Recognition and processing of a new repertoire of DNA substrates by human 3-methyladenine DNA glycosylase (AAG)

The human 3-methyladenine DNA glycosylase (AAG) recognizes and excises a broad range of purines damaged by alkylation and oxidative damage, including 3-methyladenine, 7-methylguanine, hypoxanthine (Hx), and 1,N[superscript 6]-ethenoadenine (εA). The crystal structures of AAG bound to εA have provided insights into the structural basis for substrate recognition, base excision, and exclusion of normal purines and pyrimidines from its substrate recognition pocket. In this study, we explore the substrate specificity of full-length and truncated Δ80AAG on a library of oligonucleotides containing structurally diverse base modifications. Substrate binding and base excision kinetics of AAG with 13 damaged oligonucleotides were examined. We found that AAG bound to a wide variety of purine and pyrimidine lesions but excised only a few of them. Single-turnover excision kinetics showed that in addition to the well-known εA and Hx substrates, 1-methylguanine (m1G) was also excised efficiently by AAG. Thus, along with εA and ethanoadenine (EA), m1G is another substrate that is shared between AAG and the direct repair protein AlkB. In addition, we found that both the full-length and truncated AAG excised 1,N[superscript 2]-ethenoguanine (1,N[superscript 2]-εG), albeit weakly, from duplex DNA. Uracil was excised from both single- and double-stranded DNA, but only by full-length AAG, indicating that the N-terminus of AAG may influence glycosylase activity for some substrates. Although AAG has been primarily shown to act on double-stranded DNA, AAG excised both εA and Hx from single-stranded DNA, suggesting the possible significance of repair of these frequent lesions in single-stranded DNA transiently generated during replication and transcription.United States. National Institutes of Health (grant ES05355)United States. National Institutes of Health (grant CA75576)United States. National Institutes of Health (grant CA55042)United States. National Institutes of Health (grant ES02109)United States. National Institutes of Health (grant T32-ES007020)United States. National Institutes of Health (grant CA80024)United States. National Institutes of Health (grant CA26731

Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets

Objective: To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. Methods: We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. Results: Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%–4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60–0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45–54 years without additional risk factors to more than 10% in patients aged 75–84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59–0.63) and slightly underestimated major bleeding risk. Conclusions: The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding

Needs and effects of irrigation in corn cultivated for grain in the Kujawsko-Pomorski region

Celem pracy było określenie częstotliwości występowania susz w okresie wzmożonych potrzeb wodnych kukurydzy uprawianej na ziarno w regionie kujawsko-pomorskim na podstawie wielkości wskaźnika standaryzowanego opadu SPI. Wykorzystując istotną zależność między zwyżkami plonów ziarna a wysokością opadów atmosferycznych dokonano także oceny potrzeb i przewidywanych efektów produkcyjnych nawadniania tej uprawy. W badaniach wykorzystano wyniki pomiarów opadów atmosferycznych w okresie od 1 lipca do 31 sierpnia w wieloleciu 1981-2010, pochodzące z placówek COBORU w Chrząstowie, Głębokim i Głodowie oraz ze Stacji Badawczej UTP w Mochełku. Na podstawie przeprowadzonych badań stwierdzono, że częstotliwość wystąpienia suszy atmosferycznej w okresie wzmożonego zapotrzebowania na wodę kukurydzy na ziarno wynosiła w regionie 26,7-40,0%, w zależności od miejscowości. Silne susze wystąpiły w latach 1983, 1989, 1992 i 1994, umiarkowana w 2005, a słabe w latach 1982, 1984 i 1999. Duże potrzeby deszczowania kukurydzy na ziarno, odpowiadające okresom suszy silnej i umiarkowanej (SPI ≤ – 1,0) stwierdzono w 5 latach na 30 analizowanych. Prognozowana zwyżka plonu ziarna kukurydzy uprawianej na glebach lekkich pod wpływem nawadniania kształtuje się w tych latach na poziomie wyższym od 3,22 t.ha-1. W kolejnych 9 latach stwierdzono średnie potrzeby deszczowania, odpowiadające wielkościom SPI w okresie lipiec-sierpień od 0 do – 1,0.The study was carried out in order to determine the frequency of droughts in the period of increased water needs of corn cultivated for grain in the region of Kujawsko-Pomorskie based on temporal variation of the standardized precipitation index SPI. Also were assessed the needs and expected productive effects of the plants grown under irrigation by a significant correlation between increases of yields of grain and the amount of rainfall. Rainfall data were derived from standard measurements of atmospheric precipitation during a period from 1 July and 31 August in the multi- annual period 1981-2010. These data were obtained from the branches of the Research Centre for Cultivar Testing (COBORU) in Chrząstowo, Głębokie and Głodowo, and the University of Technology and Life Sciences Research Centre in Mochełek. The results of carried research showed that the frequency of occurrence of dry spell during the period of increased needs for water of corn amounted to 26.7-40.0% in the region depended on the locality. Strong droughts occurred in the year 1983, 1989, 1992 and 1994, moderate drought in 2005 and weak droughts in 1982, 1984 and 1999. Great irrigation needs of corn which corresponded to periods of strong and moderate droughts (SPI ≤ – 1.0) have been identified in 5 years of the 30 examined. The expected increase in the yield of corn grain cultivated on light soils under irrigation during those years exceeds 3.22 t.ha-1. In the 9 years occurred medium-level irrigation needs, which in the period of July-August, correspond to SPI values between 0 and – 1.0

