journal
https://read.qxmd.com/read/34325466/novel-bile-acid-biosynthetic-pathways-are-enriched-in-the-microbiome-of-centenarians
#1
Yuko Sato, Koji Atarashi, Damian R Plichta, Yasumichi Arai, Satoshi Sasajima, Sean M Kearney, Wataru Suda, Kozue Takeshita, Takahiro Sasaki, Shoki Okamoto, Ashwin N Skelly, Yuki Okamura, Hera Vlamakis, Youxian Li, Takeshi Tanoue, Hajime Takei, Hiroshi Nittono, Seiko Narushima, Junichiro Irie, Hiroshi Itoh, Kyoji Moriya, Yuki Sugiura, Makoto Suematsu, Nobuko Moritoki, Shinsuke Shibata, Dan R Littman, Michael A Fischbach, Yoshifumi Uwamino, Takashi Inoue, Akira Honda, Masahira Hattori, Tsuyoshi Murai, Ramnik J Xavier, Nobuyoshi Hirose, Kenya Honda
Centenarians display decreased susceptibility to ageing-associated illness, chronic inflammation, and infectious disease1-3 . Here we show that centenarians have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids (BAs), including iso-, 3-oxo-, allo-, 3-oxoallo-, and isoallo-lithocholic acid (LCA). Among these BAs, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian's faecal microbiota, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo...
July 29, 2021: Nature
https://read.qxmd.com/read/34321666/rewiring-of-the-ubiquitinated-proteome-determines-ageing-in-c-elegans
#2
Seda Koyuncu, Rute Loureiro, Hyun Ju Lee, Prerana Wagle, Marcus Krueger, David Vilchez
Ageing is driven by a loss of cellular integrity1 . Given the major role of ubiquitin modifications in cell function2 , here we assess the link between ubiquitination and ageing by quantifying whole-proteome ubiquitin signatures in Caenorhabditis elegans. We find a remodelling of the ubiquitinated proteome during ageing, which is ameliorated by longevity paradigms such as dietary restriction and reduced insulin signalling. Notably, ageing causes a global loss of ubiquitination that is triggered by increased deubiquitinase activity...
July 28, 2021: Nature
https://read.qxmd.com/read/34321665/mechanisms-of-brca1-bard1-nucleosome-recognition-and-ubiquitylation
#3
Qi Hu, Maria Victoria Botuyan, Debiao Zhao, Gaofeng Cui, Elie Mer, Georges Mer
The BRCA1-BARD1 tumour suppressor is an E3 ubiquitin ligase necessary for the repair of DNA double-strand breaks by homologous recombination1-10 . The BRCA1-BARD1 complex localizes to damaged chromatin after DNA replication and catalyses the ubiquitylation of histone H2A and other cellular targets11-14 . The molecular bases for the recruitment to double-strand breaks and target recognition of BRCA1-BARD1 remain unknown. Here we use cryo-electron microscopy to show that the ankyrin repeat and tandem BRCT domains in BARD1 adopt a compact fold and bind to nucleosomal histones, DNA and monoubiquitin attached to H2A amino-terminal K13 or K15, two signals known to be specific for double-strand breaks15,16 ...
July 28, 2021: Nature
https://read.qxmd.com/read/34321664/molecular-architecture-of-the-developing-mouse-brain
#4
Gioele La Manno, Kimberly Siletti, Alessandro Furlan, Daniel Gyllborg, Elin Vinsland, Alejandro Mossi Albiach, Christoffer Mattsson Langseth, Irina Khven, Alex R Lederer, Lisa M Dratva, Anna Johnsson, Mats Nilsson, Peter Lönnerberg, Sten Linnarsson
The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell-cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. A complete understanding of this process requires a systematic characterization of cell states over the entire spatiotemporal range of brain development. The ability of single-cell RNA sequencing and spatial transcriptomics to reveal the molecular heterogeneity of complex tissues has therefore been particularly powerful in the nervous system...
