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A GRK-isoform immunoassay was used to quantify GPCR phosphorylation and evaluate the potency of GRK inhibitors in a controlled cellular system.

In adults, oscillatory brain activity during sleep is related to memory consolidation. Here, the authors measure brain activity from infants who are exposed to novel word meanings, and show that infant sleep results in the retention and reorganization of recently encoded memories.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

A comprehensive characterisation of Omicron-BA.1 and VOC Delta in numerous in vitro and in vivo models uncovers the factors that led to its global dominance.

Pathologic protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells via extracellular vesicles or direct cell-to-cell contact. Here, Liu et al. show that viral glycoproteins can contribute to intercellular proteopathic seed transmission via both routes.

Identification of cancer genes altered by non-genetic mechanisms in B-cell lymphoma is challenging. Here, the authors report the development of transposon tools to perform genome-wide recessive screens in vivo and validate identified putative tumor suppressor genes using a CRISPR/Cas9 validation platform.

How extracellular calcium can trigger Nlrp3 inflammasome activation has been somewhat controversial and unclear. Here the authors show calciprotein particles are taken up by myeloid cells via calcium-sensing receptor-dependent macropinocytosis in response to high levels of extracellular Ca2+ and this pathway might be critical to inflammatory conditions.

Döring, van der Vorst, Yan, Neideck et al. present a non-canonical chemokine pathway involving CCL17 signaling through CCR8, which induces CCL3 expression independent of CCR4 and suppresses the functions of atheroprotective T_reg cells.

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Human TNF is required for respiratory-burst-dependent immunity to Mycobacterium tuberculosis in macrophages but seems to be largely redundant physiologically.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.

Ruth Loos and colleagues report results of a large genome-wide association study for body mass index. They identify 18 new loci associated with this trait, some of which map near key hypothalamic regulators of energy balance.

Grammar learning requires memory for temporally organised, rule-based patterns in speech. Here, the authors use event-related potentials to show that 6 to 8 month-old infants can form memory of dependencies between nonadjacent elements in sentences of an unknown language, regardless of whether they nap or stay awake after encoding.

The selective hydrogenation of trace acetylene to ethylene is a well-established process for purifying fossil-derived ethylene streams. Here, the authors present a self-repairing Pd-C laterally condensed catalyst that improves selectivity, prevents sub-surface hydride formation, and achieves high ethylene productivity, effectively bridging the gap between powder catalysts and single-crystal model catalysts.

Springtails are omnipresent soil arthropods, vital for ecosystems. In the first global assessment of springtails, this study shows a 20-fold biomass difference between the tundra and the tropics, with distinct temperature-related patterns for diversity and metabolism that suggest climate change may restructure the functioning of soil biodiversity.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

In infants, superiority of semantic over episodic memory formation has been postulated. Here, authors show that both types of memory coexist in one-year-olds, with consolidation during sleep affecting whether an experienced event is recognized as a detailed episode or as general semantic knowledge.

A transcriptome-wide association study identifies associations of genetically predicted gene expression with breast cancer risk. This analysis finds 48 candidate genes implicated in breast cancer susceptibility, including 14 at novel loci.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

Molecular networking connects molecules based on their fragment ion mass spectra (MS²), but may leave adduct species from the same molecular family separate. To address this issue, the authors develop a networking approach that fuses MS¹- and MS²-based networks and integrate it into the GNPS environment.

Bone marrow-derived cells can rapidly enter the systemic circulation, but how this is achieved is unclear. Grüneboom et al. identify tiny capillaries, termed trans-cortical vessels (TCVs), that connect the bone marrow cavity to the systemic vasculature, and show that the majority of blood in long bones passes through TCVs.

Due to the pulsed nature of X-ray free electron laser (XFEL) instruments the majority of protein crystals, which are injected using continuous jet injection techniques are wasted. Here, the authors present a microfluidic device to deliver aqueous protein crystal laden droplets segmented with an immiscible oil and demonstrate that with this device an approx. 60% reduction in sample waste was achieved for data collection of 3-deoxy-D-manno-octulosonate 8-phosphate synthase crystals at the EuXFEL.

Over 170 susceptibility loci have been identified by genome-wide association studies in breast cancer. Here, the authors interrogated the role of risk-associated variants from non-breast tissue, and using expression quantitative trait loci, identify potential target genes of known breast cancer susceptibility variants, as well as 11 regions not previously known to be associated with breast cancer risk.

The use of chiral molecules for optoelectronics remains underexplored. Here, the authors perform Mueller matrix spectroscopy on thin films of enantiopure prolinol functionalized squaraines and report an extraordinarily high circular dichroism, thus providing a benchmark material for chiroptical applications.

The melanoma-driver mutations in NRAS and BRAF are mutually exclusive but the contribution of RAF signalling downstream of NRAS remains to be clarified. Here, using mouse models, the authors show specific roles of each member of the RAF family at different stages of melanomagenesis.

A large-scale meta-analysis across eight biobank datasets identifies common genetic variants associated with mosaic loss of the X chromosome in female participants.

Lifespan can be affected by both physiological ageing and specific sets of pathologies associated with old age. Here the authors report a resource of large-scale cross-sectional phenotyping of aging male mice at different time points to analyse a large set of phenotypes and molecular markers, including during genetic and diet interventions affecting lifespan.

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade.

Here, the authors perform a meta-analysis in 26,699 people with seizures and 492,324 controls to identify 25 genome-wide significant copy-number variants. The discovered loci point to known disease genes and associations with clinical annotations.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

Geoffrey Woods, Jan Senderek and colleagues show that biallelic mutations in PRDM12 cause congenital insensitivity to pain. They further show that PRDM12 is expressed in nociceptors and their progenitors and participates in sensory neuron development in Xenopus.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

Roger Milne and colleagues conduct a genome-wide association study for estrogen receptor (ER)-negative breast cancer combined with BRCA1 mutation carriers in a large cohort. They identify ten new risk variants and find high genetic correlation between breast cancer risk for BRCA1 mutation carriers and risk of ER-negative breast cancer in the general population.

Association analysis identifies 65 new breast cancer risk loci, predicts target genes for known risk loci and demonstrates a strong overlap with somatic driver genes in breast tumours.

The ONCOBIOME network has generated new tools to measure dysbiosis and completed numerous trials aimed at modifying the microbiota to enhance cancer treatment; this Review summarizes the key advances and the progress toward translating them into clinical practice.