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Population-level distributions of SARS-CoV-2 viral load can correlate with epidemic trends. Here, the authors use viral loads to nowcast epidemic growth rates over two-week periods and investigate how the relationship varies by peak viral load, viral dynamics, and sampling approaches.

Efforts to apply targeted protein degradation for antibiotic development are limited by our understanding of prokaryotic protein degradation. Here, the authors establish a chemical-genetic platform and predictive model to determine the degradation potential of essential mycobacterial proteins.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Qiu et al. provide insight into the metabolic adaptations that enable breast cancer cells to proliferate in the face of glutaminolysis blockade.

The variability in patient response to radiation treatment is difficult to predict. Here, using more than 500 cell lines the authors measure response to radiation exposure and a large panel of compounds, and show that response can be predicted by genetic alterations of the cells.

Individual boutons on mouse corticostriatal axons exhibit differential selectivity for rewarded and unrewarded movements during motor learning, and the proportion of reward-responsive boutons increases.

Split-And-pool Metagenomic Plot-sampling sequencing (SAMPL-seq) can be applied to complex microbial communities to reveal spatial co-localization of microbes at the micron scale.

Cross-species transcriptomics on vulnerable neuronal populations unravels the transcription factor CREB3 and its regulatory network as resilience markers of ALS. Genetics and epidemiology further identify the protective rare variant CREB3R119G.

A study using iPhones and Apple Watches to track and analyze cognitive health over 18 months in more than 23,000 US adults demonstrates the feasibility of remote cognitive health monitoring and uncovers potential methods for early detection of cognitive decline.

Using a transposon-based approach to create a set of large genomic rearrangements, Dauban et al. demonstrate that interactions of lamina-associated domains with the nuclear lamina involve multiple contacts of varying strength.

Amplification-free single-cell whole-genome sequencing shows that genomic, evolutionary and biophysical factors collectively drive cell-to-cell variation in mitochondrial DNA copy number.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Embryonal tumour with multilayered rosettes (ETMR) is a rare and aggressive paediatric brain tumour. Here, the authors analyse intratumour heterogeneity and the tumour microenvironment in ETMR using single-cell and spatial transcriptomics, in vitro cultures, and a 3D forebrain organoid model, finding important aspects – such as the communication with pericytes – for ETMR development and response to therapy.

Amyloid precursor protein has been identified as an inhibitor of HIV-1 replication. Here, Gu et al further characterise the details and impact of this interaction on HIV replication in myeloid cells that contribute to neurological disease.

The existence of a common substrate for emotional valence and anxiety remained elusive. Here we show that excitatory neurons of the anterior insular cortex (aIC), including neurons projecting to the basolateral amygdala (aIC-BLA) encode both states.

Treatment with the oncolytic herpes virus CAN-3110 is associated with improved survival responses in patients with recurrent glioblastoma, particularly in individuals who are seropositive for HSV1.

A ligand-restricted strategy is developed to realize the synthesis of dual-atom catalysts with high pairing ratio and tunable atomic distances.

Resting-state functional connectivity has helped reveal the brain's network organization, yet its relevance to cognitive task activations has been unclear. The authors found that estimating activity flow over resting-state networks allows prediction of held-out activations, suggesting activity flow as a linking mechanism between resting-state networks and cognitive task activations.

Ex vivo normothermic machine perfusion has been proposed to protect donor kidneys. Here, the authors show that red blood cell-based human kidney perfusion and associated hemolysis contribute to iron accumulation, ferroptosis, and kidney injury.

IFNγ signaling is important in the pathogenesis and immune response, emphasizing the need for investigation of its role. Here, the authors show that IFNγ plays a key role in shaping immune microenvironment in AML and developing resistance, providing insights for potential therapeutic strategies.

Venniro et al. report that drug-addicted rats reliably choose contact with another rat over drugs, even when group-housed between tests. They also do not show the increase in drug craving that normally occurs during forced abstinence.

Subcellular in situ spatial transcriptomics offers the promise to address biological problems that were previously inaccessible but requires accurate cell segmentation to uncover insights. Here, authors present BIDCell, a biologically informed, deep learning-based cell segmentation framework.

Co-dependency mapping assays have revealed genetic dependencies in cancer and could shed light on chromatin crosstalk mechanisms. Here, the authors establish a pipeline to integrate co-dependency mapping screens with molecular information in pan-cancer cell lines in order to reveal chromatin complexes and potential drug targets.

ZO-1, a cell junction protein, is essential for angiogenesis. Here the authors identify in endothelial cells unexpected associations of ZO-1 with stress granule proteins, such as YB-1, that are crucial for cytoprotection, implicating the ZO-1-YB-1 interaction in angiogenesis.

