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Nature
Resumen/Descripción – provisto por la editorial en inglés
Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.Palabras clave – provistas por la editorial
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Disponibilidad
| Institución detectada | Período | Navegá | Descargá | Solicitá |
|---|---|---|---|---|
| No detectada | desde jul. 2012 / hasta dic. 2023 | Nature.com | ||
| No detectada | desde jul. 2006 / hasta ago. 2012 | Ovid |
Información
Tipo de recurso:
revistas
ISSN impreso
0028-0836
ISSN electrónico
1476-4687
Editor responsable
Springer Nature
País de edición
Reino Unido
Fecha de publicación
1869-
Tabla de contenidos
Phosphorylation of muramyl peptides by NAGK is required for NOD2 activation
Che A. Stafford; Alicia-Marie Gassauer; Carina C. de Oliveira Mann; Maria C. Tanzer
; Evelyn Fessler; Benedikt Wefers; Dennis Nagl; Gunnar Kuut; Karolina Sulek; Catherine Vasilopoulou; Sophia J. Schwojer; Andreas Wiest; Marie K. Pfautsch; Wolfgang Wurst; Monica Yabal; Thomas Fröhlich; Matthias Mann; Nicolas Gisch; Lucas T. Jae; Veit Hornung
<jats:title>Abstract</jats:title><jats:p>Bacterial cell wall components provide various unique molecular structures that are detected by pattern recognition receptors (PRRs) of the innate immune system as non-self. Most bacterial species form a cell wall that consists of peptidoglycan (PGN), a polymeric structure comprising alternating amino sugars that form strands cross-linked by short peptides. Muramyl dipeptide (MDP) has been well documented as a minimal immunogenic component of peptidoglycan<jats:sup>1–3</jats:sup>. MDP is sensed by the cytosolic nucleotide-binding oligomerization domain-containing protein 2<jats:sup>4</jats:sup> (NOD2). Upon engagement, it triggers pro-inflammatory gene expression, and this functionality is of critical importance in maintaining a healthy intestinal barrier function<jats:sup>5</jats:sup>. Here, using a forward genetic screen to identify factors required for MDP detection, we identified <jats:italic>N</jats:italic>-acetylglucosamine kinase (NAGK) as being essential for the immunostimulatory activity of MDP. NAGK is broadly expressed in immune cells and has previously been described to contribute to the hexosamine biosynthetic salvage pathway<jats:sup>6</jats:sup>. Mechanistically, NAGK functions upstream of NOD2 by directly phosphorylating the <jats:italic>N</jats:italic>-acetylmuramic acid moiety of MDP at the hydroxyl group of its C6 position, yielding 6-<jats:italic>O</jats:italic>-phospho-MDP. NAGK-phosphorylated MDP—but not unmodified MDP—constitutes an agonist for NOD2. Macrophages from mice deficient in NAGK are completely deficient in MDP sensing. These results reveal a link between amino sugar metabolism and innate immunity to bacterial cell walls.</jats:p>
Palabras clave: Multidisciplinary.
Pp. No disponible
How to make water that's full of holes
Benjamin Thompson; Shamini Bundell
Palabras clave: Multidisciplinary.
Pp. No disponible
Selective TnsC recruitment enhances the fidelity of RNA-guided transposition
Florian T. Hoffmann; Minjoo Kim; Leslie Y. Beh; Jing Wang; Phuc Leo H. Vo; Diego R. Gelsinger; Jerrin Thomas George; Christopher Acree; Jason T. Mohabir; Israel S. Fernández; Samuel H. Sternberg
Palabras clave: Multidisciplinary.
Pp. No disponible
RASA2 ablation in T cells boosts antigen sensitivity and long-term function
Julia Carnevale; Eric Shifrut; Nupura Kale; William A. Nyberg; Franziska Blaeschke; Yan Yi Chen; Zhongmei Li; Sagar P. Bapat; Morgan E. Diolaiti; Patrick O’Leary; Shane Vedova; Julia Belk; Bence Daniel; Theodore L. Roth; Stefanie Bachl; Alejandro Allo Anido; Brooke Prinzing; Jorge Ibañez-Vega; Shannon Lange; Dalia Haydar; Marie Luetke-Eversloh; Maelys Born-Bony; Bindu Hegde; Scott Kogan; Tobias Feuchtinger; Hideho Okada; Ansuman T. Satpathy; Kevin Shannon; Stephen Gottschalk; Justin Eyquem; Giedre Krenciute; Alan Ashworth; Alexander Marson
<jats:title>Abstract</jats:title><jats:p>The efficacy of adoptive T cell therapies for cancer treatment can be limited by suppressive signals from both extrinsic factors and intrinsic inhibitory checkpoints<jats:sup>1,2</jats:sup>. Targeted gene editing has the potential to overcome these limitations and enhance T cell therapeutic function<jats:sup>3–10</jats:sup>. Here we performed multiple genome-wide CRISPR knock-out screens under different immunosuppressive conditions to identify genes that can be targeted to prevent T cell dysfunction. These screens converged on RASA2, a RAS GTPase-activating protein (RasGAP) that we identify as a signalling checkpoint in human T cells, which is downregulated upon acute T cell receptor stimulation and can increase gradually with chronic antigen exposure. RASA2 ablation enhanced MAPK signalling and chimeric antigen receptor (CAR) T cell cytolytic activity in response to target antigen. Repeated tumour antigen stimulations in vitro revealed that RASA2-deficient T cells show increased activation, cytokine production and metabolic activity compared with control cells, and show a marked advantage in persistent cancer cell killing. RASA2-knockout CAR T cells had a competitive fitness advantage over control cells in the bone marrow in a mouse model of leukaemia. Ablation of RASA2 in multiple preclinical models of T cell receptor and CAR T cell therapies prolonged survival in mice xenografted with either liquid or solid tumours. Together, our findings highlight RASA2 as a promising target to enhance both persistence and effector function in T cell therapies for cancer treatment.</jats:p>
Palabras clave: Multidisciplinary.
Pp. No disponible
Postcranial evidence of late Miocene hominin bipedalism in Chad
G. Daver; F. Guy; H. T. Mackaye; A. Likius; J. -R. Boisserie; A. Moussa; L. Pallas; P. Vignaud; N. D. Clarisse
Palabras clave: Multidisciplinary.
Pp. No disponible
Wellcome says it has perpetuated ‘systemic racism’ in science
Sarah Wild
Palabras clave: Multidisciplinary.
Pp. No disponible
Could long COVID be linked to herpes viruses? Early data offer a hint
Emily Waltz
Palabras clave: Multidisciplinary.
Pp. No disponible
My life at the helm of a top African cancer-treatment centre
Christopher Bendana
Palabras clave: Multidisciplinary.
Pp. No disponible
Harmony on the farm: integrating crops, trees, goats and bees
Christopher Bendana
Palabras clave: Multidisciplinary.
Pp. No disponible
Publisher Correction: A transcriptomic axis predicts state modulation of cortical interneurons
Stéphane Bugeon; Joshua Duffield; Mario Dipoppa; Anne Ritoux; Isabelle Prankerd; Dimitris Nicoloutsopoulos; David Orme; Maxwell Shinn; Han Peng; Hamish Forrest; Aiste Viduolyte; Charu Bai Reddy; Yoh Isogai; Matteo Carandini; Kenneth D. Harris
Palabras clave: Multidisciplinary.
Pp. No disponible