Pathogenesis articles within Nature

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  • Article |

    A high-fat diet increases the number of intestinal stem cells in mammals, both in vivo and in intestinal organoids; a pathway that involves PPAR-δ confers organoid-initiating capacity to non-stem cells and induces them to form in vivo tumours after loss of the Apc tumour suppressor.

    • Semir Beyaz
    • , Miyeko D. Mana
    •  & Ömer H. Yilmaz

  • Letter |

    Treatment of children with human cadaver-derived growth hormone (c-hGH) contaminated with prions resulted in transmission of Creutzfeldt–Jakob disease (CJD); unexpectedly, in an autopsy study of eight such iCJD patients, the authors found amyloid-β deposition in the grey matter typical of that seen in Alzheimer's disease and amyloid-β in the blood vessel walls characteristic of cerebral amyloid angiopathy, consistent with iatrogenic transmission of amyloid-β pathology in addition to CJD and suggests that healthy c-hGH-exposed individuals may also be at risk of Alzheimer's disease and cerebral amyloid angiopathy.

    • Zane Jaunmuktane
    • , Simon Mead
    •  & Sebastian Brandner

  • Letter |

    Cryptosporidium is an important cause of diarrhoeal disease in young children but until now it has been difficult to study; here, the parasite is genetically modified, paving the way for in-depth investigation and the development of effective treatments.

    • Sumiti Vinayak
    • , Mattie C. Pawlowic
    •  & Boris Striepen

  • Review Article |

    Extracellular ATP released from cells during inflammatory responses predominantly functions as a signalling molecule through the activation of purinergic P2 receptors and contributes to both beneficial and detrimental inflammatory responses; this review examines P2 receptor signalling via ATP and its effect on the outcome of inflammatory and infectious diseases.

    • Marco Idzko
    • , Davide Ferrari
    •  & Holger K. Eltzschig

  • Letter |

    The airway mucin Muc5b (but not Muc5ac) is required for mucociliary clearance, defence against bacterial infection in the airways and middle ear, and maintenance of immune homeostasis in the lungs; Muc5b deficiency causes accumulation of apoptotic macrophages, impairment of phagocytosis and reduced production of interleukin-23, leading to infection and inflammation.

    • Michelle G. Roy
    • , Alessandra Livraghi-Butrico
    •  & Christopher M. Evans

  • Letter |

    In neonatal mice, susceptibility to infection is due to an enriched subset of arginase-2-expressing CD71+ erythroid cells, which suppresses the systemic activation of immune cells, thereby protecting neonates against aberrant inflammation triggered by colonization with commensal microbes.

    • Shokrollah Elahi
    • , James M. Ertelt
    •  & Sing Sing Way

  • Outlook |

    Multi-protein inflammasomes are being implicated in a surprising number of diseases, and researchers are keen to find out why.

    • Katharine Gammon

  • Letter |

    Failure of integrin-mediated cell-matrix attachment is sufficient to initiate dermal fibrosis and autoimmunity in mouse models of scleroderma; integrin-modulating therapies prevent the recruitment and activation of plasmacytoid dendritic cells that appear central to immunological dysregulation and maintenance of the pro-fibrotic synthetic programme.

    • Elizabeth E. Gerber
    • , Elena M. Gallo
    •  & Harry C. Dietz

  • Outlook |

    Science is finally getting to grips with this enigmatic autoimmune disease.

    • James Mitchell Crow

  • Outlook |

    Severe psoriasis carries cardiovascular risks. Dermatologists should consider more than just patients' outer layers, argues Henning Boehncke.

    • Wolf-Henning Boehncke

  • Letter |

    A cell-autonomous role for the COUP-TFII transcription factor in prostate cancer cells is identified, in which COUP-TFII inhibits TGF-β signalling by binding to SMAD4; COUP-TFII promotes prostate tumorigenesis and metastasis in a mouse model, and is associated with more aggressive disease in human prostate cancers.

    • Jun Qin
    • , San-Pin Wu
    •  & Sophia Y. Tsai

  • Letter |

    A meta-analysis of previous genome-wide association studies of Crohn’s disease and ulcerative colitis, the two most common forms of inflammatory bowel disease, with a combined total of more than 75,000 cases and controls, finds that most loci contribute to both phenotypes and other immune-mediated disorders.

    • Luke Jostins
    • , Stephan Ripke
    •  & Judy H Cho

  • Letter |

    Individuals with the red hair/fair skin phenotype usually carry a polymorphism in the gene encoding the melanocortin 1 receptor (Mc1r) that results in the production of pigment containing a high pheomelanin-to-eumelanin ratio; here it is shown in a mouse model that inactivation of Mc1r promotes melanoma formation in the presence of the Braf oncogene, thus suggesting that pheomelanin synthesis is carcinogenic by an ultraviolet-radiation-independent mechanism.

    • Devarati Mitra
    • , Xi Luo
    •  & David E. Fisher

  • Letter |

    Neurons and oligodendrocytes differentiated from induced pluripotent stem cells (iPSCs) of patients with inherited TLR3 and UNC-93B deficiencies are found to be more susceptible to infection by HSV-1 than control cells because they fail to induce a normal interferon response, whereas neural stem cells and astrocytes are not susceptible.

