ATP-dependent DNA ligases

By catalyzing the joining of breaks in the phosphodiester backbone of duplex DNA, DNA ligases play a vital role in the diverse processes of DNA replication, recombination and repair. Three related classes of ATP-dependent DNA ligase are readily apparent in eukaryotic cells. Enzymes of each class comprise catalytic and non-catalytic domains together with additional domains of varying function. DNA ligase I is required for the ligation of Okazaki fragments during lagging-strand DNA synthesis, as well as for several DNA-repair pathways; these functions are mediated, at least in part, by interactions between DNA ligase I and the sliding-clamp protein PCNA. DNA ligase III, which is unique to vertebrates, functions both in the nucleus and in mitochondria. Two distinct isoforms of this enzyme, differing in their carboxy-terminal sequences, are produced by alternative splicing: DNA ligase IIIα has a carboxy-terminal BRCT domain that interacts with the mammalian DNA-repair factor XrccI, but both α and β isoforms have an amino-terminal zinc-finger motif that appears to play a role in the recognition of DNA secondary structures that resemble intermediates in DNA metabolism. DNA ligase IV is required for DNA non-homologous end joining pathways, including recombination of the V(D)J immunoglobulin gene segments in cells of the mammalian immune system. DNA ligase IV forms a tight complex with Xrcc4 through an interaction motif located between a pair of carboxy-terminal BRCT domains in the ligase. Recent structural studies have shed light on the catalytic function of DNA ligases, as well as illuminating protein-protein interactions involving DNA ligases IIIα and IV

Bile acid retention and activation of endogenous hepatic farnesoid-X-receptor in the pathogenesis of fatty liver disease in ob/ob-mice

The nuclear bile acid receptor FXR (farnesoid-X-receptor) has recently been implicated in the pathophysiology of non-alcoholic fatty liver disease because selective FXR-agonists improve glucose and lipid metabolism in rodent models of obesity. However, the regulation of FXR and other relevant nuclear receptors as well as their lipogenic target genes in fatty liver is still not revealed in detail. Livers were harvested from 14-week-old male ob/ob mice and wild-type controls. Serum bile acids were quantified by radioimmunoassay. mRNA and protein expression of transporters and nuclear receptors was analyzed by reverse transcriptase-polymerase chain reaction and Western blotting, whereas DNA binding to the IR-1 element was examined by electrophoretic mobility shift assay. In this study we show: (i) bile acid retention in ob/ob mice, (ii) a resulting FXR upregulation and binding to the IR-1 element in ob/ob animals and (iii) concomitant activation of the fatty acid synthase as a potential lipogenic FXR target gene in vivo. The present study suggests a potential role of hepatic bile acid retention and FXR activation in the induction of lipogenic target genes. Differences between intestinal and hepatic FXR could explain apparent contradictory information regarding its effects on fatty liver diseas

Prompt neutrino fluxes from atmospheric charm

We calculate the prompt neutrino flux from atmospheric charm production by cosmic rays, using the dipole picture in a perturbative QCD framework, which incorporates the parton saturation effects present at high energies. We compare our results with the next-to-leading order perturbative QCD result and find that saturation effects are large for neutrino energies above 10^6 GeV, leading to a substantial suppression of the prompt neutrino flux. We comment on the range of prompt neutrino fluxes due to theoretical uncertainties.Comment: 13 pages with 11 figures; expanded discussion, added references, version to be published in Phys. Rev.

