ZFTA-RELA is the most recurrent genetic alteration seen in paediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumours in mice1. Despite its oncogenic potential, ZFTA-RELA (ZR) is observed nearly exclusively in childhood EPN, with tumours located distinctly in the supratentorial brain of the central nervous system1. We proposed that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZR. To test this hypothesis, we performed combined single-nucleus assay for transposase-accessible chromatin and RNA (snMultiome) sequencing of the developing mouse forebrain compared with ZR-driven mouse and human EPN. We demonstrated that specific developmental lineage programs present in transient progenitor cells and regulated by PLAG/L family transcription factors were at risk of neoplastic transformation. Binding of this chromatin network by ZR or other PLAG/L family motifs targeting fusion oncoproteins led to persistent chromatin accessibility at oncogenic loci and oncogene expression. Cross-species analysis of mouse and human ZR EPN revealed significant cell type heterogeneity indicating incomplete neurogenic and gliogenic differentiation, with a small percentage of cycling progenitor-like or radial glial-like cells that established a putative tumour cell hierarchy. In vivo lineage tracing studies identified neoplastic clones that aggressively dominated tumour growth and established the entire EPN cellular hierarchy. These findings identify developmental epigenomic states that are critical for fusion-oncoprotein-driven transformation and show how these states continue to shape tumour progression.

A fundamental paradigm in neuroscience is that neurons represent the world through fixed tuning functions, with stable mappings from stimulus features to firing rates1. Here, we report that tuning can instead shift rapidly and coherently across a neural population, enabling a dynamic transition from detecting a broad category to discriminating individual exemplars. We set out to address a longstanding debate in visual neuroscience about whether the inferotemporal cortex uses a specialized code for specific object categories or a general-purpose code that applies to all objects. We found that face-selective cells in macaque inferotemporal cortex initially adopted a general code optimized for face detection. However, after a rapid concerted population event lasting less than 20 ms, the neural code transformed into a face-specific one, with two striking features: response gradients to principal detection-related dimensions reversed direction, and new tuning emerged for multiple higher-dimensional features that support fine face discrimination. These dynamics in face patches were specific to face stimuli and did not occur in response to non-face objects. Thus, for faces, face cells transition from detection to discrimination by switching from an object-general code to a face-specific one. More broadly, our findings indicate that there is a previously unknown mechanism for neural representation: concerted stimulus-dependent switching of the neural code used by a cortical area.

Frequency combs have revolutionized metrology, ranging and optical clocks1, motivating substantial efforts on the development of chip-scale comb sources2,3. Some on-chip comb sources exist and have been implemented through electro-optic modulation4,5, mode-locked lasers6,7, quantum cascade lasers8-10 or soliton formation by Kerr nonlinearity11,12. However, widespread deployment of on-chip comb sources has remained elusive, as they still require radiofrequency sources, high-Q (high-quality factor) resonators or complex stabilization schemes while facing efficiency challenges. Here, we demonstrate an on-chip frequency comb source based on the integration of a lithium niobate nanophotonic circuit with a semiconductor laser that can alleviate these challenges. We show the formation of temporal topological solitons in an on-chip nanophotonic parametric oscillator with quadratic nonlinearity and low finesse. These solitons, independent of the dispersion regime, consist of phase defects separating two π-out-of-phase continuous wave solutions at the signal frequency, which is half the input pump frequency13,14. We use on-chip cross-correlation for temporal measurements and confirm formation of topological solitons as short as 60 fs around 2 μm, in agreement with a generalized parametrically forced Ginzburg-Landau theory15-17. Moreover, we demonstrate a proof-of-concept turn-key operation of a hybrid-integrated source of topological frequency comb. Topological solitons are potential candidates for the development of integrated comb sources, which are dispersion-sign agnostic and do not require high-Q resonators or high-speed modulators, and can provide access to hard-to-reach spectral regions, including mid-infrared regions18.

Charging rates, cycling performance and safety of solid-state batteries using metal negative electrodes are often limited by dendrites1-3, the growth of which depends on coupling between electrochemical and mechanical driving forces. Previously, it has been assumed that dendrites propagate when plating-induced stresses reach the fracture stress of the solid electrolyte. Here we show that dendrites can propagate at far lower stresses. Using operando birefringence microscopy4, we directly measure stresses around growing dendrites in garnet Li6.6La3Zr1.6Ta0.4O12, a highly stable solid electrolyte5-7. Plating-induced stresses are present throughout growth and approach the mechanical fracture stress for the slowest-growing dendrites. As current densities and dendrite velocities increase, the stresses accompanying dendrite growth surprisingly decrease, with dendrite propagation occurring at stresses up to 75% lower than under mechanical load alone. Cryogenic scanning transmission electron microscopy (STEM) of dendrites propagated at high current reveals electrolyte decomposition to new phases, associated with which is a net molar volume contraction. The electrochemically induced mode of embrittlement may be mitigated through understanding and control of the nature of phase transitions accompanying instability.

During the early and mid-Holocene, the Sahara and Sahel experienced a humid phase, the so-called African Humid Period (AHP)1. The AHP started around 14.8 thousand years before present (kyr BP), peaked between 9.0 kyr BP and 6.0 kyr BP and experienced short-lived droughts of as yet poorly constrained age and duration2,3. Here we show that the AHP was punctuated by two droughts of decadal-scale duration, at about 9.3 kyr BP and 8.2 kyr BP, and another more tentatively identified drought at 6.3 kyr BP. Our findings arise from a multiproxy time series from the annually layered (varved) sedimentary archive of Lake Yoa in Chad, which covers the past 10.25 kyr continuously. During the more prominent drought at 8.2 kyr BP, pollen and diatom data, along with leaf-wax isotopes and geochemical source area indicators, imply that a reduction in local precipitation and fluvial supply to Lake Yoa caused a lake-level drop accompanied by an expansion of reed belts along the shore. The proxy data, together with our climate simulations, suggest that the 8.2 kyr BP drought event was a direct and rapid response to a potential weakening of the Atlantic Meridional Overturning Circulation (AMOC) owing to sudden freshwater input into the North Atlantic. The results underline the need for improved decadal predictions4 to better anticipate such drought risks in the future.