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Institución detectada Período Navegá Descargá Solicitá
No detectada desde mar. 1997 / hasta dic. 2023 Science Journals

Información

Tipo de recurso:

revistas

ISSN impreso

0036-8075

ISSN electrónico

1095-9203

Editor responsable

American Association for the Advancement of Science (AAAS)

País de edición

Estados Unidos

Fecha de publicación

Cobertura temática

Tabla de contenidos

Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies

Daniel ReichartORCID; Eric L. LindbergORCID; Henrike MaatzORCID; Antonio M. A. Miranda; Anissa ViveirosORCID; Nikolay ShvetsovORCID; Anna GärtnerORCID; Emily R. NadelmannORCID; Michael LeeORCID; Kazumasa KanemaruORCID; Jorge Ruiz-OreraORCID; Viktoria StrohmengerORCID; Daniel M. DeLaughterORCID; Giannino PatoneORCID; Hao Zhang; Andrew WoehlerORCID; Christoph LippertORCID; Yuri KimORCID; Eleonora Adami; Joshua M. GorhamORCID; Sam N. Barnett; Kemar BrownORCID; Rachel J. BuchanORCID; Rasheda A. ChowdhuryORCID; Chrystalla Constantinou; James Cranley; Leanne E. FelkinORCID; Henrik FoxORCID; Ahla GhauriORCID; Jan GummertORCID; Masatoshi KandaORCID; Ruoyan Li; Lukas MachORCID; Barbara McDonoughORCID; Sara Samari; Farnoush Shahriaran; Clarence YappORCID; Caroline StanasiukORCID; Pantazis I. TheotokisORCID; Fabian J. TheisORCID; Antoon van den Bogaerdt; Hiroko WakimotoORCID; James S. WareORCID; Catherine L. WorthORCID; Paul J. R. BartonORCID; Young-Ae Lee; Sarah A. TeichmannORCID; Hendrik MiltingORCID; Michela NosedaORCID; Gavin Y. OuditORCID; Matthias HeinigORCID; Jonathan G. SeidmanORCID; Norbert HubnerORCID; Christine E. SeidmanORCID

<jats:p>Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene expression at single-cell resolution. Together, these data illuminate both shared and distinct cellular and molecular architectures of human heart failure and suggest candidate therapeutic targets.</jats:p>

Palabras clave: Multidisciplinary.

Pp. No disponible

Comment on “Pushing the frontiers of density functionals by solving the fractional electron problem”

Igor S. Gerasimov; Timofey V. LosevORCID; Evgeny Yu. EpifanovORCID; Irina RudenkoORCID; Ivan S. BushmarinovORCID; Alexander A. RyabovORCID; Petr A. ZhilyaevORCID; Michael G. MedvedevORCID

<jats:p> Kirkpatrick <jats:italic>et al</jats:italic> . (Reports, 9 December 2021, p. 1385) trained a neural network–based DFT functional, DM21, on fractional-charge (FC) and fractional-spin (FS) systems, and they claim that it has outstanding accuracy for chemical systems exhibiting strong correlation. Here, we show that the ability of DM21 to generalize the behavior of such systems does not follow from the published results and requires revisiting. </jats:p>

Palabras clave: Multidisciplinary.

Pp. No disponible

Response to Comment on “Pushing the frontiers of density functionals by solving the fractional electron problem”

James KirkpatrickORCID; Brendan McMorrowORCID; David H. P. TurbanORCID; Alexander L. GauntORCID; James S. Spencer; Alexander G. D. G. Matthews; Annette Obika; Louis Thiry; Meire Fortunato; David Pfau; Lara Román CastellanosORCID; Stig PetersenORCID; Alexander W. R. Nelson; Pushmeet Kohli; Paula Mori-Sánchez; Demis HassabisORCID; Aron J. CohenORCID

<jats:p> Gerasimov <jats:italic>et al</jats:italic> . claim that the ability of DM21 to respect fractional charge (FC) and fractional spin (FS) conditions outside of the training set has not been demonstrated in our paper. This is based on (i) asserting that the training set has a ~50% overlap with our bond-breaking benchmark (BBB) and (ii) questioning the validity and accuracy of our other generalization examples. We disagree with their analysis and believe that the points raised are either incorrect or not relevant to the main conclusions of the paper and to the assessment of general quality of DM21. </jats:p>

Palabras clave: Multidisciplinary.

