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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.

Resistance to BRAF inhibitors limits their clinical benefit in melanoma patients. Here, the authors show that the Aryl hydrocarbon Receptor (AhR) is a key mediator of resistant genes and use resveratrol, an AhR antagonist, to revert resistance in melanoma bearing mice.

Herpes simplex virus 1 (HSV-1) infection disrupts transcription termination by RNA Polymerase II. Here, Djakovic et al. identify the immediate-early protein ICP22 protein of HSV-1 to induce open chromatin downstream of genes upon read-through transcription involving the histone chaperone FACT.

In rodent models of type 2 diabetes, sustained remission of hyperglycemia can be induced by FGF1 action in the mediobasal hypothalamus. Here, the authors show that FGF1-injection is followed by marked changes in glial cell populations and that the sustained glycemic response is dependent on intact melanocortin signaling.

Tagging and tracking the blood plasma proteome as a discovery tool reveals widespread endogenous transport of proteins into the healthy brain and the pharmacologically modifiable mechanisms by which the brain endothelium regulates this process with age.

GROWdb defines US river microbiomes at the genome level.

Brown adipose tissue activation of thermogenesis is accompanied by a sequence of events commonly associated with apoptosis, however they evade cell death. Assali et al. show that NCLX prevents mitochondrial calcium overload and apoptosis. Deletion of NCLX, converts a thermogenic signal into a death pathway.

Molecular imaging can stratify patients according to presence or absence of a drug target, and can distinguish between drug responders and nonresponders. The authors of this Review discuss the integration of molecular imaging in drug development and how this technology can address key questions in the preclinical and clinical evaluation of new targeted drugs.

A paleogenome from an approximately 100,000-year-old polar bear shows massive prehistoric, and largely unidirectional, gene flow from polar bears into brown bears at a time of climate change-induced overlap in the ranges of the two species. This admixture event cannot be detected using genomic data from living polar bears.

The authors investigated the mechanisms underlying hippocampal sharp waves. They found that CA3 axo-axonic cells (AACs) stopped firing during sharp waves in vivo. They also identified GABAergic cells in the medial septum that are activated during sharp waves and project to CA3; these cells may inhibit AACs during sharp waves.

The authors discovered a far distant genomic region containing multiple clusters of regulatory elements that drive coordinated Hoxa expression across chromatin topologically associating domains in cranial neural crest, and are required for patterning of facial structures.

Semantic heterogeneity exists regarding terminology for active surveillance (AS) for prostate cancer. A panel of leading specialists in prostate cancer and AS involved in the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) consortium participated in a consensus-forming project to reach international consensus on definitions of terms related to this management option. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.

Synthetic receptors can be used to help understand biological systems, but rarely compete in terms of affinity or selectivity. Now, a glucose-binding compound has been prepared that, despite its symmetry and simplicity, can match all but the strongest glucose-binding proteins. The high binding affinity and outstanding selectivity of this receptor may translate into biomedical applications.

Rajderkar et al. provide a genome-wide compendium of transcriptional enhancers active in human craniofacial development, along with single-cell resources for studies of mammalian craniofacial morphogenesis.

A method of droplet manipulation is described that uses electrical signals to induce the liquid to dewet, rather than wet, a hydrophilic conductive surface.

Typhoid fever is caused by Salmonella enterica serovar Typhi (S. Typhi). This study examines ∼2,000 clinical isolates of S. Typhi to show highly structured/geographically restricted genomes except rapidly disseminating H58 subclade, and design a genotyping framework for tracking the disease.

For many applications, positron emission tomography tracers must be produced with high specific activity. Here the authors identify variables leading to increased specific activity when tracers are synthesized in microliter volumes, and show that specific activity can influence tracer biodistribution.

A positron emission tomography imaging tracer is developed to image mitochondrial function in vivo, and application of this tracer to a mouse model of lung cancer identifies distinct functional mitochondrial heterogeneity between tumour cells.

Next generation sequencing allows the identification of oncogenic driver genes in pancreatic cancer. Here, in an effort to identify additional causal genes, the authors develop a high throughput in vivoscreen and identify genes that whilst infrequently mutated in pancreatic cancer contribute to tumour formation.

Human development provides a roadmap for advancing pluripotent stem cell-based regenerative therapies. Here the authors mapped human skeletogenesis using RNA sequencing on 5 cell types from a single foetal stage as well as chondrocytes at 4 stages in vivo and 2 stages during in vitro differentiation.

Noninvasively monitoring immune function by positron emission tomography could affect the diagnosis and treatment evaluation of immunological disorders. Progress, however, has been hampered by the lack of probes with distinct biodistribution patterns. Radu et al. exploit the fact that many immune cells utilize a salvage pathway for nucleotide generation during DNA synthesis to develop [¹⁸F]FAC (1-(2′-deoxy-2′[¹⁸F]fluoroarabinofuranosyl) cytosine), a new probe with increased accumulation in proliferating T cells. Studies in mice show it has advantages over commonly used probes and may be clinically useful.

Cataloging microbial genomes from Earth’s environments expands the known phylogenetic diversity of bacteria and archaea.

This study shows that, despite malignant transformation, autoimmune checkpoints are still functional in B-cell leukaemia, with targeted activation of these checkpoints effectively killing patient-derived B-cell leukaemia in a transplant model; the results represent a novel strategy to overcome drug resistance in leukaemia patients.

According to instance theory, semantic knowledge emerges from episodic memories without a distinct semantic memory system. In this Perspective, Jamieson et al. propose instance theory as a general theory of cognition across memory, language and associative learning, and outline future work to extend this approach.