Description of atomic excitations in heavy-ion reactions

Excitations of the atomic shell in heavy-ion collisions are influenced by the presence of a nuclear reaction. In the present Rapid Communication we point out the equivalence between a semiclassical description based on the nuclear autocorrelation function with an earlier model which employs a distribution of reaction times f(T). For the example of U+U collisions, results of coupled-channel calculations for positron creation and K-hole excitations are discussed for two schematic reaction models

Positron production in crossed beams of bare uranium nuclei

Positron creation in crossed-beam collisions of high-energy, fully stripped heavy ions is investigated within the coupled-channel formalism. In comparison with fixed-target collisions of highly stripped heavy-ion projectiles positron production probabilities are enhanced by more than one order of magnitude. The increase results from the possibility to excite electrons from the negative energy continuum into all bound states. The positron spectrum is shifted towards higher energies because of the absence of electron screening. Rutherford scattering as well as nuclear collisions with time delay are investigated. We also discuss the filling of empty bound states by electrons from pair-production processes

Role and regulation of TET-mediated DNA modifications in gene expression

In the mammalian genome, cytosine methylation (5mC) plays a central role in the epigenetic regulation of gene expression and has been implicated in a variety of biological processes, including genome stability, imprinting or differentiation. Compared to other epigenetic marks, DNA methylation has been thought to be relatively stable. However, genome-wide loss of 5mC, or DNA demethylation, has been observed in specific developmental stages and in various types of cancer. The discovery of the TET family of enzymes in 2009 was a watershed moment in comprehending the mechanisms of DNA demethylation. TET proteins oxidize 5mC to 5- hydroxymethylcytosine (5hmC), 5-formlycytosine (5fC) and 5-carboxylcytosine (5caC), which not only serve as key intermediates in active DNA demethylation pathways, but can also act as independent epigenetic marks. In this study, various aspects of TET-mediated DNA demethylation have been intensively investigated. Using quantitative mass-spectrometry-based proteomics readers for the different cytosine derivatives in mouse embryonic stem cells (ESCs), neuronal progenitor cells, and adult mouse brain tissue were identified. Readers for these modifications are only partially overlapping and are dynamic during differentiation. Moreover, the oxidized derivatives of 5mC recruit distinct transcription regulators as well as a large number of DNA repair proteins, implicating DNA damage response as the main pathway contributing to active DNA demethylation. To identify additional non-canonical DNA bases, highly sensitive quantitative mass-spectrometry led to the discovery of 5-hydroxymethyluracil (5hmU) in ESCs. Genomic 5hmU is not generated via deamination of 5hmC, as widely suggested, but through direct oxidation of thymine by TET proteins. In addition, screening for specific 5hmU readers identified different transcriptional and epigenetic factors, implicating that this mark has a specific function in ESCs. So far, only little is known how TET enzymes are regulated and how they are modified by posttranslational modifications (PTMs). Mapping TET phosphorylation and glycosylation sites at amino acid resolution revealed that these PTMs are interdependent and mostly occur at regulatory protein regions. Finally, a reporter gene based assay could demonstrate that in vitro methylation causes gene silencing while subsequent oxidation, resulting in DNA demethylation, leads to gene reactivation in vivo. Different knockout and rescue experiments clearly show that oxidation of methylcytosine by TET proteins and subsequent removal by TDG or NEIL glycosylases and the base excision repair pathway results in reactivation of epigenetically silenced genes. In conclusion, this work provides new insights how TET proteins can set DNA modifications, how these oxidized bases are read by various factors and how TET proteins can be posttranslationally modified. Furthermore, removal of 5mC is achieved through TET-mediated oxidation and depends on the activity of specific glycosylases, which leads to gene reactivation

Electron emission and positron production in deep inelastic heavy-ion reactions

Atomic excitations are used to obtain information on the course of a nuclear reaction. Employing a semiclassical picture we calculate the emission of δ electrons and positrons in deep inelastic nuclear reactions for the example of U+U collisions incorporating nuclear trajectories resulting from two different nuclear friction models. The emission spectra exhibit characteristic deviations from those expected for elastic Coulomb scattering. The theoretical probabilities are compared with recent experimental data by Backe et al. A simple model is used to estimate the influence of a threebody breakup of the compound system upon atomic excitations

The effect of Diabrotica-resistant corn cultivars on the larval development in lab-based studies

Der Einfluss Diabrotica-resistenter Maissorten auf die Larvenentwicklung in Laboruntersuchunge

