Search

Neural mechanism underlying behavioural flexibility is not fully understood. Here authors study decision-making of macaques in a reversal task. They identify two complementary cognitive processes. Distinct neural patterns link these processes to the dorsomedial prefrontal cortex, thalamus, and hippocampus.

A combination of biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.

How landscapes are arranged affects soil pathogenic fungi worldwide. The authors reveal the global pattern and pronounced scale-dependency of landscape complexity and land-cover quantity on soil pathogenic fungal diversity.

Using chemical photoswitchable reagents to exert purely wavelength-dependent control over biological systems in deep tissue and in vivo requires a concentration-independent design paradigm. Here, such photoswitchable ligands are realized by ensuring that E/Z isomers have opposing efficacies yet similarly high affinity, allowing them to probe transient receptor potential C4 and C5 channel functions up to the tissue level.

An allosteric site on the E3 ligase adapter cereblon can be targeted to modulate the efficacy of cereblon in targeted protein degradation applications.

Quantum error correction codes protect quantum information, but running algorithms also requires the ability to perform gates on logical qubits. A lattice surgery scheme for fault-tolerant gates has now been demonstrated in a quantum repetition code.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

The distinct architecture of the Escherichia coli membrane transporter LetA mediates lipid trafficking across the bacterial envelope in partnership with the tunnel-like complex LetB.

In this study, authors employ fragment-based lead discovery to identify WRN inhibitors. The fragment hits reveal an additional allosteric pocket and uncover a previously uncharacterized structural conformation of the WRN helicase domain with unique orientations of the ATPase domains

Natural product–inspired compounds are primed to interact with and manipulate biological processes, but obtaining these complex molecules poses synthetic challenges. The development of a 12-step, 1-pot cascade reaction leads to the 'centrocountins', tetrahydroindoloquinolizines that modulate mitosis by targeting the centrosome-associated proteins nucleophosmin and Crm1.

Methane emission occurs in natural wetlands on a large scale, but the corresponding trace element emissions have not been studied. Here, the authors study selenium and arsenic emission in a pristine peatland and show that this causes large amounts of those trace elements to enter the biogeochemical cycle.

Multi-ancestry genome-wide and transcriptome-wide association studies of aortic stenosis identify more than 200 independent risk loci and provide insights into its genetic architecture.

Here the authors show that endogenous or therapeutically delivered GDF-15 activates brainstem neurons that trigger splenic β-adrenergic signaling. This, in turn, suppresses autoreactive T cells and reduces neuroinflammation, identifying a possible target for multiple sclerosis treatment.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

In this work, fragments identified by 19F-NMR are optimized into submicromolar binders of the MITF transcription factor. These results support direct targeting of bHLH-LZ DNA binding domains and provide a foundation for the development of new melanoma therapies.

Global mean surface warming has been slow over the past 15 years. An analysis of climate simulations suggests that the low warming rate can be explained by an unusual phase of El Niño/Southern Oscillation and solar and aerosol variability.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

Chure et al. analyse experimental data to show that E. coli bacteria maintain stable protein density ratios between cytoplasm and membranes. In addition, they develop a biophysical model that predicts surface-to-volume ratio from ribosomal content and protein partitioning across cell compartments.

North Atlantic waters have been aging over the past three decades, indicating a slowdown in ocean ventilation. By combining observations with models, this slowdown is likely driven by climate change.

Cavity-mediated interactions lead to collective effects and ordering in ultracold atomic systems. Here, the authors demonstrate the interplay of different ordered states of ultracold Fermi gases in a cavity, resulting from an intriguing coexistence of photon coupling with both atoms and atom-pairs.

GaitDynamics is a generative foundation model for accurately and efficiently estimating the motion and forces of human gaits from kinematic data, which will have impacts in injury prevention, therapies and performance coaching.

