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Tips and tricks to plan your career in science

Is my red your red? Neuroscience has an answer

Daily briefing: Heatwaves can be directly linked to emissions from specific companies

AI tool detects LLM-generated text in research papers and peer reviews

Heatwaves linked to emissions of individual fossil-fuel and cement producers

Gating and noelin clustering of native Ca2+-permeable AMPA receptors

Abstract AMPA-type ionotropic glutamate receptors (AMPARs) are integral to fast excitatory synaptic transmission and have vital roles in synaptic plasticity, motor coordination, learning and memory1. Whereas extensive structural studies have been conducted on recombinant AMPARs and native calcium-impermeable (CI)-AMPARs alongside their auxiliary proteins2–5, the molecular architecture of native calcium-permeable (CP)-AMPARs has remained undefined. Here, to determine the subunit composition, physiological architecture and gating mechanisms of CP-AMPARs, we visualize these receptors, immunoaffinity purified from rat cerebella, and resolve their structures using cryo-electron microscopy (cryo-EM). Our results indicate that the predominant assembly consists of GluA1 and GluA4 subunits, with the GluA4 subunit occupying the B and D positions, and auxiliary subunits, including transmembrane AMPAR regulatory proteins (TARPs) located at the B′ and D′ positions, and cornichon homologues (CNIHs) or TARPs located at the A′ and C′ positions. Furthermore, we resolved the structure of the noelin (NOE1)–GluA1–GluA4 complex, in which NOE1 specifically binds to the GluA4 subunit at the B and D positions. Notably, NOE1 stabilizes the amino-terminal domain layer without affecting gating properties of the receptor. NOE1 contributes to AMPAR function by forming dimeric AMPAR assemblies that are likely to engage in extracellular networks, clustering receptors in synaptic environments and modulating receptor responsiveness to synaptic inputs.

Probing non-equilibrium topological order on a quantum processor

Abstract Out-of-equilibrium phases in many-body systems constitute a new paradigm in quantum matter—they exhibit dynamical properties that may otherwise be forbidden by equilibrium thermodynamics. Among these non-equilibrium phases are periodically driven (Floquet) systems1–5, which are generically difficult to simulate classically because of their high entanglement. Here we realize a Floquet topologically ordered state theoretically proposed in ref. 6, on an array of superconducting qubits. We image the characteristic dynamics of its chiral edge modes and characterize its emergent anyonic excitations. Devising an interferometric algorithm allows us to introduce and measure a bulk topological invariant to probe the dynamical transmutation of anyons for system sizes up to 58 qubits. Our work demonstrates that quantum processors can provide key insights into the thus-far largely unexplored landscape of highly entangled non-equilibrium phases of matter.

Coenzyme Q headgroup intermediates can ameliorate a mitochondrial encephalopathy

Allergy-triggering proteins share a common characteristic

The emergence of globular clusters and globular-cluster-like dwarfs

Abstract Globular clusters (GCs) are among the oldest and densest stellar systems in the Universe, yet how they form remains a mystery1. Here we present a suite of cosmological simulations in which both dark-matter-free GCs and dark-matter-rich dwarf galaxies naturally emerge in the Standard Cosmology. We show that these objects inhabit distinct locations in the size–luminosity plane and that they have similar ages, age spread, metallicity and metallicity spread to globulars and dwarfs in the nearby Universe. About half of our simulated globulars form by means of regular star formation near the centres of their host dwarf, with the rest forming further out, triggered by mergers. The latter are more tidally isolated and more likely to survive to the present day. Finally, our simulations predict the existence of a new class of object that we call ‘globular-cluster-like dwarfs’ (GCDs). These form from a single, self-quenching, star-formation event in low-mass dark-matter halos at high redshift and have observational properties intermediate between globulars and dwarfs. We identify several dwarfs in our Galaxy, such as Reticulum II (refs. 2–4), that could be in this new class. If so, they promise unprecedented constraints on dark-matter models and new sites to search for metal-free stars.