Role and regulation of TET-mediated DNA modifications in gene expression

In the mammalian genome, cytosine methylation (5mC) plays a central role in the epigenetic regulation of gene expression and has been implicated in a variety of biological processes, including genome stability, imprinting or differentiation. Compared to other epigenetic marks, DNA methylation has been thought to be relatively stable. However, genome-wide loss of 5mC, or DNA demethylation, has been observed in specific developmental stages and in various types of cancer. The discovery of the TET family of enzymes in 2009 was a watershed moment in comprehending the mechanisms of DNA demethylation. TET proteins oxidize 5mC to 5- hydroxymethylcytosine (5hmC), 5-formlycytosine (5fC) and 5-carboxylcytosine (5caC), which not only serve as key intermediates in active DNA demethylation pathways, but can also act as independent epigenetic marks. In this study, various aspects of TET-mediated DNA demethylation have been intensively investigated. Using quantitative mass-spectrometry-based proteomics readers for the different cytosine derivatives in mouse embryonic stem cells (ESCs), neuronal progenitor cells, and adult mouse brain tissue were identified. Readers for these modifications are only partially overlapping and are dynamic during differentiation. Moreover, the oxidized derivatives of 5mC recruit distinct transcription regulators as well as a large number of DNA repair proteins, implicating DNA damage response as the main pathway contributing to active DNA demethylation. To identify additional non-canonical DNA bases, highly sensitive quantitative mass-spectrometry led to the discovery of 5-hydroxymethyluracil (5hmU) in ESCs. Genomic 5hmU is not generated via deamination of 5hmC, as widely suggested, but through direct oxidation of thymine by TET proteins. In addition, screening for specific 5hmU readers identified different transcriptional and epigenetic factors, implicating that this mark has a specific function in ESCs. So far, only little is known how TET enzymes are regulated and how they are modified by posttranslational modifications (PTMs). Mapping TET phosphorylation and glycosylation sites at amino acid resolution revealed that these PTMs are interdependent and mostly occur at regulatory protein regions. Finally, a reporter gene based assay could demonstrate that in vitro methylation causes gene silencing while subsequent oxidation, resulting in DNA demethylation, leads to gene reactivation in vivo. Different knockout and rescue experiments clearly show that oxidation of methylcytosine by TET proteins and subsequent removal by TDG or NEIL glycosylases and the base excision repair pathway results in reactivation of epigenetically silenced genes. In conclusion, this work provides new insights how TET proteins can set DNA modifications, how these oxidized bases are read by various factors and how TET proteins can be posttranslationally modified. Furthermore, removal of 5mC is achieved through TET-mediated oxidation and depends on the activity of specific glycosylases, which leads to gene reactivation

Influence of repeated pyrethroid applications on the sensitivity of pyrethroid-resistant pollen beetles (Meligethes aeneus F.) and their offspring

In der Vergangenheit erfolgte die Kontrolle von Rapsglanzkäfern hauptsächlich durch die Anwendung von synthetischen Pyrethroiden. Durch die häufige und einseitige Nutzung dieser Insektizidgruppe entstand ein hoher Selektionsdruck, der die Ausbildung einer Resistenz zur Folge hatte, die sich über ganz Deutschland und viele europäische Länder ausgebreitet hat. Das Ausweichen auf Insektizide mit anderen Wirkmechanismen ist nur bedingt möglich, da nur wenige solcher Produkte verfügbar sind.Um die Sensitivität von adulten Rapsglanzkäfern und deren Nachkommen gegenüber lambda-cyhalothrin zu untersuchen, wurde 2012 ein Feldversuch mit zwei unbehandelten Kontrollparzellen und zwei fünfmal mit lambda-cyhalothrin behandelten Parzellen durchgeführt. Um die Sensitivität der Käfer, die Dosierungen von 0.015 bis 0.375 μg lambda-cyhalothrin cm–2 ausgesetzt waren, zu überprüfen, wurde der Adult-Vial-Test genutzt. Alle Proben wurden als resistent oder hoch resistent eingestuft. Über den Versuchszeitraum wurden Schwankungen in der Sensitivität festgestellt. Es traten nur geringe Sensitivitätsunterschiede zwischen Käfern aus behandelten und unbehandelten Parzellen auf. Dennoch waren die Sen­sitivitätsschwankungen zwischen aufeinanderfolgenden Sammelterminen in den behandelten Parzellen geringer.Die mittels Photoeklektoren gefangenen Jungkäfer wiesen ein ähnliches Resistenzniveau wie die Elterngeneration auf. Im Vergleich zur Sensitivität der überwinterten Generation zeigten die Jungkäfer geringere LD50-Werte. Die Anzahl der zur Verpuppung in den Boden abwandernden Larven war in den mit lambda-cyhalothrin behandelten Parzellen 18% geringer als in den unbehandelten Par­zellen. Ähnliche Unterschiede wurden bei der Anzahl der schlüpfenden Jungkäfer festgestellt. Dies deutet auf einen unerheblichen Effekt der Pyrethroid-Applikationen auf die Populationsdynamik von resistenten Rapsglanzkäfern hin. DOI: 10.5073/JfK.2014.03.01, https://doi.org/10.5073/JfK.2014.03.01In the past, control of pollen beetles was mainly based on the application of synthetic pyrethroids. The frequent and indiscriminate use of this insecticide class resulted in a high selection pressure, ensuing in the formation of resistance, which has spread over the whole area of Germany and many European countries. Replacement by insecticides with other modes of action is limited as few alternative products are available.To analyze the relative sensitivity of adult pollen beetles and their offspring to lambda-cyhalothrin, a field trial was conducted in 2012 which included two control plots without insecticide applications and two plots sprayed five times with lambda-cyhalothrin. The Adult-Vial-Test was used to analyze the sensitivity of the beetles when exposed to dosages from 0.015 to 0.375 μg lambda-cyhalothrin cm–2. All samples were classified as resistant or highly resistant. Over the trial period fluctuations of the sensitivity were noticed. Only small differences occurred between the sensitivity of beetles from treated and untreated plots. However, the fluctuation of the sensitivity between successive sampling dates was smaller in treated plots.New generation pollen beetles were caught by using photoeclectors and the resistance classified relative to their parent generation. In comparison to the sensitivity of the overwintered generation, new generation beetles showed lower LD50-values. The number of larvae migrating to soil for pupation in plots treated with lambda-cyhalothrin, was 18% lower than in untreated plots. Similar differences occurred with the number of emerging adults of the new generation. This indicates a negligible effect of pyrethroid applications on population dynamics of resistant pollen beetles. DOI: 10.5073/JfK.2014.03.01, https://doi.org/10.5073/JfK.2014.03.0

