107 research outputs found

    G-quadruplex structures mark human regulatory chromatin

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    G-quadruplex (G4) structural motifs have been linked to transcription, replication and genome instability and are implicated in cancer and other diseases. However, it is crucial to demonstrate the bona fide formation of G4 structures within an endogenous chromatin context. Herein we address this through the development of G4 ChIP-seq, an antibody-based G4 chromatin immunoprecipitation and high-throughput sequencing approach. We find ∼10,000 G4 structures in human chromatin, predominantly in regulatory, nucleosome-depleted regions. G4 structures are enriched in the promoters and 5' UTRs of highly transcribed genes, particularly in genes related to cancer and in somatic copy number amplifications, such as MYC\textit{MYC}. Strikingly, de novo\textit{de novo} and enhanced G4 formation are associated with increased transcriptional activity, as shown by HDAC inhibitor-induced chromatin relaxation and observed in immortalized as compared to normal cellular states. Our findings show that regulatory, nucleosome-depleted chromatin and elevated transcription shape the endogenous human G4 DNA landscape.European Molecular Biology Organization (EMBO Long-Term Fellowship), University of Cambridge, Cancer Research UK (Grant ID: C14303/A17197), Wellcome Trust (Grant ID: 099232/z/12/z

    Re-entrant DNA gels

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    DNA is acquiring a primary role in material development, self-assembling by design into complex supramolecular aggregates, the building block of a new-materials world. Using DNA nanoconstructs to translate sophisticated theoretical intuitions into experimental realizations by closely matching idealized models of colloidal particles is a much less explored avenue. Here we experimentally show that an appropriate selection of competing interactions enciphered in multiple DNA sequences results into the successful design of a one-pot DNA hydrogel that melts both on heating and on cooling. The relaxation time, measured by light scattering, slows down dramatically in a limited window of temperatures. The phase diagram displays a peculiar re-entrant shape, the hallmark of the competition between different bonding patterns. Our study shows that it is possible to rationally design biocompatible bulk materials with unconventional phase diagrams and tuneable properties by encoding into DNA sequences both the particle shape and the physics of the collective response

    The role of microglia in human disease: therapeutic tool or target?

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    Hot atmospheres of galaxies, groups, and clusters of galaxies

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    Most of the ordinary matter in the local Universe has not been converted into stars but resides in a largely unexplored diffuse, hot, X-ray emitting plasma. It pervades the gravitational potentials of massive galaxies, groups and clusters of galaxies, as well as the filaments of the cosmic web. The physics of this hot medium, such as its dynamics, thermodynamics and chemical composition can be studied using X-ray spectroscopy in great detail. Here, we present an overview of the basic properties and discuss the self similarity of the hot "atmospheres" permeating the gravitational halos from the scale of galaxies, through groups, to massive clusters. Hot atmospheres are stabilised by the activity of supermassive black holes and, in many ways, they are of key importance for the evolution of their host galaxies. The hot plasma has been significantly enriched in heavy elements by supernovae during the period of maximum star formation activity, probably more than 10 billion years ago. High resolution X-ray spectroscopy just started to be able to probe the dynamics of atmospheric gas and future space observatories will determine the properties of the currently unseen hot diffuse medium throughout the cosmic web.Comment: Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

    Impact of Age on the Cerebrovascular Proteomes of Wild-Type and Tg-SwDI Mice

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    The structural integrity of cerebral vessels is compromised during ageing. Abnormal amyloid (Aβ) deposition in the vasculature can accelerate age-related pathologies. The cerebrovascular response associated with ageing and microvascular Aβ deposition was defined using quantitative label-free shotgun proteomic analysis. Over 650 proteins were quantified in vessel-enriched fractions from the brains of 3 and 9 month-old wild-type (WT) and Tg-SwDI mice. Sixty-five proteins were significantly increased in older WT animals and included several basement membrane proteins (nidogen-1, basement membrane-specific heparan sulfate proteoglycan core protein, laminin subunit gamma-1 precursor and collagen alpha-2(IV) chain preproprotein). Twenty-four proteins were increased and twenty-one decreased in older Tg-SwDI mice. Of these, increases in Apolipoprotein E (APOE) and high temperature requirement serine protease-1 (HTRA1) and decreases in spliceosome and RNA-binding proteins were the most prominent. Only six shared proteins were altered in both 9-month old WT and Tg-SwDI animals. The age-related proteomic response in the cerebrovasculature was distinctly different in the presence of microvascular Aβ deposition. Proteins found differentially expressed within the WT and Tg-SwDI animals give greater insight to the mechanisms behind age-related cerebrovascular dysfunction and pathologies and may provide novel therapeutic targets

    Catálogo Taxonômico da Fauna do Brasil: setting the baseline knowledge on the animal diversity in Brazil

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    The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others
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