July 28, 2021: Nature
https://read.qxmd.com/read/34321663/bard1-reads-h2a-lysine-15-ubiquitination-to-direct-homologous-recombination
#5
Jordan R Becker, Gillian Clifford, Clara Bonnet, Anja Groth, Marcus D Wilson, J Ross Chapman
Protein ubiquitination at sites of DNA double-strand breaks (DSBs) by RNF168 recruits BRCA1 and 53BP11,2 , which are mediators of the homologous recombination and non-homologous end joining DSB repair pathways, respectively3 . Non-homologous end joining relies on 53BP1 binding directly to ubiquitinated lysine 15 on H2A-type histones (H2AK15ub)4,5 (which is an RNF168-dependent modification6 ), but how RNF168 promotes BRCA1 recruitment and function remains unclear. Here we identify a tandem BRCT-domain-associated ubiquitin-dependent recruitment motif (BUDR) in BRCA1-associated RING domain protein 1 (BARD1) (the obligate partner protein of BRCA1) that, by engaging H2AK15ub, recruits BRCA1 to DSBs...
July 28, 2021: Nature
https://read.qxmd.com/read/34321662/possible-poriferan-body-fossils-in-early-neoproterozoic-microbial-reefs
#6
Elizabeth C Turner
Molecular phylogeny indicates that metazoans (animals) emerged early in the Neoproterozoic era1 , but physical evidence is lacking. The search for animal fossils from the Proterozoic eon is hampered by uncertainty about what physical characteristics to expect. Sponges are the most basic known animal type2,3 ; it is possible that body fossils of hitherto-undiscovered Proterozoic metazoans might resemble aspect(s) of Phanerozoic fossil sponges. Vermiform microstructure4,5 , a complex petrographic feature in Phanerozoic reefal and microbial carbonates, is now known to be the body fossil of nonspicular keratosan demosponges6-10 ...
July 28, 2021: Nature
https://read.qxmd.com/read/34321661/in-silico-saturation-mutagenesis-of-cancer-genes
#7
Ferran Muiños, Francisco Martínez-Jiménez, Oriol Pich, Abel Gonzalez-Perez, Nuria Lopez-Bigas
Despite the existence of good catalogues of cancer genes1,2 , identifying the specific mutations of those genes that drive tumorigenesis across tumour types is still a largely unsolved problem. As a result, most mutations identified in cancer genes across tumours are of unknown significance to tumorigenesis3 . We propose that the mutations observed in thousands of tumours-natural experiments testing their oncogenic potential replicated across individuals and tissues-can be exploited to solve this problem. From these mutations, features that describe the mechanism of tumorigenesis of each cancer gene and tissue may be computed and used to build machine learning models that encapsulate these mechanisms...
July 28, 2021: Nature
https://read.qxmd.com/read/34321660/structural-basis-of-ketamine-action-on-human-nmda-receptors
#8
Youyi Zhang, Fei Ye, Tongtong Zhang, Shiyun Lv, Liping Zhou, Daohai Du, He Lin, Fei Guo, Cheng Luo, Shujia Zhu
Ketamine is a non-competitive channel blocker of N-methyl-D-aspartate (NMDA) receptors1 . A single sub-anaesthetic dose of ketamine produces rapid (within hours) and long-lasting antidepressant effects in patients who are resistant to other antidepressants2,3 . Ketamine is a racemic mixture of S- and R-ketamine enantiomers, with S-ketamine isomer being the more active antidepressant4 . Here we describe the cryo-electron microscope structures of human GluN1-GluN2A and GluN1-GluN2B NMDA receptors in complex with S-ketamine, glycine and glutamate...
