1,342 research outputs found

    Suvremeni kriĆŸari u Europi. Tradicija, obitelj i vlasniĆĄtvo: analiza transnacionalnih, ultrakonzervativnih, katolicizmom inspiriranih mreĆŸa utjecaja

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    Three recent events affecting human rights in sexuality and reproduction (a proposed ban on abortion in Poland, blocking support for She Decides in Croatia and halting a civil union law in Estonia) were spearheaded by organizations which appear to be the national antennae of the transnational, socially conservative network called Tradition, Family and Property (TFP). TFP refers to a set of interrelated conservative, Catholic-inspired organizations which share a common world view inspired by the TFP founder, Plinio CorrĂȘa de Oliveira. Originating in Brazil in 1960 and eventually spreading throughout the world, TFP has long been an insurrection movement within Catholicism, with a distinct way of working by fusing social conservatism with economic hyper-liberalism and a legacy of complicity with far-right movements. Having withered away from Latin America, TFP is now an active European network with positions against sexual and reproductive rights (SRR ) among its priorities. TFP’s influence on SRR takes three main routes: social mobilization; norm entrepreneur and entering decision-making spaces. TFP has found new horizons in Eastern Europe and ambitions to influence the European Union and the United Nations. The reactionary narrative of TFP espousing religious orthodoxy and sanctifying economic inequality could become attractive to some by offering religious legitimization for illiberalism and authoritarianism.Tri nedavna događaja koja se tiču seksualnih i reproduktivnih prava (predloĆŸena zabrana pobačaja u Poljskoj, blokiranje potpore inicijativi She Decides u Hrvatskoj i zaustavljanje zakona o civilnom partnerstvu u Estoniji) potaknule su organizacije koje se doimaju poput nacionalne antene transnacionalne, socijalno konzervativne mreĆŸe Tradicija, obitelj i vlasniĆĄtvo (Tradition, Family and Property – TFP). TFP je oznaka za skup međupovezanih konzervativnih i katolicizmom nadahnutih organizacija koje dijele svjetonazor blizak osnivaču TFP-a Plinia CorrĂȘe de Oliveira. Nastao u Brazilu 1960-ih, a zatim proĆĄiren svijetom, TFP je već dugo pobunjenički pokret unutar katolicizma, a kojeg odlikuje specifičan način djelovanja kroz spajanje socijalnog konzervativizma, ekonomskog hiperliberalizma i naslijeđe bliskosti s krajnje desnim pokretima. Oslabljen u Latinskoj Americi, TFP je sada aktivna europska mreĆŸa s dominantnim stavovima protiv seksualnih i reproduktivnih prava (SRR ). Utjecaj TFP-a na seksualna i reproduktivna prava zbiva se putem druĆĄtvene mobilizacije, normativnog poduzetniĆĄtva i ulaska u prostore donoĆĄenja odluka. TFP-u su se u Istočnoj Europi otvorili novi horizonti i ambicije za utjecaj na Europsku uniju i Ujedinjene narode. Reakcionarni narativ TFP-a, koji promiče pravovjernost i posvećuje ekonomske nejednakosti, mogao bi postati privlačan kao religijska legitimacija iliberalizma i autoritarizma

    Robust signatures in the current-voltage characteristics of DNA molecules oriented between two graphene nanoribbon electrodes

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    In this work we numerically calculate the electric current through three kinds of DNA sequences (telomeric, \lambda-DNA, and p53-DNA) described by different heuristic models. A bias voltage is applied between two zig-zag edged graphene contacts attached to the DNA segments, while a gate terminal modulates the conductance of the molecule. The calculation of current is performed by integrating the transmission function (calculated using the lattice Green's function) over the range of energies allowed by the chemical potentials. We show that a telomeric DNA sequence, when treated as a quantum wire in the fully coherent low-temperature regime, works as an excellent semiconductor. Clear steps are apparent in the current-voltage curves of telomeric sequences and are present independent of lengths and sequence initialisation at the contacts. The current-voltage curves suggest the existence of stepped structures independent of length and sequencing initialisation at the contacts. We also find that the molecule-electrode coupling can drastically influence the magnitude of the current. The difference between telomeric DNA and other DNA, such as \lambda-DNA and DNA for the tumour suppressor p53, is particularly visible in the length dependence of the current

    Characterization of the 6-methyl isoxanthopterin (6-MI) base analog dimer, a spectroscopic probe for monitoring guanine base conformations at specific sites in nucleic acids

