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JOURNAL ARTICLE
Kayarash Karimian, Aljona Groot, Vienna Huso, Ramin Kahidi, Kar-Tong Tan, Samantha Sholes, Rebecca Keener, John F McDyer, Jonathan K Alder, Heng Li, Andreas Rechtsteiner, Carol W Greider
Short telomeres cause age-related disease and long telomeres predispose to cancer; however, the mechanisms regulating telomere length are unclear. We developed a nanopore-based method, Telomere Profiling, to determine telomere length at nearly single nucleotide resolution. Mapping telomere reads to chromosome ends showed chromosome end-specific length distributions that could differ by more than six kilobases. Telomere lengths in 147 individuals showed certain chromosome ends were consistently longer or shorter...
April 11, 2024: Science
#2
JOURNAL ARTICLE
Liang Chi, Can Liu, Inta Gribonika, Julia Gschwend, Dan Corral, Seong-Ji Han, Ai Ing Lim, Claudia A Rivera, Verena M Link, Alexandria C Wells, Nicolas Bouladoux, Nicholas Collins, Djalma S Lima-Junior, Michel Enamorado, Barbara Rehermann, Sophie Laffont, Jean-Charles Guéry, Roxane Tussiwand, Christoph Schneider, Yasmine Belkaid
Males and females exhibit profound differences in immune responses and disease susceptibility. However, the factors responsible for sex differences in tissue immunity remain poorly understood. Here, we uncover a dominant role for type 2 innate lymphoid cells (ILC2) in shaping sexual immune dimorphism within the skin. Mechanistically, negative regulation of ILC2 by androgens leads to a reduction in dendritic cell (DC) accumulation and activation in males, and reduced tissue immunity. Collectively, this work reveals an androgen-ILC2-DC axis in controlling sexual immune dimorphism...
April 4, 2024: Science
#3
JOURNAL ARTICLE
Franz Puttur, Clare M Lloyd
Androgen signaling skews skin immunity toward reduced inflammation in male mice.
April 4, 2024: Science
#4
JOURNAL ARTICLE
George Cameron, Dominika T Gruszka, Rhian Gruar, Sherry Xie, Çağla Kaya, Kim A Nasmyth, Jonathan Baxter, Madhusudhan Srinivasan, Hasan Yardimci
Newly copied sister chromatids are tethered together by the cohesin complex, but how sister chromatid cohesion is coordinated with DNA replication is poorly understood. Prevailing models suggest cohesin complexes, bound to DNA before replication, remain behind the advancing replication fork to keep sister chromatids together. By visualizing single replication forks colliding with pre-loaded cohesin complexes, we find that the replisome instead pushes cohesin to where a converging replisome is met. While the converging replisomes are removed during DNA replication termination, cohesin remains on nascent DNA and provides cohesion...
March 14, 2024: Science
#5
EDITORIAL
H Holden Thorp
No abstract text is available yet for this article.
March 14, 2024: Science
#6
JOURNAL ARTICLE
Mariana Noto Guillen, Carmen Li, Brittany Rosener, Amir Mitchell
Numerous nonantibiotic drugs have potent antibacterial activity and can adversely impact the human microbiome. The mechanistic underpinning of this toxicity remains largely unknown. We investigated the antibacterial activity of 200 drugs using genetic screens with thousands of barcoded Escherichia coli knockouts. We analyzed 2 million gene-drug interactions underlying drug-specific toxicity. Network-based analysis of drug-drug similarities revealed that antibiotics clustered into modules consistent with the mode of action of their established classes, while nonantibiotics remained unconnected...
March 14, 2024: Science
#7
JOURNAL ARTICLE
Adityanarayanan Radhakrishnan, Daniel Beaglehole, Parthe Pandit, Mikhail Belkin
Understanding how neural networks learn features, or relevant patterns in data, for prediction is necessary for their reliable use in technological and scientific applications. In this work, we presented a unifying mathematical mechanism, known as Average Gradient Outer Product (AGOP), that characterized feature learning in neural networks. We provided empirical evidence that AGOP captured features learned by various neural network architectures, including transformer-based language models, convolutional networks, multi-layer perceptrons, and recurrent neural networks...