The success of allogeneic hematopoietic stem cell transplantation for the treatment of haematological cancers is limited by the morbidity and mortality associated with graft-versus-host disease (GVHD). Here the authors show that the microbial metabolite desaminotyrosine contributes to graft-versus-leukemia responses while protecting against GVHD and promoting mTORC1 and STING-dependent intestinal regeneration.

Wearable data from 7,013 participants in the All of Us Research Program show that park accessibility across 53 US cities is positively associated with daily step counts, providing a mechanism for how urban green space can improve health.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The authors present the results of a phase I/II clinical trial using autologous CD133+ bone marrow stem cell therapy to restore fertility in patients with Asherman Syndrome. The intervention was safe and showed promising results for the restoration of menstruation and reproductive function.

The impact of tumour heterogeneity on metastatic potential in prostate cancer remains poorly understood. Here, the analysis of single nuclei RNA sequencing and whole-genome sequencing from samples from five patients suggests an interplay between clonal evolution and cellular plasticity driving metastatic seeding.

This research quantifies hospital admissions in Shanghai for mental and behavioral disorders linked to humid heat, projecting a 68.2% increase by the 2090s under high greenhouse gas emissions and emphasizing the importance of mitigation strategies to reduce future morbidity burdens.

Efficient lead optimization in drug discovery requires improving potency, synthetic accessibility, and physicochemical properties. Here, the authors utilize machine learning to screen large chemical spaces, demonstrating automated selection of optimized molecules to improve cycle times.

How the brain adapts its representations to prioritize task-relevant information remains unclear. Here, the authors show that both monkey brains and deep learning models stretch neural representations along goal-relevant dimensions, with spike timing playing a key role.

Gassler et al. implant a free-living bacterium into fungal cells to study early steps in the establishment of an endosymbiosis. They observe vertical transmission of the bacteria despite initial host stress, with fungal defense responses attenuating over time, indicating a shift from antagonism toward commensalism.

The complement system depends on C3 cleavage that is critical to all three activation pathways, but currently structural data is lacking. Here authors present cryo-EM structures revealing a charge switch-over mechanism.

Human transplantation with allogeneic donor organs results in non-matching of MHC and differential presentation of T cell antigens. Here the authors show that in a lung transplanted SARS-CoV-2 infected patient T cell responses generated from the host may not be able to recognise infected cells within the graft and this may contribute to virus persistence.

Variants in NOS1AP can cause monogenic nephrotic syndrome. Here, the authors show that disrupting the intergenic NOS1AP splice isoform that is more prevalent in podocytes leads to monogenic kidney disease responsive to RAAS inhibition.

Combining fossil records and vegetation modelling, this study shows that global warming during the Paleocene-Eocene Thermal Maximum 56 million years ago exceeded the adaptation capacity of vegetation, disrupting the global climate regulation system.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The microbial metabolite trimethylamine (TMA), the precursor of TMAO, which is associated with adverse cardiometabolic outcomes, is shown to have beneficial metabolic and anti-inflammatory effects in the host in the context of obesity.

Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) are emerging candidates for organic 2D crystal materials, but the precise implantation of chirality has yet to be demonstrated. Here, the authors report a side chain-induced chirality amplification strategy to achieve tunable chiral expression in 2D c-MOFs.

Through the programmable self-assembly of lipid-inspired radially symmetric DNA, porous molecular membranes and cell-sized compartments are formed with applications in bottom-up biology and soft robotics.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Georgiadis and colleagues conduct micron-resolution fibre mapping on multiple histological tissue sections. Their light-scattering technique works across different sample preparations and tissue types, including formalin-fixed paraffin-embedded brain sections.

This genomic study of magnetic resonance imaging-based brain age in 56,348 people identifies 59 genetic loci, links brain aging to mental and physical health, and suggests high blood pressure and type 2 diabetes as causal factors of brain aging.

The role of ecological factors in modulating the spread of antibiotic-resistance bacteria in the gut remains unclear. Here, the authors use anaerobic microcosms to study the population growth of four clinical E. coli strains in the gut microbiome.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.