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The authors report a memristor-based system that analyzes raw analog signals from a genomic sequencer directly in memory. By bypassing slow data conversion, the system achieves substantial improvements in speed and efficiency, enabling real-time, on-site genomic analysis.

Osteocytes are the master regulatory cells within the skeleton. Here, the authors map the transcriptome of osteocytes from diverse skeletal sites, ages and between sexes and identify an osteocyte transcriptome signature associated with rare skeletal disorders and common complex skeletal diseases.

Blood–brain barrier dysfunction occurs in ageing and in neurodegenerative diseases. Here, the authors use scRNA-seq to identify transcriptomic changes in endothelial cell subtypes in the aged mouse brain, some of which may generalize to human and can be reversed by treatment with a GLP-1R agonist.

Thermostable antibodies called SPEARs enable rapid immunostaining with improved tissue penetration.

Therapy resistant dormant myeloma cells contribute to disease relapse. Here, the authors use intravital microscopy to track the location of these cells and demonstrate that they hone to the endosteal niche within the bone.

Cox and colleagues develop PXS-5505, a first-in-class selective pan-lysyl oxidase inhibitor and show that it reduces chemotherapy-induced desmoplasia and stiffness, thereby improving chemotherapy response and survival in pancreatic cancer models.

Multi-omics analyses powerfully combine gene expression and translation, however no available controls can be used across these techniques. Here the authors develop pREF, a universal control construct designed for use in DNA, RNA and protein analyses.

Osteoarthritis is a chronic, heritable disease with no available treatment. Here, the authors show that a validated, rapid-throughput joint phenotyping pipeline detects osteoarthritis in the mouse knee following surgical provocation, in aging and after single gene deletion or point mutation.

Phenotypic screens in organoids and primary cells are scaled up using perturbation pooling.

Studying chemosensory processing desires precise chemical cue presentation, behavioral response monitoring, and large-scale neuronal activity recording. Here, the authors report a fluidics-based toolkit for studying chemosensation in larval zebrafish, and used it to reveal the brainwide neural representations of cadaverine sensing and its binasal input-dependent behavioral avoidance.

Pugh and colleagues use single-cell RNA sequencing, CRISPR screens and functional assays to define a gradient of developmental and wound-response cell states in glioblastoma stem cells, revealing insights into glioblastoma origins and potential therapeutic targets.

Longitudinal population deep sequencing of Streptococcus pneumoniae sampled from infants and their mothers improves our understanding of the dynamics of colonization, transmission, inter-strain competition and the impact of antibiotic treatment.

Liu et al. reveal that human TOPORS is a SUMO1-selective SUMO-targeted ubiquitin ligase (STUbL). The parallel action of TOPORS and the STUbL RNF4 defines a general mechanistic principle governing pathways driven by direct SUMO–ubiquitin crosstalk.

Genome-wide association analyses identify 301 new loci influencing bone mineral density and 13 loci influencing fracture risk. Integrative analyses of epigenomic data and mouse knockout phenotypes provide additional insights into osteoporosis pathophysiology.

Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.

David Evans, Brent Richards and colleagues carried out a genome-wide association study in 142,487 individuals from the UK Biobank and identified 153 new loci associated with heel bone mineral density. They also conducted in vivo studies that implicated GPC6 and several other genes in osteoporosis.

The inherent inaccuracy of viral RNA polymerases promotes viral evolution, but the importance of viral genetic diversity during infection is unclear. Here, Cheung et al.show that influenza strains with enhanced polymerase fidelity and low mutational frequency display reduced pathogenicity in mice.

A consortium reports the tripling of the number of genetic markers in Phase II of the International HapMap Project. This map of human genetic variation will continue to revolutionize discovery of susceptibility loci in common genetic diseases, and study of genes under selection in humans.

Memory B cells need to be reactivated to produce high affinity antibody responses on subsequent antigen encounters. Here the authors show that memory B cells localise to lymph node subcapsular proliferative foci (SPF), which have distinct properties from the germinal centre, for rapid expansion and the induction of B memory responses.

Plasticity and clonal population structure in bacterial genomes can hinder traditional SNP-based genetic association studies. Here, Corander and colleagues present a method to identify variable-length sequence elements enriched in a phenotype of interest, and demonstrate its use in human pathogens.

This Review summarizes progress in our understanding of the mechanisms by which different bone cell types support tumour cell dormancy and reactivation, and highlights new therapeutic approaches to control dormancy and bone metastasis by targeting the bone microenvironment.

The volume of literature attesting to the clinical benefits of exercise training in patients with stable chronic systolic heart failure is substantial. Exercise training can improve symptoms and exercise capacity, as well as reducing morbidity, mortality, and rates of emergency hospitalization associated with this condition. In this article, Dr. Coats reviews the modes and intensity of exercise training, selection of patients, duration of training effects, and discusses other clinical guidance for using this treatment option in patients with stable chronic systolic heart failure.

Tom Karlsen and colleagues report an association study for primary sclerosing cholangitis (PSC), a severe liver disease, using the Immunochip array. They identify nine loci newly associated with PSC and examine pleiotropy with other autoimmune disorders.

Li, Chen, Vong, Zhao et al. show that glucagon-like peptide-1 receptor agonist reverses transcriptomic aging signatures in mouse glial and neurovascular cells. This study suggests that glucagon-like peptide-1 receptor agonists may be considered as a therapeutic option for patients at risk of age-related neurodegeneration.

This Perspective proposes operational definitions to define the hallmarks of cancer cell dormancy and, based on the latest evidence pertaining to the role of the microenvironment in regulating dormancy, presents key stages in the life cycle of a dormant cancer cell that could be targeted.

The procedure details the preparation of mixed bone marrow radiation chimeras for the labeling of osteoclasts and osteomorphs, and the imaging of the mouse tibia for the longitudinal study of endosteal and bone marrow niches.

A systematic review of evidence, across the key pillars of prevention, diagnosis, treatment and prognosis, outlines milestones that need to be met to enable the broad clinical implementation of precision medicine in diabetes care.

New speckle diffraction tomography demonstrates high-resolution refractive index mapping of thick scattering tissue, red blood cell imaging behind turbid layers, and nanoscale features in the cornea using spatiotemporal gating and inverse-scattering model.

Sabeti et al. build on their This paper builds on previous work of detecting selection on human genes, using the many more markers available in the Phase II HapMap project. Three examples of apparent population-specific selection based on geographic area are described, and how these may relate to human biology is discussed.

The majority of individuals with cancer, notably those with breast or prostate cancer, will develop bone metastases. In this Primer, Coleman and colleagues discuss the epidemiology, pathophysiology and diagnosis of metastatic bone disease and highlight the specific treatment strategies to prevent disease progression and to manage skeletal morbidities.

Ahmad, Lim, Morieri, Tam et al perform a systematic review and meta-analysis of biomarkers, genetic markers, and risk scores for prediction of cardiovascular outcomes in Type 2 diabetes. A few prognostic markers are identified that provide incremental predictive utility beyond established cardiovascular risk factors.

Virginie Rozot and Elisa Nemes et al. report comprehensive profiling of immune responses from participants in a recent clinical trial of the H4:IC31 and BCG vaccines against Mycobacterium tuberculosis infection. Using a novel analysis platform, they uncover complex vaccine-induced modulation of different immune cell subsets.