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Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

The promise of engineered T cells for treating cancer has been mitigated by their poor persistence when transferred to patients. Pule et al. now show that dual-specific T cells that recognize an Epstein-Barr virus (EBV) antigen and a tumor antigen survive longer in individuals with neuroblastoma. Engineering virus-specific T cells to recognize tumor antigens may improve the efficacy of this immunotherapy in latently infected cancer patients (pages 1148–1150).

The genome sequence of the nematode wormCaenorhabditis elegansis now "essentially complete", and this achievement is marked by the publication of a series of papers. At 97 mega base-pairs, corresponding to 19,099 predicted genes, this is the biggest genome yet sequenced, and the first genome sequence for a multicellular organism.

Whole-genome sequencing analyses of African populations provide insights into continental migration, gene flow and the response to human disease, highlighting the importance of including diverse populations in genomic analyses to understand human ancestry and improve health.

A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.

A CalpL–CalpT–CalpS cascade mediated by cyclic oligoadenylates is identified as a mechanism to detect viral RNA and activate subsequent antivirus responses in microorganisms.

Comprehensive mutation libraries are an invaluable resource for screens in yeast, but anecdotal cases link phenotypes to the neighbor of a mutated gene rather than the mutant itself. The authors show that the neighboring gene effect is widespread and present software that uses protein-protein interaction networks to predict it.

T-helper-1-cell cytokines tumour necrosis factor and interferon-γ are shown to drive tumour cells into senescence in a mouse model of β-cell carcinoma and human carcinoma cells.

Amanda Spurdle, Ian Tomlinson, Douglas Easton and colleagues conduct a GWAS meta-analysis and identify five new risk loci for endometrial cancer. Functional studies show that one risk-associated SNP is located in an active chromatin region that interacts with the KLF5 promoter.

Tracking of nanoparticle dynamics in solution often require labelling. Here, the authors use a high-finesse microcavity and simultaneously measure dispersive frequency shifts of three transverse modes, demonstrating 3D tracking of unlabelled single nanospheres, and quantitatively determine their physical properties.

Myosins have roles in many biological processes that go beyond muscle contraction and vesicle transport, including furrowing during cytokinesis, signal transduction and RNA polymerase I–dependent transcription. Studying these various complex processes will require the use of isoform-specific small molecules that alter motor activity. The marine natural product pentabromopseudilin is now shown to act as an allosteric effector of myosin function and potent inhibitor of vertebrate myosin-5a–dependent motor activity.

Multiple myeloma is a cancer of the plasma cells, and the complete aetiology of the disease is still unclear. Here the authors perform an additional GWAS analysis followed by a meta-analysis with existing GWAS and replication genotyping and identify 6 novel risk loci and utilise gene expression, epigenetic profiling and in situ Hi-C data to further our understanding of MM susceptibility.

Hippocampal neurons track events as abstract units of episodic experience. These event representations can be transferred between different experiences and are separately manipulable from hippocampal representations of continuous changes in space.

Grieger, Takele, Vesco, et al. perform a systematic review and meta-analysis of gestational weight gain interventions. Findings indicate lifestyle interventions that reduce excessive gestational weight gain provide greater benefits for women with a normal BMI and higher HDL cholesterol levels at the initiation of interventions.

Montserrat Garcia-Closas and colleagues report a meta-analysis of three genome-wide association studies for estrogen receptor (ER)-negative breast cancer, including 4,193 ER-negative breast cancer cases and 35,194 controls, with replication using the iCOGS custom genotyping array in 40 studies, including 6,514 cases and 41,455 controls. They identify four loci associated with ER-negative but not ER-positive breast cancer.

Carl Anderson, Jeffrey Barrett and colleagues use whole-genome sequencing and imputation to explore the genetic architecture of inflammatory bowel disease. They identify a low-frequency missense variant in ADCY7 that doubles risk of ulcerative colitis and detect a burden of very rare, damaging missense variants in known Crohn's disease risk genes.

Chiea Chuen Khor, Tin Aung, Francesca Pasutto, Janey Wiggs and colleagues report a global genome-wide association study of exfoliation syndrome and a fine-mapping analysis of a previously identified disease-associated locus, LOXL1. They identify a rare protective variant in LOXL1 exclusive to the Japanese population and five new common variant susceptibility loci.

The African Genome Variation Project contains the whole-genome sequences of 320 individuals and dense genotypes on 1,481 individuals from sub-Saharan Africa; it enables the design and interpretation of genomic studies, with implications for finding disease loci and clues to human origins.

GABA_B receptors are the most abundant inhibitory G protein–coupled receptors in the mammalian brain. Using high-resolution proteomics, the authors show that native GABA_B receptors are macromolecular complexes with previously unknown complexity in subunit composition. This molecular diversity in structure and assembly encodes the diversity of GABA_B physiology in the CNS.

Here 106 genomic loci associated with age at menarche, a marker of puberty timing in females, are identified; these loci show enrichment for genes involved in nuclear hormone receptor function, body mass index, and rare disorders of puberty, and for genes located in imprinted regions, with parent-of-origin specific effects at several loci.

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.

Richard Houlston and colleagues identify four new susceptibility loci for colorectal cancer through a meta-analysis of genome-wide association data, followed by replication testing in a large collection of independent samples. The study brings to ten the number of confirmed loci harboring low-penetrance risk alleles for this common malignancy.

The Immunological Genome Project aims to build a comprehensive database of gene-expression and gene-regulatory networks in the mouse immune system. Here Turley and colleagues analyze the transcriptomes of lymph-node stromal cells under steady-state and inflammatory conditions.

Neurons that sense touch, sound and acceleration respond rapidly to specific mechanical signals. But what are the proteins that transduce these signals? Current studies are directed towards characterizing channel proteins as candidate transduction molecules and determining how they are mechanically gated.

Rosalind Eeles, Christopher Haiman and colleagues report genome-wide association and meta-analyses of prostate cancer in populations of European, African, Japanese and Latino ancestry. They identify 23 new susceptibility loci, including one associated with early-onset prostate cancer.

Infiltration of various immune cell types into the fat tissue and liver has been implicated in obesity-induced insulin resistance. Jerry Olefsky and his colleagues now show that neutrophils are one of the earliest immune cells to arrive in these tissues, that they release the protease neutrophil elastase and that this enzyme degrades IRS-1, a key member of the insulin signaling pathway. These results show that neutrophils contribute to insulin resistance and how they may do so.