    • Fabien G. Lafaille
    • , Itai M. Pessach
    •  & Luigi D. Notarangelo

  • News & Views |

    The identification of a signalling protein that regulates the accumulation of fat and connective tissue in breasts may help to explain why high mammographic density is linked to breast-cancer risk. It may also provide a marker for predicting this risk.

    • Victoria L. Seewaldt

  • Letter |

    IL-22 is one of the factors that, although important for wound healing, also promote tumorigenesis; the regulation of IL-22BP, the IL-22 binding protein, via the NLRP3 and NLRP6 inflammasomes provides an unanticipated mechanism, controlling IL-22 and thereby the development of colon cancer.

    • Samuel Huber
    • , Nicola Gagliani
    •  & Richard A. Flavell

  • Books & Arts |

    Nathan Wolfe applauds a tome on interspecies disease transmission that mixes research with human stories.

    • Nathan Wolfe

  • Outlook |

    Smoking and COPD have one of the strongest relationships in clinical epidemiology. But don't forget the genetics, says Edwin K. Silverman

    • Edwin K. Silverman

  • Outlook |

    COPD is one of the world's biggest killers, but awareness is low, diagnosis is often missed, and in many countries the extent of the problem is not even well-documented.

    • Amber Dance

  • News & Views |

    A tightly regulated enzyme balances energy production and the synthesis of macromolecules from glucose in cancer cells. Upsetting this balance by stimulating the enzyme's activity can suppress tumour growth in mice.

    • Lei Jiang
    •  & Ralph J. DeBerardinis

  • Letter |

    B-cell receptor (BCR) signalling in chronic lymphocytic leukaemia (CLL) is found not to be dependent on exogenous antigens; instead, signalling may involve the binding of the BCR heavy-chain complementarity-determining region to self epitopes on the same receptor, a finding that may have important implications for understanding the pathogenesis of CLL and potential therapeutic approaches.

    • Marcus Dühren-von Minden
    • , Rudolf Übelhart
    •  & Hassan Jumaa

  • Letter |

    Mutations in angiotensin-converting enzyme 2 are shown to predispose mice to colitis as a consequence of neutral amino acid malabsorption and a change in the resident microbiota; these results could explain how protein malnutrition — affecting up to one billion people — leads to intestinal inflammation.

    • Tatsuo Hashimoto
    • , Thomas Perlot
    •  & Josef M. Penninger

  • Letter |

    Medulloblastoma is the most common brain tumour in children; using exome sequencing of tumour samples the authors show that these cancers have low mutation rates and identify 12 significantly mutated genes, among them the gene encoding RNA helicase DDX3X.

    • Trevor J. Pugh
    • , Shyamal Dilhan Weeraratne
    •  & Yoon-Jae Cho

  • Letter |

    Both heterozygous loss and homozygous loss of Tsc1 in mouse cerebellar Purkinje cells (PCs) result in autistic-like behaviours, which can be prevented by treatment with the mTOR inhibitor, rapamycin; these findings demonstrate critical roles for PCs in autistic-like behaviours in mice.

    • Peter T. Tsai
    • , Court Hull
    •  & Mustafa Sahin

  • Comment |

    Frank Aarestrup explains how he helped Denmark to cut the use of antibiotics in its livestock by 60%, and calls on the rest of the world to follow suit.

    • Frank Aarestrup

  • Article |

    Myocardial infarction accelerates atherosclerosis through activation of the sympathetic nervous system, and the consequent release of haematopoietic stem and progenitor cells.

    • Partha Dutta
    • , Gabriel Courties
    •  & Matthias Nahrendorf

  • News & Views |

    Alterations in brain blood vessels in mice precede the neural dysfunction associated with Alzheimer's disease. The finding highlights potential targets for drug development. See Letter p.512

    • Peter Carmeliet
    •  & Bart De Strooper

  • Outlook |

    Decades of study into the causes of diabetes have produced no definitive answers.

    • Erika Jonietz

  • News & Views |

    The expression level of a single gene can determine head size in zebrafish, mirroring a human anatomical feature associated with neurological disorders such as autism and schizophrenia. See Letter p.363

    • Dheeraj Malhotra
    •  & Jonathan Sebat

  • Perspective |

    A review of allergic host defences argues that allergic immunity has an important role in host defence against noxious environmental substances.

    • Noah W. Palm
    • , Rachel K. Rosenstein
    •  & Ruslan Medzhitov

  • Outlook |

    Researchers have plenty of theories about what might cause multiple sclerosis. But for now, the factor that triggers the disease remains elusive.

    • Lauren Gravitz

  • Letter |

    In a mouse model and in human medulloblastoma patients, the metastases in an individual have similar genomic alterations and DNA methylation patterns, but these patterns are highly divergent from those of the primary tumour, indicating that therapies will need to be tailored to fit the molecular alterations present in the primary tumour and/or the metastases.

    • Xiaochong Wu
    • , Paul A. Northcott
    •  & Michael D. Taylor

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