March 7, 2024: Science
#8
JOURNAL ARTICLE
Rohith Krishna, Jue Wang, Woody Ahern, Pascal Sturmfels, Preetham Venkatesh, Indrek Kalvet, Gyu Rie Lee, Felix S Morey-Burrows, Ivan Anishchenko, Ian R Humphreys, Ryan McHugh, Dionne Vafeados, Xinting Li, George A Sutherland, Andrew Hitchcock, C Neil Hunter, Alex Kang, Evans Brackenbrough, Asim K Bera, Minkyung Baek, Frank DiMaio, David Baker
Deep learning methods have revolutionized protein structure prediction and design but are currently limited to protein-only systems. We describe RoseTTAFold All-Atom (RFAA) which combines a residue-based representation of amino acids and DNA bases with an atomic representation of all other groups to model assemblies containing proteins, nucleic acids, small molecules, metals, and covalent modifications given their sequences and chemical structures. By fine tuning on denoising tasks we obtain RFdiffusionAA, which builds protein structures around small molecules...
March 7, 2024: Science
#9
JOURNAL ARTICLE
So-Yon Lim, Jina Lee, Christa E Osuna, Pratik Vikhe, Dane R Schalk, Elsa Chen, Emily Fray, Mithra Kumar, Nancy Schultz-Darken, Eva Rakasz, Saverio Capuano, Ruby A Ladd, Hwi Min Gil, David T Evans, Emily K Jeng, Michael Seaman, Malcolm Martin, Christiaan Van Dorp, Alan S Perelson, Hing C Wong, Janet D Siliciano, Robert Siliciano, Jeffrey T Safrit, Douglas F Nixon, Patrick Soon-Shiong, Michel Nussenzweig, James B Whitney
The eradication of the viral reservoir represents the major obstacle to the development of a clinical cure for established HIV-1 infection. Here, we demonstrate that the administration of Anktiva (N-803) and broadly neutralizing antibodies (bNAbs) resulted in sustained viral control after discontinuation of antiretroviral therapy (ART) in SHIV-AD8-infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation and transient viremia, but only limited reductions in the SHIV reservoir...
February 29, 2024: Science
#10
JOURNAL ARTICLE
Morgan E Wirthlin, Tobias A Schmid, Julie E Elie, Xiaomeng Zhang, Amanda Kowalczyk, Ruby Redlich, Varvara A Shvareva, Ashley Rakuljic, Maria B Ji, Ninad S Bhat, Irene M Kaplow, Daniel E Schäffer, Alyssa J Lawler, Andrew Z Wang, BaDoi N Phan, Siddharth Annaldasula, Ashley R Brown, Tianyu Lu, Byung Kook Lim, Eiman Azim, Nathan L Clark, Wynn K Meyer, Sergei L Kosakovsky Pond, Maria Chikina, Michael M Yartsev, Andreas R Pfenning, Gregory Andrews, Joel C Armstrong, Matteo Bianchi, Bruce W Birren, Kevin R Bredemeyer, Ana M Breit, Matthew J Christmas, Hiram Clawson, Joana Damas, Federica Di Palma, Mark Diekhans, Michael X Dong, Eduardo Eizirik, Kaili Fan, Cornelia Fanter, Nicole M Foley, Karin Forsberg-Nilsson, Carlos J Garcia, John Gatesy, Steven Gazal, Diane P Genereux, Linda Goodman, Jenna Grimshaw, Michaela K Halsey, Andrew J Harris, Glenn Hickey, Michael Hiller, Allyson G Hindle, Robert M Hubley, Graham M Hughes, Jeremy Johnson, David Juan, Irene M Kaplow, Elinor K Karlsson, Kathleen C Keough, Bogdan Kirilenko, Klaus-Peter Koepfli, Jennifer M Korstian, Amanda Kowalczyk, Sergey V Kozyrev, Alyssa J Lawler, Colleen Lawless, Thomas Lehmann, Danielle L Levesque, Harris A Lewin, Xue Li, Abigail Lind, Kerstin Lindblad-Toh, Ava Mackay-Smith, Voichita D Marinescu, Tomas Marques-Bonet, Victor C Mason, Jennifer R S Meadows, Wynn K Meyer, Jill E Moore, Lucas R Moreira, Diana D Moreno-Santillan, Kathleen