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    We here characterize local conformations of site-specifically placed pairs of guanine (G) residues in RNA and DNA, using 6-methyl isoxanthopterin (6-MI) as a conformational probe. 6-MI is a base analog of G and spectroscopic signals obtained from pairs of adjacent 6-MI residues reflect base–base interactions that are sensitive to the sequence context, local DNA conformation and solvent environment of the probe bases. CD signals show strong exciton coupling between stacked 6-MI bases in double-stranded (ds) DNA; this coupling is reduced in single-stranded (ss) DNA sequences. Solvent interactions reduce the fluorescence of the dimer probe more efficiently in ssDNA than dsDNA, while self-quenching between 6-MI bases is enhanced in dsDNA. 6-MI dimer probes closely resemble adjacent GG residues, in that these probes have minimal effects on the stability of dsDNA and on interactions with solvent additive betaine. They also serve as effective template bases, although further polymerase-dependent extension of DNA primers past 6-MI template bases is significantly inhibited. These probes are also used to monitor DNA ‘breathing’ at model replication forks. The 6-MI dimer probe can serve in many contexts as a useful tool to investigate GG conformations at specific sites within the nucleic acid frameworks of functioning macromolecular machines in solution

    HOXB13, a Target of DNMT3B, Is Methylated at an Upstream CpG Island, and Functions as a Tumor Suppressor in Primary Colorectal Tumors

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    A hallmark of cancer cells is hypermethylation of CpG islands (CGIs), which probably arises from upregulation of one or more DNA methyltransferases. The purpose of this study was to identify the targets of DNMT3B, an essential DNA methyltransferase in mammals, in colon cancer.Chromatin immunoprecipitation with DNMT3B specific antibody followed by CGI microarray identified genes with or without CGIs, repeat elements and genomic contigs in RKO cells. ChIP-Chop analysis showed that the majority of the target genes including P16, DCC, DISC1, SLIT1, CAVEOLIN1, GNA11, TBX5, TBX18, HOXB13 and some histone variants, that harbor CGI in their promoters, were methylated in multiple colon cancer cell lines but not in normal colon epithelial cells. Further, these genes were reactivated in RKO cells after treatment with 5-aza-2'-deoxycytidine, a DNA hypomethylating agent. COBRA showed that the CGIs encompassing the promoter and/or coding region of DCC, TBX5, TBX18, SLIT1 were methylated in primary colorectal tumors but not in matching normal colon tissues whereas GNA11 was methylated in both. MassARRAY analysis demonstrated that the CGI located approximately 4.5 kb upstream of HOXB13 +1 site was tumor-specifically hypermethylated in primary colorectal cancers and cancer cell lines. HOXB13 upstream CGI was partially hypomethylated in DNMT1(-/-) HCT cells but was almost methylation free in cells lacking both DNMT1 and DNMT3B. Analysis of tumor suppressor properties of two aberrantly methylated transcription factors, HOXB13 and TBX18, revealed that both inhibited growth and clonogenic survival of colon cancer cells in vitro, but only HOXB13 abolished tumor growth in nude mice.This is the first report that identifies several important tumor suppressors and transcription factors as direct DNMT3B targets in colon cancer and as potential biomarkers for this cancer. Further, this study shows that methylation at an upstream CGI of HOXB13 is unique to colon cancer

    Dimensional Reduction and Screening Masses in Pure Gauge Theories at Finite Temperature

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    We studied screening masses in the equilibrium thermodynamics of SU(2) and SU(3) pure gauge theories on the lattice. At a temperature of 2 Tc we found strong evidence for dimensional reduction in the non-perturbative spectrum of screening masses. Mass ratios in the high temperature SU(3) theory are consistent with those in the pure gauge theory in three dimensions. At the first order SU(3) phase transition we report the first measurement of the true scalar screening mass.Comment: 34 pages, 10 figure

    Transformation of spin information into large electrical signals via carbon nanotubes

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    Spin electronics (spintronics) exploits the magnetic nature of the electron, and is commercially exploited in the spin valves of disc-drive read heads. There is currently widespread interest in using industrially relevant semiconductors in new types of spintronic devices based on the manipulation of spins injected into a semiconducting channel between a spin-polarized source and drain. However, the transformation of spin information into large electrical signals is limited by spin relaxation such that the magnetoresistive signals are below 1%. We overcome this long standing problem in spintronics by demonstrating large magnetoresistance effects of 61% at 5 K in devices where the non-magnetic channel is a multiwall carbon nanotube that spans a 1.5 micron gap between epitaxial electrodes of the highly spin polarized manganite La0.7Sr0.3MnO3. This improvement arises because the spin lifetime in nanotubes is long due the small spin-orbit coupling of carbon, because the high nanotube Fermi velocity permits the carrier dwell time to not significantly exceed this spin lifetime, because the manganite remains highly spin polarized up to the manganite-nanotube interface, and because the interfacial barrier is of an appropriate height. We support these latter statements regarding the interface using density functional theory calculations. The success of our experiments with such chemically and geometrically different materials should inspire adventure in materials selection for some future spintronicsComment: Content highly modified. New title, text, conclusions, figures and references. New author include

