Plant mitochondria possess a short-patch base excision DNA repair pathway

Despite constant threat of oxidative damage, sequence drift in mitochondrial and chloroplast DNA usually remains very low in plant species, indicating efficient defense and repair. Whereas the antioxidative defense in the different subcellular compartments is known, the information on DNA repair in plant organelles is still scarce. Focusing on the occurrence of uracil in the DNA, the present work demonstrates that plant mitochondria possess a base excision repair (BER) pathway. In vitro and in organello incision assays of double-stranded oligodeoxyribonucleotides showed that mitochondria isolated from plant cells contain DNA glycosylase activity specific for uracil cleavage. A major proportion of the uracil–DNA glycosylase (UDG) was associated with the membranes, in agreement with the current hypothesis that the DNA is replicated, proofread and repaired in inner membrane-bound nucleoids. Full repair, from uracil excision to thymidine insertion and religation, was obtained in organello following import of a uracil-containing DNA fragment into isolated plant mitochondria. Repair occurred through single nucleotide insertion, which points to short-patch BER. In vivo targeting and in vitro import of GFP fusions showed that the putative UDG encoded by the At3g18 630 locus might be the first enzyme of this mitochondrial pathway in Arabidopsis thaliana

Diastereoselective Dearomatizing Cyclizations of 5-Arylpentan-2-ones by Samarium Diiodide – A Computational Analysis

This study analyzes the samarium diiodide-promoted cyclizations of 5-arylpentan-2-ones to dearomatized bicyclic products utilizing density functional theory. The reaction involves a single electron transfer to the carbonyl group, which occurs synchronously with the rate determining cyclization event, and a second subsequent proton-coupled electron transfer. These redox reactions are accurately computed employing small core pseudo potentials explicitly involving all f-electrons of samarium. Comparison of the energies of the possible final products rules out thermodynamic control of the observed regio- and diastereoselectivities. Kinetic control via appropriate transition states is correctly predicted, but to obtain reasonable energy levels the influence of the co-solvent hexamethylphosphortriamide has to be estimated by using a correction term. The steric effect of the bulky samarium ligands is decisive for the observed stereoselectivity. Carbonyl groups in para-position of the aryl group change the regioselectivity of the cyclization and lead to spiro compounds. The computations suggest again kinetic control of this deviating outcome. However, the standard mechanism has to be modified and the involvement of a complex activated by two SmI2 moieties is proposed in which two electrons are transferred simultaneously to form the new C–C bond. Computation of model intermediates show the feasibility of this alternative mechanism

Prognostic factors in non small cell lung cancer

peer reviewedRésumé : Le cancer pulmonaire non à petites cellules est le plus fréquent des cancers du poumon et son pronostic reste très réservé. Les rechutes sont fréquentes et peuvent même s’observer dans des stades précoces de la maladie, en dépit d’une prise en charge chirurgicale à visée curative. Cette revue de la littérature donne un aperçu des facteurs pronostiques principaux dont les deux plus importants, conditionnant la stratégie thérapeutique, demeurent la stadification («staging») et l’histologie de la tumeur. D’autres facteurs péjoratifs pourraient également s’avérer utiles pour les cliniciens, notamment en orientant le patient vers des thérapies adjuvantes.Summary : Non small cell lung cancer is the most frequent type of lung cancer and its prognosis is still very poor. Relapse is frequent and can be observed even in early stages of the disease, in spite of a surgical management with curative intent. This paper gives an overview of the main prognostic factors, the two most important of which remain the staging and tumor histology. These also determine the therapeutic strategy. Other factors of poor prognosis might also be useful for clinicians, particularly in their decision to refer patients for adjuvant therapies. Keywords : Non-small cell lung cancer – Prognostic factors – Pulmonary oncology – Surger

Tax Burden of Russian Oil Companies after Tax Consolidation

This article takes studying the impact of tax consolidation on oil companies' tax burden as its focus. Oil companies are crucial for the Russian economy while oil and gas money are as well important for the Russian budget. Besides, a lot of oil companies being major taxpayers have had the opportunity to consolidate corporate profit tax since 2012. The article's goal is to analyze the results of creating consolidated groups of taxpayers for tax burden in terms of corporate profit tax exemplified by oil companies in order to assess the importance of profit tax consolidation as a way of reducing corporate profit tax. Upon analyzing the data provided by the Federal Tax Service of Russia and 2010-2015 oil companies' financial reports, it is possible to conclude that the largest tax burden falls on fossil fuel industry in comparison with other industries what can be explained first of all by the mineral extraction tax. Corporate profit tax burden for most oil companies in 2014 accounted for 5% of revenue. At the same time, profit tax burdens on consolidated groups of taxpayers producing oil vary a lot; in 2012, the general trend was falling, but then it started to grow again. Thus, it is impossible to state that tax obligations and corporate profit tax burden have significantly decreased as a result of creating consolidated groups of taxpayers for oil producers. Quantitative analysis of money spent for paying the profit tax might be interestingfor describing consequences of creating consolidated groups of taxpayers

Genetic alterations in gliosarcoma and giant cell glioblastoma

The majority of glioblastomas develop rapidly with a short clinical history (primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress from diffuse astrocytoma or anaplastic astrocytoma. IDH mutations are the genetic hallmark of secondary glioblastomas. Gliosarcomas and giant cell glioblastomas are rare histological glioblastoma variants, which usually develop rapidly. We determined the genetic patterns of 36 gliosarcomas and 19 giant cell glioblastomas. IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in 18 of 19 giant cell glioblastomas analyzed, indicating that they are histological variants of primary glioblastoma. Furthermore, LOH 10q (88%) and TERT promoter mutations (83%) were frequent in gliosarcomas. Copy number profiling using the 450k methylome array in 5 gliosarcomas revealed CDKN2A homozygous deletion (3 cases), trisomy chromosome 7 (2 cases), and monosomy chromosome 10 (2 cases). Giant cell glioblastomas had LOH 10q in 50% and LOH 19q in 42% of cases. ATRX loss was detected immunohistochemically in 19% of giant cell glioblastomas, but absent in 17 gliosarcomas. These and previous results suggest that gliosarcomas are a variant of, and genetically similar to, primary glioblastomas, except for a lack of EGFR amplification, while giant cell glioblastoma occupies a hybrid position between primary and secondary glioblastomas. This article is protected by copyright. All rights reserved

