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- Gao, YX, et al.
(author)
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
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Journal article (peer-reviewed)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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- Geisler, D., et al.
(author)
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CAPOS : The bulge Cluster APOgee Survey I. Overview and initial ASPCAP results
- 2021
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 652
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Journal article (peer-reviewed)abstract
- Context. Bulge globular clusters (BGCs) are exceptional tracers of the formation and chemodynamical evolution of this oldest Galactic component. However, until now, observational difficulties have prevented us from taking full advantage of these powerful Galactic archeological tools. Aims. CAPOS, the bulge Cluster APOgee Survey, addresses this key topic by observing a large number of BGCs, most of which have only been poorly studied previously. Even their most basic parameters, such as metallicity, [alpha/Fe], and radial velocity, are generally very uncertain. We aim to obtain accurate mean values for these parameters, as well as abundances for a number of other elements, and explore multiple populations. In this first paper, we describe the CAPOS project and present initial results for seven BGCs. Methods. CAPOS uses the APOGEE-2S spectrograph observing in the H band to penetrate obscuring dust toward the bulge. For this initial paper, we use abundances derived from ASPCAP, the APOGEE pipeline. Results. We derive mean [Fe/H] values of -0.85 +/- 0.04 (Terzan 2), -1.40 +/- 0.05 (Terzan 4), -1.20 +/- 0.10 (HP 1), -1.40 +/- 0.07 (Terzan 9), -1.07 +/- 0.09 (Djorg 2), -1.06 +/- 0.06 (NGC 6540), and -1.11 +/- 0.04 (NGC 6642) from three to ten stars per cluster. We determine mean abundances for eleven other elements plus the mean [alpha/Fe] and radial velocity. CAPOS clusters significantly increase the sample of well-studied Main Bulge globular clusters (GCs) and also extend them to lower metallicity. We reinforce the finding that Main Bulge and Main Disk GCs, formed in situ, have [Si/Fe] abundances slightly higher than their accreted counterparts at the same metallicity. We investigate multiple populations and find our clusters generally follow the light-element (anti)correlation trends of previous studies of GCs of similar metallicity. We finally explore the abundances of the iron-peak elements Mn and Ni and compare their trends with field populations. Conclusions. CAPOS is proving to be an unprecedented resource for greatly improving our knowledge of the formation and evolution of BGCs and the bulge itself.
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- Hatos, Andras, et al.
(author)
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DisProt : intrinsic protein disorder annotation in 2020
- 2020
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:D1, s. D269-D276
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Journal article (peer-reviewed)abstract
- The Database of Protein Disorder (DisProt, URL:https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.
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- Lazar, Tamas, et al.
(author)
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PED in 2021 : A major update of the protein ensemble database for intrinsically disordered proteins
- 2021
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 49:D1, s. 404-411
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Journal article (peer-reviewed)abstract
- The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.0, has been completely redesigned and reimplemented with cutting-edge technology and now holds about six times more data (162 versus 24 entries and 242 versus 60 structural ensembles) and a broader representation of state of the art ensemble generation methods than the previous version. The database has a completely renewed graphical interface with an interactive feature viewer for region-based annotations, and provides a series of descriptors of the qualitative and quantitative properties of the ensembles. High quality of the data is guaranteed by a new submission process, which combines both automatic and manual evaluation steps. A team of biocurators integrate structured metadata describing the ensemble generation methodology, experimental constraints and conditions. A new search engine allows the user to build advanced queries and search all entry fields including cross-references to IDP-related resources such as DisProt, MobiDB, BMRB and SASBDB. We expect that the renewed PED will be useful for researchers interested in the atomic-level understanding of IDP function, and promote the rational, structure-based design of IDP-targeting drugs.
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- Quaglia, Federica, et al.
(author)
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DisProt in 2022 : improved quality and accessibility of protein intrinsic disorder annotation
- 2022
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 50:D1, s. D480-D487
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Journal article (peer-reviewed)abstract
- The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure.
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- Giorgini, Ludovico T., et al.
(author)
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Two-loop corrections to the large-order behavior of correlation functions in the one-dimensional N-vector model
- 2020
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In: Physical Review D. - : American Physical Society (APS). - 1550-7998 .- 1550-2368. ; 101:12
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Journal article (peer-reviewed)abstract
- For a long time, the predictive limits of perturbative quantum field theory have been limited by our inability to carry out loop calculations to an arbitrarily high order, which become increasingly complex as the order of perturbation theory is increased. This problem is exacerbated by the fact that perturbation series derived from loop diagram (Feynman diagram) calculations represent asymptotic (divergent) series which limits the predictive power of perturbative quantum field theory. Here, we discuss an ansatz that could overcome these limits, based on the observations that (i) for many phenomenologically relevant field theories, one can derive dispersion relations which relate the large-order growth (the asymptotic limit of infinite loop order) with the imaginary part of arbitrary correlation functions, for negative coupling (unstable vacuum), and (ii) one can analyze the imaginary part for negative coupling in terms of classical field configurations (instantons). Unfortunately, the perturbation theory around instantons, which could lead to much more accurate predictions for the large-order behavior of Feynman diagrams, poses a number of technical as well as computational difficulties. Here, we study, to further the above-mentioned ansatz, correlation functions in a one-dimensional (1D) field theory with a quartic self-interaction and an O(N) internal symmetry group, otherwise known as the 1D N-vector model. Our focus is on corrections to the large-order growth of perturbative coefficients, i.e., the limit of a large number of loops in the Feynman diagram expansion. We evaluate, in momentum space, the two-loop corrections for the two-point correlation function, and its derivative with respect to the momentum, as well as the two-point correlation function with a wigglet insertion. Also, we study the four-point function. These quantities, computed at zero momentum transfer, enter the renormalization-group functions (Callan-Symanzik equation) of the model. Our calculations pave the way for further development of related methods in field theory and for a better understanding of field-theoretical expansions at large order.
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