A multimodal analysis of patients with 22 different immune-mediated monogenic diseases versus matched healthy controls leads to the development of the immune health metric, which could be implemented broadly to predict responses to aging, vaccination and other immune perturbations.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer. Here, the authors develop a NLPHL specific model to identify 34 distinct cell states across 14 cell types that co-occur within 3 lymphocyte predominant ecotypes (LPEs) for 171 cases.

The pairing of genes is essential for robust expression of segmentation clock genes during development in zebrafish embryos.

Using a single-nucleus multi-omics approach, a study jointly profiles the reorganization of the epigenome and the three-dimensional chromatin conformation during the development of the human hippocampus and prefrontal cortex.

Yang et al. show that plasma membrane curvature promotes the site-specific formation of contacts with the endoplasmic reticulum through junctophilin-2 tethers in cardiomyocytes.

Correlation network inference is typically based on the significance of the correlation coefficients, but this procedure is not guaranteed to capture biological mechanisms. Here, the authors develop a cutoff selection algorithm that maximizes the overlap between inferred networks and prior knowledge.

This study develops a distributive justice framework for allocating subnational carbon budgets. Applying it to the EU, it reveals substantial within-country differences in production- and consumption-based allocations, with implications for designing equitable net-zero pathways.

Understanding of the immune microenvironment in pediatric acute T cell lymphoblastic leukemia is limited. By analyzing single-cell transcriptome, surface protein expression and immune repertoire data, the authors here identify non-malignant CD4^-CD8^- TCRαβ T cells that are present in a subset of patients with Rap1 signaling in leukemia cells and are associated with adverse clinical outcome in patients with low minimal residual disease.

The authors test artificial neural networks with stimuli whose activations are matched to those of a natural stimulus. These ‘model metamers’ are often unrecognizable to humans, demonstrating a discrepancy between human and model sensory systems.

Dengue is a major public health concern in the Americas, and the Caribbean can be a source for reintroduction and spread. Here, the authors use travel surveillance data and genomic epidemiology to reconstruct Dengue epidemic dynamics in the Caribbean from 2009-2022.

In this study, Yang et al. compile a global dataset to uncover the degree to which plants coordinate root and seed traits. They report a global positive correlation between root diameter and seed size, driven by dual roles of arbuscular mycorrhiza in phosphorus uptake and pathogen defence.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

Transcription factors of the AP-1 family can play diverse roles despite recognizing the same DNA sequence. Here the authors investigate the DNA binding activities of AP-1 members in mouse macrophages and apply a machine learning approach to identify motifs predicted to drive factor-specific binding profiles.

The authors performed genome-wide microRNA (miRNA) expression profiling in post-mortem brains from individuals with autism spectrum disorder (ASD) and controls, and identified miRNAs and co-regulated modules perturbed in ASD.

Using metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma mouse models, an ATP citrate lyase inhibitor reduces tumour burden and enhances efficacy of current standards of care.

Phaeocystales are ecologically significant nanoplankton whose evolutionary history and functional diversity remain incompletely characterized. Here, the authors integrate genomic and transcriptomic data to reveal their lineage diversification, metabolic plasticity, and adaptation to polar and temperate regimes.

Mammalian recombination activating genes RAG1 and RAG2 are essential for the production and diversification of antibodies and T-cell receptors via V(D)J recombination in lymphocytes but are absent in simpler eukaryotes such as the yeast Saccharomyces cerevisiae. Here the authors integrate mouse RAG1/2 in S. cerevisiae and demonstrate the ability to create combinatorial diversity starting from a single genetic locus in vivo.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

In patient with glioblastoma, a major cause of resistance to chemotherapy and radiotherapy is the high degree to intratumoral heterogeneity and cell plasticity. Here, the authors demonstrate that chemoradiation induces the reprograming of glioblastoma cells into an invasive and vessel co-opting state, termed VC-Resist, capable of promoting resistance to therapy.

Here, the authors profile the gut microbiota and metabolites of Indian agrarians to understand the impact of fermented foods consumption, and identify seasonal variation in the gut microbiota structure and predict the drivers of this instability.

APOBEC mutational signatures are commonly found in multiple cancer types. Here, the authors utilize multi-omics analyses to reveal that the cooccurrence of APOBEC associated mutagenesis and tobacco-smoking-related mutations affects lung tumor evolution and age at onset of lung cancer from smokers.

Schwannomas are regularly treated with radiotherapy, but the molecular effects on these tumours and their microenvironment remain unclear. Here, the authors show that radiotherapy can induce epigenetic reprogramming and immune infiltration in schwannomas, and develop the snARC-seq approach to analyse the epigenomic evolution at the single-cell level.

Aging is a risk factor for Parkinson’s disease; however, how DNA damage accumulation, a hallmark of aging, contributes to its pathophysiology remains incompletely understood. Here, the authors identify a blood-based DNA damage signature that is associated with disease progression in patients with Parkinson’s disease.