JCI early table of contents for Mar. 15, 2013

Public release date: 15-Mar-2013
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Contact: Jillian Hurst
press_releases@the-jci.org
Journal of Clinical Investigation

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-Universitt Erlangen-Nrnberg, 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-3? 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 ?-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

###

---

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AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Public release date: 15-Mar-2013
[ | E-mail | Share ]

Contact: Jillian Hurst
press_releases@the-jci.org
Journal of Clinical Investigation

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-Universitt Erlangen-Nrnberg, 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-3? 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 ?-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

###

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Source: http://www.eurekalert.org/pub_releases/2013-03/joci-jet030813.php

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