Health sciences articles within Nature Communications

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  • 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
    | Open Access

    Some animal populations are able to shift their birth sex ratio from the expected unity. This study shows, using fluorescencein situhybridization, that in a captive population of pygmy hippopotamus the males appear to be able to adjust the ratio of X- and Y-chromosome-bearing spermatozoa in their ejaculates.

    • Joseph Saragusty
    • , Robert Hermes
    •  & Thomas B. Hildebrandt

  • 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

    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

  • 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 |

    PADI4 is an enzyme that converts arginine residues to citrulline. Here, Tanikawa and colleagues show that, in response to DNA damage, histone H4 and Lamin C are citrullinated in a p53 and PADI4-dependent manner andPadi4-dependent manner and Padi4 null mice are resistant to radiation-induced apoptosis in the thymus.

    • Chizu Tanikawa
    • , Martha Espinosa
    •  & Koichi Matsuda

  • Article
    | Open Access

    Epitopes presented by MHC-II molecules bind to T-cell receptors to activate CD4+ T cells. In this study, changes in the carboxy-terminal region of the influenza hemagglutinin epitope HA305-320alters the strength of binding to the T-cell receptor, thus modulating T-cell receptor usage and activation.

    • David K. Cole
    • , Kathleen Gallagher
    •  & Andrew Godkin

  • Article
    | Open Access

    The signalling cascade involved in lung ischaemia–reperfusion-induced oedema is poorly understood. Using knockout mice, Weissmannet al. propose a model in which reactive oxygen species production by endothelial NOX2 leads to phospholipase C-γ activation, DAG kinase inhibition and subsequent TRPC6 activation.

    • Norbert Weissmann
    • , Akylbek Sydykov
    •  & Alexander Dietrich

  • Article |

    Osteoblast maturation is regulated by c-Src and IL-6, but how these signalling pathways are integrated is not known. Here c-Src is shown to induce 1GFBP5 in immature osteoblasts in a STAT3 and IL-6-dependent manner, in mature osteoblasts, which express lower levels of c-Src, this signalling is lost.

    • Barbara Peruzzi
    • , Alfredo Cappariello
    •  & Anna Teti

  • Article
    | Open Access

    In vertebrates parasite-mediated selection is thought to maintain polymorphism in MHC genes where specific resistance MHC alleles increase under emerging selection. Here, experimental evidence is shown from six stickleback fish populations that varying parasite selection helps maintain MHC polymorphism.

    • Christophe Eizaguirre
    • , Tobias L. Lenz
    •  & Manfred Milinski

  • Article
    | Open Access

    Membrane repair of myocytes is important to prevent such disease as muscular dystrophy but the properties of this repair are not well characterised. In this study, vitamin E is shown to be important in the repair of myocyte cell membranes in cultured cells and in intact muscle.

    • Amber C. Howard
    • , Anna K. McNeil
    •  & Paul L. McNeil

  • Article |

    Encephalization—increase of brain size relative to body size—has occurred in two distinct evolutionary lineages; Neanderthals and modern humans. However, the 3D endocranial surface shape analysis reported here reveals unique structures at the base of the brain inHomo sapiens, which may have contributed to learning and social capacities.

    • Markus Bastir
    • , Antonio Rosas
    •  & Jean-Jacques Hublin

  • Article
    | Open Access

    New approaches are required to combatPlasmodium falciparuminfection. In this proteome-wide study, 1305 phosphorylation sites are identified and 36 kinases are shown to have crucial roles in parasite survival, providing new insights into parasite biology and potential new drug targets for anti-malarial chemotherapy.

    • Lev Solyakov
    • , Jean Halbert
    •  & Christian Doerig

  • Article |

    The processes that regulate melanoblast migration during development are also thought to be involved in melanoma metastasis. Here, Prex1 null mice are shown to have a melanoblast migration defect and, when crossed to a mouse model of melanoma, are resistant to metastasis, suggesting a role for Prex1 in metastatic melanoma.

    • Colin R. Lindsay
    • , Samuel Lawn
    •  & Owen J. Sansom

  • Article |

    Erythropoietin circulates in the blood and is essential for erythropoiesis but its role in metabolic homeostasis has not been examined. Tenget al. show that when the erythropoietin receptor is only expressed in erthyroid cells, mice develop obesity and insulin resistance, suggesting that the receptor has a key role in fat mass accumulation.

