Nature, Published online: 13 May 2026; doi:10.1038/d41586-026-01373-3Antibiotics designed by artificial intelligence, immunotherapy for resistant infections and other highlights from studies and trials.
Science Journals
Nature, Published online: 13 May 2026; doi:10.1038/d41586-026-01486-9State control of the media is shown to alter the training data of large language models (LLMs) through its impact on the information environment. This has a substantial effect on the output of LLMs, with states rated more favourably in their own language when they have tighter media control.
Nature, Published online: 13 May 2026; doi:10.1038/d41586-026-01378-yGovernments must create meaningful incentives for biopharmaceutical companies to develop antimicrobial products.
Nature, Published online: 13 May 2026; doi:10.1038/d41586-026-01380-4Trials of drugs to fight deadly resistant infections are advancing, but they might fall victim to overuse of agricultural fungicides just like their predecessors.
Nature, Published online: 13 May 2026; doi:10.1038/d41586-026-01376-0Plans to address drug resistance typically focus on the use of antibiotics, but there are signs that compounds with incidental antibacterial effects might be part of the problem, too.
Nature, Published online: 13 May 2026; doi:10.1038/d41586-026-01081-yNavigating by the stars.
Nature, Published online: 13 May 2026; doi:10.1038/d41586-026-00909-xTrajectories of obesity prevalence over the past 45 years reveal patterns of growth, plateau and decline that differ across high-, middle- and low-income countries.
Nature, Published online: 13 May 2026; doi:10.1038/d41586-026-01546-0Drug arrives years after pandemic’s peak, but could still offer protection to vulnerable populations.
Nature, Published online: 13 May 2026; doi:10.1038/d41586-026-01322-0Pregnancy poses many challenges, including protecting against infection and increased nutritional demands. Pregnancy-associated gut changes offer some help.
The ryanodine receptor (RYR) genes encode evolutionarily conserved calcium release channels involved in a wide range of calcium-dependent biological processes. Here, we show that the sole <i>Drosophila</i> RYR gene (<i>dRyR</i>) functions in differentiated somatic and cardiac muscle as well as in developing embryonic myotubes. In the larval body wall muscles, dRyR protein localizes at the SR membranes, and <i>dRyR</i> knockdown adversely affects muscle contractility, suggesting its conserved role in calcium-triggered E-C coupling. After <i>dRyR</i> attenuation, sarcomere, and mitochondrial patterns are severely impaired, showing <i>dRyR</i> involvement in structural muscle properties. However, <i>dRyR</i> is also prominently expressed and functionally required in growing embryonic muscles. <i>dRyR</i> loss of function leads to myotube growth defects and thin myofiber phenotypes, while its overexpression induces myofiber splitting. Given the structural and functional conservation of <i>dRyR</i>, we used <i>Drosophila</i> to test the impact of one human <i>RYR1</i> variant of unknown significance (VUS). Larvae carrying <i>p.Met4881Ile RYR1</i> VUS showed impaired mobility and altered structural muscle properties reminiscent of those seen in <i>dRyR</i> knockdown, thus indicating it is likely pathogenic. Overall, we show that <i>Drosophila dRyR</i> plays a conserved role in setting muscle contractility and structural muscle features. Our findings underline the still under-investigated role of <i>dRyR</i> as a promyogenic factor and provide a first example of the impact assessment of a human <i>RYR1</i> VUS in <i>Drosophila</i>.
