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JCI early table of contents for Mar. 15, 2013

Cytoskeletal dysregulation underlies Buruli ulcer formation

Mycobacterium ulcerans infects the skin and subcutaneous tissues and secretes a lipid toxin, mycolactone, which causes open skin lesions, known as Buruli ulcers. In this issue of the Journal of Clinical Investigation, researchers led by Caroline Demangel at the Pasteur Institue in Paris investigated the molecular actions of mycolactone and found that it dysregulates the cellular skeleton (cytoskeleton) through activation of a protein known as N-WASP. They found that excessive N-WASP activity caused defects in cell adhesion and migration that impaired the integrity of the skin. Demangel and colleagues demonstrated that they could block the degradation process by administration of the N-WASP inhibitor wiskostatin. These results reveal the molecular pathogenesis of M. ulcerans and suggest that drugs that disrupt mycolactone/N-WASP interaction could be used to treat Buruli ulcers.

Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation

Caroline Demangel
Institut Pasteur, Paris Cedex 15, FRA
Phone: 33 1 40 61 30 66; E-mail:

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Sorting out fertility after childhood cancer

As success rates in treating childhood cancers have improved, greater emphasis is being placed on quality of life issues following successful treatment. Many cancer treatments can lead to infertility, but there are few methods to preserve the fertility of children who have not entered puberty. Spermatogonial stem cells (SSCs), which produce sperm cells, are present prior to the start of puberty. In theory, SSCs could be removed via biopsy prior to the start of treatment and then retransplanted following remission; however, there is a potential risk of reintroducing malignant material during transplantation. To overcome this hurdle, Serena Dovey and colleagues at the University of Pittsburgh characterized the cell surface markers of human spermatogonia in testicular tissue from organ donors. In this issue of the Journal of Clinical Investigation, Dovey and colleagues report the development of a multi-parameter sorting approach to separate SSCs from cancerous cells. Sorted SSCs exhibited were able to function properly when transplanted into mice, but did not form tumors. These results suggest that SSC transplantation could be a viable method to preserve fertility in male childhood cancer survivors.

Eliminating malignant contamination from therapeutic human spermatogonial stem cells

Kyle Orwig
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Phone: 412-641-2460; Fax: 412-641-3899; E-mail:

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Autocrine production of IL-11 mediates tumorigenicity in hypoxic cancer cells

Giovanni Melillo
Bristol-Myers Squibb, Princeton, NJ, USA
Phone: 609-2526975; Fax: 609-252-7821; E-mail:

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Myeloid cell-specific serine palmitoyltransferase subunit 2 haploinsufficiency reduces murine atherosclerosis

Xian-Cheng Jiang
SUNY Downstate Medical Center, Brooklyn, NY, USA
Phone: 718-270-6701; E-mail:

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Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK

Clemens Neufert
Friedrich-Alexander-Universitt Erlangen-Nrnberg, Erlangen, UNK, DEU
Phone: 49 9131 8535000; E-mail:

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GSK-3α is a central regulator of age-related pathologies in mice

Thomas Force
Temple University, Philadelphia, PA, USA

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Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis

Aleeza Roth
University of North Carolina Chapel Hill, Chapel Hill, NC, USA
Phone: 9196198839; E-mail:

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Hepatic glucose sensing is required to preserve β-cell glucose competence

Bernard Thorens
University of Lausanne, Lausanne, CHE
Phone: 41 21 692 3981; Fax: 41 21 692 3985; E-mail:

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Calcium influx through L-type CaV1.2 Ca2+ channels regulates mandibular development

Geoffrey Pitt
Duke University Medical Center, Durham, NC, USA
Phone: 919-668-7641; E-mail:

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Contact: Jillian Hurst
Journal of Clinical Investigation

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