A high-fat diet affects tumor-to-nerve signaling and promotes cachexia in mice.A high-fat diet affects tumor-to-nerve signaling and promotes cachexia in mice.
A mechanosensitive ion channel regulates liver cell proliferation after injury.A mechanosensitive ion channel regulates liver cell proliferation after injury.
An artificial neural network built into a computer memory chip reconstructs the human cortex with high accuracy in real time.An artificial neural network built into a computer memory chip reconstructs the human cortex with high accuracy in real time.
Mihaljević L, Kim DE, Bandawane PD
… +30 more, Eisenach HE, Borst AJ, Courbet A, Weidle C, Carr KD, Bettin E, Liu Q, Trejos AT, Majumder S, Kokane S, Stevens A, Muratspahić E, Schlichthaerle T, Expòsit M, Li X, Lamb M, Azcárraga Murray AN, Ravichandran R, Williams EC, Hu S, Stuart L, Grillová L, Thomson NR, Landreh M, Chang P, Giacani L, Caimano MJ, Hawley KL, King NP, Baker D
Developing therapies and vaccines against integral membrane proteins is hindered by their extensive hydrophobic surfaces, which complicate production and structural analysis. Here, we describe a general deep learning-bas...Developing therapies and vaccines against integral membrane proteins is hindered by their extensive hydrophobic surfaces, which complicate production and structural analysis. Here, we describe a general deep learning-based design approach for solubilizing native membrane proteins while preserving their sequence, fold, active-site, and ligand-binding properties. Genetically encoded de novo protein WRAPs [water-soluble RFdiffused amphipathic proteins] surround the lipid-interacting hydrophobic surfaces, rendering them thermostable and water-soluble without the need for detergents. We design WRAPs for both monomeric and oligomeric beta-barrel outer membrane proteins and helical multipass transmembrane proteins. A 2.95-angstrom-resolution cryo-electron microscopy structure of WRAPed mycobacterial porin demonstrates that WRAPs can be used for the structural determination of membrane proteins in solution. As a step toward syphilis vaccine development, we generated soluble versions of antigens.
Local fibroblast development and densities influence organ health and disease, although it remains unclear how tissue fibroblast topography is controlled in situ. Here, we defined Group 2 innate lymphoid cells (ILC2s) as...Local fibroblast development and densities influence organ health and disease, although it remains unclear how tissue fibroblast topography is controlled in situ. Here, we defined Group 2 innate lymphoid cells (ILC2s) as key regulators of fibroblast homeostasis in the pancreas. ILC2s colocalized with fibroblasts expressing the genes in an interstitial niche of the exocrine pancreas, which encapsulates the organ parenchyma. ILC2s specifically regulated the expansion of fibroblasts, which have progenitor capacity, while restraining differentiated intraparenchymal fibroblasts during inflammation. These circuits reinforced fibroblast numbers after injury and set an inflammatory threshold. The ILC2 and fibroblast progenitor niche expanded around tumors and controlled cancer-associated fibroblast ontogeny and density. Hence, ILC2-fibroblast dialogue represents a regulatory node that locally orchestrates tissue homeostasis and pathology.
Wurtzite AlScN ferroelectrics exhibit exceptional polarization and thermal stability, making them highly promising for a wide range of electronic applications. However, a more profound understanding is required regarding...Wurtzite AlScN ferroelectrics exhibit exceptional polarization and thermal stability, making them highly promising for a wide range of electronic applications. However, a more profound understanding is required regarding the atomic-scale mechanism through which cation substitution lowers the switching energy barrier and thus reduces the coercive field. We used spherical aberration-corrected transmission electron microscopy to reveal a periodic modulation of cation-anion spacing along the polarization direction, forming alternating atomic dipole layers. This modulation arises from energetically favorable chemical ordering of aluminum and scandium atoms between adjacent layers, with layer-resolved asymmetry in atomic arrangement. In situ imaging directly captures atomic-scale, noncollective, stepwise polarization switching, revealing intermediate states and local spacing fluctuations. Compositional inhomogeneity in these dipole layers creates multiple transient states that reduce the switching energy barrier. Our findings connect atomic-scale dipole structures to polarization switching kinetics, enabling the rational design of wurtzite ferroelectrics.