    • Ruifeng Teng
    • , Oksana Gavrilova
    •  & Constance Tom Noguchi

  • Article
    | Open Access

    MicroRNAs bind to the 3′-untranslated region of genes to regulate expression. In this study, an RNA-binding protein, RMB38, is shown to selectively regulate the access of some microRNAs to their targets, and control the expression of some p53 target genes.

    • Nicolas Léveillé
    • , Ran Elkon
    •  & Reuven Agami

  • Article
    | Open Access

    During cell division, a cytoplasmic bridge—the midbody—forms between the nascent daughter cells, but it has been unclear under which conditions this is retained by a daughter cell or released. Now, Ettinger and colleagues show that midbody-release occurs more frequently in stem cells compared with cancer cells.

    • Andreas W. Ettinger
    • , Michaela Wilsch-Bräuninger
    •  & Wieland B. Huttner

  • Article |

    The fusion of satellite cells to muscle fibres during adult life is required for both muscle growth and regeneration but it is unknown whether non-muscle cells contribute to this process. Now, Dellavalle and colleagues show that pericytes, cells associated with the vasculature can contribute to both growth and regeneration of muscle fibres.

    • A. Dellavalle
    • , G. Maroli
    •  & G. Cossu

  • Article |

    The generation of human cell lines using somatic cell nuclear transfer has been difficult to achieve. In this study, Egliet al. show that while mouse eggs reprogram somatic cells within hours, human eggs arrest after nuclear transfer which may be due to a lack of genome transcription.

    • Dieter Egli
    • , Alice E. Chen
    •  & Kevin Eggan

  • Article
    | Open Access

    The risk factors associated with both ischemic and haemorrhagic stroke are not fully understood. Here a certain strain of the bacteria,Streptococcus mutans, which expresses a collagen-binding protein, is shown to be associated with haemorrhagic stroke in both animal models and human patients.

    • Kazuhiko Nakano
    • , Kazuya Hokamura
    •  & Takashi Ooshima

  • Article |

    Cellular senescence is characterized by the cessation of cell growth and the expression of the p16 protein. In this study, inhibition or loss of p300, a histone acetyltransferase, is shown to result in senescence that occurs independently of p16 and is associated with histone hypoacetylation and altered replication timing.

    • Alexandre Prieur
    • , Emilie Besnard
    •  & Jean-Marc Lemaitre

  • Article |

    Protein microarrays are useful both in basic research and also in disease monitoring and diagnosis, but their dynamic range is limited. By using plasmonic gold substrates with near-infrared fluorescent enhancement, Tabakman et al. demonstrate a multiplexed protein array with improved detection limits and dynamic range.

    • Scott M. Tabakman
    • , Lana Lau
    •  & Hongjie Dai

  • Article |

    Recent technological advances have allowed the expansion of spermatogonial stem cellsin vitro; however, in vivo conditions are required for the full differentiation of the cells. In this study, an in vitroorgan culture system is developed that allows the differentiation of the germ cells in the laboratory.

    • Takuya Sato
    • , Kumiko Katagiri
    •  & Takehiko Ogawa

  • Article
    | Open Access

    Many mammals are born with an immature intestinal epithelium, which adapts to a changing diet during the weaning period. Muncanet al. show that the transcriptional repressor Blimp1is expressed in the intestine of mice at birth, and that expression is lost at the transition to the weaning stage.

    • Vanesa Muncan
    • , Jarom Heijmans
    •  & Gijs R. van den Brink

  • Article
    | Open Access

    Pluripotent stem cells can be generated from the somatic cells of humans and are a useful model to study disease. Here, pluripotent stem cells are made from a patient with familial Parkinson's disease, and the resulting neurons exhibit elevated levels of α-synuclein, recapitulating the molecular features of the patient's disease.

    • Michael J. Devine
    • , Mina Ryten
    •  & Tilo Kunath

  • Article |

    MITF is a transcription factor required for melanocyte development, which is activated in some melanomas. Zhao and colleagues show that USP13 removes ubiquitin from MITF, stabilizes MITF protein levels and enhances colony formation, suggesting that USP13 may be a therapeutic target in melanoma.

    • Xiansi Zhao
    • , Brian Fiske
    •  & David E Fisher

  • Article
    | Open Access

    Chk2 is a kinase that is a potential chemotherapeutic target. Here, Chk2 and the kinase ERK are shown to functionally interact, and are elevated in expression in human diffuse B-cell lymphomas. Combinatorial inhibition of the kinases was also shown to block tumour growth in anin vivomouse model.

    • Bojie Dai
    • , X. Frank Zhao
    •  & Ronald B. Gartenhaus

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