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Fgf17 in young CSF boosts oligodendrocyte progenitor cell proliferation and differentiation in the aged hippocampus, improving memory function.

Specific cancer cell vulnerabilities can provide an opportunity for the development of novel cancer therapeutics. In this study the authors demonstrate that targeting ADAR1 represents a potential therapeutic vulnerability in cancers with activated interferon response signatures.

Components of the hedgehog signaling pathways play key roles during embryonic development and in several human diseases.

The solution structure of the complex of the SRY HMG-domain with DNA provides clues to the mechanism of sequence recognition in the minor groove.

Analysis of genomic and clinical features of acute erythroid leukemia in comparison to other myeloid disorders supports its distinct classification, defines subgroups and suggests therapeutic vulnerabilities.

A functional genomics approach in patient derived cell lines of Favorable Histology Wilms Tumor identifies suppression of TRIP13 through the nuclear export inhibitor, KPT-330, leads to decreased viability and synergy with doxorubicin.

Structural variants (SVs) contribute to the genetic architecture of many brain-related disorders. Here, the authors integrate SV calls from genome sequencing (n = 755) with RNA-seq data (n = 629) from post-mortem dorsal lateral prefrontal cortex to annotate the gene regulatory effects of SVs in the human brain and their potential to contribute to disease.

Large-scale loss-of-function screens and TP53 saturation mutagenesis screens in human cancer cell lines suggest that mutational processes combine with phenotypic selection to shape the landscape of somatic mutations at the TP53 locus.

Golub and colleagues identify the phosphate exporter XPR1 as a therapeutic vulnerability in ovarian and uterine cancers, and show that phosphate efflux inhibition reduces tumor cell viability through accumulation of intracellular phosphate.

Andrew Jackson, Peter Nürnberg and colleagues identify mutations in PLK4 and TUBGCP6 in individuals with microcephaly, primordial dwarfism, retinopathy and other congenital anomalies. These findings extend the spectrum of human phenotypes associated with centriole dysfunction.

The start-up of the new femtosecond hard X-ray laser facility in Stanford, the Linac Coherent Light Source, has brought high expectations for a new era for biological imaging. The intense, ultrashort X-ray pulses allow diffraction imaging of small structures before radiation damage occurs. This new capability is tested for the problem of structure determination from nanocrystals of macromolecules that cannot be grown in large crystals. Over three million diffraction patterns were collected from a stream of nanocrystals of the membrane protein complex photosystem I, which allowed the assembly of a three-dimensional data set for this protein, and proves the concept of this imaging technique.

BET-bromodomain inhibitors could be used to treat medulloblastoma tumors with Myc amplifications. Here, the authors show that both the response and resistance to BET inhibitors in mice is mediated by bHLH/homeobox transcription factors.

Z-lock is introduced as a new method to control protein activity with light. It relies on a steric block placed over important regions of the target protein that can be released reversibly. Z-lock was applied to regulate cofilin and αTAT activity.

Small molecule drugs can affect clearance of monoclonal antibodies, but this hasn’t been assessed for oral HIV-1 pre-exposure prophylaxis. Here, the authors find that faster serum clearance of an experimental IgG1 monoclonal antibody, VRC01, is associated with use of tenofovir-emtricitabine, possibly explained by increased epithelial intestinal permeability.

The targeting of angiogenesis is a growing area of cancer therapy.In vivo imaging techniques allow the noninvasive evaluation of changes in tumor vasculature in response to antiangiogenic agents. Zee et al. provide an overview of MRI, CT, PET and ultrasound techniques, highlighting their application in renal, prostate and bladder cancer.

Over the past 620,000 years, three distinct phases of climate variability in eastern Africa coincided with shifts in hominin evolution and dispersal, according to an analysis of environmental proxy records from a core collected in the Chew Bahir basin of Ethiopia.

The perinuclear actin cap determines nuclear morphology but its regulation is currently poorly understood. Here, the authors find that an activator of the Rac1 GTPase, STEF/TIAM2, localises to the nuclear envelope and contributes to perinuclear actin and myosin tension, which in turn regulates the actin cap.

Many individual genetic risk loci associate with multiple diseases, but the molecular basis of these loci often remains unclear. Here, the authors provide a framework to reveal the genetic cross-disease associations at the PROCR vascular disease locus.

Hamish Scott and colleagues report that germline mutations in GATA2 segregate with myelodysplastic syndrome and acute myeloid leukemia in four pedigrees. The resulting alterations occur in a conserved zinc finger DNA-binding domain of GATA2.

Engrafted mesenchymal stem cells (MSCs) promote breast cancer metastasis formation. Breast cancer cells induce MSCs to produce the cytokine CCL5, which then acts on breast tumour cells, enhancing their ability to migrate and extravasate blood vessel at the site of future metastases.

T- and NK-cell lymphomas (TCL) are a group of lymphoid malignancies characterized by poor prognosis, but the absence of appropriate pre-clinical models has hampered the development of effective therapies. Here the authors establish several pre-clinical models and identify vulnerabilities that could be further exploited to treat patients afflicted by these diseases.