Behavioral flexibility, the ability to adjust behavioral strategies in response to changing environmental contingencies and internal demands, is fundamental to cognitive functions. Despite a large body of pharmacology and lesion studies, the precise neurophysiological mechanisms that underlie behavioral flexibility are still under active investigations. This work is aimed to determine the role of a brainstem-to-prefrontal cortex circuit in flexible rule switching. We trained mice to perform a set-shifting task in which they learned to switch attention to distinguish complex sensory cues. Using chemogenetic inhibition, we selectively targeted genetically defined locus coeruleus (LC) neurons or their input to the medial prefrontal cortex (mPFC). We revealed that suppressing either the LC or its mPFC projections severely impaired switching behavior, establishing the critical role of the LC-mPFC circuit in supporting attentional switching. To uncover the neurophysiological substrates of the behavioral deficits, we paired endoscopic calcium imaging of the mPFC with chemogenetic inhibition of the LC in task-performing mice. We found that mPFC prominently responded to attentional switching and that LC inhibition not only enhanced the engagement of mPFC neurons but also broadened single-neuron tuning in the task. At the population level, LC inhibition disrupted mPFC dynamic changes and impaired the encoding capacity for switching. Our results highlight the profound impact of the ascending LC input on modulating prefrontal dynamics and provide new insights into the cellular and circuit-level mechanisms that support behavioral flexibility.
The meninges, which envelop and protect the brain, host a dense network of resident macrophages with diverse roles in regulating homeostasis and neuroinflammation. Despite their importance, we have a limited understanding of their behavior in vivo. Many dynamic cellular functions of macrophages involve intracellular Ca<sup>2+</sup> signaling. However, virtually nothing is known about the spatiotemporal Ca<sup>2+</sup> dynamics of meningeal macrophages in vivo. We developed a chronic intravital two-photon imaging approach and related computational analysis tools to interrogate meningeal macrophage Ca<sup>2+</sup> dynamics, at subcellular resolution, in a novel Pf4-Cre:Ai162 conditional GCaMP6s reporter mouse model. Using imaging in awake mice, we characterized Ca<sup>2+</sup> activity in meningeal macrophages at steady state and in response to cortical spreading depolarization (CSD), an aberrant pro-inflammatory brain hyperexcitability event implicated in migraine, traumatic brain injury, and stroke. In homeostatic meninges, macrophages in the dural perivascular niche exhibited several Ca<sup>2+</sup> dynamic features, including event duration and signal frequency spectrum, distinct from those localized to the interstitial, non-perivascular niche. Simultaneous tracking of macrophage Ca<sup>2+</sup> dynamics and local vasomotion revealed a subset of dural perivascular macrophages whose activity was coupled to locomotion-driven diameter fluctuations of their associated vessels. Most perivascular and non-perivascular meningeal macrophages displayed propagating intracellular Ca<sup>2+</sup> activity and synchronized intercellular Ca<sup>2+</sup> elevations, potentially driven by extrinsic factors. In response to CSD, the majority of perivascular and non-perivascular meningeal macrophages showed a persistent decrease in Ca<sup>2+</sup> activity, while a smaller subset displayed Ca<sup>2+</sup> elevations. Mechanistically, calcitonin gene-related peptide receptor signal…
Fever is a hallmark of malaria. Several studies have linked febrile temperatures to reduced parasite viability, but also to increased cytoadhesion, a key driver of pathology. However, different mechanisms have been proposed to cause changes in cytoadhesion and parasite sensitivity to heat. Here, we demonstrate that exposure of <i>Plasmodium falciparum</i>-infected red blood cells (iRBCs) to physiologically relevant febrile heat stress (39 °C), derived from patient data, enhances cytoadhesion through increased trafficking of the major virulence factor PfEMP1 to the iRBC surface. This phenomenon is not limited to PfEMP1 and common laboratory strains, as it extends to the surface nutrient channel PSAC in four clinical isolates of diverse geographic origin. The increased surface protein display occurs without changes in overall protein expression or parasite developmental progression. Using phosphoproteomics and proximity labelling, we find that elevated temperature also increases trafficking and phosphorylation of exported proteins into the RBC. Enhanced export is likely reliant on the presence of a transmembrane domain as shown by NanoLuc reporter assays. Collectively, our results indicate that febrile temperatures commonly experienced during infection can accelerate protein export, likely at the parasitophorous vacuole. This enhanced export following heat stress is relevant because increased cytoadhesion could influence disease severity through earlier iRBC sequestration and elevated bound parasite mass.
The asymmetry of lipid membranes is tightly regulated in eukaryotic cells, and auditory hair cells are no exception.