Plants activate pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) to combat pathogens. However, how these systems coordinate immune activation while preventing autoimmunity remains poorly understood....Plants activate pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) to combat pathogens. However, how these systems coordinate immune activation while preventing autoimmunity remains poorly understood. In this study, we uncovered a regulatory mechanism in which surface immune signaling unlocks nucleotide-binding leucine-rich repeat (NLR) immune receptor activation through mRNA splicing. We identified an N-terminal prodomain in the potato late blight resistance protein Rpi-vnt1.1 that inhibits resistosome formation, preventing potential autoactivation of this NLR. Upon pathogen perception, PTI signaling induced alternative splicing of Rpi-vnt1.1 mRNA, removing this inhibitory element. This primed Rpi-vnt1.1 for activation by the effector AVRvnt1, enabling resistosome assembly and immune signaling. The widespread conservation of N-terminal extensions in coiled coil-type NLRs points to a common regulatory mechanism in preventing potential autoactivation while preserving pathogen sensitivity.
Despite delays and staff shortages, agency should be able to fully spend 2026 budget, but new grants will likely remain below historic levels.Despite delays and staff shortages, agency should be able to fully spend 2026 budget, but new grants will likely remain below historic levels.
Data security experts say increased oversight is needed, but researchers are struggling to comply.Data security experts say increased oversight is needed, but researchers are struggling to comply.
Google Quantum AI and Collaborators†, Gyawali G, Kumar S
… +219 more, Lensky YD, Rosenberg E, Szasz A, Cochran T, Chen R, Karamlou AH, Yosri N, Meeks S, Kechedzhi K, Berndtsson J, Westerhout T, Asfaw A, Abanin D, Acharya R, Aghababaie Beni L, Andersen TI, Ansmann M, Arute F, Arya K, Astrakhantsev N, Atalaya J, Babbush R, Ballard B, Bardin J, Bengtsson A, Bilmes A, Bortoli G, Bourassa A, Bovaird J, Brill L, Broughton M, Browne D, Buchea B, Buckley B, Buell D, Burger T, Burkett B, Bushnell N, Cabrera A, Campero J, Chang HS, Chen Z, Chiaro B, Claes J, Cleland A, Cogan J, Collins R, Conner P, Courtney W, Crook AL, Das S, Debroy DM, Del Toro Barba A, Demura S, De Lorenzo L, Di Paolo A, Donohoe P, Drozdov I, Dunsworth A, Earle C, Eickbusch A, Elbag A, Elzouka M, Erickson C, Faoro L, Fatemi R, Ferreira V, Flores Burgos L, Forati E, Fowler A, Foxen B, Ganjam S, Gasca R, Giang W, Gidney C, Gilboa D, Gosula R, Grajales Dau A, Graumann D, Greene A, Gross J, Habegger S, Hamilton M, Hansen M, Harrigan M, Harrington S, Heslin S, Heu P, Hill G, Hilton J, Hoffmann M, Huang HY, Huff A, Huggins WJ, Ioffe LB, Isakov SV, Jeffrey E, Jiang Z, Jones C, Jordan S, Joshi C, Juhas P, Kafri D, Kang H, Khaire T, Khattar T, Khezri M, Kieferová M, Kim S, Klimov P, Klots A, Kobrin B, Korotkov A, Kostritsa F, Kreikebaum J, Kurilovich V, Landhuis D, Langley B, Laptev P, Lau KM, Ledford J, Lee J, Lee K, Lester B, Le Guevel L, Li W, Lill A, Liu W, Livingston W, Locharla A, Lundahl D, Lunt A, Madhuk S, Maloney A, Mandrà S, Martin L, Martin S, Martin O, Maxfield C, McClean J, McEwen M, Megrant A, Mi X, Miao K, Mieszala A, Molavi R, Molina S, Montazeri S, Morvan A, Movassagh R, Neill C, Nersisyan A, Newman M, Nguyen A, Nguyen M, Ni CH, Ottosson K, Pizzuto A, Potter R, Pritchard O, Pryadko L, Quintana C, Ramachandran G, Reagor M, Rhodes D, Roberts G, Rocque C, Rubin N, Saei N, Sankaragomathi K, Satzinger K, Schurkus H, Schuster C, Shearn M, Shorter A, Shutty N, Shvarts V, Sivak V, Skruzny J, Small S, Smith WC, Springer S, Sterling G, Suchard J, Szalay M, Sztein A, Thor D, Torunbalci MM, Vaishnav A, Vdovichev S, Vidal G, Vollgraff Heidweiller C, Waltman S, Wang SX, White T, Wong K, Woo BWK, Xing C, Yao ZJ, Yeh P, Ying B, Yoo J, Young G, Zalcman A, Zhang Y, Zhu N, Zobrist N, Boixo S, Kelly J, Lucero E, Chen Y, Smelyanskiy V, Neven H, Kovrizhin D, Knolle J, Halimeh JC, Aleiner I, Moessner R, Roushan P
Disorder-induced phenomena in quantum many-body systems pose a challenge for analytical and numerical approaches at relevant time and system scales. To reduce the cost of disorder sampling, we investigated quantum circui...Disorder-induced phenomena in quantum many-body systems pose a challenge for analytical and numerical approaches at relevant time and system scales. To reduce the cost of disorder sampling, we investigated quantum circuits initialized in states that form tunable superpositions over all disorder configurations, which in lattice gauge theories can be interpreted as superpositions over gauge sectors. On the experimentally accessible timescales, we observed localization in the absence of disorder in one and two dimensions: Perturbations failed to diffuse despite fully disorder-free evolution and initial states. However, entropy measurements revealed that superposition-prepared states fundamentally differ from those obtained by direct disorder sampling. Leveraging superposition, we propose an algorithm with a polynomial speedup in sampling disorder configurations, a long-standing challenge in many-body localization studies.
