Molecular medicine

  • Article
    | Open Access

    Fusion gene research traditionally focuses on fusions that result in hybrid proteins or promoter switching events. Here, the authors demonstrate enrichment of fusions in miRNA host genes in breast cancer, highlighting that disparate fusions could have convergent impact on miRNA.

    • Helena Persson
    • , Rolf Søkilde
    •  & Carlos Rovira
  • Article
    | Open Access

    Traditional approaches used in the pharmaceutical industry are not precise or versatile enough for customized medicine formulation and manufacture. Here the authors produce a method to form coatings, with accurate dosages, as well as a means of closely controlling dissolution kinetics.

    • Olga Shalev
    • , Shreya Raghavan
    •  & Max Shtein
  • Article
    | Open Access

    The Singapore Genome Variation projects characterized the genetics of Singapore’s Chinese, Malay, and Indian populations. The Singapore Integrative Omics Study introduced here goes further in providing multi-omic measurements in individuals from these populations, including genetic, transcriptome, lipidome, and lifestyle data, and will facilitate the study of common diseases in Asian communities.

    • Woei-Yuh Saw
    • , Erwin Tantoso
    •  & Yik-Ying Teo
  • Article
    | Open Access

    Deep penetrating nevi (DPN) are unusual melanocytic neoplasms with unknown genetic drivers. Here the authors show that majority of DPN harbor activating mutations in the β-catenin and the MAP-kinase pathways; this characteristic can help in the classification and grading of these distinctive neoplasms.

    • Iwei Yeh
    • , Ursula E. Lang
    •  & Arnaud de la Fouchardière
  • Article
    | Open Access

    Megakaryocyte maturation is thought to occur as the cells migrate from a vessel-distant (endosteal) niche to the vessel within the bone. Here, the authors show that megakaryocytes represent largely sessile cells in close contact with the vasculature and homogeneously distributed in the bone marrow.

    • David Stegner
    • , Judith M. M. vanEeuwijk
    •  & Katrin G. Heinze
  • Article
    | Open Access

    Humans are less sensitive to the therapeutic effects of botulinum neurotoxin B (BoNT/B) than the animal models it is tested on due to differences between the human and the mouse receptors. Here, the authors engineer BoNT/B to improve its affinity to human receptors and enhance its therapeutic efficacy.

    • Liang Tao
    • , Lisheng Peng
    •  & Min Dong
  • Article
    | Open Access

    Sodium/proton exchangers (NHEs) are critical regulators of pH within the cell and the extracellular microenvironment. Here, the authors show that hypoxia induces mobilization of NHE6 from endosomal compartment to the plasma membrane in a PKC-dependent manner inducing hyper acidification of endosomes and drug resistance.

    • Fabrice Lucien
    • , Pierre-Paul Pelletier
    •  & Claire M. Dubois
  • Article
    | Open Access

    A major cause of transplanted organ failure is graft arteriosclerosis. Qiuet al. show that a key protease of post-translational SUMO modification, SENP1, is crucial for graft arteriosclerosis by regulating the activity of GATA2 transcription factor in the endothelium, and promoting endothelial inflammation and alloimmunity.

    • Cong Qiu
    • , Yuewen Wang
    •  & Luyang Yu
  • Article
    | Open Access

    Benzoxaboroles have been shown to be active against different pathogens. Here, the authors show that the benzoxaborole AN3661 inhibitsPlasmodium falciparum in vitroand in mouse models, and identify a homologue of a mammalian cleavage and polyadenylation specificity factor as a drug target.

    • Ebere Sonoiki
    • , Caroline L. Ng
    •  & Philip J. Rosenthal
  • Article
    | Open Access

    What keeps blood from clotting in homeostasis is a puzzle. Here, the authors suggest that lack of the enzyme disulfide isomerase (PDI) in the blood is key, and show that PDI is secreted only after vascular injury to act on substrates that include vitronectin, affecting its binding to αVβ3 and αIIbβ3 integrins and enabling thrombus formation.