Animals flexibly change their behavior depending on context. It is reported that the hippocampus is one of the most prominent regions for contextual behaviors, and its sequential activity shows context dependency. However, how such context-dependent sequential activity is established through reorganization of neuronal activity (remapping) remains unclear. To better understand the formation of hippocampal activity and its contribution to context-dependent flexible behavior, we present a novel biologically plausible reinforcement learning model. In this model, Context selector promotes the formation of context-dependent sequential activity and allows for flexible switching of behavior in multiple contexts. This model reproduces a variety of findings from neural activity, optogenetic inactivation, human fMRI, and clinical research. Furthermore, our model predicts that imbalances in the ratio between sensory and contextual representations in Context selector account for schizophrenia and autism spectrum disorder-like behaviors.
Skin cooling is detected by primary afferents that express the Trpm8 channel, but how this information is conveyed to the brain remains poorly understood. We have previously identified a population of lamina I projection neurons belonging to the anterolateral system (ALS) that receive numerous contacts from Trpm8-expressing primary afferents. Here, using a semi-intact somatosensory preparation, we provide evidence that these cells correspond to the cold-selective ALS neurons identified in previous physiological studies. We also confirm the presence of synapses from Trpm8 afferents onto these cells at the ultrastructural level and with optogenetics. Based on our previous transcriptomic findings, we identify calbindin as a molecular marker, and show that this can be used to target the cold-selective ALS neurons for anterograde tracing studies. We provide evidence that they project to brain regions that have been implicated in thermosensation: the rostralmost part of the lateral parabrachial area, the caudal part of the periaqueductal grey matter, and the posterior triangular and ventral posterolateral nuclei of the thalamus. Our findings provide important insights into the organisation of neuronal circuits that underlie thermoregulation and the perception of cold stimuli applied to the skin.
Learning to adapt voluntary movements to an external perturbation, whether mechanical or visual, is faster during a second encounter than during the first. The mechanisms underlying this phenomenon, known as savings, remain unclear. Recent studies propose that the high dimensionality of neural control enables the retention of learning traces that may facilitate savings. To test this idea, we used MotorNet, a framework for training recurrent neural networks (RNNs) to control biomechanical models of the human upper limb. RNNs were trained to perform reaching movements with a velocity-dependent force field (FF) and without (NF) in the sequence NF1 (baseline), FF1 (adaptation), NF2 (washout), and FF2 (re-adaptation). RNNs showed behaviural signatures of savings in the absence of any explicit contextual input signalling the presence or absence of the FF. Savings was more robust in RNNs with larger numbers of units. We identified a component of RNN activity associated with savings—a shift in preparatory activity that persisted even after washout. Displacing this preparatory activity in the direction of the shift enhanced savings, whereas perturbations in the opposite direction reduced or eliminated savings. These findings suggest a potential neural basis for motor memory retention underlying savings that is reliant on the high dimensionality of neural circuits for control, and is independent of cognitive or strategic learning.
The integration-segregation theory proposes that early facilitation and later inhibition (i.e. inhibition of return [IOR]) in exogenous attention arises from the competition between cue-target event integration and segregation. Although widely supported behaviorally, the theory lacked direct neural evidence. Here, we used event-related functional magnetic resonance imaging (fMRI) in human participants with an optimized cue-target paradigm to test this account. Cued targets elicited stronger activation in the frontoparietal attention networks, including the bilateral frontal eye field (FEF), intraparietal sulcus (IPS), right temporoparietal junction (TPJ), and left dorsal anterior cingulate cortex (dACC), consistent with the notion of attentional demand of reactivating the cue-initiated representations for integration. In contrast, uncued targets engaged the medial temporal cortex, particularly the bilateral parahippocampal gyrus (PHG) and superior temporal gyrus (STG), reflecting the segregation processes associated with new object-file creation and novelty encoding. These dissociable activations provide the first direct neuroimaging evidence for the integration-segregation theory. Moreover, we observed neural interactions between IOR and cognitive conflict, suggesting a potential modulation of conflict processing by attentional orienting. Taken together, these findings provide new insights into exogenous attention by clarifying the neural underpinnings of integration and segregation and uncovering the interaction between spatial orienting and conflict processing.
