1,491 research outputs found

    Social Status Affects the Degree of Sex Difference in the Songbird Brain

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    It is thought that neural sex differences are functionally related to sex differences in the behaviour of vertebrates. A prominent example is the song control system of songbirds. Inter-specific comparisons have led to the hypothesis that sex differences in song nuclei size correlate with sex differences in song behaviour. However, only few species with similar song behaviour in both sexes have been investigated and not all data fit the hypothesis. We investigated the proposed structure – function relationship in a cooperatively breeding and duetting songbird, the white-browed sparrow weaver (Plocepasser mahali). This species lives in groups of 2–10 individuals, with a dominant breeding pair and male and female subordinates. While all male and female group members sing duet and chorus song, a male, once it has reached the dominant position in the group, sings an additional type of song that comprises a distinct and large syllable repertoire. Here we show for both types of male – female comparisons a male-biased sex difference in neuroanatomy of areas of the song production pathway (HVC and RA) that does not correlate with the observed polymorphism in song behaviour. In contrast, in situ hybridisation of mRNA of selected genes expressed in the song nucleus HVC reveals a gene expression pattern that is either similar between sexes in female – subordinate male comparisons or female-biased in female – dominant male comparisons. Thus, the polymorphic gene expression pattern would fit the sex- and status-related song behaviour. However, this implies that once a male has become dominant it produces the duetting song with a different neural phenotype than subordinate males

    Reliable identification of protein-protein interactions by crosslinking mass spectrometry

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    Protein-protein interactions govern most cellular pathways and processes, and multiple technologies have emerged to systematically map them. Assessing the error of interaction networks has been a challenge. Crosslinking mass spectrometry is currently widening its scope from structural analyses of purified multi-protein complexes towards systems-wide analyses of protein-protein interactions (PPIs). Using a carefully controlled large-scale analysis of Escherichia coli cell lysate, we demonstrate that false-discovery rates (FDR) for PPIs identified by crosslinking mass spectrometry can be reliably estimated. We present an interaction network comprising 590 PPIs at 1% decoy-based PPI-FDR. The structural information included in this network localises the binding site of the hitherto uncharacterised protein YacL to near the DNA exit tunnel on the RNA polymerase.TU Berlin, Open-Access-Mittel – 2021DFG, 390540038, EXC 2008: Unifying Systems in Catalysis "UniSysCat"DFG, 392923329, GRK 2473: Bioaktive Peptide - Innovative Aspekte zur Synthese und BiosyntheseDFG, 426290502, Erfassung der strukturellen Organisation des Mycoplasma pneumoniae Proteoms mittels in-Zell Crosslinking-Massenspektrometri

    Intradermal Electroporation of Naked Replicon RNA Elicits Strong Immune Responses

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    RNA-based vaccines represent an interesting immunization modality, but suffer from poor stability and a lack of efficient and clinically feasible delivery technologies. This study evaluates the immunogenic potential of naked in vitro transcribed Semliki Forest virus replicon RNA (RREP) delivered intradermally in combination with electroporation. Replicon-immunized mice showed a strong cellular and humoral response, contrary to mice immunized with regular mRNA. RREP-elicited induction of interferon-γ secreting CD8+ T cells and antibody responses were significantly increased by electroporation. CD8+ T cell responses remained substantial five weeks post vaccination, and antigen-specific CD8+ T cells with phenotypic characteristics of both effector and central memory cells were identified. The immune response during the contraction phase was further increased by a booster immunization, and the proportion of effector memory cells increased significantly. These results demonstrate that naked RREP delivered via intradermal electroporation constitute an immunogenic, safe and attractive alternative immunization strategy to DNA-based vaccines

    Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance

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    This paper presents DELPHI measurements and interpretations of cross-sections, forward-backward asymmetries, and angular distributions, for the e+e- -> ffbar process for centre-of-mass energies above the Z resonance, from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are consistent with the predictions of the Standard Model and are used to study a variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering and several models which include physics beyond the Standard Model: the exchange of Z' bosons, contact interactions between fermions, the exchange of gravitons in large extra dimensions and the exchange of sneutrino in R-parity violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.

    A Determination of the Centre-of-Mass Energy at LEP2 using Radiative 2-fermion Events

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    Using e+e- -> mu+mu-(gamma) and e+e- -> qqbar(gamma) events radiative to the Z pole, DELPHI has determined the centre-of-mass energy, sqrt{s}, using energy and momentum constraint methods. The results are expressed as deviations from the nominal LEP centre-of-mass energy, measured using other techniques. The results are found to be compatible with the LEP Energy Working Group estimates for a combination of the 1997 to 2000 data sets.Comment: 20 pages, 6 figures, Accepted by Eur. Phys. J.