M Morrill, Gerard Muntané, William J Murphy, Arcadi Navarro, Martin Nweeia, Sylvia Ortmann, Austin Osmanski, Benedict Paten, Nicole S Paulat, Andreas R Pfenning, BaDoi N Phan, Katherine S Pollard, Henry E Pratt, David A Ray, Steven K Reilly, Jeb R Rosen, Irina Ruf, Louise Ryan, Oliver A Ryder, Pardis C Sabeti, Daniel E Schäffer, Aitor Serres, Beth Shapiro, Arian F A Smit, Mark Springer, Chaitanya Srinivasan, Cynthia Steiner, Jessica M Storer, Kevin A M Sullivan, Patrick F Sullivan, Elisabeth Sundström, Megan A Supple, Ross Swofford, Joy-El Talbot, Emma Teeling, Jason Turner-Maier, Alejandro Valenzuela, Franziska Wagner, Ola Wallerman, Chao Wang, Juehan Wang, Zhiping Weng, Aryn P Wilder, Morgan E Wirthlin, James R Xue, Xiaomeng Zhang
Vocal production learning is a convergently evolved trait in vertebrates. To identify brain genomic elements associated with mammalian vocal learning, we integrated genomic, anatomical and neurophysiological data from the Egyptian fruit-bat with analyses of the genomes of 215 placental mammals. First, we identified a set of proteins evolving more slowly in vocal learners. Then, we discovered a vocal-motor cortical region in the Egyptian fruit-bat, an emergent vocal learner, and leveraged that knowledge to identify active cis -regulatory elements in the motor cortex of vocal learners...
February 29, 2024: Science
#11
JOURNAL ARTICLE
Shuai Li, Lixin Lu, Swarnendu Bhattacharyya, Carolyn Pearce, Kai Li, Emily T Nienhuis, Gilles Doumy, R D Schaller, S Moeller, M-F Lin, G Dakovski, D J Hoffman, D Garratt, Kirk A Larsen, J D Koralek, C Y Hampton, D Cesar, Joseph Duris, Z Zhang, Nicholas Sudar, James P Cryan, A Marinelli, Xiaosong Li, Ludger Inhester, Robin Santra, Linda Young
Attosecond-pump/attosecond-probe experiments have long been sought as the most straightforward method to observe electron dynamics in real time. Although numerous successes have been achieved with overlapped near infrared femtosecond and extreme ultraviolet attosecond pulses combined with theory, true attosecond-pump/attosecond-probe experiments have been limited. We used a synchronized attosecond x-ray pulse pair from an x-ray free electron laser to study the electronic response to valence ionization in liquid water via all x-ray attosecond transient absorption spectroscopy (AX-ATAS)...
February 15, 2024: Science
#12
EDITORIAL
H Holden Thorp
No abstract text is available yet for this article.
February 13, 2024: Science
#13
JOURNAL ARTICLE
Freysteinn Sigmundsson, Michelle Parks, Halldór Geirsson, Andrew Hooper, Vincent Drouin, Kristín S Vogfjörd, Benedikt G Ófeigsson, Sonja H M Greiner, Yilin Yang, Chiara Lanzi, Gregory P De Pascale, Kristín Jónsdóttir, Sigrún Hreinsdóttir, Valentyn Tolpekin, Hildur María Friðriksdóttir, Páll Einarsson, Sara Barsotti
Many examples of exposed giant dike swarms can be found where lateral magma flow exceeded hundreds of kilometers. We show that massive magma flow into dikes can be established with only modest overpressure in a magma body, if a large enough pathway opens at its boundary, and gradual build-up of high tensile stress has occurred along the dike pathway prior to onset of diking. This explains rapid initial magma flow rates, modeled up to about 7400 m3 /s into a dike approximately 15 km long, propagating under the town of Grindavík, Southwest Iceland, in November 2023...