Evaluation of requirements and expected effects of sprinkler irrigation in spring cereals in the Kujawsko-Pomorskie region

Badania przeprowadzono w celu określenia częstotliwości występowania susz w okresie wzmożonych potrzeb wodnych zbóż jarych oraz oceny potrzeb i przewidywanych efektów produkcyjnych deszczowania tych roślin w regionie kujawsko-pomorskim, na podstawie zmienności czasowej wskaźnika standaryzowanego opadu SPI. Materiał stanowiły wyniki standardowych pomiarów opadów atmosferycznych w okresie od 1 maja do 30 czerwca w wieloleciu 1981-2010. Dane opadowe pozyskano z placówek COBORU w Chrząstowie, Głębokim i Głodowie oraz ze Stacji Badawczej UTP w Mochełku. W wyniku przeprowadzonych badań stwierdzono, że częstotliwość wystąpienia warunków posusznych w okresie wzmożonego zapotrzebowania na wodę przez zboża jare wynosiła w regionie 23,3-30,0%, zależnie od miejscowości. Susze ekstremalne wystąpiły w latach 2000 i 2008, silna w 1983, umiarkowana w 1989, a słabe w latach 1992, 2003 i 2006. Bardzo duże i duże potrzeby deszczowania zbóż jarych, odpowiadające okresom suszy ekstremalnej, silnej i umiarkowanej (SPI ≤ -1,0) zidentyfikowano w 4 latach na 30 analizowanych. Przewidywana zwyżka plonu ziarna zbóż jarych uprawianych na glebach lekkich pod wpływem deszczowania kształtuje się na poziomie wyższym od 1,8 t.ha-1. W kolejnych 8 latach stwierdzono średnie potrzeby deszczowania, odpowiadające wielkościom SPI w okresie maj-czerwiec od 0 do -1,0.The work was carried out in order to determine the frequency of droughts in the period of increased water needs of spring cereals. In addition, based on the time variation of the standardized precipitation index SPI assessed the needs and the expected production results of the plants irrigated in the Kujawsko-Pomorskie region. Data consisted of the results of standard measurements of rainfall from 1 May to 30 June in the period 1981-2010. Rainfall data were obtained from the branches COBORU in Chrząstowo, Głębokie and Głodowo and also from the Research Station of University and Technology and Life Science in Mochełek. Based on the results of the study, it was found that, during the period of high demand for water of spring cereals, the frequency of drought conditions in the region accounted of 23,3-30,0%, depending on the locality. Extreme droughts occurred in years 2000 and 2008, strong in 1983, moderate in 1989 and weak in 1992, 2003 and 2006. Among the analyzed 30 years, in 4 years were identified very high- and high-level requirements of irrigation in spring cereals corresponding to periods of extreme, strong and moderate droughts (SPI ≤ -1.0). The expected increase in grain yield of spring cereals cultivated on light soils under irrigation is assessed at the level higher than 1.8 t·ha-1. In the subsequent 8 years, occurred medium-level irrigation needs, which in the period of May-June corresponded to the values of the SPI at the level between 0.0 and -1.0

Evaluation of needs and expected effects of sprinkler irrigation in potato cultivated in the Kujawsko-Pomorskie region

The study was carried out in order to determine the frequency of droughts in the period of increased water needs in potato, and to assess the needs and expected productive effects of the plants grown under irrigation on the basis of temporal variation of the standardized precipitation index SPI in the Kujawsko- Pomorskie district. Rainfall data were derived from standard measurements of atmospheric precipitation in between 1 July and 31 August in the multi-annual period 1981-2010.These data were obtained from the branches of COBORU in Chrząstowo, Głębokie and Głodowo, and the University of Technology and Life Sciences Research Centre in Mochełek. The results of carried research showed that the frequency of occurrence of dry spell during the period of increased needs for water of potato amounted to 26.7-40.0% in the region, depending on the locality. Strong droughts occurred in the year 1983, 1989, 1992 and 1994, moderate drought in 2005 and weak droughts in 1982, 1984 and 1999. Great irrigation needs of potato which corresponded to periods of strong and moderate droughts (SPI ≤ - 1.0) have been identified in 5 years of the 30 years examined. The expected increase in the yield of potato tubers grown on light soils under irrigation during those years exceeded 15.7t.ha-1. In the 9 years of the 30 have occurred mediumlevel irrigation needs, which in the period of July-August, corresponded to SPI values between 0 and -1.0