Think Like a Dog最新文献

Looking for Treats 寻找食物

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.5

引用次数: 0

Being Loyal 忠诚

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.18

引用次数: 0

Scott’s Acknowledgments 斯科特的应答

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.27

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Getting the Basics Right 掌握基本知识

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.23

引用次数: 0

Sadie’s Twelve Most Important Lessons for a Better Life 赛迪的美好生活的12个最重要的教训

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.25

引用次数: 0

Eat, Sleep, Play 吃，睡，玩

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.17

引用次数: 0

Embracing Change 拥抱变化

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.13

T. Yager

引用次数: 37

Leaving Your Mark 留下印记

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.24

{"title":"Leaving Your Mark","authors":"","doi":"10.2307/j.ctvcj2rgj.24","DOIUrl":"https://doi.org/10.2307/j.ctvcj2rgj.24","url":null,"abstract":"Nature reviews | CanCer Associations between the intestinal microbiome and colorectal cancer (CRC) development have been proposed. However, direct links between the presence of an individual bacterial species and the generation of mutations driving tumorigenesis have been harder to pinpoint. Certain strains of Escherichia coli present in the stool and tumour biopsy samples of patients with CRC harbour a pathogenicity island, pks, encoding a series of enzymes that produce a genotoxin known as colibactin. Only last year, colibactin–DNA adenine adducts unique to mammalian cells infected with pks+ E. coli were identified. Now with the application of organoid technology, PleguezuelosManzano et al. have discovered two co-occurring mutational patterns in DNA that arise following exposure to pks+ E. coli, firmly establishing causality. To examine the consequences of genotoxic E. coli exposure on host epithelial cells, the authors developed a co-culture system wherein a pks+ E. coli strain derived from a CRC biopsy sample was microinjected into the lumen of clonal human intestinal organoids. DNA damage, specifically double-strand breaks and interstrand crosslinks, characteristic of that previously seen to be induced by pks+ E. coli was observed. However, infection of intestinal organoids with an isogenic mutant strain knocked out for clbQ (pksΔclbQ E. coli), which encodes an enzyme involved in the biosynthetic pathway of colibactin, did not result in DNA damage, confirming the phenotype was specific to the activity of colibactin. Next, to investigate the long-term effects of colibactin exposure, single cell-derived organoids were repeatedly injected with pks+ E. coli or pksΔclbQ E. coli over 5 months before subclonal organoids were derived from individual cells within the original cultures. Whole genome sequencing (WGS) of the clonal organoids before and after exposure to the genotoxic pks+ E. coli revealed an increase in the presence of single base substitutions (SBSs) compared with those subclones treated with pksΔclbQ E. coli. Typically these substitutions were changes of T to any of the other three nucleotides and occurred preferentially in the middle base of ATA, ATT and TTT triplets. The authors defined this as a pks-specific SBS signature (SBS-pks) as it could not be detected in organoids injected with pksΔclbQ E. coli. A second mutational signature characterized by a small insertion and deletion (indel) was also identified (ID-pks). This particular mutational pattern took the form of a single deletion of T in long poly-T stretches. In addition, both mutational signatures were further characterized by the presence of adenine residues upstream of the mutated sites. Taken altogether, the SBS-pks, ID-pks and associated recurrent patterns, collectively known as the pks-mutational signature, is distinct from those induced by other known environmental mutagens. Moving away from the in vitro set-up to investigate the potential presence of this pks-signatu","PeriodicalId":308734,"journal":{"name":"Think Like a Dog","volume":"127 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116078165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Avoiding Certain Dogs 避开某些狗

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.10

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Being Persistent 是持久的

Think Like a Dog Pub Date : 2019-04-01 DOI: 10.2307/j.ctvcj2rgj.6

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