July 28, 2021: Nature
https://read.qxmd.com/read/34321659/regulated-control-of-gene-therapies-by-drug-induced-splicing
#9
Alex Mas Monteys, Amiel A Hundley, Paul T Ranum, Luis Tecedor, Amy Muehlmatt, Euyn Lim, Dmitriy Lukashev, Rajeev Sivasankaran, Beverly L Davidson
So far, gene therapies have relied on complex constructs that cannot be finely controlled1,2 . Here we report a universal switch element that enables precise control of gene replacement or gene editing after exposure to a small molecule. The small-molecule inducers are currently in human use, are orally bioavailable when given to animals or humans and can reach both peripheral tissues and the brain. Moreover, the switch system, which we denote Xon , does not require the co-expression of any regulatory proteins...
July 28, 2021: Nature
https://read.qxmd.com/read/34321650/a-caffeine-buzz-gives-bees-flower-power
#10
(no author information available yet)
No abstract text is available yet for this article.
July 28, 2021: Nature
https://read.qxmd.com/read/34321649/daily-briefing-how-sars-cov-2-infects-cells
#11
Flora Graham
No abstract text is available yet for this article.
July 28, 2021: Nature
https://read.qxmd.com/read/34321648/water-transformed-into-shiny-golden-metal
#12
Davide Castelvecchi
No abstract text is available yet for this article.
July 28, 2021: Nature
https://read.qxmd.com/read/34321647/has-the-world-s-oldest-known-animal-been-discovered
#13
Benjamin Thompson, Noah Baker
No abstract text is available yet for this article.
July 28, 2021: Nature
https://read.qxmd.com/read/34321646/sponge-like-fossil-could-be-earth-s-earliest-known-animal
#14
Max Kozlov
No abstract text is available yet for this article.
July 28, 2021: Nature
https://read.qxmd.com/read/34321645/mini-metavehicles-zip-and-swerve-on-light-power
#15
(no author information available yet)
No abstract text is available yet for this article.
July 28, 2021: Nature
https://read.qxmd.com/read/34321644/how-to-get-media-coverage-and-boost-your-science-s-impact
#16
Rebecca Fuoco
No abstract text is available yet for this article.
July 28, 2021: Nature
https://read.qxmd.com/read/34321642/protein-pile-up-plays-havoc-in-ageing-nematode-worms
#17
Bart P Braeckman
No abstract text is available yet for this article.
July 28, 2021: Nature
https://read.qxmd.com/read/34320609/rapid-and-stable-mobilization-of-cd8-t-cells-by-sars-cov-2-mrna-vaccine
#18
Valerie Oberhardt, Hendrik Luxenburger, Janine Kemming, Isabel Schulien, Kevin Ciminski, Sebastian Giese, Benedikt Csernalabics, Julia Lang-Meli, Iga Janowska, Julian Staniek, Katharina Wild, Kristi Basho, Mircea Stefan Marinescu, Jonas Fuchs, Fernando Topfstedt, Ales Janda, Oezlem Sogukpinar, Hanna Hilger, Katarina Stete, Florian Emmerich, Bertram Bengsch, Cornelius F Waller, Siegbert Rieg, Sagar, Tobias Boettler, Katharina Zoldan, Georg Kochs, Martin Schwemmle, Marta Rizzi, Robert Thimme, Christoph Neumann-Haefelin, Maike Hofmann
SARS-CoV-2 spike mRNA vaccines1-3 mediate protection from severe disease as early as 10 days post prime vaccination3 , when neutralizing antibodies are hardly detectable4-6 . Vaccine-induced CD8+ T cells may thus be the main mediators of protection at this early stage7,8 . The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. We show on a single epitope level that a stable and fully functional CD8+ T cell response is vigorously mobilized one week after bnt162b2 prime vaccination when circulating CD4+ T cells and neutralizing antibodies are still weakly detectable...
July 28, 2021: Nature
https://read.qxmd.com/read/34321643/covid-vaccines-slash-viral-spread-but-delta-is-an-unknown
#19
Smriti Mallapaty
No abstract text is available yet for this article.
July 27, 2021: Nature
https://read.qxmd.com/read/34316041/the-unnoticed-eye-motions-that-help-us-see-the-world
#20
(no author information available yet)
No abstract text is available yet for this article.
July 27, 2021: Nature
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