human Wig-1. Induction of Wig-1 expression by doxycycline inhibited cell growth in a long-term assay but did not cause any changes in cell cycle distribution nor increased fraction of apoptotic cells. Using co-immunoprecipitation and mass spectrometry, we identified two Wig-1-binding proteins, hnRNP A2/B1 and RNA Helicase A, both of which are involved in RNA processing. The binding was dependent on the presence of RNA. Our results establish a link between the p53 tumor suppressor and RNA processing via hnRNPA2/B1 and RNA Helicase A.Structured summaryMINT-6542926, MINT-6542899:WIG1 (uniprotkb:Q9HA38) physically interacts (MI:0218) with hnRNP A2/B1 (uniprotkb:P22626) by anti bait coimmunoprecipitation (MI:0006)MINT-6542945:RHA (uniprotkb:Q08211) physically interacts (MI:0218) with hnRNP A2/B1 (uniprotkb:P22626) by anti bait coimmunoprecipitation (MI:0006)MINT-6542918, MINT-6542891:WIG1 (uniprotkb:Q9HA38) physically interacts (MI:0218) with RHA (uniprotkb:Q08211) by anti bait coimmunoprecipitation (MI:0006)MINT-6542867:WIG1 (uniprotkb:Q9HA38) physically interacts (MI:0218) with RHA (uniprotkb:Q08211) by anti tag coimmunoprecipitation (MI:0007)MINT-6542879:WIG1 (uniprotkb:Q9HA38) physically interacts (MI:0218) with hnRNP A2/B1(uniprotkb:P22626) by anti tag coimmunoprecipitation (MI:0007

Эндотелийзависимые механизмы формирования кислородтранспортной функции крови при окислительном стрессе

ЭНДОТЕЛИЙЭПИТЕЛИЙКРОВЬКИСЛОРОДА АКТИВНЫЕ ФОРМЫОКСИДАТИВНЫЙ СТРЕССОБМЕН ВЕЩЕСТВАНТИОКСИДАНТЫАЗОТА ОКСИД

Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

<p>Abstract</p> <p>Background</p> <p>In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe.</p> <p>Methods</p> <p>We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries.</p> <p>Results</p> <p>Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised.</p> <p>Conclusion</p> <p>The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.</p

Målmedvetna lärare - Så arbetar lärare med mål

Syftet med det här arbetet är att ta reda på hur lärare inom NO-ämnena i grundskolan arbetar med målen i kursplanen. Fem lärare har intervjuats om hur de arbetar och vad de anser om målstyrning. Det vanligaste sättet som lärarna arbetar är att de formulerar om kursplanemålen så att de ska bli lättare för eleverna att förstå. Målen diskuterar de med eleverna i början av varje nytt arbetsområde och i samband med bedömning. Eleverna har inte så stort inflytande över själva målen men de har stora möjligheter att påverka hur de ska arbeta för att nå målen. Lärarna är i huvudsak positiva till målstyrningen och menar att det är viktigt att eleverna vet vilka förväntningar skolan har på dem och vad de ska göra för att förbättra sina resultat. Det största problemet är enligt lärarna att bedömningen riskerar att inte bli likvärdig då olika lärares tolkningar av målen skiljer sig åt

Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden

OBJECTIVE: To investigate the risk of squamous cell and basal cell skin cancer in patients with rheumatoid arthritis naive to biologic drugs, in patients starting tumour necrosis factor (TNF) inhibitor treatment, and in the general population. DESIGN: Population based cohort study. SETTING: Nationwide data from Sweden. PARTICIPANTS: Cohort of patients with rheumatoid arthritis naive to biologics (n=46 409), cohort of patients with rheumatoid arthritis starting TNF inhibitor treatment as first biologic in 1998-2012 (n=12 558), and matched general population comparator cohort, identified through national quality of care and health registers. MAIN OUTCOME MEASURE: Hazard ratio of first in situ or invasive squamous cell skin cancer (1998-2012) and first basal cell cancer (2004-12). RESULTS: For basal cell cancer, the hazard ratio was 1.22 (95% confidence interval 1.07 to 1.41) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.14 (0.98 to 1.33; 236 v 1587 events) comparing TNF inhibitor treated patients with biologics-naive patients. For squamous cell cancer, the hazard ratio was 1.88 (1.74 to 2.03) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.30 (1.10 to 1.55; 191 v 847 events) comparing TNF inhibitors with biologics-naive patients; the latter translated to an annual number needed to harm in the order of 1600. Among people with a history of squamous cell or basal cell cancer, TNF inhibitors did not further increase risks. CONCLUSION: A small to moderately increased risk of basal cell cancer was seen in biologics-naive rheumatoid arthritis patients, with no further effect of TNF inhibitors. For squamous cell cancer, the risk was nearly doubled in biologics-naive patients, with a further 30% increase in risk among patients treated with TNF inhibitors; this translates to one additional case for every 1600 years of treatment experience, assuming that this association reflected causality. Vigilance regarding skin malignancies may be advisable in rheumatoid arthritis, irrespective of TNF inhibitor treatment. Most of the increase in risk for non-melanoma skin cancer in patients with rheumatoid arthritis treated with TNF inhibitors originates from factors other than that treatment

Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: maternal characteristics

Background Use of benzodiazepine (BZD) drugs or hypnotic benzodiazepine receptor agonists (HBRAs) during pregnancy may represent a hazard for the foetus. In order to analyse this in an adequate way, knowledge of maternal characteristics as putative confounders is needed. Methods In the Swedish Medical Birth Register, 2149 pregnant women using BZDs or HBRAs were identified, 1944 of them in early pregnancy. These women were compared with other women (n = 859 455) giving births during the same period (1 July 1995-31 December 2004). The following maternal characteristics were studied: age, parity, smoking habits, education, previous miscarriages, years of involuntary childlessness as an estimate of subfertility, concomitant drug use and some pregnancy complications. Results Use and/or reporting of BZDs or HBRAs increased with maternal age. It was higher at first and 4+ parity and increased markedly with maternal smoking. Women with low education reported a higher use than women with high education. Previous miscarriage or subfertility had little impact on the use of these drugs. Preterm birth and caesarean section (also at term birth) were more common than expected. In women using BZDs or HBRAs, other types of psychoactive drugs were used in excess. Conclusions Women using BZDs or HBRAs differ in many aspects from women not using those drugs. These differences may act as confounders in the analysis of pregnancy outcome

Recombinant plasmid expressing the entire coding region of the Bmyc putative protein

An expression vector with the entire coding region of Bmyc oncogene was constructed. The longest predicted open reading frame of Bmyc (178 amino acid residues) was expressed as a fusion protein with the trpE protein (308 amino acid residues) in transformed bacteria. The newly synthesized 58 Kd protein reacted with an anti pan-myc serum. The fusion protein isolated from a preparative Western blot was used as immunogen to generate rabbit anti myc specific immune sera.Grant from King Gustav V Anniversary Fund, by PHS grant number 2 R01 CA 14054-16 awarded by the National Cancer Institute, DHHS, and by grant from the Cancer Research Institute/Concern Foundation for Cancer Research

Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations

Background Exposure to Benzodiazepines (BZD) during foetal life has been suggested to contribute to neonatal morbidity and some congenital malformations, for example, orofacial clefts. Here we aimed to study the neonatal outcome and congenital malformations in neonates whose mothers reported use of BZD and/or hypnotic benzodiazepine receptor agonists (HBRA) during pregnancy. Methods In the Swedish Medical Birth Register we identified 1979 infants whose mothers (n = 1944) reported use of BZD and/or HBRA in early pregnancy. An additional 401 infants were studied, born to 390 mothers who were prescribed such drugs during late pregnancy. Neonatal outcome including congenital malformations after exposure was compared with that of all births (n = 873 879). Results An increased risk for preterm birth and low birth weight was detected in the exposed population. The rate of relatively major congenital malformations was moderately increased among infants exposed in early pregnancy (adjusted OR = 1.24, 95%CI 1.00-1.55), not explained by known teratogenic maternal co-medication. A higher than expected number of infants with pylorostenosis or alimentary tract atresia (especially small gut) was found. This was, however, based on only seven infants for each group of malformation without association to any specific BZD or HBRA. The earlier proposed increased risk for orofacial clefts was not confirmed in our study. Conclusions Maternal use of BZD and/or HBRA may increase the risk for preterm birth and low birth weight and cause neonatal symptoms, but does not appear to have a strong teratogenic potential. The tentative association with pylorostenosis and alimentary tract atresia needs confirmation. Copyright (C) 2007 John Wiley & Sons, Ltd

Rat c-raf is located on chromosome 4 and may be activated by sequences from chromosome 13

Activated forms of the protooncogene c-raf have been found to transform established lines of rodent fibroblasts after transfection with DNA from several human and rat tumors. Using Southern blot analysis of DNAs from rat x mouse somatic cell hybrids, we have mapped c-raf to rat chromosome 4. An exogenous sequence that was found juxtaposed to c-raf within transforming DNA originally derived from a rat hepatocellular carcinoma was localized to chromosome 13