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Peer-reviewade publikationer — 50304 artiklar

eLife 2026-05-14
Effort produces after-effects costly for others but valued for self
Engaging in prosocial behavior requires effort, yet people are often averse to exerting effort for others’ benefit. However, it remains unclear how effort exertion affects subsequent reward evaluation during prosocial acts. Here, we combined high-temporal-resolution electroencephalography with a paradigm that independently manipulated physical effort and monetary reward for self and others to elucidate the neural mechanisms underlying the reward after-effect of prosocial effort expenditure. We found dissociable reward after-effects for self-benefiting and other-benefiting effort. For self-benefiting rewards, the reward positivity (RewP) increased with effort demand, suggesting an effort-enhancement effect. In contrast, for other-benefiting rewards, the RewP decreased as effort increased, demonstrating an effort-discounting effect. Critically, this dissociation was contingent upon high reward magnitude and modulated by individual differences in effort discounting, yet remained distinct from performance evaluation. Our findings reveal distinct neural computations for self- and other-benefiting efforts, offering new insights into how prior effort expenditure shapes reward evaluation during prosocial behavior.
eLife 2026-05-14
Identification of the regulatory elements and protein substrates of lysine acetoacetylation
Short-chain fatty acylations establish connections between cell metabolism and regulatory pathways. Lysine acetoacetylation (Kacac) was recently identified as a new histone mark. However, regulatory elements, substrate proteins, and epigenetic functions of Kacac are not yet fully understood, hindering further in-depth understanding of acetoacetate-modulated (patho)physiological processes. Here, we created a chemo-immunological approach for reliable detection of Kacac, and demonstrated that acetoacetate serves as the primary precursor for histone Kacac. We report the enzymatic addition of the Kacac mark by the acyltransferases GCN5, p300, and PCAF, and its removal by the deacetylase HDAC3. Furthermore, we establish acetoacetyl-CoA synthetase as a key regulator of cellular Kacac levels. A comprehensive proteomic analysis has identified 139 Kacac sites on 85 human proteins. Bioinformatics analysis of Kacac substrates and RNA sequencing data reveal the broad impacts of Kacac on multifaceted cellular processes. These findings unveil pivotal regulatory mechanisms for the acetoacetate-mediated Kacac pathway, opening a new avenue for further investigation into ketone body functions in various pathophysiological states.
eLife 2026-05-14
Subregional activity in the dentate gyrus is amplified during elevated cognitive demands
Neural activity in the dentate gyrus (DG) supports the detection and discrimination of novelty, context, and patterns. Granule cell activation differs between the supra- and infrapyramidal blades across hippocampal-dependent tasks, yet how excitatory dynamics shape this blade-specific bias under varying cognitive demands remains unclear. Here, we combined an automated touchscreen pattern separation task in mice with temporally controlled tagging of active neurons to determine how increasing cognitive demand influences spatial activity patterns in the DG. As task difficulty increased, activation became progressively biased toward the suprapyramidal blade and was accompanied by structured distributions of active mature granule cells (mGCs) along both the radial and transverse axes. Selective inhibition of mGCs did not alter these spatial patterns, but profoundly impaired performance, as mice were no longer able to discriminate between closely spaced locations. In contrast, chemogenetic inhibition of adult-born dentate granule cells (abDGCs) beyond a critical maturation window impaired performance under high-demand conditions, increased overall mGC activity, and disrupted blade-specific organization even in animals that successfully completed the task. These findings demonstrate that high cognitive demand recruits spatially organized mGC activity and support a modulatory role for abDGCs in shaping dentate circuit dynamics.