Farm-like indoor microbiota in non-farm homes protects children from asthma development

Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today(1). The asthma-protective effect of farms appears to be associated with rich home dust microbiota(2,3), which could be used to model a health-promoting indoor microbiome. Here we show by modeling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts(4) that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases. The protective microbiota had a low abundance of Streptococcaceae relative to outdoor-associated bacterial taxa. The protective effect was independent of richness and total bacterial load and was associated with reduced proinflammatory cytokine responses against bacterial cell wall components ex vivo. We were able to reproduce these findings in a study among rural German children(2) and showed that children living in German non-farm homes with an indoor microbiota more similar to Finnish farm homes have decreased asthma risk. The indoor dust microbiota composition appears to be a definable, reproducible predictor of asthma risk and a potential modifiable target for asthma prevention.Peer reviewe

Phenology of the avian spring migratory passage in Europe and North America : Asymmetric advancement in time and increase in duration

Climate change has been shown to shift the seasonal timing (i.e. phenology) and distribution of species. The phenological effects of climate change on living organisms have often been tested using first occurrence dates, which may be uninformative and biased. More rarely investigated is how different phases of a phenological sequence (e.g. beginning, central tendency and end) or its duration have changed over time. This type of analysis requires continuous observation throughout the phenological event over multiple years, and such data sets are rare. In this study we examined the impact of temperature on long-term change of passage timing and duration of the spring migration period in birds, and which species' traits explain species-specific variation. Data used covered 195 species from 21 European and Canadian bird observatories from which systematic daily sampling protocols were available. Migration dates were negatively associated with early spring temperature and timings had in general advanced in 57 years. Short-distance migrants advanced the beginning of their migration more than long-distance migrants when corrected for phylogenic relatedness, but such a difference was not found in other phases of migration. The advancement of migration has generally been greater for the beginning and median phases of migration relative to the end, leading to extended spring migration seasons. Duration of the migration season increased with increasing temperature. Phenological changes have also been less noticeable in Canada even when corrected for rate of change in temperature. To visualize long-term changes in phenology, we constructed the first multi-species spring migration phenology indicator to describe general changes in median migration dates in the northern hemisphere. The indicator showed an average advancement of one week during five decades across the continents (period 1959-2015). The indicator is easy to update with new data and we therefore encourage future research to investigate whether the trend towards longer periods of occurrence or emergence in spring is also evident in other migratory populations. Such phenological changes may influence detectability in monitoring schemes, and may have broader implications on population and community dynamics.Peer reviewe

Neutrino Interactions at Ultrahigh Energies

We report new calculations of the cross sections for deeply inelastic neutrino-nucleon scattering at neutrino energies between 10^{9}\ev and 10^{21}\ev. We compare with results in the literature and assess the reliability of our predictions. For completeness, we briefly review the cross sections for neutrino interactions with atomic electrons, emphasizing the role of the $W$-boson resonance in $\bar{\nu}_{e}e$ interactions for neutrino energies in the neighborhood of 6.3\pev. Adopting model predictions for extraterrestrial neutrino fluxes from active galactic nuclei, gamma-ray bursters, and the collapse of topological defects, we estimate event rates in large-volume water \v{C}erenkov detectors and large-area ground arrays.Comment: 32 pages, 11 figures, uses RevTeX and boxedep

Разработка магнитной оправки для алмазного выглаживания

Объектом исследования является магнитная оправка. Актуальность разработки оправки для алмазного выглаживания заключается в том, что в процессе выглаживания требуется стабильное усилие выглаживания независимо от неточности геометрической формы детали и погрешностей установки. Целью данной выпускной квалификационной работы является разработка оправки для алмазного выглаживания, которая не имеет пару трения и позволяет проводить выглаживание с маленьким колебанием усилия выглаживания. Рассматриваемые вопросы: как проводить алмазное выглаживание без силы трения, как регулировать усилия выглаживания для магнитной оправки и и т. д.The object of study is a magnetic mandrel. The relevance of the development of the mandrel for diamond smoothing is that the smoothing process requires a stable smoothing force, regardless of the inaccuracy of the geometric shape of the part and the installation errors. The purpose of this final qualifying work is to develop a mandrel for diamond smoothing, which does not have a friction pair and allows smoothing with a small fluctuation in the effort of smoothing. Questions to be addressed: how to carry out diamond smoothing without friction, how to adjust the smoothing efforts for a magnetic mandrel and etc