Inflammation during viral infection can rouse dormant cancer cells

Using biobanks to boost research: a how-to guide

Probing the Kitaev honeycomb model on a neutral-atom quantum computer

How did the oldest star clusters form?

ACLY inhibition promotes tumour immunity and suppresses liver cancer

Abstract Immunosuppressive tumour microenvironments are common in cancers such as metabolic dysfunction-associated steatohepatitis (MASH)-driven hepatocellular carcinoma (HCC) (MASH-HCC)1–3. Although immune cell metabolism influences effector function, the effect of tumour metabolism on immunogenicity is less understood4. ATP citrate lyase (ACLY) links substrate availability and mitochondrial metabolism with lipid biosynthesis and gene regulation5–7. Although ACLY inhibition shows antiproliferative effects in various tumours, clinical translation has been limited by challenges in inhibitor development and compensatory metabolic pathways8–12. Here, using a mouse model of MASH-HCC that mirrors human disease, genetic inhibition of ACLY in hepatocytes and tumours reduced neoplastic lesions by over 70%. To evaluate the therapeutic potential of this pathway, a novel small-molecule ACLY inhibitor, EVT0185 (6-[4-(5-carboxy-5-methyl-hexyl)-phenyl]−2,2-dimethylhexanoic acid), was identified via phenotypic screening. EVT0185 is converted to a CoA thioester in the liver by SLC27A2 and structural analysis by cryo-electron microscopy reveals that EVT0185-CoA directly interacts with the CoA-binding site of ACLY. Oral delivery of EVT0185 in three mouse models of MASH-HCC dramatically reduces tumour burden as monotherapy and enhances efficacy of current standards of care including tyrosine kinase inhibitors and immunotherapies. Transcriptomic and spatial profiling in mice and humans linked reduced tumour ACLY with increases in the chemokine CXCL13, tumour-infiltrating B cells and tertiary lymphoid structures. The depletion of B cells blocked the antitumour effects of ACLY inhibition. Together, these findings illustrate how targeting tumour metabolism can rewire immune function and suppress cancer progression in MASH-HCC.

Strengthening excellence in agricultural sciences education through mentorship systems for undergraduate students to promote sustainable agricultural development

The study examines the role of mentorship in delivering high-quality undergraduate education in the agricultural sciences, and to find ways to improve mentorship systems in agricultural science education and promote sustainable agricultural development. A questionnaire survey was conducted with 329 samples, as well as a case study on a mentorship system. The questionnaire comprised 7 topics and 20 items related to mentoring relationships. The results show that mentorship played a crucial role in cultivating excellent students in agricultural science by exerting significant influences on their experience/skills/technical abilities, innovation and practical abilities, and team-work spirit. Decision-making and problem-solving abilities were also noticed as well. For mentorship opportunities to be successful, students must be aware of them. They should be of excellent quality and receive support from national bodies. Agricultural sciences education should help students fully understand the mentorship systems. Our findings offer both theoretical significance and practical value for the establishment of innovative approaches for nurturing agricultural talent and for promoting the sustainable agricultural development.

EEG Sonification improves sleep staging performance in novice stagers

Sleep staging is a critical tool used in research and clinical settings to evaluate and diagnose sleep conditions; however, sleep staging is labor intensive and may be challenging for inexperienced practitioners. We explored whether adding an auditory representation (sonification) of the EEG to a standard visual representation could improve sleep staging performance or reduce workload. This is the first study to investigate the effects of sonification on sleep staging performance. We performed a within-subjects study in which 40 participants completed an online sleep staging task with and without sonified EEG. EEG was sonified by minimal transformation in which the raw EEG signal was played as an audio signal. Contrary to our hypothesis, we found adding sonification did not result in improvements in accuracy, speed, or workload for the entire subject group. However, when we stratified participants by sleep staging experience, we found sonification improved accuracy for the least experienced participants. These findings suggest EEG sonification may be useful as a tool to enable novice sleep stagers to reach acceptable performance levels faster.