eLife 2026-05-14
A meta-analysis suggests that TMS targeting the hippocampal network selectively improves episodic memory
Episodic memory is critically dependent on the hippocampal network and is frequently impaired in many clinical disorders. Recent findings highlight Hippocampal Indirectly Targeted Stimulation (HITS) as a promising, network-guided non-invasive transcranial magnetic stimulation (TMS) procedure to enhance episodic memory performance. Here, we report the first comprehensive meta-analysis of HITS effects on episodic memory, encompassing both healthy individuals and clinical populations. HITS using parieto-occipital network targets robustly improved episodic memory, with effects selective for episodic memory versus other non-memory cognitive domains. Efficacy was significantly greater when memory performance was assessed using memory tasks sensitive to recollection, which is strongly linked to hippocampal network function, compared to recognition or other types of episodic memory tasks. Efficacy was also significantly greater when HITS was delivered before the memory tasks were administered versus in the period between study and test phases of tasks. No serious adverse events were reported. These findings establish HITS as a robust approach for episodic memory enhancement, suggesting potential for clinical translation in memory disorders. Selectivity of effects for episodic memory generally and for recollection-format tests in particular indicates cognitive and mechanistic specificity, supporting the potential for targeted and selective neuromodulation of hippocampal networks and their associated functions.
PLOS Biology 2026-05-13
Acoustic delivery of indocyanine green via biosynthetic gas vesicles for tumor photothermal therapy
<p>by Jiaqi Zhang, Licong Huang, Shuhui Wang, Jingwen Ding, Yuping Yang, Chenhui Li, Ping Zhao, Qian Li, Fei Yan</p> Photothermal therapy (PTT) serves as a complementary strategy to conventional cancer treatments. Indocyanine green (ICG) is the only U.S. Food and Drug Administration (FDA)-approved photothermal agent. However, its clinical application is hindered by poor stability, short blood half-life, and lack of tumor targeting. Herein, we developed biosynthetic gas vesicles (GVs) covalently conjugated with ICG (ICG-GVs) for remotely controlled, visibly acoustic delivery of ICG to tumors in a subcutaneous xenograft model of MB49 murine bladder cancer in C57BL/6 mice. The resulting ICG-GVs exhibit uniform morphology (~200 nm) with an ICG loading rate of 58%, good colloidal stability, and enable trimodal imaging (ultrasound, near-infrared fluorescence, and photoacoustic) for real-time visualization of delivery. Pharmacokinetic analysis revealed that ICG-GVs significantly prolong ICG circulation half-life and increase AUC. Ultrasound-triggered GV cavitation enhanced intratumoral ICG delivery, achieving tumor temperatures >60 °C upon laser irradiation, leading to complete tumor regression and prolonged survival without detectable toxicity. This study provides a clinically translatable strategy for precise and effective ICG-based PTT.
PLOS Biology 2026-05-13
Premotor cortex hemodynamic responses primarily reflect perceptual rather than specific motor aspects of decision making
<p>by Jeff Boucher, Shihab Shamma, Yves Boubenec</p> Decisions are driven by perception, but also by non-perceptual factors. It remains an open question, however, whether frontal brain regions involved in perceptual decision-making tend to uniquely reflect the perception of an animal, or the final choice of action driven by perceptual and non-perceptual factors. Using functional ultrasound imaging (fUSI), we investigated how the premotor cortex (PMC) in ferrets represents stimuli in a Go/NoGo auditory categorization task, varying the difficulty in order to manipulate the rates of perceptual errors relative to non-perceptual errors. We found that on Easy error trials, where error in perception was less likely, PMC activity was similar to correct answers for the same stimulus category. In contrast, on Difficult error trials, PMC activity more closely reflected the choice the animal made, being similar to correct answers for the opposite category. These results together are consistent with PMC activity reflecting the reward-predictive perceptual category. Perceptual errors could be refined further by assessing licking patterns, but licking patterns alone did not explain the effect. This study advances our understanding of the functional role of the frontal cortex in decision-making, suggesting that the PMC integrates sensory inputs to guide behavior based on perceptual information, rather than motivational information.
NEJM 2026-05-13
Inflammatory Myopathies
New England Journal of Medicine, Volume 394, Issue 19, Page 1925-1938, May 14/21, 2026.