Diseases articles within Nature Communications

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  • Article
    | Open Access

    During red blood cell infection, malaria parasites export hundreds of proteins that remodel the host cell surface. Cowman and colleagues identify a putative protein translocator complex spatially associated with exported proteins, revealing the cellular domains involved in protein export.

    • David T. Riglar
    • , Kelly L. Rogers
    •  & Alan F. Cowman

  • Article
    | Open Access

    Selected reaction monitoring mass spectrometry (SRM-MS) can quantify dynamic changes in protein expression with high sensitivity. Karlsson et al. define optimal detection parameters for 10,412 distinct group A Streptococcus pyogenespeptides, which facilitates proteome-wide SRM-MS studies in this bacterium.

    • Christofer Karlsson
    • , Lars Malmström
    •  & Johan Malmström

  • Article
    | Open Access

    The gut microbiota has emerged as an environmental factor that can influence the development of obesity and diabetes. Here, Karlsson et al. report compositional and functional alterations of the gut metagenome in patients with symptomatic atherosclerosis.

    • Fredrik H. Karlsson
    • , Frida Fåk
    •  & Jens Nielsen

  • Article
    | Open Access

    Malaria can persist at levels that escape detection by standard microscopy, but can be detected by PCR. Okell et al.now show that rates of submicroscopic infection can be predicted using more widely available microscopy data, and are most epidemiologically significant in areas with low malaria transmission.

    • Lucy C. Okell
    • , Teun Bousema
    •  & Chris J. Drakeley

  • Article |

    Polycystic kidney disease family proteins form heteromeric complexes with transient receptor potential channel subunits of the TRPP subfamily. Yu and colleagues find that the polycystic kidney disease protein, PKD1L3, is an ion channel pore-forming subunit in the acid-sensing PKD1L3/TRPP3 complex.

    • Yong Yu
    • , Maximilian H. Ulbrich
    •  & Jian Yang

  • Article
    | Open Access

    Multiple sclerosis is characterized by the activation of microglia cells. Davalos et al. investigate the early stages of neuroinflammation in mice and reveal that the plasma protein fibrinogen induces microglial clustering around the brain vasculature, which facilitates lesion formation and focal axonal damage.

    • Dimitrios Davalos
    • , Jae Kyu Ryu
    •  & Katerina Akassoglou

  • Article |

    Multifunctional S100 proteins are upregulated in brain injury, but their role in neurodegeneration is not clear. Dmytriyeva and colleagues study in vivomodels of brain trauma and find that the S100A4 protein and its peptide mimetics protect neurons via the interleukin-10 receptor and the Janus kinase (JAK)/STAT pathway.

    • Oksana Dmytriyeva
    • , Stanislava Pankratova
    •  & Darya Kiryushko

  • Article
    | Open Access

    Prion proteins are implicated in a range of neurodegenerative diseases, which are, in part, due to a disruption of metal homeostasis. Wattet al.use selective antagonists to show that prion proteins mediate zinc uptake by interacting with GluA2-lacking, GluA1-containing AMPA receptors.

    • Nicole T. Watt
    • , David R. Taylor
    •  & Nigel M. Hooper

  • Article |

    Mice lacking the anti-inflammatory cytokine IL-10 can develop colitis, which depends on inappropriate responses to commensal bacteria. Hoshiet al. now show that these responses are driven by colonic mononuclear phagocytes, providing insight to the initiating events, which may underlie inflammatory bowel disease.

    • Namiko Hoshi
    • , Dominik Schenten
    •  & Ruslan Medzhitov

  • Article |

    One of the five IL-17 receptors, IL-17RD lacks a motif thought to be required for downstream signalling. Melletet al. show that IL-17RD tunes IL-17A-dependent signalling; in its absence, MAPK signalling and neutrophil recruitment are impaired, but NF-κB activation is enhanced.

    • Mark Mellett
    • , Paola Atzei
    •  & Paul N. Moynagh

  • Article |

    Vascular calcification is commonly associated with advanced stages of atherosclerosis. Woldtet al. show that the nuclear hormone receptor PPARγ in vascular smooth muscle cells protects mice from vascular calcification by inhibiting Wnt5a signalling triggered by activation of the cell-surface receptor LRP1.

    • Estelle Woldt
    • , Jérome Terrand
    •  & Philippe Boucher

  • Article
    | Open Access

    Fragile X syndrome is a major genetic cause of autism and is caused by loss of the fragile X mental retardation protein. In a mouse model of fragile X syndrome, Junget al. show that an absence of neuronal endocannabinoid signalling is responsible for the neurophysiological and behavioural defects.

