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• Ageing: Senescent cells cleared out
A newly developed molecule causes ageing cells to commit suicide, restoring some signs of health and stamina in old mice.Damaged cells that stop dividing, called senescent cells, accumulate with age, and are thought to contribute to inflammation, tissue damage and age-related diseases. To find
• Cancer: How fat boosts breast cancer
A molecule made by fat cells in human breast tissue increases the growth of certain breast-cancer cells. The finding suggests a potential reason why larger breast size seems to correlate with a higher risk of cancer.Fat cells are thought to interact with cancer cells
• Five ways consortia can catalyse open science
An analysis of more than 50 collaborations shows the secrets of success, write Joel Cutcher-Gershenfeld and colleagues from the Stakeholder Alignment Collaborative.
• Animal welfare: Make animal models more meaningful
Non-human primates are our most intelligent animal models, but are, paradoxically, the ones most severely deprived of the environmental substrates needed for healthy brain development. For animal models to be biologically relevant, we need to remove the stress of captivity. We must identify and reproduce
• Pets: Millennia together
Dogs, cats and birds have lived alongside humans for thousands of years. Our interconnected lives offer physical and psychological benefits, as well as some risks.
• Environment: Hothouse of disease
Dogs and cats in temperate regions are encountering pathogens that once thrived only in the tropics. As the climate warms and pests migrate north, animals, and some humans, are facing new health risks.
• Transboundary health impacts of transported global air pollution and internat...
Millions of people die every year from diseases caused by exposure to outdoor air pollution. Some studies have estimated premature mortality related to local sources of air pollution, but local air quality can also be affected by atmospheric transport of pollution from distant sources. International trade is contributing to the globalization of emission and pollution as a result of the production of goods (and their associated emissions) in one region for consumption in another region. The effects of international trade on air pollutant emissions, air quality and health have been investigated regionally, but a combined, global assessment of the health impacts related to international trade and the transport of atmospheric air pollution is lacking. Here we combine four global models to estimate premature mortality caused by fine particulate matter (PM2.5) pollution as a result of atmospheric transport and the production and consumption of goods and services in different world regions. We find that, of the 3.45 million premature deaths related to PM2.5 pollution in 2007 worldwide, about 12 per cent (411,100 deaths) were related to air pollutants emitted in a region of the world other than that in which the death occurred, and about 22 per cent (762,400 deaths) were associated with goods and services produced in one region for consumption in another. For example, PM2.5 pollution produced in China in 2007 is linked to more than 64,800 premature deaths in regions other than China, including more than 3,100 premature deaths in western Europe and the USA; on the other hand, consumption in western Europe and the USA is linked to more than 108,600 premature deaths in China. Our results reveal that the transboundary health impacts of PM2.5 pollution associated with international trade are greater than those associated with long-distance atmospheric pollutant transport.
• CRISPR?Cas systems exploit viral DNA injection to establish and maintain adap...
Clustered regularly interspaced short palindromic repeats (CRISPR)?Cas systems provide protection against viral and plasmid infection by capturing short DNA sequences from these invaders and integrating them into the CRISPR locus of the prokaryotic host. These sequences, known as spacers, are transcribed into short CRISPR RNA guides that specify the cleavage site of Cas nucleases in the genome of the invader. It is not known when spacer sequences are acquired during viral infection. Here, to investigate this, we tracked spacer acquisition in Staphylococcus aureus cells harbouring a type II CRISPR?Cas9 system after infection with the staphylococcal bacteriophage ?12. We found that new spacers were acquired immediately after infection preferentially from the cos site, the viral free DNA end that is first injected into the cell. Analysis of spacer acquisition after infection with mutant phages demonstrated that most spacers are acquired during DNA injection, but not during other stages of the viral cycle that produce free DNA ends, such as DNA replication or packaging. Finally, we showed that spacers acquired from early-injected genomic regions, which direct Cas9 cleavage of the viral DNA immediately after infection, provide better immunity than spacers acquired from late-injected regions. Our results reveal that CRISPR?Cas systems exploit the phage life cycle to generate a pattern of spacer acquisition that ensures a successful CRISPR immune response.
• Fleeting factors, turning back time
Old cells and tissues become young again after a short dose of reprogramming factors.
• Inheritance of protection from osmotic stress
Exposure of mother worms to mild osmotic stress induces gene expression changes in offspring that protect them from strong osmotic stress. Inheritance of protection is now shown to depend on altered insulin-like signalling in the maternal germline, which confers protection through increased expression of zygotic gpdh-2, a rate-limiting enzyme in glycerol biosynthesis.
• Insulin-like signalling to the maternal germline controls progeny response to...
Burton et al. show that Caenorhabditis elegans parental exposure to osmotic stress protects progeny from osmotic stress through insulin-like signalling, linking maternal germline signalling to progeny metabolism.
• Refining the role of de novo protein-truncating variants in neurodevelopmenta...
Mark Daly and colleagues use population reference samples to refine the role of de novo protein-truncating variants in neurodevelopmental disorders. They show that variants independently observed in population reference samples do not contribute substantively to neurodevelopmental risk, and they use a loss-of-function intolerance metric to identify a small subset of genes that contain the entire observed signal of associated de novo protein-truncating variants in these disorders.
• Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with...
Evan Eichler and colleagues use single-molecule molecular-inversion probes to sequence the coding and splicing regions of 208 candidate genes in more than 11,730 individuals with neurodevelopmental disorders. They report 91 genes with an excess of de novo or private disruptive mutations, identify 25 genes showing a bias for autism versus intellectual disability, and highlight a network associated with high-functioning autism.
• Corrigendum: Rare variants of large effect in BRCA2 and CHEK2 affect risk of ...
• To B-1 or not to B-1
The transcription factor Bhlhe41 determines the survival and repertoire of B-1a cells.
• DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma
DNA methylation sequencing and bioinformatic analyses uncover an epigenetic disease spectrum in Ewing sarcoma. These characteristic epigenome patterns correlate with state of differentiation and disease aggressiveness, and pave the way for the development of biomarkers.
• Whole genome sequencing resource identifies 18 new candidate genes for autism...
Yuen et al. developed a cloud-based database with 5,205 whole genomes from families with autism spectrum disorder (ASD). They identified 18 new candidate ASD-risk genes and approximately 100 risk genes and copy-number loci, which account for 11% of the cases. They also found that individuals bearing mutations in ASD-risk genes had lower adaptive ability.
• Cancer therapy-induced PAFR ligand expression: any role for caspase activity?
Our recent Opinion article discussed the oncogenic effects of engaging apoptosis and their impact on cancer (Nat. Rev. Cancer16, 539?548; 2016). We would like to thank Roger Chammas, Luciana Nogueira de Sousa Andrade and Sonia Jancar for their correspondence on our
• Interrogating open issues in cancer precision medicine with patient-derived x...
Patient-derived xenografts (PDXs) have emerged as an important platform to elucidate new treatments and biomarkers in oncology. PDX models are used to address clinically relevant questions, including the contribution of tumour heterogeneity to therapeutic responsiveness, the patterns of cancer evolutionary dynamics during tumour progression and
• Pain: A gatekeeper circuit
The dissection of a circuit for the descending modulation of pain processing in the spinal cord that is recruited by stress.