    U-Compare bio-event meta-service: compatible BioNLP event extraction services

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    AbstractBackgroundBio-molecular event extraction from literature is recognized as an important task of bio text mining and, as such, many relevant systems have been developed and made available during the last decade. While such systems provide useful services individually, there is a need for a meta-service to enable comparison and ensemble of such services, offering optimal solutions for various purposes.ResultsWe have integrated nine event extraction systems in the U-Compare framework, making them inter-compatible and interoperable with other U-Compare components. The U-Compare event meta-service provides various meta-level features for comparison and ensemble of multiple event extraction systems. Experimental results show that the performance improvements achieved by the ensemble are significant. ConclusionsWhile individual event extraction systems themselves provide useful features for bio text mining, the U-Compare meta-service is expected to improve the accessibility to the individual systems, and to enable meta-level uses over multiple event extraction systems such as comparison and ensemble.This research was partially supported by KAKENHI 18002007 [YK, MM, JDK, SP, TO, JT]; JST PRESTO and KAKENHI 21500130 [YK]; the Academy of Finland and computational resources were provided by CSC -- IT Center for Science Ltd [JB, FG]; the Research Foundation Flanders (FWO) [SVL]; UK Biotechnology and Biological Sciences, Research Council (BBSRC project BB/G013160/1 Automated Biological Event Extraction from the Literature for Drug Discovery) and JISC, National Centre for Text Mining [SA]; the Spanish grant BIO2010-17527 [MN, APM]; NIH Grant U54 DA021519 [AO, DRR]Peer Reviewe

    Classification of HIV-1 Sequences Using Profile Hidden Markov Models

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    Accurate classification of HIV-1 subtypes is essential for studying the dynamic spatial distribution pattern of HIV-1 subtypes and also for developing effective methods of treatment that can be targeted to attack specific subtypes. We propose a classification method based on profile Hidden Markov Model that can accurately identify an unknown strain. We show that a standard method that relies on the construction of a positive training set only, to capture unique features associated with a particular subtype, can accurately classify sequences belonging to all subtypes except B and D. We point out the drawbacks of the standard method; namely, an arbitrary choice of threshold to distinguish between true positives and true negatives, and the inability to discriminate between closely related subtypes. We then propose an improved classification method based on construction of a positive as well as a negative training set to improve discriminating ability between closely related subtypes like B and D. Finally, we show how the improved method can be used to accurately determine the subtype composition of Common Recombinant Forms of the virus that are made up of two or more subtypes. Our method provides a simple and highly accurate alternative to other classification methods and will be useful in accurately annotating newly sequenced HIV-1 strains

    Breast cancer incidence and mortality in Tyrol/Austria after fifteen years of opportunistic mammography screening

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    <p>Abstract</p> <p>Background</p> <p>The aim of this study was to analyse breast cancer incidence and mortality in Tyrol from 1970 to 2006, namely after performing more than a decade of opportunistic mammography screening and just before piloting an organised screening programme. Our investigation was conducted on a population level.</p> <p>Methods</p> <p>To study time trends in breast cancer incidence and mortality, we applied the age-period-cohort model by Poisson regression to the official mortality data covering more than three decades from 1970 to 2006 and to the incidence data ranging from 1988 to 2006. In addition, for incidence data we analysed data on breast cancer staging and compared these with EU guidelines.</p> <p>Results</p> <p>For the analysis of time trend in breast cancer mortality in age groups 40-79, an age-period-cohort model fits well and shows for years 2002-2006 a statistically significant reduction of 26% (95% CI 13%-36%) in breast cancer mortality as compared to 1992-1996.</p> <p>We see only slight non-significant increases in breast cancer incidence. For the past five years, incidence data show a 10% proportion of in situ cases, and of 50% for cases in stages II+.</p> <p>Conclusions</p> <p>The opportunistic breast cancer screening programme in Tyrol has only in part exploited the mortality reduction known for organised screening programmes. There seems to be potential for further improvement, and we recommend that an organised screening programme and a detailed screening database be introduced to collect all information needed to analyse the quality indicators suggested by the EU guidelines.</p

    Regulation of the Na,K-ATPase Gamma-Subunit FXYD2 by Runx1 and Ret Signaling in Normal and Injured Non-Peptidergic Nociceptive Sensory Neurons

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    Dorsal root ganglia (DRGs) contain the cell bodies of sensory neurons which relay nociceptive, thermoceptive, mechanoceptive and proprioceptive information from peripheral tissues toward the central nervous system. These neurons establish constant communication with their targets which insures correct maturation and functioning of the somato-sensory nervous system. Interfering with this two-way communication leads to cellular, electrophysiological and molecular modifications that can eventually cause neuropathic conditions. In this study we reveal that FXYD2, which encodes the gamma-subunit of the Na,K-ATPase reported so far to be mainly expressed in the kidney, is induced in the mouse DRGs at postnatal stages where it is restricted specifically to the TrkB-expressing mechanoceptive and Ret-positive/IB4-binding non-peptidergic nociceptive neurons. In non-peptidergic nociceptors, we show that the transcription factor Runx1 controls FXYD2 expression during the maturation of the somato-sensory system, partly through regulation of the tyrosine kinase receptor Ret. Moreover, Ret signaling maintains FXYD2 expression in adults as demonstrated by the axotomy-induced down-regulation of the gene that can be reverted by in vivo delivery of GDNF family ligands. Altogether, these results establish FXYD2 as a specific marker of defined sensory neuron subtypes and a new target of the Ret signaling pathway during normal maturation of the non-peptidergic nociceptive neurons and after sciatic nerve injury
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