Articles in 2014

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  • After decades of decline, South Africa's Medical Research Council has undergone a dramatic turnaround in recent years, with a more than 50% increase in government funding. But as the leader credited with this turnaround prepares to step down at the end of next month, onlookers worry about what lies ahead for the institute. Linda Nordling reports.

    • Linda Nordling
    News Feature
  • Numerous neurodegenerative diseases show deposition of protein aggregates, which are thought to cause neuronal damage. This Review discusses how cell-to-cell transmission of these pathogenic misfolded proteins is involved in initiation and progression of the disease and examines the clinical relevance of different strains in the heterogeneity of neurodegenerative disorders.

    • Jing L Guo
    • Virginia M Y Lee
    Review Article
  • Immune surveillance has been proposed to eliminate transformed cells and thereby limit tumor formation. Axel Kallies and colleagues now report that spontaneous B cell lymphoma development in Blimp1-deficient or Bcl6-overexpressing mice is accelerated by T cell deficiency and identify the Fas-Fas ligand pathway as a crucial mediator of T cell control of lymphoma growth.

    • Shoukat Afshar-Sterle
    • Dimitra Zotos
    • Axel Kallies
  • Diagnosis of bacterial infections is largely based on nonspecific criteria, with definitive diagnoses made only after biopsy or culture. Frank Hernandez and his colleagues demonstrate noninvasive imaging of Staphylococcus aureus infections in mice with an activatable fluorescent molecular imaging probe. The approach exploits the properties of micrococcal nuclease and uses short, synthetic oligonucleotides that are highly sensitive to micrococcal nuclease but are rendered resistant to mammalian serum nucleases by chemical modifications.

    • Frank J Hernandez
    • Lingyan Huang
    • James O McNamara II
    Technical Report
  • Although numerous studies have demonstrated anti-atherosclerotic effects of high-density lipoprotein (HDL), drugs that elevate HDL cholesterol levels have failed in the clinic. Stanley Hazen and colleagues provide a potential explanation for this paradox by showing that within human atherosclerotic plaques and plasma of individuals with coronary artery disease, apoA1—the major apolipoprotein present in HDL—is modified by oxidation of a specific tryptophan residue, impairing the anti-atherosclerotic function of apoA1 and HDL.

    • Ying Huang
    • Joseph A DiDonato
    • Stanley L Hazen
  • Gaucher's disease is a lysosomal storage disease caused by mutations in the glucocerebrosidase gene. Now, Anthony Futerman and his colleagues report that the expression of proteins linked to a form of cell death called necroptosis is increased in Gaucher's disease and that blocking these proteins can improve disease in a mouse model.

    • Einat B Vitner
    • Ran Salomon
    • Anthony H Futerman
  • In heart muscle cells, sarcoplasmic reticulum calcium overload leads to spontaneous calcium waves that can cause arrhythmias and sudden cardiac death. S.R. Wayne Chen and his colleagues now detail the molecular mechanism by which intra–sarcoplasmic reticulum calcium ions interact with the gate of the calcium release channel RyR2, explaining how calcium waves are initiated and thereby contribute to calcium-triggered arrhythmias.

    • Wenqian Chen
    • Ruiwu Wang
    • S R Wayne Chen
  • In a new study by Kamran Atabai and colleagues, the milk fat globule protein, Mfge8, is found to promote the uptake of dietary fat and the absorption of fatty acids by peripheral organs via activation of integrin signaling and the expression of fatty acid transporters. They also found that genetic deletion of Mfge8 protected mice from diet-induced obesity and insulin resistance.

    • Amin Khalifeh-Soltani
    • William McKleroy
    • Kamran Atabai
  • Understanding how and where HIV-1 infection persists in the body is crucial for efforts to eradicate the viral reservoir. Now Mathias Lichterfeld and his colleagues report that HIV-1 can infect CD4+ T memory stem cells (TSCM cells) and that infected TSCM cells constitute a stable component of the viral reservoir in individuals treated with antiretroviral therapy.

    • Maria J Buzon
    • Hong Sun
    • Mathias Lichterfeld
    Brief Communication
  • PET imaging using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) has been widely used for the detection of plaque inflammation. Here, however, Nobuhiro Tahara and colleagues explore the possibility of using 18F-labeled mannose (2-deoxy-2-[18F]fluoro-d-mannose, [18F]FDM), a structural analog to FDG, as an alternative and potentially more specific PET tracer than FDG for assessing the risk of acute vascular events in patients. The approach targets the mannose receptor–bearing macrophages that are abundant in high-risk atherosclerotic plaques, with feasibility demonstrated in a rabbit model of atherosclerosis.

    • Nobuhiro Tahara
    • Jogeshwar Mukherjee
    • Jagat Narula
    Technical Report
  • Retinoic acid and arsenic therapies have shown considerable efficacy in patients with acute promyelocytic leukemia, but their exact mechanism of action remains unclear. Here, Hugues de Thé and colleagues uncover a therapeutic effect mediated by nuclear body reformation and p53 activation that involves the induction of a senescence transcriptional program. These data suggest that redifferentiation and apoptosis induction may not be sufficient for the effect of these agents in patients and uncover alternative therapeutic routes that could be applied to other tumor and treatment types.

    • Julien Ablain
    • Kim Rice
    • Hugues de Thé
  • Monoclonal antibodies (mAbs) that bind the stalk domain of the influenza hemagglutinin glycoprotein have been shown to have broadly neutralizing activity against diverse influenza subtypes. In this study, DiLillo et al. report that, unlike strain-specific anti–hemagglutinin head domain mAbs, anti-stalk mAbs can mediate antibody-dependent cell cytotoxicity and require interactions with Fc receptors for their in vivo neutralizing activity.

    • David J DiLillo
    • Gene S Tan
    • Jeffrey V Ravetch
  • The measurement of metabolites such as creatine, which are involved in the tissue creatine kinase reaction, enable the study of the effects of energy deprivation on the heart. Haris and colleagues introduce a new magnetic resonance imaging technique that maps the distribution of creatine in the heart that does not use radiation or exogenous contrast agents and offers higher sensitivity compared to proton (1H) magnetic resonance spectroscopy methods. Feasibility is demonstrated in vivo in infarcted swine myocardium using a standard clinical MRI scanner.

    • Mohammad Haris
    • Anup Singh
    • Ravinder Reddy
    Technical Report