February 8, 2024: Science
#14
JOURNAL ARTICLE
Transition of human γ-tubulin ring complex into a closed conformation during microtubule nucleation.
Cláudia Brito, Marina Serna, Pablo Guerra, Oscar Llorca, Thomas Surrey
Microtubules are essential for intracellular organization and chromosome segregation. They are nucleated by the γ-tubulin ring complex (γTuRC). However, isolated vertebrate γTuRC adopts an open conformation that deviates from the microtubule structure, raising the question of the nucleation mechanism. Here we determine cryo-electron microscopy structures of human γTuRC bound to a nascent microtubule. Structural changes of the complex into a closed conformation ensure that γTuRC templates the 13-protofilament microtubules that exist in human cells...
February 2, 2024: Science
#15
JOURNAL ARTICLE
Demin Ma, Meiqin Hu, Xiaotong Yang, Qiang Liu, Fan Ye, Weijie Cai, Yong Wang, Ximing Xu, Shenghai Chang, Ruiying Wang, Wei Yang, Sheng Ye, Nannan Su, Minrui Fan, Haoxing Xu, Jiangtao Guo
Insects rely on a family of seven-transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities such as sweet and bitter. Here we report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels, composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBD, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBD...
February 2, 2024: Science
#16
COMMENT
Bryce T Nicholls, Brett P Fors
A bio-based plastic advances recycling.
April 12, 2024: Science
#17
COMMENT
Ramon Massana
A bacterial endosymbiont of marine algae evolved to an organelle.
April 12, 2024: Science
#18
COMMENT
Zibin Chen
A design strategy boosts electrical properties of ferroelectric materials and devices.
April 12, 2024: Science
#19
JOURNAL ARTICLE
David H Cook, Punit Kumar, Madelyn I Payne, Calvin H Belcher, Pedro Borges, Wenqing Wang, Flynn Walsh, Zehao Li, Arun Devaraj, Mingwei Zhang, Mark Asta, Andrew M Minor, Enrique J Lavernia, Diran Apelian, Robert O Ritchie
Single-phase body-centered cubic (bcc) refractory medium- or high-entropy alloys can retain compressive strength at elevated temperatures but suffer from extremely low tensile ductility and fracture toughness. We examined the strength and fracture toughness of a bcc refractory alloy, NbTaTiHf, from 77 to 1473 kelvin. This alloy's behavior differed from that of comparable systems by having fracture toughness over 253 MPa·m1/2 , which we attribute to a dynamic competition between screw and edge dislocations in controlling the plasticity at a crack tip...
April 12, 2024: Science
#20
JOURNAL ARTICLE
Min Zhang, Shun Lan, Bing B Yang, Hao Pan, Yi Q Liu, Qing H Zhang, Jun L Qi, Di Chen, Hang Su, Di Yi, Yue Y Yang, Rui Wei, Hong D Cai, Hao J Han, Lin Gu, Ce-Wen Nan, Yuan-Hua Lin
Ultrahigh-power-density multilayer ceramic capacitors (MLCCs) are critical components in electrical and electronic systems. However, the realization of a high energy density combined with a high efficiency is a major challenge for practical applications. We propose a high-entropy design in barium titanate (BaTiO3 )-based lead-free MLCCs with polymorphic relaxor phase. This strategy effectively minimizes hysteresis loss by lowering the domain-switching barriers and enhances the breakdown strength by the high atomic disorder with lattice distortion and grain refining...
April 12, 2024: Science
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