Avoiding chromosome pathology when replication forks collide

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2013 Macmillan Publishers Limited.Chromosome duplication normally initiates through the assembly of replication fork complexes at defined origins1, 2. DNA synthesis by any one fork is thought to cease when it meets another travelling in the opposite direction, at which stage the replication machinery may simply dissociate before the nascent strands are finally ligated. But what actually happens is not clear. Here we present evidence consistent with the idea that every fork collision has the potential to threaten genomic integrity. In Escherichia coli this threat is kept at bay by RecG DNA translocase3 and by single-strand DNA exonucleases. Without RecG, replication initiates where forks meet through a replisome assembly mechanism normally associated with fork repair, replication restart and recombination4, 5, establishing new forks with the potential to sustain cell growth and division without an active origin. This potential is realized when roadblocks to fork progression are reduced or eliminated. It relies on the chromosome being circular, reinforcing the idea that replication initiation is triggered repeatedly by fork collision. The results reported raise the question of whether replication fork collisions have pathogenic potential for organisms that exploit several origins to replicate each chromosome.THe MRC, the Leverhulme Trust, and the BBSRC

AN APPLICATION OF SAFETY-FIRST PROBABILITY LIMITS IN A DISCRETE STOCHASTIC FARM MANAGEMENT PROGRAMMING MODEL

A sequential decision-making model was developed, and data from farm-raised catfish production were used to demonstrate its use. Outcomes of sequences of decisions which satisfied chance constraints on ending cash balances were traced through a specified time period. Discrete choice variables were specified due to the fixed nature of pond facilities. Recourse actions specified were sale of production in excess of endogenously determined transfer levels or purchase of inputs to supplement needs of the next production stage. Production activities cannot be changed during the planning period. Only yield variability was considered due to its impact on relative competitiveness among growth stages. Deviations were calculated from endogenously determined target levels based on goal and probability limits.Farm Management,

Pyrimido[1,2-a]-purin-10(3H)-one, M(1)G, is less prone to artifact than base oxidation

Pyrimido[1,2-a]-purin-10(3H)-one (M(1)G) is a secondary DNA damage product arising from primary reactive oxygen species (ROS) damage to membrane lipids or deoxyribose. The present study investigated conditions that might lead to artifactual formation or loss of M(1)G during DNA isolation. The addition of antioxidants, DNA isolation at low temperature or non-phenol extraction methods had no statistically significant effect on the number of M(1)G adducts measured in either control or positive control tissue samples. The number of M(1)G adducts in nuclear DNA isolated from brain, liver, kidney, pancreas, lung and heart of control male rats were 0.8, 1.1, 1.1, 1.1, 1.8 and 4.2 M(1)G/10(8) nt, respectively. In rat liver tissue, the mitochondrial DNA contained a 2-fold greater number of M(1)G adducts compared with nuclear DNA. Overall, the results from this study demonstrated that measuring M(1)G is a reliable way to assess oxidative DNA damage because the number of M(1)G adducts is significantly affected by the amount of ROS production, but not by DNA isolation procedures. In addition, this study confirmed that the background number of M(1)G adducts reported in genomic DNA could have been overestimated by one to three orders of magnitude in previous reports

Local water markets for irrigation in southern Spain: A multicriteria approach

Spanish authorities have recently approved a new legislative framework for the creation of local water markets to improve allocative efficiency for this scarce resource. This paper analyses the potential impacts of the policy. A utility function for three groups of farmers was elicited, using a method that does not require interaction with the decision‐makers. Utility was measured as a function of the first two moments of the distribution of total gross margin. The utility functions were then used to simulate farmers' responses to changes in the price of water.Resource /Energy Economics and Policy,

‘Yuk, the Skin of Insects!’ Tracking Sources of Errors in Second Language Reading Comprehension

This article submitted to IUPUI ScholarWorks as part of the OASIS Project.Readers for whom English is a second language often misinterpret texts. One source for such errors is failing to accurately recognize phonemic and graphemic features, leading to interpreting a text within a framework not intended by the author. Teachers can help second language readers become more perceptive by preparing students for the material and providing practice in recognizing the text's syntactic connections