Pp. No disponible

Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models

Alexander A. CohenORCID; Neeltje van DoremalenORCID; Allison J. GreaneyORCID; Hanne AndersenORCID; Ankur Sharma; Tyler N. StarrORCID; Jennifer R. KeeffeORCID; Chengcheng FanORCID; Jonathan E. SchulzORCID; Priyanthi N. P. Gnanapragasam; Leesa M. KakutaniORCID; Anthony P. WestORCID; Greg SaturdayORCID; Yu E. LeeORCID; Han Gao; Claudia A. JetteORCID; Mark G. LewisORCID; Tiong K. TanORCID; Alain R. Townsend; Jesse D. BloomORCID; Vincent J. MunsterORCID; Pamela J. BjorkmanORCID

<jats:p>To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.</jats:p>

Palabras clave: Multidisciplinary.

Pp. No disponible

The continuum of Drosophila embryonic development at single-cell resolution

Diego CalderonORCID; Ronnie Blecher-GonenORCID; Xingfan Huang; Stefano SecchiaORCID; James KentroORCID; Riza M. DazaORCID; Beth MartinORCID; Alessandro DuljaORCID; Christoph SchaubORCID; Cole TrapnellORCID; Erica Larschan; Kate M. O’Connor-GilesORCID; Eileen E. M. FurlongORCID; Jay ShendureORCID

<jats:p> <jats:italic>Drosophila melanogaster</jats:italic> is a powerful, long-standing model for metazoan development and gene regulation. We profiled chromatin accessibility in almost 1 million and gene expression in half a million nuclei from overlapping windows spanning the entirety of embryogenesis. Leveraging developmental asynchronicity within embryo collections, we applied deep neural networks to infer the age of each nucleus, resulting in continuous, multimodal views of molecular and cellular transitions in absolute time. We identify cell lineages; infer their developmental relationships; and link dynamic changes in enhancer usage, transcription factor (TF) expression, and the accessibility of TFs’ cognate motifs. With these data, the dynamics of enhancer usage and gene expression can be explored within and across lineages at the scale of minutes, including for precise transitions like zygotic genome activation. </jats:p>

Palabras clave: Multidisciplinary.

Pp. No disponible

A key time for UK–Europe science

Peter Mathieson

<jats:p> The opening line of a recent <jats:italic>Financial Times</jats:italic> article put it best: “Relations between the UK and EU badly need a reset.” Although the article was mostly about geopolitics, the disconnect also applies to science and the current uncertainty about whether the UK will remain an associated partner in European Union (EU) research programs such as Horizon Europe. In the post-Brexit era, and with a new UK Prime Minister to be named shortly, the UK and EU should be considering how best to maximize the potential of the numerous brilliant scientists, technicians, academics, and clinicians working in the universities and research institutes of all European countries, including the UK. </jats:p>

Palabras clave: Multidisciplinary.

Pp. 559-559

News at a glance

Shraddha Chakradhar (eds.)

Palabras clave: Multidisciplinary.

Pp. 560-561

Innovation bill will reshape science agencies

Jeffrey Mervis

<jats:p>CHIPS and Science Act creates NSF tech directorate and boosts applied research</jats:p>

Palabras clave: Multidisciplinary.

Pp. 562-563

Ordinary computer matches Google’s quantum computer

Adrian Cho

<jats:p>High-profile claim of “quantum supremacy” fades</jats:p>

Palabras clave: Multidisciplinary.

Pp. 563-564

Ambitious bill leads to 40% cut in emissions, models show

Erik Stokstad

<jats:p>But more action is needed to reach Biden’s pledge to halve greenhouse gas emissions by 2030</jats:p>

Palabras clave: Multidisciplinary.

Pp. 564-565