Genomic stability is critical for cellular function; however, in the central nervous system, highly metabolically active differentiated neurons are challenged to maintain their genome over the organismal lifespan without replication. DNA damage in neurons increases with chronological age and accelerates in neurodegenerative disorders, resulting in cellular and systemic dysregulation. Distinct DNA damage response strategies have evolved with a host of polymerases. The Y-family translesion synthesis (TLS) polymerases are well known for bypassing and repairing damaged DNA in dividing cells. However, their expression, dynamics, and role, if any, in enduring postmitotic differentiated neurons of the brain are completely unknown. We show through systematic longitudinal studies for the first time that DNA polymerase kappa (POLK), a member of the Y-family polymerases, is highly expressed in mouse neurons. With chronological age, there is a progressive and significant reduction of nuclear POLK with a concomitant accumulation in the cytoplasm that is predictive of brain tissue age. The reduction of nuclear POLK in old brains is congruent with an increase in DNA damage markers. The nuclear POLK colocalizes with damaged sites and DNA repair proteins. The cytoplasmic POLK accumulates with stress granules and endo/lysosomal markers. Nuclear POLK expression is significantly higher in GABAergic interneurons (INs) compared to excitatory pyramidal neurons and lowest in non-neurons, possibly reflective of the inherent biological differences such as firing rates and neuronal activity. INs associated with microglia have significantly higher levels of cytoplasmic POLK in old age. Finally, we show that neuronal activity itself can lead to an increase in nuclear POLK levels and a reduction of the cytoplasmic fraction. Our findings open a new avenue in understanding how different classes of postmitotic neurons deploy TLS polymerase(s) to maintain their genomic integrity over time, which …
Gata3 is an essential transcription factor for the development of several distinct immune cell lineages such as T cells, natural killer (NK) cells, and innate lymphoid cells (ILCs). As such, the levels and timing of <i>Gata3</i> expression are critical for directing lineage fate decisions. The <i>Gata3</i> locus has a complex and dynamic distal regulatory enhancer landscape. Recently, we identified a non-coding RNA, <i>Dreg1</i>, located immediately upstream of the classic +280 kb T/NK cell enhancer (Tce1). To test its function, we excised the <i>Dreg1</i> locus in mice and observed a selective reduction of group 2 ILCs (ILC2) across multiple tissues, but mature T, NK, and other ILC lineages remained unchanged. In bone marrow, common innate lymphoid cell progenitors (ILCPs) increased while ILC2 progenitors (ILC2P) decreased, with a modest reduction of <i>Gata3</i> in upstream progenitors consistent with an early developmental bottleneck. Chromatin profiling showed the Dreg1 locus is accessible in early lymphoid progenitors and became decorated with H3K27ac in ILCP in a Tcf1-dependent manner. Furthermore, Tcf1-deficient cells did not express <i>Dreg1</i> and showed alterations in the epigenetic landscape of the <i>Dreg1</i> locus. Finally, we discovered that potential homologues of <i>Dreg1</i> harboured in a syntenic enhancer of <i>GATA3</i> are also highly expressed in human ILC2. Taken together, we conclude that <i>Dreg1</i> is a Tcf1-dependent non-coding RNA critical for fine tuning the high level of <i>Gata3</i> required for the optimal development of the ILC2 lineage.
Proceedings of the National Academy of Sciences, Volume 123, Issue 19, May 2026.
Nature, Published online: 12 May 2026; doi:10.1038/s41586-026-10615-3Author Correction: Predictive coding of reward in the hippocampus
Nature, Published online: 12 May 2026; doi:10.1038/s41586-026-10618-0Author Correction: A mechanical ratchet drives unilateral cytokinesis
Nature, Published online: 12 May 2026; doi:10.1038/d41586-026-01518-4Cruise-ship hantavirus cluster exposes a wider preparedness gap
Nature, Published online: 12 May 2026; doi:10.1038/d41586-026-01334-wAn unexpected creature munches on cherry blossom flowers, and the value of drawing art is considered in this week’s pick from the Nature archive.