Samarium Diiodide Acting on Acetone - Modeling Single Electron Transfer Energetics in Solution

Samarium diiodide is a versatile single electron transfer (SET) agent with various applications in organic chemistry. Lewis structures regularly insinuate the existence of a ketyl radical when samarium diiodide binds a carbonyl group. The study presented here investigates this electron transfer by the means of computational chemistry. All electron CASPT2 calculations with the inclusion of scalar relativistic effects predict an endotherm electron transfer from samarium diiodide to acetone. Energies calculated with the PBE0-D3(BJ) functional and a small core pseudopotential are in good agreement with CASPT2. The calculations confirm the experimentally measured increase of the samarium diiodide reduction potential through the addition of hexamethylphosphoramide also known as HMPA

2003 Ruby Yearbook

A digitized copy of the 2003 Ruby, the Ursinus College yearbook.https://digitalcommons.ursinus.edu/ruby/1106/thumbnail.jp

Decision Making in Tree Selection Contemplating Conflicting Goals via Marteloscope Exercises

The implementation of biodiversity conservation measures in forests managed for timber production usually implies trade-offs between ecological and economic objectives. In continuous cover forestry these trade-offs emerge at the scale of selecting individual trees for timber harvesting or habitat retention. Tree selection determines both the economic viability of timber management and the prevalence of tree-related microhabitats, considered a multi-taxon indicator of forest biodiversity. Recent studies find that tree selection is influenced by several factors, such as individual management preferences and goals, professional education and institutional context. To gain a deeper understanding of tree-selection practices in the context of retention forestry, we analyse four tree-selection exercises on silvicultural training sites (Marteloscopes) performed by groups with different professional backgrounds: conservationists, foresters, and students of each. Based on qualitative data from participant observations and group discussions, we explore their decision-making strategies, reasoning, and practices. Our analysis provides novel insights into decision-making processes when implementing conservation measures, especially with regard to dealing with trade-offs and uncertainties. Our findings indicate that tree-selection decisions are not merely the result of cognitive and rational weighing processes. They can be understood as practices requiring experience, professional routine, and intuition. These practices differ across professional cultures. Despite these differences, the participants of the analysed Marteloscope exercises developed an understanding of the other stakeholders motivations and restrictions. The setting stimulated a change of perspective that built awareness in many of the participants of their own routines and biases. This may facilitate professional cooperation, cross-disciplinary learning, and the implementation of biodiversity conservation

Lääketieteen opiskelijoiden ja erikoistuvien lääkäreiden opetuksen vaikutukset yliopistosairaalassa

Tutkimuksen kohteena oli Helsingin yliopistollinen keskussairaala (HYKS). Tutkimuksessa selvitettiin erikoislääkäreiden työajan jakautumista, lääketieteen opiskelijoiden ja erikoistuvien lääkäreiden opetustoimintaan liittyviä tehtäviä sairaalassa sekä siitä koettuja hyötyjä ja haittoja. Lisäksi selvitettiin opettamisesta koituvia henkilöstökustannuksia. Tarkasteltaviksi tulosyksiköiksi valittiin isoilla sekä kirurgisilla että konservatiivisilla erikoisaloilla koulutusta antavia tulosyksiköitä. Tarkasteltava ajankohta oli vuosi 2017. Aineisto kerättiin vuoden 2018 aikana haastattelemalla pääasiassa esimiesasemassa olevia lääkäreitä HYKSin kolmessa eri tulosyksikössä. Yhteensä 18:n haastattelun avulla selvitettiin 265:n lääkärin työajan jakaumat ja vastaukset muihin tutkimuskysymyksiin. Henkilöstökustannuksien arvioimiseen käytettiin HYKSin lääkäreiden palkkakustannuksia ja haastatteluista saatuja työaika-arvioita. Tutkimuksessa ilmeni, että yliopistosairaalan erikoislääkäreiden työajasta menee yhteensä 12,6% lääketieteen opiskelijoiden ja erikoistuvien lääkäreiden opetus ja ohjaustoimintaan. Tämä vastaa henkilöstökustannuksissa noin 26 miljoonaa euroa. Opetustoiminta on monipuolista ja se koostuu muun muassa käytännön opettamisesta, konsultointeihin vastaamisesta ja teoreettisesta opettamisesta. Kokonaisuudessaan opetustoiminta koettiin tärkeänä asiana ja siitä koettiin olevan enemmän hyötyä kuin haittaa. Yliopistosairaalalla on iso ja tärkeä yhteiskunnallinen vastuu lääketieteen opiskelijoiden ja erikoistuvien lääkäreiden opettamisessa. Lähes kaikki (92%) yliopistosairaalan erikoislääkäreistä osallistuu opetustoimintaan. Valtion koulutuskorvaus ei arvion mukaan kata kaikkia opetustoiminnan kustannuksia. Koulutuskorvaus lääkäreiden peruskoulutukseen sekä lääkäreiden ja hammaslääkäreiden jatkokoulutukseen HUSille vuonna 2017 oli noin 14 miljoonaa euroa, eli noin 12 miljoonaa euroa vähemmän kuin arvioitu opetuksen osuus henkilöstökustannuksista