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Membrane ion channels can be responsive to a variety of stimuli such as pressure, temperature, or pH. Here, the authors show that simply shining 365 nm light activates a native potassium channel in rodent pain-sensing neurons, delivering powerful analgesia without drugs or genetic manipulations.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Here authors used patient-derived forebrain organoids to reveal how LIS1 mutations cause varying severity in a neurodevelopmental disorder, uncovering links between cytoskeletal defects, protein stress, and potential therapeutic strategies.

Peptidoglycan released by neighbouring kin or non-kin cell lysis induces physiological changes that protect from a range of stresses, including phage predation.

Sarcomas are a group of mesenchymal malignancies which are molecularly heterogeneous. Here, the authors develop an in vivo muscle electroporation system for gene delivery to generate distinct subtypes of orthotopic genetically engineered mouse models of sarcoma, as well as syngeneic allograft models with scalability for preclinical assessment of therapeutics.

Targeting the interaction between transcription factor TEAD and its co-repressor VGL4 is an attractive strategy to chemically modulate Hippo signaling. Here, the authors develop a proteomimetic with stabilized tertiary structure that inhibits the TEAD:VGL4 interaction in vitro and in cells.

The International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

Innate lymphoid cells (ILC) are important immune cells for maintaining the gut homeostasis. Here the authors show that c-FLIP, an anti-apoptotic molecule, is important for the development of NKP46⁺ ILC1, including conventional natural killer (cNK) cells, and ILC3, with cNK being more critical for ameliorating intestinal inflammation.

Attenuating effects of the ketogenic diet on colorectal cancer (CRC) cell growth has been previously described. Here, using a mouse model of CRC with a humanized microbiome, the authors identify a shift toward gut bacterial species that produce stearic acid in ketogenic conditions, resulting in elevated levels of free stearate in the gut lumen, which they then show exhibits tumor-suppressing properties.

GLP-1 is an incretin hormone and neuromodulator produced by gut enterocytes and CNS neurons. Brierley et al. find that GLP-1 from peripheral and central sources acts independently through distinct gut–brain circuits to suppress eating.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

The EWSR1::FLI1 fusion protein is the oncogenic driver of Ewing sarcoma (EwS). Here, the authors find that EWSR1::FLI1 plays a non-canonical role in mRNA decay via interactions with the CCR4-NOT deadenylation complex and the RNA-binding protein HuR. This role uncovers a new therapeutic vulnerability of EwS to HuR inhibition.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

Brain-wide recordings in mice reveal that prior expectations are distributed through recurrent loops across all levels of cortical and subcortical processing.

Pattern-triggered immunity is activated by recognition of microbe-derived structures by host pattern recognition receptors. Here the authors use a genotype-by sequencing approach to show that bacterial translation initiation factor 1 triggers PTI in Arabidopsis thaliana after recognition by the RLP32 receptor.

A newly identified gene, sex chromosome activation (SOA), is a master regulator of dosage compensation in Anopheles gambiae.

Efstathiou et al. describe an Argonaute-dependent endoplasmic reticulum (ER)-associated RNA silencing pathway that acts together with ER-associated protein degradation to preserve ER homeostasis and function.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

N-terminal protein acetylation is required for plant viability. Here the authors show that reducing N-terminal acetylation by NatA leads to an increase in global protein turnover that is facilitated by absent masking of a novel N-degron

Spontaneous parthenogenesis in sunflower has been used to develop a scalable doubled haploid breeding system.

Rapid extracellular antigen profiling of a cohort of 194 individuals infected with SARS-CoV-2 uncovers diverse autoantibody responses that affect COVID-19 disease severity, progression and clinical and immunological characteristics.

This study describes a projection from the medial prefrontal cortex to the central amygdala that is involved in the regulation of defensive responses to threat.

Different gut bacteria have been shown to promote colorectal cancer (CRC) progression. The authors identify formate as an oncometabolite derived from Fusobacterium nucleatum, which promotes CRC formation by increasing cancer stemness.

The authors study mechanisms underlying neuromodulatory control of transitions between brain and behavioral states. They identify a mechanism whereby modulation of Gq activity in basolateral amygdala parvalbumin interneurons mediates the transition to a fear-associated network and behavioral state.

Fungal infections are severely underestimated as a cause of mortality, and alternative drugs are urgently needed. Here, Schaefer et al. show that a synthetic polymer mimicking defensins shows different, but synergistic activity with known antifungals.

Dual RNA sequencing and a time course infection model of vaginal epithelial cells with four Candida pathogens reveal a homogenous protective mitochondria-associated type I interferon host response at early time points, followed by distinct species-specific pathogenicity patterns.

’Layer-by-layer (LbL) assembly is currently one of the most widely used techniques for the fabrication of multicomponent architectures with nanometer scale control but achieving control over the 3D structure, and thus the ability to predict and understand the device performance, is challenging. Here, the authors use neutron scattering to determine the average conformation of individual deuterated polyelectrolyte chains inside LbL assembled films.

Bacterial pathogens have evolved intricate mechanisms to evade the human immune system, including the production of immunomodulatory enzymes. Here, the authors establish the mechanisms of recognition and specific deglycosylation of IgG antibodies by the multi-modular enzymes EndoS and EndoS2

The lysosomal polyamine transporter ATP13A2 controls the cellular polyamine content, and impaired lysosomal polyamine export represents a lysosome-dependent cell death pathway that may be implicated in ATP13A2-associated neurodegeneration.

WHaloCaMP is a chemigenetic calcium indicator that can be combined with different rhodamine dyes for multiplexed or FLIM imaging in vivo, as demonstrated for calcium imaging in neuronal cultures, brain slices, Drosophila, zebrafish larvae and the mouse brain.

Climate change is expected to impact microbes degrading organic matter in northern peatlands. Here, using a warming experiment, the authors show that communities remain stable after three years of warming, likely due to metabolic versatility and an ability to obtain electron acceptors from organic matter cleavage.

CTLA-4 is critical for balancing protective immunity with self-tolerance. Here the authors identify homozygous DEF6 mutations in patients with severe autoimmunity, one of which received and responds to CTLA-4-Ig, and show that DEF6 is crucial for CTLA-4 cell surface trafficking and immune regulatory function.

Bio-hybrid LEDs (HLED) are an environmental friendly alternative to LEDs based on inorganic phosphors but achieving long term is challenging. Here, the authors present a long-living Bio-HLED based on a zero-thermal-quenching biophosphor design and investigate the photo-induced heat generation and dissipation processes.

Eberhard et al. show that SEMA3A regulates liver sinusoidal endothelial cell fenestrations by signaling through NRP1 and LIMK1, revealing a pathway that connects hyperlipidemia to the development of steatotic liver disease.