Browse Articles

The effects of task similarity during representation learning in brains and neural networks

Abstract The complexity of our environment poses significant challenges for adaptive behavior. Recognizing shared structures across tasks can theoretically improve learning through generalization. However, how such shared representations emerge and influence performance remains poorly understood. Contrary to expectations, our findings revealed that individuals trained on tasks with similar low-dimensional structures performed worse than those trained on dissimilar tasks. Magnetoencephalography revealed correlated neural representations in the same-structure group and anticorrelated ones in the different-structure group. Crucially, practice reduced this performance gap and shifted the neural representations of the tasks in the same-structure group towards anticorrelation, resembling those in the different-structure group. A neural network model trained on similar tasks replicated these findings: tasks with similar structures require more iterations to orthogonalize their representations. These results highlight a complex interplay between task similarity, neural dynamics, and behavior, challenging traditional assumptions about learning and generalization.

High-throughput two-photon volumetric brain imaging in freely moving mice

Mechanistic insights into histone recognition and H3K14 acetylation by the NuA3 histone acetyltransferase complex

Abstract The NuA3 histone acetyltransferase complex in budding yeast, composed of six subunits, specifically acetylates lysine 14 on histone H3 (H3K14), thereby regulating various biological processes. Despite its importance, the structural basis and mechanism underlying histone tail recognition and substrate specificity of the NuA3 complex have remained elusive. Here we report cryo-electron microscopy structures of the NuA3 complex in its apo form, bound to acetyl-coenzyme A (acetyl-CoA), and in a complex with both the histone H3 tail and acetyl-CoA. Our structure shows that the histone tail-binding cleft of NuA3 is formed cooperatively by two subunits, the catalytic subunit Sas3 and the non-catalytic subunit Nto1. A hydrophobic part of the cleft engages the region preceding H3K14 (residues 9-12), while a network of polar interactions between the cleft and the backbone of H3 residues 12-15, particularly involving Gly13, contributes to substrate specificity.

Charge transfer in triphenylamine–tetrazine covalent organic frameworks for solar-driven hydrogen peroxide production

Structural basis of sodium ion-dependent carnitine transport by OCTN2

Abstract Carnitine is essential for the import of long-chain fatty acids into mitochondria, where they are used for energy production. The carnitine transporter OCTN2 (novel organic cation transporter 2, SLC22A5) mediates carnitine uptake across the plasma membrane and as such facilitates fatty acid metabolism in most tissues. OCTN2 dysfunction causes systemic primary carnitine deficiency (SPCD), a potentially lethal disorder. Despite its importance in metabolism, the mechanism of high-affinity, sodium ion-dependent transport by OCTN2 is unclear. Here we report cryo-EM structures of human OCTN2 in three conformations: inward-facing ligand-free, occluded carnitine- and Na + -bound, and inward-facing ipratropium-bound. These structures define key interactions responsible for carnitine transport and identify an allosterically coupled Na + binding site housed within an aqueous cavity, separate from the carnitine-binding site. Combined with electrophysiology data, we provide a framework for understanding variants associated with SPCD and insight into how OCTN2 functions as the primary human carnitine transporter.

Multilayered regulation of TORC1 signaling by Ait1, Gcn2, and SEAC/GATOR during nitrogen limitation and starvation

Wiedemann–Franz behavior at the Weyl points in compressively strained HgTe

Abstract Weyl semimetals, with their unique electronic band structure, have drawn significant interest for their potential to explore quantum anomalies in condensed matter systems. In this study, we investigate the large positive magneto-thermal conductance associated with the gravitational anomaly – one of the predicted anomalies – for a Weyl semimetal based on a compressively strained HgTe layer. We clearly identify the Weyl regime in our device and accurately extract the thermal conductance by performing thermometry measurements at liquid helium temperatures using fully electronic methods. We observe the anticipated increase in thermal conductance, and it perfectly matches the electrical conductance according to the Wiedemann–Franz law. This finding indicates that, despite the unique electronic spectrum of Weyl semimetals, the mechanism governing heat transport in this system is the same as that for electrical transport, with no additional violations of conservation laws.