Happy or not? An investigative study on well-being and anhedonia in everyday life

Anhedonia, the inability to experience pleasure or interest in activities, is a key symptom across various psychiatric disorders, including depression. It links to poor quality of life, higher suicide risk, and poorer prognosis. While anhedonia is often studied in clinical populations, its prevalence in healthy individuals and its dimensional nature remain underexplored. This study examined the prevalence of anhedonia in 128 German university students, comparing those with and without psychiatric symptoms and modeling psychiatric symptoms as predictor of anhedonia, measured with the Dimensional Anhedonia Rating Scale (DARS). Results showed that the clinical group demonstrated relatively low levels of anhedonia (total DARS-26: 85.03 ± 12.88) that did not differ from the healthy group (88.80 ± 7.88). Considerable variability suggests that a purely categorical approach to anhedonia may not capture its full complexity. Multiple regression analyses revealed that negative symptoms (e.g., affective flattening) were the strongest predictor of anhedonia, both in the full (b = −0.54, p < .001) and within the (sub-)clinical sample (b = −0.64, p < .001). Anxiety was also a significant predictor in the (sub-)clinical group (b = −1.06, p = .01), underscoring its impact on reward processing. Depression did not emerge as a strong predictor (b = −0.21, p = .49) when considered alongside other variables, indicating that its link to anhedonia may be mediated by other factors. Multigroup confirmatory factor analysis of the DARS showed that the 17-item version provided a better fit than the 26-item version, reinforcing the shorter version as a more efficient tool for assessing anhedonia. Taken together, the present findings support the use of a dimensional approach to anhedonia, which offers a more nuanced view of the underlying psychological and neurological mechanisms. Future research should explore anhedonia in larger, diverse samples for a comprehensive understanding of the link between anhedonia and mental illness. Registration: The study was pre-registered on OSF: https://doi.org/10.17605/OSF.IO/234A7.

A haplotype-resolved pangenome of the barley wild relative Hordeum bulbosum

Abstract Wild plants can contribute valuable genes to their domesticated relatives 1 . Fertility barriers and a lack of genomic resources have hindered the effective use of crop–wild introgressions. Decades of research into barley’s closest wild relative, Hordeum bulbosum , a grass native to the Mediterranean basin and Western Asia, have yet to manifest themselves in the release of a cultivar bearing alien genes 2 . Here we construct a pangenome of bulbous barley comprising 10 phased genome sequence assemblies amounting to 32 distinct haplotypes. Autotetraploid cytotypes, among which the donors of resistance-conferring introgressions are found, arose at least twice, and are connected among each other and to diploid forms through gene flow. The differential amplification of transposable elements after barley and H.   bulbosum diverged from each other is responsible for genome size differences between them. We illustrate the translational value of our resource by mapping non-host resistance to a viral pathogen to a structurally diverse multigene cluster that has been implicated in diverse immune responses in wheat and barley.

The role of structural connectivity on brain function through a Markov model of signal transmission

Structure determines function. However, this universal theme in biology has been surprisingly difficult to observe in human brain neuroimaging data. Here, we link structure to function by hypothesizing that brain signals propagate as a Markovian process on an underlying structure. We focus on a metric called commute time: the average number of steps for a random walker to go from region A to B and then back to A. Commute times based on white matter tracts from diffusion MRI exhibit an average ± standard deviation Spearman correlation of −0.26 ± 0.08 with functional MRI connectivity data across 434 UK Biobank individuals and −0.24 ± 0.06 across 400 HCP Young Adult brain scans. The correlation increases to −0.36 ± 0.14 and to −0.32 ± 0.12 when the principal contributions of both commute time and functional connectivity are compared for both datasets. The correlations are stronger by 33% compared to broadly used communication measures such as search information and communicability. The difference further widens to a factor of 5 when commute times are correlated to the principal mode of functional connectivity from its eigenvalue decomposition. Overall, the study points to the utility of commute time to account for the role of polysynaptic (indirect) connectivity underlying brain function by assuming that signals randomly traverse along the underlying brain structure.