    DNA models of trinucleotide frameshift deletions: the formation of loops and bulges at the primer–template junction

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    Although mechanisms of single-nucleotide residue deletion have been investigated, processes involved in the loss of longer nucleotide sequences during DNA replication are poorly understood. Previous reports have shown that in vitro replication of a 3â€Č-TGC TGC template sequence can result in the deletion of one 3â€Č-TGC. We have used low-energy circular dichroism (CD) and fluorescence spectroscopy to investigate the conformations and stabilities of DNA models of the replication intermediates that may be implicated in this frameshift. Pyrrolocytosine or 2-aminopurine residues, site-specifically substituted for cytosine or adenine in the vicinity of extruded base sequences, were used as spectroscopic probes to examine local DNA conformations. An equilibrium mixture of four hybridization conformations was observed when template bases looped-out as a bulge, i.e. a structure flanked on both sides by duplex DNA. In contrast, a single-loop structure with an unusual unstacked DNA conformation at its downstream edge was observed when the extruded bases were positioned at the primer–template junction, showing that misalignments can be modified by neighboring DNA secondary structure. These results must be taken into account in considering the genetic and biochemical mechanisms of frameshift mutagenesis in polymerase-driven DNA replication

    High resolution synchrotron imaging of wheat root hairs growing in soil and image based modelling of phosphate uptake

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    Root hairs are known to be highly important for uptake of sparingly soluble nutrients, particularly in nutrient deficient soils. Development of increasingly sophisticated mathematical models has allowed uptake characteristics to be quantified. However, modelling has been constrained by a lack of methods for imaging live root hairs growing in real soils.We developed a plant growth protocol and used Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM) to uncover the 3D interactions of root hairs in real soil. We developed a model of phosphate uptake by root hairs based directly on the geometry of hairs and associated soil pores as revealed by imaging.Previous modelling studies found that root hairs dominate phosphate uptake. By contrast, our study suggests that hairs and roots contribute equally. We show that uptake by hairs is more localised than by roots and strongly dependent on root hair and aggregate orientation.The ability to image hair-soil interactions enables a step change in modelling approaches, allowing a more realistic treatment of processes at the scale of individual root hairs in soil pores

    Typhoid conjugate vaccine effectiveness in Malawi: evaluation of a test-negative design using randomised, controlled clinical trial data

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    Background Typhoid conjugate vaccines are being introduced in low-income and middle-income countries to prevent typhoid illness in children. Vaccine effectiveness studies assess vaccine performance after introduction. The test-negative design is a commonly used method to estimate vaccine effectiveness that has not been applied to typhoid vaccines because of concerns over blood culture insensitivity. The overall aim of the study was to evaluate the appropriateness of using a test-negative design to assess typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine (Vi-TT) effectiveness using a gold standard randomised controlled trial database. Methods Using blood culture data from a randomised controlled trial of Vi-TT in Malawi, we simulated a test-negative design to derive vaccine effectiveness estimates using three different approaches and compared these to randomised trial efficacy results. In the randomised trial, 27 882 children aged 9 months to 12 years were randomly assigned (1:1) to receive a single dose of Vi-TT or meningococcal capsular group A conjugate vaccine between Feb 21 and Sept 27, 2018, and were followed up for blood culture-confirmed typhoid fever until Sept 30, 2021. Findings For all three test-negative design approaches, vaccine effectiveness estimates (test-negative design A, 80·3% [95% CI 66·2 to 88·5] vs test-negative design B, 80·5% [66·5 to 88·6] vs test-negative design C, 80·4% [66·9 to 88·4]) were almost identical to the randomised trial results (80·4% [95% CI 66·4 to 88·5]). Receipt of Vi-TT did not affect the risk of non-typhoid fever (vaccine efficacy against non-typhoid fever –0·4% [95% CI –4·9 to 3·9] vs –1% [–5·6 to 3·3] vs –2·5% [–6·4 to 1·3] for test-negative design A, test-negative design B, and test-negative design C, respectively). Interpretation This study validates the test-negative design core assumption for typhoid vaccine effectiveness estimation and shows the accuracy and precision of the estimates compared with the randomised controlled trial. These results show that the test-negative design is suitable for assessing typhoid conjugate vaccine effectiveness in post-introduction studies using blood culture surveillance
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