Text-to-music generation models capture musical semantic representations in the human brain

The structural basis for the selective antagonism of soluble TNF-alpha by shark variable new antigen receptors

Nucleoplasmic Lamin A/C controls replication fork restart upon stress by modulating local H3K9me3 and ADP-ribosylation levels

Abstract Mild replication interference is a consolidated strategy for cancer chemotherapy. Tolerance to mild replication stress (RS) relies on active fork slowing, mediated by transient fork reversal and RECQ1-assisted restart, and modulated by PARP1 and nuclear architectural components via yet-elusive mechanisms. We combined acute protein inactivation with cell biology and single-molecule approaches to investigate the role of Lamin A/C upon mild RS. We found that Lamin A/C dynamically interacts with replication factories throughout the nucleus and, together with its nucleoplasmic partner LAP2α, is required to induce active fork slowing and maintain chromosome stability upon mild genotoxic treatments. Inactivating nucleoplasmic Lamin A/C reduces poly-ADP-ribosylation (PAR) levels at nascent DNA, triggering deregulated RECQ1-mediated restart of reversed forks. Moreover, we found that the heterochromatin mark H3K9me3, previously reported at stalled forks, also accumulates in response to mild RS. H3K9me3 accumulation requires Lamin A/C, which prevents its premature removal by the histone demethylase JMJD1A/KDM3A. H3K9me3 loss per se phenocopies Lamin A/C inactivation, reducing PAR levels and deregulating fork restart by RECQ1. Hence, nucleoplasmic Lamin A/C, H3K9me3 and PARylation levels are crucial, mechanistically linked modulators of fork dynamics upon mild RS, with important implications for chemotherapy response and for Lamin A/C dysfunction in human disease.

Strain-driven domain wall network with chiral junctions in an antiferromagnet

Abstract Antiferromagnetic materials have recently emerged as promising candidates in spintronics. At the same time, more complex localized non-coplanar magnetic states such as skyrmions are in the research focus due to their intriguing dynamical and transport properties. Recently, a conceptual shift has occurred to envision the use of such magnetic defects not only in one-dimensional race track devices but also to exploit their unique properties in two-dimensional networks. Here we use local strain in a collinear antiferromagnetic film to induce a complex domain wall network. Using spin-polarized scanning tunneling microscopy we characterize the different building blocks of the network – ranging from collinear magnetic domains, over non-collinear domain walls, to non-coplanar localized domain wall junctions – on the atomic scale. We find that the triple domain wall junctions exhibit a structural handedness. The origin is an exchange-driven lateral relaxation as explained using first-principles calculations. We predict that the domain wall junctions exhibit topological orbital magnetization generated by their non-coplanar spin structure, implying topological transport properties due to the network.

Chain-ordered Pt atoms with delocalized electronic structure for improved hydrogen production

The role of attention in multi attribute decision making

mTORC1 signaling in group 2 innate lymphoid cells coordinates neuro-immune crosstalk in allergic lung inflammation

A thermo-electroreduction strategy unlocks propylene glycol synthesis from glycerol at ampere level current density

Thaw slumps alter ecosystem carbon budget in alpine grassland on the Tibetan Plateau

Development of ACE2-tropic-betacoronavirus therapeutics for future pandemic preparedness

Room-temperature valley-selective emission in Si-MoSe2 heterostructures enabled by high-quality-factor chiroptical cavities

Ocean driven retreat of the Northeast Greenland Ice Stream following the Last Glacial Maximum

Abstract The Northeast Greenland Ice Stream (NEGIS), the largest ice stream draining the Greenland Ice Sheet (GrIS), is losing mass at an accelerating rate due to atmospheric and ocean-driven melting. Holding the equivalent of 1.1–1.4 metres of sea-level rise, its collapse will have a significant impact on global sea levels making it crucial to understand the controls on its dynamic behaviour. The NEGIS retreated from the continental shelf edge by 21.6 ka BP, with this study confirming continued grounding line retreat to ~100 km from the shelf edge by 20.3 ka BP, earlier than previously reported. This early retreat was driven by warm Return Atlantic Water (RAW) and amplified by a retrograde seabed, which together drove initial grounding line retreat. The presence of a series of grounding zone wedges indicates a quasi-stable grounding line, which was fronted by an ice shelf. Grounding-line retreat took place between 20.3 and 15.2 ka BP. However, ice-shelf break up caused by enhanced sub-ice shelf melt rates driven by RAW ingression, coupled with surface thinning instigated by atmospheric warming during Greenland Interstadial I, triggered rapid retreat of the ice stream after 15.2 ka BP. Our findings confirm the dominant role of oceanic forcing in grounding line stability and ice-shelf break up.

Entropic order