    • Sheryl R. Bowley
    • , Chao Fang
    •  & Bruce Furie
  • Article
    | Open Access

    Humans that reach high altitude soon after the first ascent show faster adaptation to hypoxia. Songet al. show that this adaptive response relies on decreased red blood cell uptake of plasma adenosine due to reduced levels of nucleoside transporter ENT1 resulting from coordinated adenosine generation by ectonucleotidase CD73 and activation of A2B receptors.

    • Anren Song
    • , Yujin Zhang
    •  & Yang Xia
  • Article
    | Open Access

    The free fatty acid-mediated inflammatory activities are regulated through TLR4. Here the authors show that palmitic acid binds to MD2, initiating complex formation with TLR4, recruitment of MyD88, and subsequent activation of pro-inflammatory molecules, and that MD2 blockade protects against diet-induced cardiac dysfunction.

    • Yi Wang
    • , Yuanyuan Qian
    •  & Guang Liang
  • Article
    | Open Access

    JAK1 mediates intracellular signalling from multiple cytokine receptors. Here, Elettoet al. identify JAK1 mutations that disrupt multiple signalling pathways and are associated with primary immunodeficiency, atypical mycobacterial infection susceptibility and early-onset metastatic bladder carcinoma.

    • Davide Eletto
    • , Siobhan O. Burns
    •  & Sergey Nejentsev
  • Article
    | Open Access

    Gene editing approaches are widely used for correcting mutations, but their application is largely limited to cells and not living animals. Here the authors show that in vivoγPNA-mediated editing of a β-globin mutation is promoted by SCF and leads to sustained normalization of blood haemoglobin levels β-thalassemic mice.

    • Raman Bahal
    • , Nicole Ali McNeer
    •  & Peter M. Glazer
  • Article
    | Open Access

    Biological applications of x-ray fluorescence (XRF) imaging are currently limited to mapping naturally occurring elements in tissues. Here, the authors encapsulate toxic elements in functionalized single walled nanotubes, and use them as non-toxic XRF contrast agents for imaging specific cellular organelles.

    • Christopher J. Serpell
    • , Reida N. Rutte
    •  & Benjamin G. Davis
  • Article
    | Open Access

    Nephropathy is a common and hard-to-treat consequence of diabetes. Here Kato et al. show that a megacluster of microRNAs regulates early development of diabetic nephropathy in mice, and that inhibition of the cluster's host long non-coding RNA transcript attenuates disease symptoms, suggesting a new therapy for diabetic nephropathy.

    • Mitsuo Kato
    • , Mei Wang
    •  & Rama Natarajan
  • Article
    | Open Access

    Dopaminergic neurons are important for regulating energy homeostasis. Here, the authors show the transcription factor FoxO1 negatively regulates tyrosine hydroxylase expression in midbrain dopaminergic neurons, and plays an important role in regulation of glucose homeostasis, energy expenditure, and resistance to diet-induced obesity.

    • Khanh V. Doan
    • , Ann W. Kinyua
    •  & Ki Woo Kim
  • Article
    | Open Access

    The platelets detect and respond to shear stress generated by blood flow. Here the authors show that the binding of the soluble von Willebrand factor to its receptor GPIba under physiological shear stress induces receptor's domain unfolding on the platelet and signalling into the platelet, leading to platelets clearance.

    • Wei Deng
    • , Yan Xu
    •  & Renhao Li
  • Article
    | Open Access

    The inorganic procoagulant polymer polyphosphate participates in thrombosis via factor XII. Here the authors use recombinant probes that specifically bind or degrade circulating polyphosphate to protect mice in arterial and venous thrombosis models without an increased bleeding risk, the primary complication of all currently used anticoagulants.

    • Linda Labberton
    • , Ellinor Kenne
    •  & Thomas Renné
  • Article
    | Open Access

    MURC protein regulates the function of caveolae, the small invaginations of the plasma membrane in muscle cells. Here the authors show that by interacting with caveolin proteins, MURC affects RhoA/ROCK signalling and regulates proliferation and migration of pulmonary artery smooth muscle cells, suggesting a new target in therapy of pulmonary hypertension.

    • Naohiko Nakanishi
    • , Takehiro Ogata
    •  & Tomomi Ueyama