New aspects of electron transfer revealed by the crystal structure of a truncated bovine adrenodoxin, Adx(4–108)

AbstractBackground: Adrenodoxin (Adx) is a [2Fe–2S] ferredoxin involved in steroid hormone biosynthesis in the adrenal gland mitochondrial matrix of mammals. Adx is a small soluble protein that transfers electrons from adrenodoxin reductase (AR) to different cytochrome P450 isoforms where they are consumed in hydroxylation reactions. A crystallographic study of Adx is expected to reveal the structural basis for an important electron transfer reaction mediated by a vertebrate [2Fe–2S] ferredoxin.Results: The crystal structure of a truncated bovine adrenodoxin, Adx(4–108), was determined at 1.85 å resolution and refined to a crystallographic R value of 0.195. The structure was determined using multiple wavelength anomalous dispersion phasing techniques, making use of the iron atoms in the [2Fe–2S] cluster of the protein. The protein displays the compact (α+β) fold typical for [2Fe–2S] ferredoxins. The polypeptide chain is organized into a large core domain and a smaller interaction domain which comprises 35 residues, including all those previously determined to be involved in binding to AR and cytochrome P450. A small interdomain motion is observed as a structural difference between the two independent molecules in the asymmetric unit of the crystal. Charged residues of Adx(4–108) are clustered to yield a strikingly asymmetric electric potential of the protein molecule.Conclusions: The crystal structure of Adx(4–108) provides the first detailed description of a vertebrate [2Fe–2S] ferredoxin and serves to explain a large body of biochemical studies in terms of a three-dimensional structure. The structure suggests how a change in the redox state of the [2Fe–2S] cluster may be coupled to a domain motion of the protein. It seems likely that the clearly asymmetric charge distribution on the surface of Adx(4–108) and the resulting strong molecular dipole are involved in electrostatic steering of the interactions with AR and cytochrome P450

TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation

The discovery of hydroxymethyl-,formyl- and carboxylcytosine, generated through oxidation of methylcytosine by TET dioxygenases, raised the question how these modifications contribute to epigenetic regulation. As they are subjected to complex regulation in vivo, we dissected links to gene expression with in vitro modified reporter constructs. We used an Oct4 promoter-driven reporter gene and demonstrated that in vitro methylation causes gene silencing while subsequent oxidation with purified catalytic domain of TET1 leads to gene reactivation. To identify proteins involved in this pathway we screened for TET interacting factors and identified TDG, PARP1, XRCC1 and LIG3 that are involved in base-excision repair. Knockout and rescue experiments demonstrated that gene reactivation depended on the glycosylase TDG, but not MBD4, while NEIL1, 2 and 3 could partially rescue the loss of TDG. These results clearly show that oxidation of methylcytosine by TET dioxygenases and subsequent removal by TDG or NEIL glycosylases and the BER pathway results in reactivation of epigenetically silenced genes