Oxygen is generated abiotically at the abyssal seafloor in the presence of polymetallic nodules, potentially by seawater electrolysis, according to in situ chamber and ex situ incubation experiments.

A single-cell transcriptomic atlas across the lifespan of the mouse, denoted Tabula Muris Senis, provides molecular information about the hallmarks of ageing in a range of tissues and cell types.

The extent, origins and consequences of genetic variation within human cell lines are studied, providing a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research.

Kynurenine, a metabolite produced by the action of the enzyme indoleamine 2,3-dioxygenase on tryptophan, accumulates under inflammatory conditions and has immunomodulatory effects. This study by Yutang Wang et al. describes a new function for kynurenine as an endogenous vasodilator under conditions of systemic inflammation, such as malaria infection and endotoxemia in mice, and provides insight into the molecular mechanisms involved (pages 265–267).

Recombination contributes to HIV evolution in patients, but its identification can be difficult. Here, the authors develop a computational tool called RAPR to track recombination in patients, identify recombination hot spots, and show contribution of recombination to antibody escape.

The start-up of the new femtosecond hard X-ray laser facility in Stanford, the Linac Coherent Light Source, has brought high expectations for a new era for biological imaging. The intense, ultrashort X-ray pulses allow diffraction imaging of small structures before radiation damage occurs. This new capability is tested for the problem of imaging a non-crystalline biological sample. Images of mimivirus are obtained, the largest known virus with a total diameter of about 0.75 micrometres, by injecting a beam of cooled mimivirus particles into the X-ray beam. The measurements indicate no damage during imaging and prove the concept of this imaging technique.

Whole-exome sequencing of human brain metastases from lung adenocarcinoma uncovers new drivers by comparison of somatic alteration frequencies in brain metastasis cases to those in primary lung adenocarcinomas.

Mitsiades and colleagues utilize functional genomics data in over 700 cancer cell lines, to identify genes with preferentially essential functions in multiple myeloma, which may represent targets for precision medicine strategies.

Gamma-ray line radiation at 511 keV is the signature of electron–positron annihilation, which comes from the general direction of the Galactic centre, but the origin of the positrons was a mystery. This paper reports a distinct asymmetry in the 511 keV line emission coming from the inner Galactic disk, which resembles an asymmetry in the distribution of low mass X-ray binaries with strong emission at photon energies >20 keV, indicating that they may be the dominant origin of the positrons.

The cellular heterogeneity in brain obscures the identification of robust cellular regulatory networks. Here the authors integrate genome-wide chromosome conformation data from sorted neurons and glia, with transcriptomic and enhancer profiles, to characterize cell-type-specific gene regulatory landscapes in the human brain, and provide insights into cell-type-specific gene regulatory networks in brain disorders.

Bone mineral density (BMD) is associated with fracture risk and many genetic loci with small effect sizes have been discovered by genome-wide association studies (GWAS). Here, the authors discover a large-effect rare loss-of-function genetic variant for BMD in the MEPE gene in the Norwegian HUNT study which replicates in the UK Biobank.

Methylation of lysine residues regulates chromatin function in part by recruiting readers to these marks. UNC1215, a selective antagonist of the methyllysine reader L3MBTL3 with a polyvalent mode of interaction, reveals BCLAF1 as a methyllysine-dependent interaction partner for L3MBTL3.

Technical limitations in simultaneous microscopic visualization of HIV transcription from individual integration sites have curtailed progress in the field. Here the authors report a branched DNA in situ hybridization method for direct single-cell visualization of HIV DNA, RNA, and protein.

Marshall Horwitz, Charles Mullighan, Kenneth Offit and colleagues report the identification of a recurrent germline PAX5 mutation in families with pre–B cell acute lymphoblastic leukemia. They also identify sporadic cases of this leukemia with the same mutation that arose somatically.

Longitudinal sampling is used to map the evolution of an HIV-1 virus from the time of infection, and the co-evolution of a broadly neutralizing antibody in the same infected patient; the findings have important implications for HIV vaccine development.

A longitudinal study of an individual patient developing neutralizing antibodies against HIV-1 (targeting the V1V2 region of gp120) reveals how such neutralizing antibodies develop and evolve over time, providing important insights relevant to vaccine development.

Kim Worley and colleagues report the whole-genome sequence of the common marmoset, Callithrix jacchus, the first New World monkey to be sequenced.

This Perspective argues that early assessments of technology-market fit, as well as how the physics governing system performance evolves with scale, can de-risk technology development and accelerate deployment. The authors highlight tools and processes that can be used to assess both these factors at an early stage.

eQTL analysis of human brain RNA-seq data targeted to genes within the 10q24.32 schizophrenia-associated locus reveals that the risk SNP in this region is selectively associated with expression of BORCS7 and a human-specific isoform of AS3MT across multiple independent samples. Expression of only the associated AS3MT isoform is higher in tissue from humans with schizophrenia than in healthy controls.

Orienting cancer drug discovery to the patient requires relating the genetic features of tumors to acquired gene and pathway dependencies and identifying small-molecule therapeutics that target them.