Fausto CC, Glykofrydis F, Kumar N
… +15 more, Schnell J, Csipan RL, De Kuyper F, Kunnan M, Grubbs B, Thornton M, Thompson M, Chang E, Wen X, Pelayo M, Achieng M, Seth A, Street K, Morsut L, Lindström NO
Human stem cell-derived miniature organs, including kidney organoids, reproduce aspects of tissue development but lack reliable spatial patterning. In embryos, spatial organization is often established by developmental o...Human stem cell-derived miniature organs, including kidney organoids, reproduce aspects of tissue development but lack reliable spatial patterning. In embryos, spatial organization is often established by developmental organizers that generate morphogenetic fields. However, how such organizing geometry operates in kidney nephrogenesis-and whether it can be reconstructed in vitro-has remained unclear. Using spatial transcriptomics of human kidney development, we found that nascent nephrons establish a collecting duct adjacent-to-distant polarity bordering a - signaling boundary. Engineered WNT-secreting cellular organizers introduced into kidney organoids restored this organizing geometry, biasing distal nephron differentiation and orienting nephron morphogenesis toward the signal source, which demonstrates that developmental signaling geometry can be reconstructed synthetically to control tissue patterning.
Cross M, Kotschi S, Wu W
… +29 more, Luciano-Mateo F, Kwon YY, Dantas E, Niazi T, Chen S, Rashidfarrokhi A, Pillai R, Sanford J, Kim J, Hsiang J, Gamallo-Lana B, Mar AC, Hao Y, Rajalingam S, Huang A, Shan J, Issa HA, Gomez M, Wang AR, Zhao X, Janowitz T, White E, Liu Y, Wong KK, Segal LN, Hui S, Goncalves MD, Froemke RC, Papagiannakopoulos T
Sickness behaviors are common in cancer-associated cachexia and affect up to half of lung cancer patients. We demonstrate that among the most common cancer mutations, loss of liver kinase B1 () promotes the development o...Sickness behaviors are common in cancer-associated cachexia and affect up to half of lung cancer patients. We demonstrate that among the most common cancer mutations, loss of liver kinase B1 () promotes the development of cachexia in preclinical models of lung cancer. In an effort to improve caloric intake with an obesogenic high-fat diet, we paradoxically observed worsened cachexia-associated sickness. We found that local production of prostaglandin E2 (PGE), rather than circulating factors, promotes sickness and that genetic, dietary, and pharmacological inhibition of tumor-derived PGE suppresses sickness and cachexia. Notably, we demonstrate that lung sensory neuron abrogation prevents PGE-dependent cachexia. Our study establishes localized tumor-derived signals to sensory neurons, rather than circulating factors, as drivers of cachexia and highlights a previously unknown role of the peripheral nervous system in cancer cachexia.
Why Antarctica became glaciated ∼34 million years ago (Ma) remains debated, as relatively warm climates and sea temperatures appear inconsistent with ice sheet formation. Although a critical decline in CO is considered p...Why Antarctica became glaciated ∼34 million years ago (Ma) remains debated, as relatively warm climates and sea temperatures appear inconsistent with ice sheet formation. Although a critical decline in CO is considered primarily responsible, evidence suggests that other factors were important, too. We investigated whether regional topographic uplift, rooted in Jurassic continental breakup and mantle-surface feedbacks, enabled nucleation of the East Antarctic Ice Sheet (EAIS). By integrating geodynamic-topographic models with ice sheet and energy balance models, we show that progressive plateau growth in East Antarctica, including Eocene uplift of the Gamburtsev Mountains, pushed landscapes above the threshold for ice sheet nucleation by ∼45 Ma. Uplift enabled EAIS growth under warmer-than-expected climates, producing hemispheric asymmetry in early glaciation and reconciling Oligocene polar warmth with the onset of the modern icehouse world.
The nation's research universities have traced an indelible path through the American story.The nation's research universities have traced an indelible path through the American story.