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.
TITLE:
Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation
AUTHOR CONTACT:
Caroline Demangel
Institut Pasteur, Paris Cedex 15, FRA
Phone: 33 1 40 61 30 66; E-mail: demangel@pasteur.fr
View this article at: http://www.jci.org/articles/view/66576?key=27d03cca761796d4a69e
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.
TITLE:
Eliminating malignant contamination from therapeutic human spermatogonial stem cells
AUTHOR CONTACT:
Kyle Orwig
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Phone: 412-641-2460; Fax: 412-641-3899; E-mail: orwigke@upmc.edu
View this article at: http://www.jci.org/articles/view/65822?key=92403084007f62aaa983
ALSO IN THIS ISSUE
TITLE:
Autocrine production of IL-11 mediates tumorigenicity in hypoxic cancer cells
AUTHOR CONTACT:
Giovanni Melillo
Bristol-Myers Squibb, Princeton, NJ, USA
Phone: 609-2526975; Fax: 609-252-7821; E-mail: Giovanni.Melillo@bms.com
View this article at: http://www.jci.org/articles/view/59623?key=09427167d2ca471d63fb
TITLE:
Myeloid cell-specific serine palmitoyltransferase subunit 2 haploinsufficiency reduces murine atherosclerosis
AUTHOR CONTACT:
Xian-Cheng Jiang
SUNY Downstate Medical Center, Brooklyn, NY, USA
Phone: 718-270-6701; E-mail: xjiang@downstate.edu
View this article at: http://www.jci.org/articles/view/60415?key=2c47d954d23f558696b6
TITLE:
Tumor fibroblast-derived epiregulin promotes growth of colitis-associated neoplasms through ERK
AUTHOR CONTACT:
Clemens Neufert
Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, UNK, DEU
Phone: 49 9131 8535000; E-mail: clemens.neufert@uk-erlangen.de
View this article at: http://www.jci.org/articles/view/63748?key=c6681cc88546bfff242d
TITLE:
GSK-3α is a central regulator of age-related pathologies in mice
AUTHOR CONTACT:
Thomas Force
Temple University, Philadelphia, PA, USA
E-mail: thomas.force@temple.edu
View this article at: http://www.jci.org/articles/view/64398?key=827027eeb251673d7eac
TITLE:
Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis
AUTHOR CONTACT:
Aleeza Roth
University of North Carolina Chapel Hill, Chapel Hill, NC, USA
Phone: 9196198839; E-mail: ajroth@med.unc.edu
View this article at: http://www.jci.org/articles/view/65292?key=104b89aefe7b5eb7d6f3
TITLE:
Hepatic glucose sensing is required to preserve β-cell glucose competence
AUTHOR CONTACT:
Bernard Thorens
University of Lausanne, Lausanne, CHE
Phone: 41 21 692 3981; Fax: 41 21 692 3985; E-mail: bernard.thorens@unil.ch
View this article at: http://www.jci.org/articles/view/65538?key=f5ec82cf2167aad8336d
TITLE:
Calcium influx through L-type CaV1.2 Ca2+ channels regulates mandibular development
AUTHOR CONTACT:
Geoffrey Pitt
Duke University Medical Center, Durham, NC, USA
Phone: 919-668-7641; E-mail: geoffrey.pitt@duke.edu
View this article at: http://www.jci.org/articles/view/66903?key=ca855a0861b197867ade
Journal
Journal of Clinical Investigation