    • Kwang-Mook Jung
    • , Marja Sepers
    •  & Olivier J. Manzoni

  • Article
    | Open Access

    Environmental factors can influence one's susceptibility to cancer, but it is not clear whether such an influence extends beyond the directly exposed generations. Here, feeding pregnant rats with a high-fat diet or a hormone derivative, the authors observe increased breast cancer risk in up to three subsequent generations.

    • Sonia de Assis
    • , Anni Warri
    •  & Leena Hilakivi-Clarke

  • Article |

    TGF-β signalling suppresses tumorigenesis in breast cancer cells but its effects on breast cancer initiating cells have not been reported. Using cells in culture, Brunaet al. show that TGF-β increases breast cancer initiating cell numbers in cells that have low levels of the tight junction protein claudin.

    • Alejandra Bruna
    • , Wendy Greenwood
    •  & Carlos Caldas

  • Article |

    The amyloid beta peptide can aggregate into insoluble plaques, which may indicate the onset of Alzheimer's disease. In a mouse model of Alzheimer's disease, Cao and colleagues report a phenotype of altered connectivity in the olfactory neuronal circuit that precedes amyloid plaque deposition.

    • Luxiang Cao
    • , Benjamin R. Schrank
    •  & Mark W. Albers

  • Article
    | Open Access

    The kinase PINK1 is mutated in Parkinson's disease and accumulates in defective mitochondria, where it recruits Parkin. Here, PINK1 is shown to be autophosphorylated and this is required for the localization of PINK1 to mitochondria with a reduced membrane potential, and for the recruitment of Parkin.

    • Kei Okatsu
    • , Toshihiko Oka
    •  & Noriyuki Matsuda

  • Article
    | Open Access

    Seasonal malaria chemoprevention can lower the incidence of malaria in areas where transmission is highly periodical. Combining data on rainfall, population and malaria endemicity, Cairnset al. identify geographical areas in sub-Saharan Africa where this intervention is likely to be effective and cost-effective.

    • Matthew Cairns
    • , Arantxa Roca-Feltrer
    •  & Brian M. Greenwood

  • Article |

    De-differentiation and proliferation of vascular smooth muscle cells is thought to have a dominant role in vascular remodelling. Here, Tanget al. identify a new type of multipotent vascular stem cell in the blood vessel wall that contributes to this process, thereby challenging the established hypothesis.

    • Zhenyu Tang
    • , Aijun Wang
    •  & Song Li

  • Article
    | Open Access

    Claudin-5 is a component of tight junctions and has important roles in mediating the permeability of the blood-brain barrier. Campbell and co-workers administer short interfering RNA against claudin-5 in a model of brain injury, finding that it enhances water movement from the brain to the blood and alleviates swelling.

    • Matthew Campbell
    • , Finnian Hanrahan
    •  & Peter Humphries

  • Article |

    Epigenetic and genetic factors have a role in obesity but the role of epigenetics in this disease is unclear. Here, Liet al. investigated global DNA methylation patterns in three breeds of pigs that have different fat contents, providing a resource for the further analysis of differentially methylated gene promoters in obesity.

    • Mingzhou Li
    • , Honglong Wu
    •  & Ruiqiang Li

  • Article |

    The detection of subclonal variants in heterogeneous cancer specimens is a challenge due to errors that occur during sequencing. In this study, a statistical algorithm and a sequencing strategy are reported that circumvent this issue and can accurately detect variants at a frequency as low as 1/10,000.

    • Moritz Gerstung
    • , Christian Beisel
    •  & Niko Beerenwinkel

  • Article
    | Open Access

    The large virus family,Paramyxoviridae, includes several human and livestock viruses. This study, testing 119 bat and rodent species distributed globally, identifies novel putative paramyxovirus species, providing data with potential uses in predictions of the emergence of novel paramyxoviruses in humans and livestock.

    • Jan Felix Drexler
    • , Victor Max Corman
    •  & Christian Drosten

  • Article |

    Fanconi's anaemia is characterized by an inability to repair DNA damage and is associated with mutations in the Fanconi anaemia nuclear complex, which includes the protein FANCM. This study reports the crystal structures of a fragment of FANCM bound to the histone-fold-containing protein complex, MHF1–MHF2.

    • Yuyong Tao
    • , Changjiang Jin
    •  & Maikun Teng

  • Article |

    Lamivudine treatment of hepatitis B is associated with drug-resistance mutations in the virus’ DNA polymerase. In this study, 11 patients with drug resistance are investigated and the primary mutation in the DNA polymerase shown to be essential but not sufficient for establishing drug resistance.