Designing and Evaluating a Transitional Academic Program

This article submitted to IUPUI ScholarWorks as part of the OASIS Project. Article reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Permission granted through posted policies on copyright owner’s website or through direct contact with copyright owner.The University of Wisconsin-Eau Claire faced the ethical dilemma of admitting non-native English speaking immigrants and refugees who were academically at-risk, but not providing the academic and language support the students needed to succeed. This paper provides a description and an evaluation of a transitional academic program designed to address these students' language and learning needs as well as help them integrate into the university. Its success is reflected not only in strong student improvement, but in the collaboration of many university departments and units to create an efficient and cost-effective administrative structure

Editorial: Nursing Papers

This post-peer-review, pre-copyedit version of the article submitted to IUPUI ScholarWorks as part of the OASIS Project. Article reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Permission granted through posted policies on copyright owner’s website or through direct contact with copyright owner.Spanning issues 3.1 and 3.2 of this journal is a series of case studies looking at the practice of fund raising cross-culturally. These articles were first presented at a seminar jointly sponsored by the Indiana Center for Intercultural Communication (ICIC) and the IU Center on Philanthropy (COP), "Case Studies of Fundraising Internationally," which was held on the Indiana University Purdue University Indianapolis campus in October 2001

Understanding Direct Mail Letters as a Genre

This post-peer-review, pre-copyedit version of the article submitted to IUPUI ScholarWorks as part of the OASIS Project.What makes non-profit, philanthropic discourse so persuasive has not been well explored to date. Using a specialized corpus of direct-mail letters from philanthropic organizations in five different fields, this study seeks to combine the tools of corpus analysis with the specificity of genre analysis in a way that has not been done before to provide a new perspective on a genre that is not well understood. The underlying goal is to look for a methodology that will provide much of the qualitative detail that is common to genre analysis while at the same time provide the reliability that is best assured by the quantitative power of computerized corpus analysis. Using Bhatia's approach to genre analysis (1993) and his exploratory efforts in investigating fundraising discourse (1997, 1998) as a foundation, key patterns in the rhetorical structure of direct-mail letters revealed through a large-scale corpus analysis are presented

Different effects of oral and transdermal hormone replacement therapies on Factor IX, APC resistance, t-PA, PAI and C- reactive protein - a cross-sectional population survey

The effects of hormone replacement therapy (HRT) on thrombosis risk, thrombotic variables, and the inflammatory marker C- reactive protein (CRP) may vary by route of administration (oral versus transdermal). We studied the relationships of 14 thrombotic variables (previously related to cardiovascular risk) and CRP to menopausal status and to use of HRT subtypes in a cross-sectional study of 975 women aged 40-59 years. Our study confirmed previously-reported associations between thrombotic variables and menopausal status. Oral HRT use was associated with increased plasma levels of Factor IX, activated protein C (APC) resistance, and CRP; and with decreased levels of tissue plasminogen activator (t-PA) antigen and plasminogen activator inhibitor (PAI) activity. Factor VII levels were higher in women taking unopposed oral oestrogen HRT. The foregoing associations were not observed in users of transdermal HRT; hence they may be consequences of the "first- pass" effect of oral oestrogens on hepatic protein synthesis. We conclude that different effects of oral and transdermal HRT on thrombotic and inflammatory variables may be relevant to their relative thrombotic risk; and suggest that this hypothesis should be tested in prospective, randomised studies

Methanation of CO over Ni catalyst: A theoretical study

Theoretical methods (generalized valence‐bond calculations) were used to examine the bond energies and geometries of numerous species chemisorbed onto Ni clusters representing Ni surface. These results were used to obtain thermochemical information and to examine various mechanisms for the methanation of CO over Ni: CO+3H^(→)_(2(Ni)) CH_4+H_2O. It is found that chemisorbed formyl radicals (Ni–CHO) lead to a favorably appearing chain reaction that is consistent with current experimental results. In addition, we find a chemisorbed C_2 species that may be the catalytically active C_(ad) formed from dissociation of CO