    • Hong Thai
    • , David S. Campo
    •  & Yury Khudyakov

  • Article
    | Open Access

    Lung injury initiates a series of wound-healing responses, which if unregulated, can lead to fibrosis. Liet al. show that the deubquitinase CYLD has a key role in the prevention of fibrosis by inhibiting transforming growth factor β-signalling through the direct deubiquitination of the protein kinase Akt.

    • Jae Hyang Lim
    • , Hirofumi Jono
    •  & Jian-Dong Li

  • Article
    | Open Access

    Hyperuricemia, or gout, is thought to arise either from urate overproduction or from decreased renal excretion of urate. Ichidaet al. show that the extra-renal excretion of urate also has a role in the pathogenesis of hyperuricemia, and propose a new classification for patients with this disease.

    • Kimiyoshi Ichida
    • , Hirotaka Matsuo
    •  & Hiroshi Suzuki

  • Article |

    The treatment ofMycobacterium tuberculosis with drugs such as isoniazid often results in drug resistance, but the mechanisms leading to the resistance are not fully known. In this study, an M. tuberculosisstrain lacking the sigma factor I is shown to be resistant to isoniazid.

    • Jong-Hee Lee
    • , Nicole C. Ammerman
    •  & William R. Bishai

  • Article |

    Bioassays are the standard way to measure prion infectivity titres, but can be time-consuming. In this study, bioassays are compared with a modified version of the protein misfolding cyclic amplification technique with beads (PMCAb), demonstrating that PMCAb can be more precise and faster than bioassays.

    • Natallia Makarava
    • , Regina Savtchenko
    •  & Ilia V. Baskakov

  • Article
    | Open Access

    Aberrant activation of the TGF-β pathway leads to fibrotic disease. Distler and colleagues show that TGF-β-mediated fibrosis requires the decrease of Dickkopf-1, an antagonist of canonical Wnt signalling, suggesting that the two pathways interact for the manifestation of this disease.

    • Alfiya Akhmetshina
    • , Katrin Palumbo
    •  & Jörg H.W. Distler

  • Article |

    Perturbation of the cardiac voltage-gated sodium channel, NaV1.5, by drugs or inherited mutation can underlie and trigger cardiac arrhythmias. Here, the role of the NaV1.5 carboxy terminus in channel inactivation is investigated, and structural details of an arrhythmia associated H6 mutant are reported.

    • Ian W. Glaaser
    • , Jeremiah D. Osteen
    •  & Robert S. Kass

  • Article |

    It is unclear whether pathogens can advantageously exploit the host's immune response. UsingCandida albicans, the authors show that host IL-17A binds to the fungi and induces nutrient starvation and autophagy, which eventually leads to enhanced biofilm formation and resistance to the hosts' defence.

    • Teresa Zelante
    • , Rossana G. Iannitti
    •  & Luigina Romani

  • Article
    | Open Access

    β-Catenin can be oncogenic but finding inhibitors has been a challenge. Here, five compounds are identified, which attenuate transcriptional β-catenin outputs in colorectal cancer cells, and the response to one of them is shown to require an intrinsically labile α-helix next to the BCL9-binding site in β-catenin.

    • Marc de la Roche
    • , Trevor J. Rutherford
    •  & Mariann Bienz

  • Article
    | Open Access

    Molecular factors, regulating the expression of specific glycolytic enzymes that favour biosynthetic processes, have remained unknown. Panasyuket al. identify PPARγ as a novel transcription factor turning on pyruvate kinase M2 and hexokinase 2, which are frequently upregulated in pathophysiological growth.

    • Ganna Panasyuk
    • , Catherine Espeillac
    •  & Mario Pende

  • Article
    | Open Access

    Myeloid cells are important in the response to severe infection by invasiveStreptococcusGroup A. In this study, a distinct population of immature myeloid cells with ring shaped nuclei that produce interferon-γ are shown to be important for protection of mice against the early stages of invasive infection.

    • Takayuki Matsumura
    • , Manabu Ato
    •  & Kazuo Kobayashi

  • Article
    | Open Access

    Spatial epidemiology studies identify malaria hotspots, which sustain transmission and so could be targeted by control programmes. This study uses spatial data on larval sites and malaria episodes to show that transmission can be disrupted by targeting vector breeding sites close to and downwind of malaria hotspots.

    • Janet T. Midega
    • , Dave L. Smith
    •  & Philip Bejon

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